Intramuscular injection of mesenchymal stem cells augments basal muscle protein synthesis after bouts of resistance exercise in male mice.

Skeletal muscle mass is critical for activities of daily living. Resistance training maintains or increases muscle mass, and various strategies maximize the training adaptation. Mesenchymal stem cells (MSCs) are multipotent cells with differential potency in skeletal muscle cells and the capacity to secrete growth factors. However, little is known regarding the effect of intramuscular injection of MSCs on basal muscle protein synthesis and catabolic systems after resistance training. Here, we measured changes in basal muscle protein synthesis, the ubiquitin-proteasome system, and autophagy-lysosome system-related factors after bouts of resistance exercise by intramuscular injection of MSCs. Mice performed three bouts of resistance exercise (each consisting of 50 maximal isometric contractions elicited by electrical stimulation) on the right gastrocnemius muscle every 48 h, and immediately after the first bout, mice were intramuscularly injected with either MSCs (2.0 × 106 cells) labeled with green fluorescence protein (GFP) or vehicle only placebo. Seventy-two hours after the third exercise bout, GFP was detected only in the muscle injected with MSCs with concomitant elevation of muscle protein synthesis. The injection of MSCs also increased protein ubiquitination. These results suggest that the intramuscular injection of MSCs augmented muscle protein turnover at the basal state after consecutive resistance exercise.

Preparation of stable and monodisperse paclitaxel-loaded bovine serum albumin nanoparticles via intermolecular disulfide crosslinking.

Paclitaxel (PTX) is one of the most used anti-cancer drugs worldwide. Due to its insolubility in water, the clinically available liquid formulation of PTX contains Cremophor EL that is responsible for severe hypersensitivity. Albumin-based nanoparticles have emerged as a promising carrier for anti-cancer drugs because albumin nanoparticles have high capacity to not only load lipophilic drugs without solubilizer but also accumulate in tumor by both passive and active mechanisms. In this study, we attempted to prepare solvent-free formulation of PTX-loaded bovine serum albumin (BSA) nanoparticles with high stability, and the in vitro stability in serum were comparatively assessed between our PTX-loaded BSA nanoparticles and clinically used nanoparticulate albumin-bound PTX (Abraxane®). PTX-loaded BSA nanoparticles were prepared by intermolecular disulfide crosslinking. When BSA molecules were used without denaturation by guanidinium, the obtained BSA nanoparticles showed broad size distribution. On the other hand, the nanoparticles composed of denatured BSA by guanidinium had a uniform size around 100 nm. The PTX encapsulation efficiency of BSA nanoparticles were approximately 30-40 %. In addition, in vitro gel filtration analysis and dialysis study demonstrated that PTX-loaded BSA nanoparticles had higher colloidal stability and sustained PTX release property than Abraxane® in serum. These results suggest that BSA nanoparticles is a promising drug carrier for improving therapeutic efficacy of PTX and reducing its adverse effects.

Preoperative low skeletal muscle volume can result in insufficient administration of S-1 adjuvant chemotherapy in older patients with stage II/III gastric cancer.

BACKGROUND AND PURPOSE: Older patients are more likely to encounter difficulties receiving chemotherapy, but the factors involved in the continuation of chemotherapy in these patients remain unclear. We investigated the importance of muscle mass as a factor involved in delivering a sufficient dose of postoperative S-1 adjuvant chemotherapy (ACT) to older patients with gastric cancer. METHODS: The subjects of this study were 79 patients aged ≥ 65 years with stage II/III gastric adenocarcinoma, who underwent curative gastrectomy and received S-1 ACT. RESULTS: The overall median relative dose intensity (RDI) was 75.0% (18.8-93.5%). Patients were divided into two groups for receiver operating characteristic analysis according to the cutoff value. Significantly more patients in the high skeletal muscle index (SMI) group achieved > 62% RDI of S-1 ACT (p = 0.03). Conversely, more patients in the low SMI group suffered from S-1-induced nausea (p = 0.03) and discontinued chemotherapy because of adverse events (p = 0.02). Multivariate analysis identified low SMI as an independent factor for insufficient S-1 dose delivery (p = 0.03, hazard ratio = 2.87). CONCLUSION: Preoperative SMI is an indicator of the low-dose intensity of S-1 ACT in older patients following curative gastrectomy.

