[A Case of Distal Gastrectomy and Left Segmentectomy for Hepatic Invasion of Gastric Cancer].

A 66-year-old male came to our hospital because of occult blood in stool and anemia. The patient was diagnosed as unresectable advanced gastric cancer,( ML/Less, type 2, tub2, cT4b[liver], cN+, cM0, cStage Ⅳ, HER2 negative). He was given oxaliplatin plus S-1 therapy. In the 3rd course of chemotherapy, he had severe anemia, and active bleeding from the tumor. To control the bleeding he underwent distal gastrectomy, lateral segmentectomy of the liver, and S4 partial hepatectomy. The patient underwent adjuvant chemotherapy with docetaxel plus S-1. Three months after surgery, lymph nodes recurrence was observed. He underwent second-line therapy with paclitaxel and ramucirumab. Seven months after surgery, lymph nodes recurrence was increased. He was switched to third-line therapy with nivolumab. He is currently arrive 12 months after surgery.

[A Case of Colon Metastasis after Surgery for Left Renal Pelvis Cancer].

The patient was a 73-year-old man. He was diagnosed with left renal pelvic carcinoma(papillary urothelial carcinoma, pT3aN0M0, Stage Ⅱ)at the age of 69. Left nephroureterectomy and partial cystectomy were performed at our hospital. At the age of 71, he was diagnosed with a recurrent bladder tumor and underwent radical cystectomy and ureteroenterostomy at a different hospital. At the age of 73, he visited our hospital with abdominal pain. Computed tomography(CT)revealed wall thickening of the descending colon and dilation of the oral tract. Emergency colonoscopy was performed. He was diagnosed with intestinal obstruction due to descending colon cancer. Colonoscopy revealed a circumferential type 2 lesion in the descending colon that was completely stenosed. Colonic stent placement was performed. A tumor biopsy confirmed the diagnosis of micropapillary adenocarcinoma. The preoperative diagnosis was descending colon cancer cT4aN2aM0, cStage Ⅲc. One month after stent placement, an open segmental resection of the descending colon with D2 dissection was performed. Immunostaining of the specimen showed CK7(+)and CK20(-), and the postoperative diagnosis was a recurrence of left renal pelvic carcinoma in the descending colon. We report a rare case of renal pelvic carcinoma that recurred in the descending colon 4 years after initial surgery.

Neurogenesis impairment with glial activation in the hippocampus-connected regions of intracerebroventricular streptozotocin-injected mice.

Adult neurogenesis in the hippocampus and subventricular zone (SVZ) is impaired by intracerebroventricular administration of streptozotocin (icv-STZ) to rodents. Although neural cells in the several brain regions which connect with the hippocampus or SVZ is thought to be involved in the adult neurogenesis, few studies have investigated morphological alterations of glial cells in these areas. The present study revealed that icv-STZ induces reduction of neural progenitor cells and a dramatic increase in reactive astrocytes and microglia especially in the hippocampus and various hippocampus-connected brain areas. In contrast, there was no significant neuronal damage excluding demyelination of the stria medullaris. The results indicate the hippocampal neurogenesis impairment of this model might be occurred by activated glial cells in the hippocampus, or hippocampus-connected regions.

4.5SH RNA counteracts deleterious exonization of SINE B1 in mice.

4.5SH RNA is a highly abundant, small rodent-specific noncoding RNA that localizes to nuclear speckles enriched in pre-mRNA-splicing regulators. To investigate the physiological functions of 4.5SH RNA, we have created mutant mice that lack the expression of 4.5SH RNA. The mutant mice exhibited embryonic lethality, suggesting that 4.5SH RNA is an essential species-specific noncoding RNA in mice. RNA-sequencing analyses revealed that 4.5SH RNA protects the transcriptome from abnormal exonizations of the antisense insertions of the retrotransposon SINE B1 (asB1), which would otherwise introduce deleterious premature stop codons or frameshift mutations. Mechanistically, 4.5SH RNA base pairs with complementary asB1-containing exons via the target recognition region and recruits effector proteins including Hnrnpm via its 5' stem loop region. The modular organization of 4.5SH RNA allows us to engineer a programmable splicing regulator to induce the skipping of target exons of interest. Our results also suggest the general existence of splicing regulatory noncoding RNAs.

Possible Role of Bent Structure of Methylated Lithocholic Acid on Artificial and Plasma Membranes.

Bile acids form micelles that are essential for the absorption of dietary lipids. However, excessive bile acid micelles can disrupt the plasma membrane by removing phospholipids, resulting in cell death. We hypothesized that the bent geometrical structure of the steroid scaffold of bile acids decreases the lipid order (similar to unsaturated phospholipids with cis double bonds), disrupting the plasma membrane. Here, lithocholic acid (LCA), a bile acid, was methylated to prevent micellization. Methylated lithocholic acid (Me-LCA) was mixed with a thin phase-separated lipid bilayer comprising 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and cholesterol (Chol). Me-LCA was not localized in the DPPC-rich rigid phase but localized in the DOPC-rich fluid phase, and excess Me-LCA did not affect the phase separation. Me-LCA is distributed in the plasma and organelle membranes. However, Me-LCA with bent structure did not affect the membrane properties, membrane fluidity, and hydrophobicity of liposomes composed of DOPC, DPPC, and Chol and also did not affect the proliferation of cells.

