Short-term outcomes of OTSC for anastomotic leakage after laparoscopic colorectal surgery.

INTRODUCTION: There are several reports on the use of the over-the-scope clip (OTSC) for gastrointestinal bleeding/fistula and endoscopic iatrogenic perforation. However, there are almost no reports on OTSC use for anastomotic leakage (AL) after colorectal cancer surgery. The purpose of this study was to evaluate the outcome of AL closure using the OTSC. MATERIAL AND METHODS: Five patients who had undergone AL after laparoscopic surgery for colorectal cancer from April 2017 to April 2019 were evaluated. RESULTS: The average distance from the anal verge of the anastomosis site was 12 (5-18) cm. The average diameter of the dehiscent part was 10.9 (9.3-14.4) mm. The average number of OTSC days after the occurrence of AL was 11 (5-22). On the contrast examination immediately after OTSC, all cases were completely closed, but in the later contrast examination, only one case remained completely closed. The average incompletely closed diameter was 3.6 (2.9-5.1) mm, and the diameter of the dehiscent part was reduced in all cases. Only one patient ultimately underwent colostomy; the rest were cured with OTSC alone. CONCLUSION: AL site closure using the OTSC after colorectal cancer surgery is a useful minimally invasive treatment when combined with appropriate drain management.

Photoinduced Pyramidal Inversion Behavior of Phosphanes Involved with Aggregation-Induced Emission Behavior.

Aggregation-induced emission (AIE) is a fascinating phenomenon because of the applications of luminescent materials in the aggregated state, which exploit the large structural changes of the molecules in the excited state. Recently, it was reported that triphenylphosphane derivatives show AIE behavior in which they undergo potentially large structural changes in the excited state. Inspired by this report, photoinduced pyramidal inversion behavior of phosphanes was investigated. In photochemical experiments, the prepared P-stereogenic phosphanes exhibited photoracemization in dilute solution, and a negative correlation was observed between the photoracemization and the AIE phenomenon. Theoretical computations revealed that the inversion barrier in the excited state was much smaller than that in the ground state. This is the first report on the photoinduced pyramidal inversion behavior of phosphanes, which will provide new and unexplored applications.

Photoinduced Pyramidal Inversion Behavior of Phosphanes Involved with Aggregation-Induced Emission Behavior.

Invited for the cover of this issue is Kenta Kokado and co-workers at Hokkaido University. The cover picture describes the interesting pyramidal inversion behavior of phosphanes in the excited state, like entering "the Mirror World", which we found in this research. Read the full text of the article at 10.1002/chem.202000264.

Functional evaluations comparing the double-tract method and the jejunal interposition method following laparoscopic proximal gastrectomy for gastric cancer: an investigation including laparoscopic total gastrectomy.

PURPOSE: Functional outcomes were prospectively compared between two types of reconstruction [double tract (L-DT; n = 15) and jejunal interposition (L-JIP; n = 15)] following laparoscopic half-proximal gastrectomy (LPG), including laparoscopic total gastrectomy (L-TG; n = 30) as a control group, at 1 year after surgery. METHODS: Clinical investigations were performed in each patient, and functional evaluations, involving the swallowing of an alimentary liquid containing acetaminophen (AAP), followed by measurements of the concentrations of AAP and hormones in the sitting (n = 5) and in the supine positions (n = 5), were carried out in each group. RESULTS: The post-/preoperative body weight ratios were significantly higher in the L-DT and L-JIP groups than in the L-TG group. The AAP levels were significantly lower in the LPG group than in the LTG group. The AAP, insulin, and gastrin levels in the L-JIP group were markedly increased in the sitting position compared with the supine position, while those in the L-DT and L-TG groups were stable in both positions. CONCLUSIONS: L-JIP and L-DT are procedures that maintain gradual intestinal absorption and help improve the quality of life. Intestinal absorption and hormonal secretion were relatively unaffected by the posture of the meal intake after L-DT, so L-DT might be the procedure providing the most stable results.

Low psoas muscle index is a poor prognostic factor for lower gastrointestinal perforation: a single-center retrospective cohort study.