A gastroduodenal artery that branched from the celiac artery in gastrectomy: A rare case of an anatomical variant.

Understanding anatomical anomalies of the branch of the celiac artery for safe gastrectomy is important. We report a case of laparoscopic distal gastrectomy with D1+ lymph node dissection for early gastric cancer with a vascular anatomical anomaly of the celiac artery. A 45-year-old woman was referred to our hospital because of early gastric cancer. Computed tomography showed an anatomical variation of the gastroduodenal artery, which branched from the celiac artery. The celiac artery also branched into the left gastric artery, the splenic artery, and the common hepatic artery. Preoperative understanding of an unusual branch of the celiac artery enabled a safe laparoscopic surgery. There were no postoperative complications. The Adachi classification or Michel classification is used for an anatomical anomaly of the celiac artery, but to the best of our knowledge, this case has not been previously classified and is the first reported case.

Skeletal Muscle Mass Before Second-line Chemotherapy Correlates With Subsequent Prognosis and Rate of Late-line Chemotherapy in Patients With Unresectable Gastric Cancer.

BACKGROUND/AIM: Chemotherapy is the standard treatment for patients with unresectable gastric cancer (UGC); however, the survival outcomes are poor. This study investigated the predictive values of skeletal muscle mass (SMM) index (SMI) before second-line chemotherapy and the survival outcomes of patients with UGC. PATIENTS AND METHODS: A total of 79 patients diagnosed with UGC at our hospital who received at least second-line palliative chemotherapy were included. The cross-sectional SMM at the third lumbar vertebra was obtained before second-line chemotherapy. SMI was defined as the muscle area normalized by height squared (m2), and SMI before second-line chemotherapy was defined as 2ndSMI. RESULTS: Using 2ndSMI for men and women (35.4 and 31.7 cm2/m2, respectively) as the cutoff value, patients were divided into high (2ndSMIHigh; n=54) and low (2ndSMILow; n=25) 2ndSMI groups. The number of patients receiving fourth-line chemotherapy was significantly higher in the 2ndSMIHigh group than in the 2ndSMILow group (p=0.039). The overall survival time after the start of second-line chemotherapy was significantly higher in the 2ndSMIHigh group than in the 2ndSMILow group (p=0.008). The incidence of grade 3 or 4 side effects was significantly higher in the 2ndSMILow than in the 2ndSMIHigh group (p=0.028). The multivariate analysis identified 2ndSMI as independent prognostic factor after the start of second-line chemotherapy. CONCLUSION: The 2ndSMILow group had a significantly worse prognosis and significantly less conversion to fourth-line chemotherapy than the 2ndSMIHigh group. Moreover, 2ndSMILow was associated with grade 3 or 4 side effects of second-line chemotherapy.

Preparation and Evaluation of Paclitaxel-Loaded PEGylated Niosomes Composed of Sorbitan Esters.

Niosomes are non-ionic surfactant (NIS)-based bilayer vesicles and, like liposomes, have great potential as drug-delivery systems. Our previous study revealed that polyethylene glycol (PEG) niosomes using different sorbitan ester (Span) surfactants (sorbitan monoester, Span 20, 40, 60, 80; sorbitan triester, Span 65) distributed within tumors similarly to PEG liposomes. The aim of this study was to encapsulate efficiently an anti-cancer drug, paclitaxel (PTX) into Span PEG niosomes, and evaluate PTX release profiles and anti-tumor efficacy of PTX-loaded Span PEG niosomes. Niosome sizes ranged between 100-150 nm, and the PTX encapsulation efficiency was more than 50%. All niosomes examined, in the presence of serum, yielded sustained PTX-release profiles. PTX release at 24 and 48 h from Span 80 PEG niosomes was significantly the highest among the other Span PEG niosomes examined. In C26 tumor-bearing mice, PTX-loaded Span 40 PEG niosomes (the lowest PTX release in vitro) suppressed tumor growth while PTX-loaded Span 80 PEG niosomes (the highest PTX release in vitro) did not. Thus, we succeeded in the control of PTX release from Span PEG niosomes by modifying the component of niosomes, and it influenced the effects of drugs loaded into niosomes. This demonstrates that the excellent NIS physicochemical properties of Spans make them an ideal candidate for anti-cancer drug-carrier niosomes.

