Deficiency of interleukin-19 exacerbates acute lung injury induced by intratracheal treatment of hydrochloric acid.

Interleukin (IL-19) belongs to the IL-10 family of cytokines and plays diverse roles in inflammation, cell development, viral responses, and lipid metabolism. Acute lung injury (ALI) is a severe respiratory condition associated with various diseases, including severe pneumonia, sepsis, and trauma, lacking established treatments. However, the role of IL-19 in acute inflammation of the lungs is unknown. We reported the impact of IL-19 functional deficiency in mice crossed with an ALI model using HCl. Lungs damages, neutrophil infiltration, and pulmonary edema induced by HCl were significantly worse in IL-19 knockout (KO) mice than in wild-type (WT) mice. mRNA expression levels of C-X-C motif chemokine ligand 1 (CXCL1) and IL-6 in the lungs were significantly higher in IL-19 KO mice than in WT mice. Little apoptosis was detected in lung injury in WT mice, whereas apoptosis was observed in exacerbated area of lung injury in IL-19 KO mice. These results are the first to show that IL-19 is involved in acute inflammation of the lungs, suggesting a novel molecular mechanism in acute respiratory failures. If it can be shown that neutrophils have IL-19 receptors and that IL-19 acts directly on them, it would be a novel drug target.

Detection of biomagnetic signals from induced pluripotent stem cell-derived cardiomyocytes using deep learning with simulation data.

The detection of spontaneous magnetic signals can be used for the non-invasive electrophysiological evaluation of induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs). We report that deep learning with a dataset that combines magnetic signals estimated using numerical simulation and actual noise data is effective in the detection of weak biomagnetic signals. To verify the feasibility of this method, we measured artificially generated magnetic signals that mimic cellular magnetic fields using a superconducting quantum interference device and attempted peak detection using a long short-term memory network. We correctly detected 80.0% of the peaks and the method achieved superior detection performance compared with conventional methods. Next, we attempted peak detection for magnetic signals measured from mouse iPS-CMs. The number of detected peaks was consistent with the spontaneous beats counted using microscopic observation and the average peak waveform achieved good similarity with the prediction. We also observed the synchronization of peak positions between simultaneously measured field potentials and magnetic signals. Furthermore, the magnetic measurements of cell samples treated with isoproterenol showed potential for the detection of chronotropic effects. These results suggest that the proposed method is effective and has potential application in the safety assessment of regenerative medicine and drug screening.

Effects of recombinant osteopontin expressed in Escherichia coli on the recovery of the endometrial epidermal growth factor profile and fertility in repeat breeder dairy cows.

Endometrial epidermal growth factor (EGF) shows a cyclic change with two peaks on days 2-4 and days 13-14 of the estrous cycle. In repeat breeder cows, loss of the peaks has been associated with reduced fertility. By infusing seminal plasma (SP) and osteopontin (OPN) derived from SP and milk into the vagina, their EGF profile and fertility are restored. However, SP is difficult to obtain, and both SP and OPN can transmit infectious diseases. While OPN can be sourced from recombinant protein without this risk, recombinant bovine OPN (rOPN) expressed in Escherichia coli should be examined for its effects on the EGF profile, since it does not undergo posttranslational modification, which is important for its biological activity. In study 1, PBS, SP (0.5 mL), and rOPN (0.3 mg) were infused into the vagina at estrus (day 0) in 74, 37, and 105 repeat breeder Holstein cows, respectively, with an altered EGF profile. The endometrial EGF concentrations were measured on day 3. Some cows (n = 58, 20, and 83, respectively) were inseminated immediately before the infusion and then diagnosed for pregnancy between days 30 and 35. The normalization rate of the EGF profile and conception rate in the rOPN group (58.1 % and 47.0 %, respectively) were not significantly different from those in the SP group (62.2 % and 45.0 %, respectively) but higher than those in PBS group (29.7 % and 28.1 %, respectively) (P < 0.05). In study 2, repeat breeder cows with an altered EGF profile were infused with PBS (n = 18) and rOPN (n = 17), while fertile controls with a normal EGF profile (n = 18) were infused with PBS. Two or three embryos were transferred into cows on day 7 and then recovered on day 14. Embryo recovery rates of the rOPN and fertile groups were comparable (58.7 % vs. 58.3 %) but higher than that of the PBS group (58.7 % vs. 32.0 %) (P < 0.05). The embryo recovery rate of cows with normalized EGF profile was higher than that of cows with unnormalized EGF profile (64.4 % vs. 16.7 %) (P < 0.05). The embryo sizes of cows in the rOPN and fertile groups were comparable but larger than those in the PBS group (P < 0.05). However, the embryo size was not correlated to the corresponding endometrial EGF concentrations. In conclusion, rOPN without posttranslational modifications normalized the EGF profile in repeat breeder cows. Improved fertility by normalization of the EGF profile could be attributed partly to the increased embryo viability up to day 14.