BACKGROUND: Various body composition indices have been reported as prognostic factors for different cancers. However, whether body composition affects prognosis after lower gastrointestinal tract perforation requiring emergency surgery and multidisciplinary treatment has not been clarified. This study examined whether body composition evaluations that can be measured easily and quickly from computed tomography (CT) are useful for predicting prognosis. METHODS: Subjects comprised 64 patients diagnosed with perforation at final diagnosis after emergency surgery for a preoperative diagnosis of lower gastrointestinal tract perforation and penetration. They were divided into a survival group and a non-survival (in-hospital mortality) group and compared. Body composition indices (psoas muscle index (PMI); psoas muscle attenuation (PMA); subcutaneous adipose tissue index (SATI); visceral adipose tissue index (VATI); visceral-to-subcutaneous fat area ratio (VSR)) were measured from preoperative CT. Cross-sectional psoas muscle area at the level of the 3rd lumbar vertebra was quantified. Optimal cut-off values were calculated using receiver operating characteristic curve analysis. Poor prognostic factors were investigated from multivariate logistic regression analyses that included patient factors, perioperative factors, intraoperative factors, and body composition indices as explanatory variables. RESULTS: The cause of perforation was malignant disease in 12 cases (18.7%), and benign disease in 52 cases (81.2%). The most common cause was diverticulum of the large intestine. Emergency surgery for the 64 patients led to survival in 52 patients and death in 12 patients. On multivariate logistic regression analysis, independent predictors of poor prognosis were Sequential Organ Failure Assessment score (odds ratio 1.908; 95% confidence interval (CI) 1.235-3.681; P = 0.0020) and PMI (odds ratio 13.478; 95%CI 1.342-332.690; P = 0.0252). The cut-off PMI was 4.75 cm2/m2 for males and 2.89 cm2/m2 for females. Among survivors, duration of hospitalization was significantly longer in the low PMI group (29 days) than in the high PMI group (22 days, p = 0.0257). CONCLUSIONS: PMI is easily determined from CT and allows rapid evaluation of prognosis following lower gastrointestinal perforation.

Oncostatin M-induced blood-brain barrier impairment is due to prolonged activation of STAT3 signaling in vitro.

Oncostatin M (OSM) is a member of the interleukin (IL)-6 family cytokines. We previously demonstrated that OSM induces blood-brain barrier (BBB) impairment. However, functional characterization of IL-6 family cytokines in BBB regulation and the cytokine-related intracellular signaling pathway remain unclear. In this study, we demonstrate that among IL-6 family cytokines, including IL-6 and leukemia inhibitory factor (LIF), OSM is the most potent molecule for inducing BBB dysfunction via prolonged activation of signal transducer and activator of transcription (STAT) 3 following Janus-activated kinase (JAK) activation. OSM but not IL-6 and LIF (100 ng/mL for 24 hours) markedly produced increased sodium fluorescein permeability and decreased transendothelial electrical resistance in rat brain endothelial cell (RBEC) monolayers. This OSM-induced BBB dysfunction was accompanied by decreased levels of claudin-5 expression in RBECs, which were ameliorated by JAK inhibitor. We examined the time-course of STAT3 phosphorylation in RBECs treated with OSM, IL-6, and LIF. OSM upregulated STAT3 phosphorylation levels during a 24 hours period with a peak at 10 minutes. While IL-6 and LIF transiently increased phosphorylated STAT3 at 10 minutes after addition, this phosphorylation decreased during the period from 1 to 24 hours after addition. These findings suggest that OSM-induced sustained increases in STAT3 phosphorylation levels largely contribute to BBB impairment. Thus, elevated OSM levels and activation of brain endothelial JAK/STAT3 signaling pathway under pathological conditions should be considered as a possible hallmark for induction and development of BBB impairment.

Brain pericyte-derived soluble factors enhance insulin sensitivity in GT1-7 hypothalamic neurons.