Preoperative Osteopenia as Risk Factor for Death from Other Diseases After Gastrectomy in Elderly Patients.

BACKGROUND/AIM: Preoperative osteopenia, defined as low bone mineral density, is a prognostic factor in patients with digestive tract cancers, including gastric cancer (GC). However, the correlation between preoperative osteopenia and GC in elderly patients is unclear. PATIENTS AND METHODS: We enrolled 251 patients who had undergone curative surgery for histopathologically diagnosed gastric adenocarcinoma from January 2008 to December 2012. Patients were classified into the non-elderly group (n=169) and the elderly group (n=82). Bone mineral density was calculated as the average pixel density (Hounsfield units) within a circle of the mid-vertebral core at the bottom of the 11th thoracic vertebra on preoperative computed tomography. RESULTS: Although overall survival was significantly shorter in the elderly compared to the non-elderly group (p=0.0062), there was no significant difference in disease-specific survival between the two groups (p=0.71) because of the higher rate of death from other diseases. In addition, the elderly group had a significantly higher incidence of osteopenia (p<0.001) and a significantly lower prognostic nutritional index (p<0.001). Multivariate analysis revealed that preoperative osteopenia and a low preoperative prognostic nutritional index were significant risk factors for death from other diseases after gastrectomy in elderly patients. CONCLUSION: In elderly patients with GC, preoperative osteopenia is an important factor to consider in terms of both curability and death from other diseases.

Suppression of Phagocytic Activity Leads to the Efficient Surface Modification of Macrophages with Liposomes for Developing a Biomimetic Drug Delivery System.

Macrophages selectively infiltrate the lesion sites of several diseases, including cancers, and, thus, have attracted attention as a biomimetic drug delivery carrier. To achieve the efficient drug loading of macrophages with minimal cytotoxicity, drugs are preferably encapsulated into nanoparticles, such as liposomes, and modified on the surface of macrophages rather than being incorporated into cells. However, liposomes are rapidly taken up by macrophages after binding to the cell surface because of their strong phagocytic activity. To overcome this, we herein attempted to modify the surface of macrophages with liposomes by suppressing their phagocytic activity using a pretreatment with anionic liposomes. We confirmed that 1,2-distearoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (DSPG)- and cholesterol-rich anionic liposomes were efficiently taken up by RAW264.7 murine macrophage-like cells. Furthermore, the cellular uptake of anionic liposomes by RAW264.7 cells was higher in the absence of fetal bovine serum (FBS) than in its presence. Moreover, the viability of RAW264.7 cells was maintained above 90% when cells were incubated with anionic liposomes for 3 h, whereas viability was markedly decreased after a 24-h incubation. Based on these results, we pretreated RAW264.7 cells by an incubation with DSPG- and cholesterol-rich liposomes for 3 h in the absence of FBS. This pretreatment significantly inhibited the internalization of other liposomes, which subsequently bound to the cell surface. Therefore, we succeeded in modifying the surface of macrophages with liposomes, and liposome-modified macrophages have potential as a biomimetic active drug delivery carrier.

Mediastinal emphysema around the left carotid arteries from a toothbrush impalement injury.

This report describes a case of a pediatric patient with a fever after an oral cavity injury caused by a toothbrush. On physical examination, no bleeds or injuries in his mouth were evident, but diagnostic imaging revealed wide mediastinal emphysema including the left carotid arteries. It shows the importance of carefully examining patients not to miss life-threating conditions.

3-deazaneplanocin A, a histone methyltransferase inhibitor, improved the chemoresistance induced under hypoxia in melanoma cells.