Oxygen-glucose deprivation-induced glial cell reactivity in the rat primary neuron-glia co-culture.

It has been demonstrated that in vivo brain ischemia induces activation and proliferation of astrocytes and microglia. However, the mechanism underlying the ischemia-induced activation and proliferation of these cells remains to be unclear. Oxygen-glucose deprivation (OGD), an in vitro ischemia mimic, has been extensively used to analyze the hypoxia response of various cell types. This study examined the OGD-induced changes in the expression level of astrocytes and microglia marker proteins and immunoreactivity for Ki-67, a marker protein for cell proliferation, using rat primary hippocampal neuron-glia co-culture (NGC) cells. Furthermore, OGD-induced changes in the expression of M1/M2 microglia phenotype-related genes were also examined. MTT assay indicated that 120 min of OGD decreased cell viability, and immunocytochemistry indicated that 120 min of OGD abolished most microtubule-associated protein 2 (MAP2)-immunopositive neurons. In contrast, glial fibrillary acidic protein (GFAP)-immunopositive astrocytes and ionized calcium-binding adapter protein-1 (Iba-1)-immunopositive microglia, and 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase)-immunopositive oligodendrocytes survived OGD. Western blot assays and double-immunofluorescent staining indicated that OGD increased the GFAP expression level and the Ki-67-immunopositive/GFAP-immunopositive cells' ratio. Real-time PCR analysis showed that OGD altered M1 microglia phenotype-related genes. Specifically, OGD decreased the expression level of CD32 and interleukin-1ß (IL-1ß) genes and increased that of the inducible nitric oxide synthase (iNOS) gene. Therefore, applying OGD to NGC cells could serve as a useful in vitro tool to elucidate the molecular mechanisms underlying brain ischemia-induced changes in GFAP expression, astrocyte proliferation, and M1 microglia phenotype-related gene expression.

Mixed-Culture Propagation of Uterine-Tissue-Resident Macrophages and Their Expression Properties of Steroidogenic Molecules.

Tissue-resident macrophages (Mø) play tissue/organ-specific roles, and the physiological/pathological implications of uterine Mø in fertility and infertility are not yet fully understood. Herein, we report a simple propagation method for tissue-resident Mø by mixed culture with the respective tissue/organ-residing cells as the niche. We successfully propagated mouse uterine Mø by mixed culture with fibroblastic cells that exhibited properties of endometrial stromal cells. Propagated mouse uterine Mø were CD206- and arginase-1-positive; iNOS- and MHC-II-negative, indicating M2 polarization; and highly phagocytic, similar to endometrial Mø. Furthermore, uterine Mø were observed to express steroidogenic molecules including SRD5A1 and exhibited gap junction formation, likely with endometrial stromal cells. Accordingly, uterine Mø propagated by mixed culture may provide a new tool for studying immune-endocrine interactions related to fertility and infertility, particularly androgen's intracrine actions in preparing the uterine tissue environment to support implantation and pregnancy as well as in the etiology of endometriosis.

FoxP2 protein decreases at a specific region in the chick midbrain after hatching.

Forkhead-box subclass P member 2 (FOXP2/FoxP2) protein, a transcription factor, regulates the development of certain brain functions, including human speech and animal vocalization. Although rapid progress has been made in demonstrating a relationship between FoxP2 expression in the brain and vocalization of the zebra finch, a typical vocal learner, the relationship in avian vocal non-learners, including chickens remains elusive. Because the midbrain plays a key role in innate vocalization development, we analyzed the FoxP2 protein in the midbrain of chicks, which do not cheep before hatching but cheep and call after hatching. Western blot analyses showed a significant reduction in FoxP2 protein in the chick midbrain after hatching compared with the findings before hatching. Quantitative immunohistochemistry revealed that FoxP2-immunoreactive (ir) cells significantly decreased at the stratum gris fibrosum (SGFS) of the optic tectum in the chick midbrain after hatching compared with the findings before hatching. These findings support the notion that FoxP2-ir cell numbers decrease at a specific region in the midbrain after hatching may be involved in innate vocalization of avian vocal non-learners.