Solitary Cardiac Metastasis from Colorectal Cancer: A Case Report.

A 73-year-old woman with silent cardiac metastasis underwent high anterior resection for rectal cancer 3 years ago. Follow-up computed tomography showed a tumor in the right atrium. Partial vascular resection of the superior vena cava and right atrium was performed. Early postoperative recurrence occurred, and chemotherapy was unsuccessful. The patient died 7 months after surgery.

[Resected Metachronous Pancreatic Metastasis from Rectal Cancer-A Case Report].

A 68-year-old woman had undergone laparoscopic high anterior resection for rectal cancer. Two years postoperatively, metachronal pulmonary metastases and cerebellar metastasis were surgically resected. Three and a half years after the primary surgery, computed tomography(CT)demonstrated a nodule at the pancreatic tail. Under suspected primary pancreatic cancer or metastasis from rectal cancer, we performed distal pancreatectomy. Histological examination of the pancreatic tumor suggested a metastasis from the rectal cancer since tumor cells were negative for CK7 and positive for CK20 and CDX2 immunohistochemically. Three months after the pancreatic resection, CT demonstrated hepatic and cerebellar metastases. After subsequent chemotherapy, liver metastasis disappeared. The cerebellar metastasis shrank with radiotherapy.

[A Case of Port-Site Herniation from an Eight mm Port after Robot-Assisted Distal Gastrectomy].

A 63-year-old-woman was diagnosed with gastric cancer cStage ⅠA after ESD, and then, underwent robot-assisted distal gastrectomy. She vomited on the postoperative day 2 and then was inserted nasogastric tube. The amount of drainage from the tube was increased on the postoperative day 5, therefore, abdominal computed tomography scan was performed, which showed herniation of small bowel at the 8 mm port site in the left upper abdomen. The emergent surgery was performed because of difficulty in manual reduction. Intraoperative findings showed that small intestine was incarcerated at the left 8 mm port-site. The intestine was released by incising the fascia of hernia orifice, then, the fascia was repaired. There was no recurrence of gastric cancer and port-site hernia for 34 months after surgery. In general, the fascia of over 10 mm port site is sutured and closed to avoid port-site hernia, however, it is unclear whether the fascia of 8 mm port-site should be closed after robotic surgery. Since we experienced this case, we have also performed fascia suture on the 8 mm port-site in all cases. And then, we could prevent occurrence of port-site hernia in the 8 mm port-site.

[A Case of Malignant Melanoma Metastasized to the Small Intestine].

A case of 69-year-old man underwent resection for the plantar surface of left foot malignant melanoma and received a sentinel biopsy of left inguinal lymph node. Two years and 10 months later, a mass of 30 mm in diameter in the ileum was detected by contrast-enhanced computed tomography, which showed abnormal uptake using FDG positron emission tomography. The partial intestinal resection was performed, and then, the mass was diagnosed as metastasis of malignant melanoma by pathological examination. Malignant melanoma is highly malignant disease that frequently shows distant metastasis. Although the malignant melanoma with distant metastasis shows poor prognosis, previous studies reported the prognosis could be improved when the patient could receive curative resection for single intraabdominal metastasis. Therefore, surgical resection should be considered for the single metastasis of malignant melanoma. We report a case of malignant melanoma with ileum metastasis resected curatively with literature review.

Improving laser cooling efficiencies of Yb-doped yttrium aluminum garnet by utilizing non-resonant anti-Stokes emission at high temperatures.

Laser cooling in solids has been demonstrated, and cooling from room temperature to cryogenic temperatures has so far been the main focus of research. However, operation at high temperatures can be advantageous. We propose that laser cooling of Yb-doped yttrium aluminum garnet ceramic discs is enhanced above 300 K. Photoluminescence (PL) spectra is evidence that the phonon-assisted energy transfer from resonant states, which exhibit a narrow PL peak, to inhomogeneously distributed energy states becomes stronger at higher temperatures. This results in an enhanced non-resonant anti-Stokes PL at high temperatures. The ideal cooling efficiency determined from the PL spectrum at 470 K is 1.7 times higher than that at 300 K.

Priming and replenishment in cardiopulmonary bypass with hydroxyethyl starch 130/0.4 decreases fluid overbalance without renal dysfunction or bleeding in adult valve surgery.

The best priming and replenishment solution in cardiopulmonary bypass remains unknown, and the efficacy and drawbacks of artificial colloid are controversial. We retrospectively compared consecutive patients undergoing elective adult valve surgery in cases wherein cardiopulmonary bypass was primed and replenished with hydroxyethyl starch 130/0.4 (n = 12) or crystalloid solution (n = 11). The fluid overbalance during cardiopulmonary bypass was much lower in the hydroxyethyl starch 130/0.4 group (mean ± standard deviation, + 95 ± 1241 mL) than in the crystalloid solution group (+ 2921 ± 1984 mL) (P < 0.001). Renal function, intraoperative and postoperative bleeding, and blood products did not deteriorate with the use of hydroxyethyl starch 130/0.4. The postoperative intubation time was shorter in the hydroxyethyl starch 130/0.4 group (16.0 ± 2.6 h) than in the crystalloid solution group (18.7 ± 2.6 h) (P = 0.018). Although prospective randomized trials are needed to verify our findings, the impact of fluid balance differences requires serious consideration.