One of common characteristics of solid tumors is low O2 level, so-called hypoxia, which plays a critical role in chemoresistance. Epigenetic mechanism such as DNA methylation and histone modification is involved in cancer development and progression. There is ample evidence that epigenetic drugs reversed acquired chemoresistance in cancer cells under normal O2 level, normoxia. However, it remains unknown whether epigenetic drugs improve acquired chemoresistance under hypoxia. The aim of our study was to investigate whether epigenetic drugs can improve the chemoresistance induced under hypoxia in cancer cells. In murine melanoma B16-BL6 (B16) cells, the culture under hypoxia, 1%O2 caused the elevated expression of hypoxia-inducible factor-1α (HIF-1α) and its target genes. The chemoresistance to 7-ethyl-10-hydroxycamptothecin (SN-38, the active metabolite of irinotecan) was also acquired under hypoxia in B16 cells. In addition, as epigenetic mechanisms, the protein expression of the enhancer of zeste homolog 2 (EZH2), histone methyltransferase and its target histone H3 trimethylation at lysine 27 (H3K27Me3) level increased under hypoxia. The induction of H3K27Me3 under hypoxia was suppressed by EZH2 siRNA and 3-deazaneplanocin A (DZNep), an EZH2 inhibitor. Furthermore, both EZH2 siRNA and DZNep significantly reduced the cell viability after SN-38 treatment and improved the chemoresistance to SN-38 under hypoxia. These results indicated that the chemoresistance to SN-38 under hypoxia would arise from epigenetic mechanism, H3K27Me3 elevation due to EZH2 induction. In conclusion, a histone methyltransferase EZH2 inhibitor, DZNep was capable of tackling acquired chemoresistance via the suppression of histone methylation induced under hypoxic tumor microenvironment.

Preoperative Osteopenia Is a Risk Factor for Death in Patients Undergoing Gastrectomy for Gastric Cancer.

BACKGROUND/AIM: Preoperative osteopenia, defined as low bone mineral density (BMD), has been reported as a prognostic factor in patients with digestive tract cancers. However, the correlation between preoperative osteopenia and the prognosis of gastric cancer (GC) remains unclear. The aim of this study was to reveal the importance of preoperative osteopenia as a prognostic factor in patients undergoing gastrectomy for GC. PATIENTS AND METHODS: We enrolled 251 patients who had undergone curative surgery for histopathologically diagnosed gastric adenocarcinoma from January 2008 to December 2012. BMD was calculated as the average pixel density (Hounsfield units) within a circle of the mid-vertebral core at the bottom of the 11th thoracic vertebra on preoperative computed tomography. RESULTS: Osteopenia had a high area under the curve and predictive value for both overall survival (OS) and disease-specific survival (DSS). The study cohort was categorized into an osteopenia group and non-osteopenia group based on the optimal BMD cutoff values for OS (157.5) and DSS (195) determined by receiver operating characteristic analysis. The multivariate analysis revealed that OS (hazard ratio=3.607, p<0.001) and DSS (hazard ratio=2.797, p=0.03) were significantly worse in patients with than without preoperative osteopenia. CONCLUSION: Preoperative osteopenia is associated with poor OS and DSS in patients undergoing gastrectomy for GC.

Comparison of Short-term Visual Acuity Changes After Trabeculotomy ab Interno Using Trabectome and Trabeculectomy ab Externo.

PURPOSE: To compare short-term visual acuity (VA) changes after trabeculotomy ab interno (TAI) using trabectome and trabeculectomy ab externo (TAE) performed on pseudophakic eyes. DESIGN: A single-center retrospective study. PARTICIPANTS: Patients with pseudophakic eyes who had primary open-angle glaucoma or exfoliation glaucoma and underwent TAI or TAE alone. METHODS: Changes in intraocular pressure (IOP), medication score, Snellen VA, and the number of eyes with vision loss (loss of ≥ 2 Snellen lines) were evaluated at baseline, week 1, and months 1, 3, and 6. The risk factors for vision loss at 6 months postoperatively were analyzed in both groups. MAIN OUTCOME MEASURES: Visual acuity changes. RESULTS: A total of 112 eyes of 112 patients were examined: 46 in the TAI group and 66 in the TAE group. Intraocular pressure was significantly lower in both groups at each visit than at baseline. The TAI group had a significantly higher mean postoperative IOP than the TAE group. Medication scores in the TAI group were significantly different after 3 months compared with baseline; however, decreased significantly at all study visits in the TAE group. The mean VA in the TAI group did not decrease significantly at each visit. In the TAE group, it decreased significantly up to 3 months but was not significantly different at 6 months. At all study visits, the number of eyes with vision loss was significantly lower in the TAI group than in the TAE group. Only 2 eyes in the TAI group (4.3%) had vision loss at 6 months, which was caused by macular edema. In the TAE group, 13 eyes (19.7%) experienced vision loss at 6 months. In all cases, the presence of preoperative split fixation [odds ratio = 7.30, P < 0.05] and the occurrence of hypotony-related complications [odds ratio = 6.76, P < 0.05] within 6 months were risk factors for vision loss. CONCLUSIONS: TAI lowered IOP less than TAE; however, there was less vision loss with TAI. For eyes with a target IOP in the mid-teens, TAI can be recommended as initial surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosuremay be found in the Footnotes and Disclosures at the end of this article.