Molecular dynamics of estrogen-related receptors and their regulatory proteins: roles in transcriptional control for endocrine and metabolic signaling.

Estrogen-related receptor (ERR) is a member of the nuclear receptor (NR) superfamily and has three subtypes α, ß, and γ. Despite their strong homology with estrogen receptor (ER) α, ERRs cannot accommodate endogenous hormones. However, they are able to regulate gene expression without ligand binding. ERRα and ERRγ orchestrate the expression of genes involved in bioenergetic pathways, while ERRß controls placental development and stem cell maintenance. Evidence from recent studies, including clinical research, has also demonstrated close associations of ERRs with the pathophysiology of hormone-related cancers and metabolic disorders including type 2 diabetes mellitus. This review summarizes the basic knowledge and recent advances in ERRs and their associated proteins, focusing on the subcellular dynamics involved in transcriptional regulation. Fluorescent protein labeling enabled monitoring of ERRs in living cells and revealed previously unrecognized characteristics. Using this technique, we demonstrated a role of ERRß in controlling estrogen signaling by regulating the subnuclear dynamics of ligand-activated ERα. Visualization of ERRs and related proteins and subsequent analyses also revealed a function of ERRγ in promoting liver lactate metabolism in association with LRPGC1, a recently identified lactic acid-responsive protein. These findings suggest that ERRs activate unique transregulation mechanisms in response to extracellular stimuli such as hormones and metabolic signals, implying an adaptive system behind the cellular homeostatic regulation by orphan NRs. Control of subcellular ERR dynamics will contribute toward the development of therapeutic approaches to treat various diseases including hormone-related cancers and metabolic disorders associated with abnormal ERR signaling pathways.

Healing Effect of Subcutaneous Administration of Granulocyte Colony-Stimulating Factor on Acute Rotator Cuff Injury in a Rat Model.

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that mobilizes bone marrow-derived cells (BMDCs) to peripheral blood and has been clinically used to treat neutropenia. Previously, we reported that BMDCs migrated into the rotator cuff repair site via peripheral blood in the healing process. However, techniques to accelerate the healing process using the peripheral blood pathway have not been established. We evaluated whether G-CSF has a noteworthy effect on improving rotator cuff healing by enhancing the influx of BMDCs into the peripheral blood. We used Sprague-Dawley rats and chimeric rats, selectively expressing green fluorescent protein (GFP) in BMDCs. Their bilateral supraspinatus tendons were resected and sutured to the greater tuberosity of the humerus using the Masson-Allen technique, and G-CSF was subcutaneously injected for 5 days after surgery. Several GFP-positive cells were observed around the enthesis in the G-CSF-treated group compared with that in the Control group. Histological analysis revealed that the tendon-to-bone maturing scores and the Safranin O-stained cartilaginous areas were significantly higher in G-CSF-injected rats than in the control rats at weeks 4 and 8 after surgery. Consistently, the ultimate force to failure in the G-CSF-treated group significantly increased compared with the Control group at weeks 4 and 8 after surgery. These results suggest that BMDCs mobilized into the peripheral blood after G-CSF administration migrated to the rotator cuff repair area and effectively enhanced rotator cuff healing by promoting tenocyte and cartilage matrix production. In conclusion, the BMDC mobilization technique by G-CSF treatment via peripheral blood will provide a potential therapeutic approach for rotator cuff healing with clinically relevant applications. Impact statement As the retear rate following rotator cuff repair is high, new methods to aid its healing are required. Granulocyte colony-stimulating factor (G-CSF) has been used clinically and may represent a novel approach to treating rotator cuff tear. Herein, using a rat model, we elucidate the kinetics of bone marrow-derived mesenchymal stem cells at the repair site following G-CSF administration and describe the underlying mechanism by which G-CSF can help promote the repair of the rotator cuff.

Subcellular dynamics of estrogen-related receptors involved in transrepression through interactions with scaffold attachment factor B1.