Insulin signaling in the hypothalamus plays an important role in food intake and glucose homeostasis. Hypothalamic neuronal functions are modulated by glial cells; these form an extensive network connecting the neurons and cerebral vasculature, known as the neurovascular unit (NVU). Brain pericytes are periendothelial accessory structures of the blood-brain barrier and integral members of the NVU. However, the interaction between pericytes and neurons is largely unexplored. Here, we investigate whether brain pericytes could affect hypothalamic neuronal insulin signaling. Our immunohistochemical observations demonstrated the existence of pericytes in the mouse hypothalamus, exhibiting immunoreactivity of platelet-derived growth factor receptor ß (a pericyte marker), and laminin, a basal lamina marker. We then exposed a murine hypothalamic neuronal cell line, GT1-7, to conditioned medium obtained from primary cultures of rat brain pericytes. Pericyte-conditioned medium (PCM), but not astrocyte- or aortic smooth muscle cell-conditioned medium, increased the insulin-stimulated phosphorylation of Akt in GT1-7 cells in a concentration-dependent manner. PCM also enhanced insulin-stimulated tyrosine phosphorylation of insulin receptor ß without changing its expression or localization in cytosolic or plasma membrane fractions. These results suggest that pericytes, rather than astrocytes, increase insulin sensitivity in hypothalamic neurons by releasing soluble factors under physiological conditions in the NVU.

Metformin induces up-regulation of blood-brain barrier functions by activating AMP-activated protein kinase in rat brain microvascular endothelial cells.

Blood-brain barrier (BBB) disruption occurs frequently in CNS diseases and injuries. Few drugs have been developed as therapeutic candidates for facilitating BBB functions. Here, we examined whether metformin up-regulates BBB functions using rat brain microvascular endothelial cells (RBECs). Metformin, concentration- and time-dependently increased transendothelial electrical resistance of RBEC monolayers, and decreased RBEC permeability to sodium fluorescein and Evans blue albumin. These effects of metformin were blocked by compound C, an inhibitor of AMP-activated protein kinase (AMPK). AMPK stimulation with an AMPK activator, AICAR, enhanced BBB functions. These findings indicate that metformin induces up-regulation of BBB functions via AMPK activation.

Victim profiles and revealed issues of type 1 Emergency Medical Team in the first minutes of a mega earthquake in Turkey.

BACKGROUND: On February 6, 2023, a series of mega-earthquakes (MEs) struck the southern parts of Turkey and northern Syria. In the first 16 days after the Turkey MEs (TMEs), the Tokushukai Medical Assistant Team (TMAT) backed by its infrastructure visited Turkey to support a local hospital. With the goal of helping local communities and working with local supporters and authorities, Turkey is on a mission to positively impact people's lives. METHODS: Data collected covered the TMAT support period in February 2023. All patients admitted to a hospital were registered through the Minimum Data Set (MDS) of the Emergency Medical Team (EMT) Coordination Cell (EMTCC). RESULTS: A total of 561 patients were hospitalized during the 16-day mission. A review of the MDS data showed a de-crease in the number of inpatients. The number of diseases directly related to the disaster was confirmed to be due to a gradual decrease in TME aftershock. However, the number of patients with nondisaster-related disease remained stable. CONCLUSION: The experience of EMT in the initial relief of MEs that struck Turkey and Syria on February 6, 2023 showed that a mobile type 1 EMT in the early stage while rebuilding the infrastructure is essential. From the analysis of patient profiles, it is clear that knowledge and experience of skin diseases is needed in the first minutes of MEs. In addi-tion, it has become clear that to ensure the quality of MDS for further analysis and to improve the efficiency and effec-tiveness of EMS, it is essential to have recorders in the EMS. These MDS recorders, called descriptors, must be isolated from the treating medical staff to eliminate subjectivity and ensure data accuracy.

Determination of the critical region of KRAS-induced actin-interacting protein for the interaction with inositol 1,4,5-trisphosphate receptor.