Impact of Robot-Assisted Minimally Invasive Esophagectomy for Esophageal Cancer: A Propensity Score-Matched Short-Term Analysis.

Background: We compared short-term clinical outcomes between robotic-assisted minimally invasive esophagectomy (RAMIE) and video-assisted thoracic esophagectomy (VATS-E) using propensity score-matched analysis. Methods: We enrolled 114 patients with esophageal cancer who underwent esophagectomy at our institution from January 2013 to January 2022. Propensity score matching was performed to minimize selection bias between the RAMIE and VATS-E groups. Results: After propensity score matching, 72 patients (RAMIE group, n = 36; VATS-E group, n = 36) were selected for analysis. No significant differences in clinical variables were observed between the two groups. The RAMIE group had a significantly longer thoracic operation time (313 ± 40 vs. 295 ± 35 min, P = 0.048), a higher number of right recurrent laryngeal nerve lymph nodes (4.2 ± 2.7 vs. 2.9 ± 1.9, P = 0.039), and a shorter postoperative hospital stay (23.2 ± 12.8 vs. 30.4 ± 18.6 days, P = 0.018) than the VATS-E group. The RAMIE group tended to have a lower rate of anastomotic leakage (13.9% vs. 30.6%) than the VATS-E group, although the difference was not statistically significant (P = 0.089). No significant differences were found in recurrent laryngeal nerve paralysis (11.1% vs. 13.9%, P = 0.722) or pneumonia (13.9% vs. 13.9%, P = 1.000) between the RAMIE group and the VATS-E group. Conclusion: Although RAMIE for esophageal cancer requires a longer thoracic surgery time, it might be a feasible and safe alternative to VATS-E for treating esophageal cancer. Further analysis is needed to clarify the advantages of RAMIE over VATS-E, especially in terms of long-term surgical outcomes.

Early postoperative visual acuity changes after trabeculectomy and factors affecting visual acuity.

PURPOSE: To investigate the early visual acuity (VA) changes that occur after trabeculectomy and their reversal with recovery. METHOD: Two hundred ninety-two eyes of 292 patients after initial trabeculectomy as a standalone procedure fulfilling the following conditions were included: 1) patients with a postoperative follow-up of at least 3 months; 2) patients with preoperative corrected VA less than 0.5 logMAR equivalent; 3) patients with reliable results of visual field; and 4) patients who had open angle glaucoma. VA and intraocular pressure (IOP) changes during the first 3 months after surgery and factors affecting VA postoperatively at 3 months were investigated. RESULTS: The mean IOPs (mmHg) after trabeculectomy were significantly lower than preoperatively during the entire period (P < 0.0001). The mean corrected VA for all patients was 0.06 ± 0.17, 0.24 ± 0.38, 0.19 ± 0.26, and 0.14 ± 0.27 preoperatively and at 1 week, 1 month, and 3 months postoperatively, respectively, showing a significant decrease from the preoperative period at all time points (P < 0.0001). VA loss of two or more levels was observed in 13 eyes (4.45%) at 3 months postoperatively. Foveal threshold (FT), shallow anterior chamber (SAC), and choroidal detachment (CD) affected the change in VA before and at 3 months after surgery (P < 0.0001, P = 0.0002, P = 0.0004, respectively). The factors that had significant effects on VA change were FT, SAC, and CD in POAG, FT and hypotonic maculopathy in NTG, and FT in XFG (p < 0.05). CONCLUSION: The frequency of serious vision loss was 4.45% for two or more levels of vision loss, and early postoperative VA changes after trabeculectomy may not be reversed even 3 months later. VA loss is influenced by preoperative FT, postoperative SAC and CD, but the impact of postoperative complications vary with disease type.

Right thoracoscopic resection in the supine position for recurrent pretracheal lymph nodes after esophagectomy.