Estrogen-related receptor (ERR), a member of the nuclear receptor superfamily, consists of three subtypes (α, ß, γ) and has strong homology with estrogen receptor. No endogenous ligands have been identified for ERRs, but they play key roles in metabolic, hormonal, and developmental processes as transcription factors without ligand binding. Although subnuclear dynamics are essential for nuclear events including nuclear receptor-mediated transcriptional regulation, the dynamics of ERRs are poorly understood. Here, we report that ERRs show subcellular kinetic changes in response to diethylstilbestrol (DES), a synthetic estrogen that represses the transactivity of all three ERR subtypes, using live-cell imaging with fluorescent protein labeling. Upon DES treatment, all ERR subtypes formed discrete clusters in the nucleus, with ERRγ also displaying nuclear export. Fluorescence recovery after photobleaching analyses revealed significant reductions in the intranuclear mobility of DES-bound ERRα and ERRß, and a slight reduction in the intranuclear mobility of DES-bound ERRγ. After DES treatment, colocalization of all ERR subtypes with scaffold attachment factor B1 (SAFB1), a nuclear matrix-associated protein, was observed in dot-like subnuclear clusters, suggesting interactions of the ERRs with the nuclear matrix. Consistently, co-immunoprecipitation analyses confirmed enhanced interactions between ERRs and SAFB1 in the presence of DES. SAFB1 was clarified to repress the transactivity of all ERR subtypes through the ERR-response element. These results demonstrate ligand-dependent cluster formation of ERRs in the nucleus that is closely associated with SAFB1-mediated transrepression. Taken together, the present findings provide a new understanding of the pathophysiology regulated by ERR/SAFB1 signaling pathways and their subcellular dynamics.

A New Technique to Repair Vesicorectal Fistula: Overlapping Rectal Muscle Plasty by Transanal Endoscopic Surgery.

OBJECTIVE: To evaluate clinical results of a novel surgical technique, we developed to repair vesicorectal fistula (VRF) occurring after prostatectomy, hospital records of the patients, who underwent the new surgical treatment, were assessed. METHODS: The novel surgical technique is called "overlapping rectal muscle plasty," which is performed under transanal endoscopic microsurgery (TEM). During the new procedure, a complete fistulectomy was first performed, and then the proper muscle layer of the rectum was folded, overlapped, and sutured to create a thick wall between the rectum and urinary bladder. This operation was carried out in 15 patients with VRF following radical prostatectomy. RESULTS: The operation was safely performed in all patients with an average time of 127.2 min. Fistula was corrected in 13 patients (86.7%), who were then freed from both urinary and intestinal diversions. CONCLUSIONS: Overlapping rectal muscle plasty by TEM is a safe procedure. The success rate seems to be acceptable in selected patients. This new repair method may be considered as a minimally invasive option in the surgical treatment of VRF after prostatectomy.

Hepatocyte growth factor regulates HIF-1α-induced nucleus pulposus cell proliferation through MAPK-, PI3K/Akt-, and STAT3-mediated signaling.

Intervertebral discs are important for maintaining mobility and offer support to the body trunk. If these discs lose their biomechanical features, lower back pain can occur. We previously reported that hepatocyte growth factor (HGF) promotes cell proliferation and suppresses apoptosis, inflammation, and matrix degradation in nucleus pulposus (NP) cells. In the present study, we investigated the molecular mechanisms of how HGF promotes the proliferation of NP cells in hypoxic conditions. Hypoxic stimulation promoted modest cell proliferation, which was further upregulated by HGF. Expression of hypoxia-inducible factor (HIF-1α) protein, which contributes to the maintenance of homeostasis in NP cells, was also upregulated in hypoxia-treated cell groups; HGF further increased HIF-1α expression in NP cells. Additionally, knockdown of HIF-1α expression significantly reduced the proliferation of NP cells. An MAPK inhibitor inhibited the expression of HIF-1α and pERK, as well as cell proliferation in a dose-dependent manner. Similarly, inhibiting the PI3K/Akt and STAT3 pathways also decreased the expression of HIF-1α and cell proliferation. These results show that under hypoxic conditions, HGF promotes NP cell proliferation via HIF-1α-, MAPK-, PI3K/Akt-, and STAT3-mediated signaling which is involved in this pathway. The control of these signaling pathways may be a target for potential therapeutic strategies for the treatment of disc degeneration in hypoxic conditions.

Novel metabolic system for lactic acid via LRPGC1/ERRγ signaling pathway.