Shogaol but not gingerol has a neuroprotective effect on hemorrhagic brain injury: Contribution of the α, ß-unsaturated carbonyl to heme oxygenase-1 expression.

We investigated the effects of shogaol, which has an α, ß-unsaturated carbonyl group, and gingerol, which does not, on primary-cultured microglia to understand how the α, ß-unsaturated carbonyl interacts with Kelch-like ECH-associated protein (Keap)1. Shogaol (1 µM) but not the same concentration of gingerol significantly increased heme oxygenase (HO)-1 protein levels in cultured microglia without cytotoxicity. In addition, shogaol suppressed the release of the inflammation marker nitric oxide induced by 30 U/ml thrombin treatment. A docking simulation suggested that the α, ß-unsaturated carbonyl of shogaol but not gingerol interacts with Keap1. Nuclear import of nuclear factor E2-related factor 2 and increased binding of the HO-1 E2 enhancer support the docking-simulation prediction. The transcription inhibitor actinomycin D (0.1 µg/ml) markedly blocked the increase of HO-1 mRNA levels by shogaol. To evaluate whether the α, ß-unsaturated carbonyl can be used for intracerebral hemorrhage (ICH) therapy, we investigated the effect of shogaol on an in vivo mouse ICH model. Intracerebroventricular injection of 0.2 nmol shogaol increased striatal HO-1 protein levels and rescued ICH-induced neuron loss. Thus, the α, ß-unsaturated carbonyl is necessary for the interaction of compounds, such as shogaol, with Keap1, and these findings may be useful for screening novel ICH therapeutic agents that increase HO-1 expression.

Claudin domain containing 1 contributing to endothelial cell adhesion decreases in presence of cerebellar hemorrhage.

The claudin family comprises four-pass transmembrane proteins involved in the formation of tight junctions (TJs). Relatively recently, claudin domain containing (CLDND) 1, also known as claudin-25, was identified as a novel member of the claudin family. In the present study, we revealed that in the adult murine brain, CLDND1 is abundant in the cerebellum among common sites of intracerebral hemorrhage. Thus, the dynamics of CLDND1 after cerebellar hemorrhage were examined. Both CLDND1 mRNA and protein levels transiently decreased at 24 hr after hemorrhagic insult. For immunostaining, an anti-CLDND1 antibody that recognizes the specific epitope in the extracellular first loop was prepared. Dual immunohistochemical staining with CD31 using coronal cryosections of intact murine cerebellum tissue revealed that CLDND1 is expressed on endothelial cells. We therefore performed an in vitro permeability test using a human brain endothelial cell (HBEC) line to reveal whether CLDND1 contributes to cell adhesion like other claudins. CLDND1 was expressed on HBECs as well as in murine cerebellum tissue, and a strong signal was observed at TJs. RNA interference against CLDND1 decreased both the mRNA and protein levels without cytotoxicity. The permeability to small molecules, but not to large ones, across confluent HBECs increased on CLDND1 knockdown compared with mock-treated cells. These results suggest that the transient decrease of CLDND1 after cerebellar hemorrhage is responsible for low-molecular-weight selective vascular hyperpermeability. © 2017 Wiley Periodicals, Inc.

Complete identification of four giant interneurons supplying mushroom body calyces in the cockroach Periplaneta americana.

Global inhibition is a fundamental physiological mechanism that has been proposed to shape odor representation in higher-order olfactory centers. A pair of mushroom bodies (MBs) in insect brains, an analog of the mammalian olfactory cortex, are implicated in multisensory integration and associative memory formation. With the use of single/multiple intracellular recording and staining in the cockroach Periplaneta americana, we succeeded in unambiguous identification of four tightly bundled GABA-immunoreactive giant interneurons that are presumably involved in global inhibitory control of the MB. These neurons, including three spiking neurons and one nonspiking neuron, possess dendrites in termination fields of MB output neurons and send axon terminals back to MB input sites, calyces, suggesting feedback roles onto the MB. The largest spiking neuron innervates almost exclusively the basal region of calyces, while the two smaller spiking neurons and the second-largest nonspiking neuron innervate more profusely the peripheral (lip) region of the calyces than the basal region. This subdivision corresponds well to the calycal zonation made by axon terminals of two populations of uniglomerular projection neurons with dendrites in distinct glomerular groups in the antennal lobe. The four giant neurons exhibited excitatory responses to every odor tested in a neuron-specific fashion, and two of the neurons also exhibited inhibitory responses in some recording sessions. Our results suggest that two parallel olfactory inputs to the MB undergo different forms of inhibitory control by the giant neurons, which may, in turn, be involved in different aspects of odor discrimination, plasticity, and state-dependent gain control. J. Comp. Neurol. 525:204-230, 2017. © 2016 Wiley Periodicals, Inc.