Mediastinal lymph node recurrence is often observed following esophageal cancer surgery; however, no treatment has been established for the same. Surgical resection is often considered for cases of recurrence in a single lymph node region, although the procedures and approaches vary depending on the recurrence site. Right thoracoscopic resection is rarely opted for owing to its high surgical difficulty. Herein, we report a successful case of right thoracoscopic resection in the supine position for recurrent pretracheal lymph nodes following esophagectomy. The intraoperative findings revealed few adhesions around the recurrent lymph nodes due to the initial surgery, and the recurrent lymph nodes were safely resected within a short period. The patient was discharged on postoperative day 4 without any complications, and there was no recurrence after 20 months. Thus, right thoracoscopic resection may be a promising treatment option for recurrent pretracheal lymph nodes after esophagectomy.

Efficient Liposome Loading onto Surface of Mesenchymal Stem Cells via Electrostatic Interactions for Tumor-Targeted Drug Delivery.

Mesenchymal stem cells (MSCs) have a tumor-homing capacity; therefore, MSCs are a promising drug delivery carrier for cancer therapy. To maintain the viability and activity of MSCs, anti-cancer drugs are preferably loaded on the surface of MSCs, rather than directly introduced into MSCs. In this study, we attempted to load liposomes on the surface of MSCs by using the magnetic anionic liposome/atelocollagen complexes that we previously developed and assessed the characters of liposome-loaded MSCs as drug carriers. We observed that large-sized magnetic anionic liposome/atelocollagen complexes were abundantly associated with MSCs via electrostatic interactions under a magnetic field, and its cellular internalization was lower than that of the small-sized complexes. Moreover, the complexes with higher atelocollagen concentrations showed lower cellular internalization than the complexes with lower atelocollagen concentrations. Based on these results, we succeeded in the efficient loading of liposomes on the surface of MSCs by using large-sized magnetic anionic liposomes complexed with a high concentration of atelocollagen. The constructed liposome-loaded MSCs showed a comparable proliferation rate and differentiation potential to non-loaded MSCs. Furthermore, the liposome-loaded MSCs efficiently adhered to vascular endothelial cells and migrated toward the conditioned medium from cancer cells in vitro and solid tumor tissue in vivo. These findings suggest that liposome-loaded MSCs could serve as an efficient cell-based drug carrier for tumor-targeted delivery.

[Preparation of Magnetized Mesenchymal Stem Cells Using Magnetic Liposomes to Enhance Their Retention in Targeted Tissue -Evaluation of Retention and Anti-inflammatory Efficiency in Skeletal Muscle].

Magnetic nanoparticle-incorporated liposomes (magnetic liposomes) are considered a promising site-specific drug delivery carrier. Although there are many reports on the development of magnetic liposomes, most of them focus on the characteristics of magnetic nanoparticles, rather than liposomes. Therefore, we first evaluated the effect of the physicochemical properties of magnetic liposomes on their interaction with cells. The highest cellular uptake and retention under a magnetic field was observed using small magnetic cationic liposomes. However, magnetic cationic liposomes exhibited strong cytotoxicity. Based on these results, we constructed complexes of less toxic magnetic anionic liposomes (Mag-AL) and atelocollagen (ATCOL), a biocompatible cationic biomaterial. The cellular associated amount of Mag-AL under a magnetic field was significantly increased when Mag-AL was complexed with ATCOL, and it was comparable to that of magnetic cationic liposomes. Additionally, Mag-AL/ATCOL complexes produced no cytotoxic effect. Moreover, liver accumulation of Mag-AL/ATCOL complexes was significantly increased at a magnetic field-exposed region after intravenous injection in rats. These results indicate that Mag-AL/ATCOL complexes may be a safe and efficient magnetic responsive drug carrier. Next, we applied Mag-AL/ATCOL complexes to prepare magnetized cells for effective cell therapy. Mesenchymal stem cells (MSCs), which have the capacity to suppress tissue inflammation, were efficiently magnetized by incubation with Mag-AL/ATCOL complexes under a magnetic field. Intramuscularly injected magnetized MSCs were significantly retained in mouse skeletal muscle in the presence of a magnetic field and modulated tissue inflammatory responses. These results suggest that magnetized MSCs are useful for muscle regeneration.