Lactic acid (LA) is a byproduct of glycolysis resulting from intense exercise or a metabolic defect in aerobic processes. LA metabolism is essential to prevent lactic acidosis, but the mechanism through which LA regulates its own metabolism is largely unknown. Here, we identified a LA-responsive protein, named LRPGC1, which has a distinct role from PGC1α, a key metabolic regulator, and report that LRPGC1 particularly mediates LA response to activate liver LA metabolism. Following LA stimulation, LRPGC1, but not PGC1α, translocates from the cytoplasm to the nucleus through deactivation of nuclear export signals, interacts with the nuclear receptor ERRγ, and upregulates TFAM, which ensures mitochondrial biogenesis. Knockout of PGC1 gene in HepG2 hepatocarcinoma cells decreased the LA consumption and TFAM expression, which were rescued by LRPGC1 expression, but not by PGC1α. These LRPGC1-induced effects were mediated by ERRγ, concomitantly with mitochondrial activation. The response element for LRPGC1/ERRγ signaling pathway was identified in TFAM promoter. Notably, the survival rate of a mouse model of lactic acidosis was reduced by the liver-targeted silencing of Lrpgc1, while it was significantly ameliorated by the pharmacological activation of ERRγ. These findings demonstrate LA-responsive transactivation via LRPGC1 that highlight an intrinsic molecular mechanism for LA homeostasis.

Status of growth plates can be monitored by MRI.

BACKGROUND: Growth plate injuries and disorders cause premature closure, resulting in shortened or deformed limbs. Quantitative assessment by MRI might monitor the status of the growth plate and may assist in the prediction of these deformations. PURPOSE: To investigate whether the status of the growth plate can be monitored by quantitative evaluation using MRI of the noninjured region of the growth plate in a physeal injury model. STUDY TYPE: Prospective, longitudinal. ANIMAL MODEL: A 3.0-mm drill was used to create an injury to the central region of the right proximal tibial growth plate in 5-week-old male Japanese white rabbits (N = 18). The left tibia served as the control. FIELD STRENGTH/SEQUENCE: 7.04T, T2 -weighted imaging, diffusion-weighted imaging. ASSESSMENT: Eight of 18 rabbits underwent MRI, proton density-weighted imaging, and T2 -weighted and diffusion-weighted imaging. T2 and apparent diffusion coefficient (ADC) maps were generated for each image. The growth plate height and the T2 and ADC values of the noninjured region were measured. Two rabbits were sacrificed at 2, 4, 6, 8, and 10 weeks postinjury. Proximal tibial bones were evaluated using microcomputed tomography, histological, and immunohistological methods. STATISTICAL TESTS: Data were compared using repeated-measures analysis of variance followed by Tukey post-hoc multiple comparison. RESULTS: Growth plate height decreased at 10 weeks postinjury (P = 0.018) on the injured side. T2 values were greater at 2 weeks postinjury (P = 0.0478) and decreased at 8 and 10 weeks (P = 0.0226, P = 0.0470, respectively) on the injured side. ADC values increased at 6 weeks on the lateral side (P = 0.0304) and decreased at 8 weeks and 10 weeks postinjury (P < 0.01) on the medial and injured sides, respectively. DATA CONCLUSION: Quantitative MRI can help monitor the status of the growth plate and capture its changes early. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:133-143.

CLEAN-NET: a modified laparoendoscopic wedge resection of the stomach to minimize the sacrifice of innocent gastric wall.

BACKGROUND: To avoid excessive sacrifice of the tissue surrounding the submucosal tumor in gastric wedge resection with a stapling device, we perform a "combined laparoscopic and endoscopic approach for neoplasia with a nonexposure technique" (CLEAN-NET). Herein the operative technique of CLEAN-NET is described and its short-term outcomes in 50 patients are evaluated. PATIENTS AND METHODS: Between December 2015 and July 2017 CLEAN-NET was performed in 50 patients with gastric submucosal tumors. During the operation, the seromuscular layer above the tumor is dissected, while the mucosa is kept unbroken. When seromuscular layer is dissected all around the tumor, the full layer is lifted, and the mucosa is stretched. The mucosa is then transected with a stapling device to execute full-thickness resection of the specimen. Finally, the seromuscular defect is repaired by hand-sewn suture. The hospital records of the 50 patients were reviewed to assess the outcomes. The margin width was compared with those measured in another group with 19 patients, who underwent conventional wedge resection with a stapling device. RESULTS: The operation was completed as CLEAN-NET and the tumor was resected en-bloc without rupture in all patients. The average operation time ranged from 50 to 220 min with an average of 105.4 min. The post-operative course was uneventful. Microscopically the surgical margin was tumor-negative (R0 resection) in all cases. The margin width in the CLEAN-NET group was smaller than that in the wedge resection group (5.4 mm ± 2.5 vs. 33.1 mm ± 14.7). CONCLUSIONS: CLEAN-NET can be performed safely with an acceptable operation time. CLEAN-NET can be a useful option in the laparoscopic surgical treatment of gastric submucosal tumors, when excessive sacrifice of the healthy gastric wall surrounding the endophytic tumor should be avoided.