KRAS-induced actin-interacting protein (KRAP) was originally characterized as a filamentous-actin-interacting protein. We have recently found that KRAP is an associated molecule with inositol 1,4,5-trisphosphate receptor (IP(3)R) and is critical for the proper subcellular localization and function of IP(3)R. However, the molecular mechanisms underlying the regulation of IP(3)R by KRAP remain elusive. In this report, to determine the critical region of KRAP protein for the regulation of IP(3)R, we generate several mutants of KRAP and examine the association with IP(3)R using coimmunoprecipitation and confocal imaging assays. Coimmunoprecipitations using the deletion mutants reveal that amino-acid residues 1-218 but not 1-199 of KRAP interact with IP(3)R, indicating that the 19-length amino-acid residues (200-218) are essential for the association with IP(3)R. This critical region is highly conserved between human and mouse KRAP. Within the critical region, substitutions of two phenylalanine residues (Phe202/Phe203) in mouse KRAP to alanines result in failure of the association with IP(3)R, suggesting that the two consecutive phenylalanine residues are indispensable for the association. Moreover, the KRAP-knockdown stable HeLa cells exhibit the inappropriate subcellular localization of IP(3)R, in which exogenous expression of full-length of KRAP properly restores the subcellular localization of IP(3)R, but not the 1-218 or 1-236 mutant, indicating that the residual carboxyl-terminal region is also required for the proper subcellular localization of KRAP-IP(3)R complex. All these results provide insight into the understandings for the molecular mechanisms underlying the regulation of IP(3)R, and would reveal a potent strategy for the drug development targeting on IP(3)R.

KRAS-induced actin-interacting protein regulates inositol 1,4,5-trisphosphate-receptor-mediated calcium release.

KRAS-induced actin-interacting protein (KRAP) was originally characterized as a filamentous- actin-interacting protein. We have recently found that KRAP is an associated molecule with inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) and is responsible for the proper subcellular localization of IP(3)R. Since it remains unknown whether KRAP regulates the IP(3)R-mediated Ca(2+) signaling, we herein examined the effects of KRAP on the IP(3)R-mediated Ca(2+) release by Ca(2+) imagings in the cultured HEK293 or MCF7 cells. Reduction of KRAP protein by KRAP-specific siRNA diminishes ATP-induced Ca(2+) release and the ATP-induced Ca(2+) release is completely quenched by the pretreatment with the IP(3)R inhibitor but not with the ryanodine receptor inhibitor, indicating that KRAP regulates IP(3)R-mediated Ca(2+) release. To further reveal mechanistic insights into the regulation of IP(3)R-mediated Ca(2+) release by KRAP, we examined the effects of the KRAP-knockdown on the releasable Ca(2+) content of intracellular Ca(2+) stores. Consequently, reduction of KRAP does not affect the amount of ionophore- or Ca(2+)-ATPase inhibitor-induced Ca(2+) release in the HEK293 cells, indicating that releasable Ca(2+) content of intracellular Ca(2+) stores is not altered by KRAP. Thus, KRAP is involved in the proper regulation of IP(3)R-mediated Ca(2+) release.

KRAS-induced actin-interacting protein is required for the proper localization of inositol 1,4,5-trisphosphate receptor in the epithelial cells.

Three inositol 1,4,5-trisphosphate receptor (IP(3)R) subtypes are differentially expressed among tissues and function as the Ca(2+) release channel on specialized endoplasmic reticulum (ER) membranes. The proper subcellular localization of IP(3)R is crucial for its proper function, but this molecular mechanism is unclear. KRAS-induced actin-interacting protein (KRAP) was originally identified as a cancer-related molecule, and is involved in the regulation of whole-body energy homeostasis and pancreatic exocrine system. We herein identified IP(3)R as an associated molecule with KRAP in vivo, and the association was validated by the co-immunoprecipitation and confocal immunostaining studies in mouse tissues including liver and pancreas. The association of KRAP with IP(3)R was also observed in the human epithelial cell lines including HCT116, HeLa and HEK293 cells. Intriguingly, KRAP interacts with distinct subtypes of IP(3)R in a tissue-dependent manner, i.e. IP(3)R1 and IP(3)R2 in the liver and IP(3)R2 and IP(3)R3 in the pancreas. The NH(2)-terminal amino acid residues 1-610 of IP(3)R are critical for the association with KRAP and KRAP-IP(3)R complex resides in a specialized ER but not a typical reticular ER. Furthermore, the localization of particular IP(3)R subtypes in tissues from KRAP-deficient mice is obviously disturbed, i.e. IP(3)R1 and IP(3)R2 in the liver and IP(3)R2 and IP(3)R3 in the pancreas. These findings demonstrate that KRAP physically associates with IP(3)R and regulates the proper localization of IP(3)R in the epithelial cells in vivo and cultured cells, and might shed light on the Ca(2+) signaling underlying physiological cellular programs, cancer development and metabolism-related diseases.