Two Cases of Rectal Cancer with Retzius Shunt Treated with Robot-Assisted Surgery.

The retroperitoneal intestinal vein-general circulation anastomotic pathway is referred to as a Retzius shunt; however, it is not a well-recognized condition. Here, we describe two patients with a Retzius shunt who underwent robot-assisted surgery for rectal cancer. The first case was an 81-year-old woman who had tested positive for fecal occult blood. A type 0-Is tumor was found in the middle rectum, and we used robot-assisted surgery for resection. Intraoperative findings included a dilated vein between the inferior mesenteric artery (IMA) and inferior mesenteric vein (IMV); further, computed tomography (CT) revealed flow into the inferior vena cava (IVC). We clipped the vein without major bleeding and the tumor-specific mesorectal excision was completed. Thereafter, we reviewed relevant literature and identified the structure to be a Retzius shunt. The second case was 77-year-old man with type 1 advanced cancer in the middle rectum who underwent robot-assisted surgery. In this case, we recognized the Retzius shunt on preoperative CT due to our experience with the first case and surgery was completed without any problems. Preoperative recognition of vascular malformations, such as the Retzius shunt by CT is critical to ensure the safety of robot-assisted surgery.

Mesenchymal Stem Cells Promote IL-6 Secretion and Suppress the Gene Expression of Proinflammatory Cytokines in Contractile C2C12 Myotubes.

Sarcopenia is not only a major cause of disability but also a risk factor for obesity and diabetes in elderly persons. Exercise is an effective method for improving the sarcopenic condition by inducing the secretion of interleukin (IL)-6, which has the capacities to both promote muscle hypertrophy and regulate lipid metabolism and glucose homeostasis, by skeletal muscle. We previously showed that mesenchymal stem cells (MSCs) promote IL-6 secretion by lipopolysaccharide-stimulated C2C12 mouse skeletal muscle myotubes via paracrine mechanisms. Therefore, in this study, we investigated the effect of paracrine actions of MSCs on IL-6 and proinflammatory cytokine expression in contractile C2C12 myotubes by applying electrical stimulation. IL-6 secretion by C2C12 myotubes was increased by electrical stimulation, and a more significant increase in IL-6 secretion was observed in electrically stimulated C2C12 myotubes cultured in conditioned medium from MSCs. The activation of nuclear factor-κB in C2C12 myotubes was also promoted by the combination of conditioned medium from MSCs and electrical stimulation. Moreover, the increases in tumor necrosis factor-α and IL-1ß mRNA expression in C2C12 myotubes induced by electrical stimulation were suppressed by culture in conditioned medium from MSCs. The present findings suggest that MSCs transplantation or injection of their extracellular vesicles improve the therapeutic effect of exercise against sarcopenia without exacerbating inflammation.

Effects of particle size and release property of paclitaxel-loaded nanoparticles on their peritoneal retention and therapeutic efficacy against mouse malignant ascites.

Malignant ascites accounts for abdominal pain, dyspnea and anorexia, all of which decrease quality of life in cancer patients. Intraperitoneal chemotherapy is a useful method for managing malignant ascites and nanoparticulate drug delivery system makes it more effective by increasing peritoneal retention of anti-cancer drugs. In this study, we prepared paclitaxel-loaded emulsions and liposomes with different particle sizes and drug release properties, and evaluated their peritoneal retention and therapeutic efficacy in Ehrlich's ascites carcinoma (EAC)-bearing mice. Liposomes with the size of 100 nm were rapidly absorbed from peritoneal cavity into blood after intraperitoneal injection into EAC-bearing mice, whereas 1000-nm liposomes were highly retained in peritoneal cavity. Accordingly, 1000 nm liposomes significantly prolonged survival time of EAC-bearing mice but did not inhibit the ascites accumulation because of too poor paclitaxel release. On the other hand, although peritoneal retention of emulsions themselves was similar irrespective of their sizes, 270-nm emulsions showed the higher PTX retention in ascites than other emulsions, and resulted in significantly prolonged survival time and lower accumulation of ascites in EAC-bearing mice. These results indicate that not only particle size but drug release property is one of key determinants of the biodisposition and therapeutic efficacy of intraperitoneally injected nanoparticulate PTX against malignant ascites.