Relationship between the antral follicle count in bovine ovaries from a local abattoir and steroidogenesis of granulosa cells cultured as oocyte-cumulus-granulosa complexes.

The antral follicle count (AFC) is used as an indicator of cow fertility. We herein investigated the relationship between AFC and the steroidogenesis of granulosa cells and confirmed the developmental competence of oocytes derived from early antral follicles (0.5-1.0 mm) using in vitro growth culture. Slaughterhouse-derived ovaries were divided into high (≥ 25) and low (< 25) AFC groups based on AFC (≥ 2.0 mm). Oocyte-cumulus-granulosa complexes (OCGCs) collected from early antral follicles were cultured for 12 days. The total number, viability, and diameter of granulosa cells and estradiol-17ß and progesterone production during the culture were evaluated. Surviving oocytes on day 12 were subjected to in vitro maturation, and their volume and nuclear status were evaluated. Some oocytes were subjected to the evaluation of developmental competence to blastocysts. Although the total number and viability of granulosa cells did not differ between the groups, granulosa cell diameters were smaller in the high AFC group than in the low AFC group. The estradiol-17ß and progesterone ratio on day 8 was higher in the high AFC group than in the low AFC group. Oocyte volumes and nuclear maturation rates were greater in the high AFC group than in the low AFC group. The development rate to blastocysts was 9.1% in the high AFC group, while no oocytes developed to blastocysts in the low AFC group. Therefore, estradiol-17ß production by granulosa cells appears to be greater in high AFC cattle than in low AFC cattle, thereby promoting the acquisition of oocyte competence.

Stabilization of Single-incision Laparoscopic Cholecystectomy by Needle Puncture and Bendable Retractor.

BACKGROUND: A recent meta-analysis and systematic review suggested that single-incision laparoscopic cholecystectomy (SILC) had a higher procedure failure rate with more blood loss and that it required a longer surgical time than conventional laparoscopic cholecystectomy. Herein, we introduce our experience with the needlescopic grasper-assisted and bendable retractor-assisted SILC technique and evaluate its safety and sustainability. METHODS: The present retrospective cohort study included 407 Japanese patients who underwent needlescopic grasper-assisted and bendable retractor-assisted SILC between January 2012 and April 2017 at our institution. RESULTS: In the present study, all patients successfully underwent needlescopic grasper-assisted and bendable retractor-assisted SILC without conversion to open surgery. Regarding surgical outcomes, mean surgical time was 58.2±23.2 minutes, and additional ports were required in 9 patients (2.2%). Postoperative morbidity developed in only 6 patients (1.4%). CONCLUSIONS: The surgical approaches defined herein were safe and sustainable with favorable surgical outcomes. Compared with conventional SILC, needlescopic grasper-assisted and bendable retractor-assisted SILC might become a mainstream procedure for minimally invasive surgery from the viewpoint of surgical difficulty.

Laparoscopic Surgery for Large Gastric Submucosal Tumors.

BACKGROUND: In general, laparoscopic resection for gastric gastrointestinal stromal tumors (GISTs) >5 cm is not recommended. However, there is a lack of evidence to support this recommendation. PATIENTS AND METHODS: This study included 108 patients who underwent laparoscopic surgery for gastric GISTs. Of the 108 patients, 23 had GISTs>5 cm. The aim of this study is to evaluate the oncological safety of laparoscopic surgery for large gastric GISTs. In addition, we performed a rapid systematic review of laparoscopic surgery for large gastric GISTs. RESULTS: In our cases, all patients were performed R0 resection without capsular rupture and surgical margins were negative on pathologic examination. In all studies, en bloc resection was achieved without capsular rupture in all patients. The average positive surgical margins rate was 1.6% in total reports. CONCLUSIONS: The laparoscopic approach for large gastric GISTs>5 cm has been proposed as safe when performed by experienced surgeons.