Brain pericytes among cells constituting the blood-brain barrier are highly sensitive to tumor necrosis factor-α, releasing matrix metalloproteinase-9 and migrating in vitro.

BACKGROUND: Increased matrix metalloproteinase (MMP)-9 in the plasma and brain is associated with blood-brain barrier (BBB) disruption through proteolytic activity in neuroinflammatory diseases. MMP-9 is present in the brain microvasculature and its vicinity, where brain microvascular endothelial cells (BMECs), pericytes and astrocytes constitute the BBB. Little is known about the cellular source and role of MMP-9 at the BBB. Here, we examined the ability of pericytes to release MMP-9 and migrate in response to inflammatory mediators in comparison with BMECs and astrocytes, using primary cultures isolated from rat brains. METHODS: The culture supernatants were collected from primary cultures of rat brain endothelial cells, pericytes, or astrocytes. MMP-9 activities and levels in the supernatants were measured by gelatin zymography and western blot, respectively. The involvement of signaling molecules including mitogen-activated protein kinases (MAPKs) and phosphoinositide-3-kinase (PI3K)/Akt in the mediation of tumor necrosis factor (TNF)-α-induced MMP-9 release was examined using specific inhibitors. The functional activity of MMP-9 was evaluated by a cell migration assay. RESULTS: Zymographic and western blot analyses demonstrated that TNF-α stimulated pericytes to release MMP-9, and this release was much higher than from BMECs or astrocytes. Other inflammatory mediators [interleukin (IL)-1ß, interferon-γ, IL-6 and lipopolysaccharide] failed to induce MMP-9 release from pericytes. TNF-α-induced MMP-9 release from pericytes was found to be mediated by MAPKs and PI3K. Scratch wound healing assay showed that in contrast to BMECs and astrocytes the extent of pericyte migration was significantly increased by TNF-α. This pericyte migration was inhibited by anti-MMP-9 antibody. CONCLUSION: These findings suggest that pericytes are most sensitive to TNF-α in terms of MMP-9 release, and are the major source of MMP-9 at the BBB. This pericyte-derived MMP-9 initiated cellular migration of pericytes, which might be involved in pericyte loss in the damaged BBB.

Neoadjuvant chemoradiotherapy for locally advanced gastric cancer with bulky lymph node metastasis: Five case reports.

BACKGROUND: Neoadjuvant chemoradiotherapy (NACRT) has not been accepted as a general therapy for gastric cancer because of its localized effect and toxicity for radiosensitive organs. However, if radiation therapy could compensate for the limited or inadequate treatment choices available for elderly patients and/or those at high risk, the available therapeutic options for advanced gastric cancer might increase. From this perspective, we present our experiences of five patients with advanced gastric cancer in whom we used NACRT therapy with interesting results. CASE SUMMARY: We admitted five patients with clinical Stage III gastric cancer and bulky lymph node metastasis or adjacent organ invasion at the time of diagnosis. A total of 50 Gy of preoperative intensity modulated radiation therapy was delivered to the patients in doses of 2.0 Gy/d, together with a regimen of concomitant chemotherapy comprising two courses of oral tegafur/gimeracil/oteracil (S-1; 65 mg/m2 per day) for three consecutive weeks followed by two weeks of rest, starting at the same time as radiotherapy. All patients underwent no residual tumor resection and a pathological complete response of the primary tumors was achieved in two patients. The incidence of hematological toxicity was low, although the digestive toxicities of anorexia and diarrhea developed in three of the five patients, necessitating termination of radiation therapy at 30 Gy and S-1 at three weeks. However, even 30 Gy of irradiation and half the dose of S-1 resulted in sufficient downstaging, indicating that even a reduced amount of NACRT could confer considerable effects. CONCLUSION: Slightly reduced NACRT might be useful and safe for patients with locally advanced gastric cancer.

Evaluation of laparoscopic surgery for small bowel obstruction and factors related to outcomes.

INTRODUCTION: In recent years, laparoscopic surgery (LS) has been performed for small bowel obstruction (SBO). However, the indications and short-term and long-term outcomes of LS for SBO have not yet been established. AIM: To evaluate the usefulness of LS for SBO compared to open surgery (OS), as well as to identify risk factors for poor outcomes after LS. MATERIAL AND METHODS: A total of 105 patients who underwent surgery for SBO were divided into OS (n = 64) and LS (n = 41) groups, and propensity score-matched analysis was used to compare the short-term and long-term outcomes of the groups. Risk factors for conversion to OS, postoperative complications, and intraoperative bowel injury in LS were also identified. RESULTS: The incidences of surgical site infection and postoperative ileus were significantly lower in the LS group. The incidence of recurrent bowel did not differ significantly between the two groups. Prior bowel obstruction was a risk factor for conversion of LS to OS (odds ratio (OR) = 24.79, p = 0.0025). Bowel diameter was a risk factor for postoperative complications (OR = 1.50, 95% CI: 1.01-2.22) and for bowel injury (OR = 1.33, 95% CI: 1.05-1.67). CONCLUSIONS: LS for SBO had better postoperative short-term outcomes than OS. The outcomes of LS for SBO were significantly affected by prior bowel obstruction and bowel diameter.

Colon cancer arising from colonic diverticulum: A case report.

BACKGROUND: Colonic diverticulosis is a common disease, and the coexistence of colonic diverticulosis and colorectal cancer is often seen clinically. It is very rare that colon cancer arises from the mucosa of a colonic diverticulum. When colon cancer arises in a diverticulum and then tends to develop outside the wall, without developing within the lumen, the differential diagnosis from complicating lesions due to colonic diverticulitis is difficult. CASE SUMMARY: A 76-year-old man was admitted to a nearby clinic with a chief complaint of discomfort and urinary frequency. Since a vesicosigmoidal fistula was seen on abdominal computed tomography, he was referred to our hospital. Laparoscopic sigmoidectomy was performed because the various diagnostic findings were diagnosed as a vesicosigmoidal fistula with diverticulitis of the sigmoid colon. However, on histopathological examination, it was diagnosed as a vesicosigmoidal fistula due to colon cancer arising in the diverticulum. Laparoscopic partial resection of the bladder was performed because local recurrence was observed in the bladder wall one and a half years after surgery. It is currently one year after reoperation, but there has been no recurrence or metastasis. CONCLUSION: Colon cancer arising in a diverticulum of the colon should be considered when diverticulitis with complications is observed.

Short- and Long-term Outcomes of 2-Step Stapled Intracorporeal Versus Extracorporeal Anastomosis in Laparoscopic Colectomy for Colon Cancer.

BACKGROUND/AIM: Intracorporeal anastomosis (IA) in laparoscopic colectomy for colon cancer is technically difficult, and there is a lack of consensus on the risk of bacterial contamination and cancer cell dissemination. In this study, short- and long-term outcomes of IA were examined. PATIENTS AND METHODS: Short and long-term outcomes of those who underwent IA (n=44) or extracorporeal anastomosis (EA) (n=61) were compared. RESULTS: IA was better than EA for blood loss, incision length, and first stool. Maximum temperature and C-reactive protein on postoperative day 1 were higher for the IA group. The rate of positive cultures from intraoperative lavage was higher for IA. The rate of positive cultures improved to an equivalent level by replacing mechanical pretreatment with chemical pretreatment. IA and EA were equivalent for the results of ascites cytology from lavage. CONCLUSION: With the use of appropriate preoperative treatment, IA takes advantage of the minimally invasive nature of laparoscopic surgery.

Recurrent Cervical Cancer with Intestinal Perforation That Was Related to Bevacizumab after Long-term NSAIDs Administration and Was Treated with Laparoscopy-assisted Anastomosis.