Percutaneous endoscopic intragastric surgery: an organ preserving approach to submucosal tumors at esophagogastric junction.

As an organ preserving option in the treatment of submucosal tumor found at the esophagogastric junction (EGJ), percutaneous endoscopic intragastric surgery (PEIGS) plays an important role, while it is not commonly performed and there have been very few reports on this unique operation. The current authors have been performing PEIGS since 1993 and have reported on its short- and long-term outcomes from one of the world largest series. Herein its confusing terminology is discussed and techniques of three different types of PEIGS (original PEIGS, single incision PEIGS, and needlescopic PEIGS) are precisely described. Although reports on clinical outcomes of PEIGS have been rarely published, both short-term and long-term outcomes seem acceptable, as far as we review our own experiences and the past literatures. PEIGS needs to be accessed by the data from larger series or RCT to be further justified and spread for the patients with submucosal tumors at EGJ to salvage their stomach.

Minimally Invasive, Organ-preserving Surgery for Large Submucosal Tumors in the Abdominal Esophagus.

BACKGROUND: Surgical resection of submucosal tumors (SMTs) in the abdominal esophagus is not standardized. Enucleation may be a minimally invasive option, whereas its oncological validity is not very clear. Moreover, how to treat the esophageal wall defect after enucleation and necessity of additional antireflux procedure are also undetermined. METHODS: In 13 patients with a SMT originating the abdominal esophagus laparoscopic enucleation was performed with preserving the integrity of submucosa. When the muscular layer defect was <4 cm it was directly closed by suturing, whereas it was left open in case the defect was larger. Fundoplication was added when the esophagus was dissected posteriorly or the myotomy was not closed. RESULTS: Tumors were resected en-bloc without rupture in all cases. In 5 patients myotomy was closed, whereas in the remaining 8 it was left open. In 11 patients fundoplication was added (Toupet in 5 and Dor in 6). The patients developed neither regurgitation nor stenosis postoperatively. The histopathologic findings revealed leiomyoma in 9 patients, whereas the other 4 were miscellaneous. The average tumor size was 5.5 cm (range, 2.8 to 8.8). Microscopically surgical margin was negative in all cases. CONCLUSIONS: Laparoscopic enucleation of SMTs in the abdominal esophagus seems to be safe, reproducible operation enabling preservation of function of the lower esophagus and esophagogastric junction. Even when the muscular defect is not approximated additional fundoplication can minimize the risk of postoperative reflux disease.

Immunohistochemical profiling of estrogen-related receptor gamma in rat brain and colocalization with estrogen receptor alpha in the preoptic area.

Estrogen-related receptor (ERR) is a member of the nuclear receptor superfamily that has strong homology with estrogen receptor (ER) α. Despite the lack of endogenous ligands, ERR serves as transcription factors through their constitutively active structure with or without interaction with ERα. Among the three subtypes of ERR (α, ß, and γ), ERRγ is highly expressed in brain, but the distribution of ERRγ is poorly characterized. Therefore, we investigated ERRγ immunoreactivity throughout the rostro-caudal axis in rat brain. Immunohistochemistry revealed localization of ERRγ protein in the cell nucleus, and a ubiquitous distribution of ERRγ in brain regions including the olfactory bulb, cerebrum, brain stem, and cerebellum. Selective intense immunoreactivity was observed in the reticular thalamic nucleus, zona incerta, circular nucleus, interpeduncular nucleus, pontine nucleus, and parasolitary nucleus. Most ERRγ-immunoreactive (ir) regions were also positive for ERα and/or ERß, which suggests that ERRγ is involved in modulation of estrogen signaling in adult rat brain. Double immunofluorescence demonstrated colocalization of ERRγ with ERα within the anteroventral periventricular nucleus of the preoptic area (AVPV) and medial preoptic nucleus (MPO), which are major target sites for estrogen action. The results of this study suggest that ERRγ function in the brain is affected by estrogens through an interaction with ERα. The findings also provide basic information on brain region-specific ERRγ function.