Bevacizumab is an effective drug for recurrent/advanced cervical cancer. A 59-year-old patient diagnosed with FIGO stage I B2 squamous cell carcinoma of the cervix at our hospital was treated with concurrent chemoradiotherapy as initial treatment. The outcome was judged as close to CR. Local recurrence in the irradiation field and paraaortic lymph node metastasis were noted 2 months after completion of this treatment. Chemotherapy of bevacizumab combined with paclitaxel plus carboplatin (TC) was initiated for recurrent cervical cancer. At 17 days after the 4th cycle, abdominal pain suddenly developed, and a close examination detected free air on abdominal CT, based on which intestinal perforation was diagnosed. Laparoscopic surgery performed to investigate the intraabdominal cavity showed that the small intestine was perforated at 2 sites. These were treated with laparoscopy-assisted partial resection of the small intestine and functional end-to-end anastomosis. Drug therapy for the recurrent cervical cancer was considered, but the primary disease rapidly aggravated and the patient died of the primary disease 11 months after completion of the initial treatment.

Functional Evaluation for Various Methods of Gastrectomy and Reconstruction for Gastric Cancer.

OBJECTIVE: This study of 45 patients aimed to retrospectively examine whether the relationships among the postoperative to preoperative body weight ratio (BWR), meal intake as a good indicator of quality of l ife (QOL), and absorptive kinetics from the small intestine could be expressed by the acetaminophen (AAP) concentration. METHODS: The postoperative/preoperative BWR and meal intake ratio (MIR) were evaluated in 30 patients who underwent open distal gastrectomy for advanced gastric cancer (ODG group) and 15 patients who underwent laparoscopic proximal gastrectomy for early gastric cancer (LPG group). In addition, all patients underwent functional evaluation using the AAP method. Correlation coefficients of the BWR and MIR with the plasma AAP concentration after meal intake were evaluated. RESULTS: There was a negative correlation between the AAP concentration at 15 min and the BWR in all patients (r = -0.438, P = 0.00259, n = 45) and a weak negative correlation between the AAP concentration at 15 min and the MIR (r = -0.309, P = 0.0368, n = 45). CONCLUSIONS: There were some relationships between slow intestinal absorption in the early postprandial phase and the maintenance of postoperative body weight and meal intake. Namely, operative methods that maintained preoperative slow intestinal absorption were thought to be better for maintaining postoperative QOL.

TNF-α-sensitive brain pericytes activate microglia by releasing IL-6 through cooperation between IκB-NFκB and JAK-STAT3 pathways.

Interleukin (IL)-6 is an important mediator of neurovascular dysfunction, neurodegeneration and/or neuroinflammation. We previously reported that brain pericytes released higher levels of IL-6 than did glial cells (astrocytes and microglia) in response to tumor necrosis factor (TNF)-α. Moreover, pericytes stimulated with TNF-α enhanced activation of BV-2 microglia. In this study, we investigated the mechanisms of TNF-α mediated induction of IL-6 release from brain pericytes and astrocytes and whether pericyte-derived IL-6 would facilitate activation of BV-2 microglia. Using rat brain pericyte and astrocyte primary cultures and pharmacological inhibitors, we found that, TNF-α induced the highest levels of IL-6 release from pericytes by activating the inhibitor kappa B (IκB)-nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and Janus family of tyrosine kinase (JAK)-signal transducer and activator of transcription (STAT)3 pathways. STAT3 contributed to TNF-α induced nuclear translocation of phospho-NFκB in pericytes. TNF-α-induced IL-6 release in astrocytes was mediated by NFκB but not by STAT3. The presence of pericytes amplified TNF-α-induced iNOS mRNA expression in BV-2 microglia. This effect was blocked by a neutralizing antibody for IL-6. These findings indicated that crosstalk between the IκB-NFκB and JAK-STAT3 pathways is a pericyte specific mechanism, not occurring in astrocytes, for TNF-α-induced IL-6 release. IL-6 derived from pericytes enhanced microglial activation. Our findings increase understanding of the role of pericyte-microglia crosstalk in the brain under neuroinflammatory conditions and suggest a potentially attractive therapeutic target for brain inflammation.