Laparoscopic Pylorus Preserving Gastrectomy vs Distal Gastrectomy for Early Gastric Cancer; A Multicenter Randomized Controlled Trial (KLASS-04).

OBJECTIVE: To evaluate the long-term outcomes of laparoscopic pylorus preserving gastrectomy (LPPG) with laparoscopic distal gastrectomy (LDG) for early gastric cancer (EGC). SUMMARY BACKGROUND DATA: PPG is considered as a function preserving surgery for EGC. However, there has been no multicenter randomized controlled trial comparing PPG with DG until now. METHODS: A multicenter randomized controlled trial (KLASS-04) with 256 patients with cT1N0M0 gastric cancer located in the mid portion of the stomach was conducted. The primary endpoint was the incidence of dumping syndrome at postoperative 1 year. Secondary endpoints included survival and recurrence, gallstone formation, nutritional parameters, gastroscopic findings, and quality of life (QOL) for 3 years. RESULTS: In the intention-to-treat analyses, there was no difference in the incidence of dumping syndrome at one year postoperatively (13.2% in LPPG vs. 15.8% in LDG, P=0.622). Gallstone formation after surgery was significantly lower in LPPG than in LDG (2.33% vs. 8.66%, P=0.026). Hemoglobin (+0.01 vs. -0.76 gm/dL, P<0.001) and serum protein (-0.15 vs. -0.35 gm/dL, P=0.002) were significantly preserved after LPPG. However, reflux esophagitis (17.8% vs. 6.3%, P=0.005) and grade IV delayed gastric emptying (16.3% vs. 3.9%, P=0.001) were more common in LPPG. Changes in body weight and postoperative QOL were not significantly different between groups. Three-year overall survival and disease-free survival were not different (1 case of recurrence of in each group, P=0.98). CONCLUSIONS: LPPG can be used as an alternative surgical option for cT1N0M0 gastric cancer in the mid portion of the stomach.

Clinical Efficacy of Laparoscopic Sentinel Node Navigation Surgery for Stomach Preservation in Patients With Early Gastric Cancer: 5-year Results of the SENORITA Trial.

OBJECTIVE: This study aimed to compare laparoscopic standard gastrectomy (LSG) and laparoscopic sentinel node navigation surgery (LSNNS) for EGC in terms of 5-year long-term oncologic outcomes. SUMMARY BACKGROUND DATA: The oncological safety of LSNNS for early gastric cancer (EGC) has not been confirmed. Three-year disease-free survival (DFS), which is the primary endpoint of the phase III multicenter randomized controlled clinical trial (SEntinel Node ORIented Tailored Approach [SENORITA] trial), did not show the non-inferiority of LSNNS relative to LSG. METHODS: The SENORITA trial, a multicenter randomized clinical trial, was designed to show that LSNNS is non-inferior to LSG in terms of 3-year DFS. In the present study, we collected 5-year follow-up data from 527 patients recruited in the SENORITA trial as the full analysis set (FAS). Disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS), and recurrence patterns were evaluated using the FAS of both LSG (n=269) and LSNNS (n=258). RESULTS: The 5-year DFS was not significantly different between the LSG and LSNNS groups (P=0.0561). During the 5-year follow-up, gastric cancer-related events, such as metachronous cancer, were more frequent in the LSNNS group than in the LSG group. However, ten recurrent cancers in the remnant stomach of both groups were curatively resected by additional gastrectomy and one by additional endoscopic resection. Two of the 198 patients who underwent local resection for stomach preservation based on the LSNNS results developed distant metastasis. However, there was no statistically significant difference in the 5-year OS and DSS (P=0.7403 and P=0.9586, respectively) between the two groups. CONCLUSION: The 5-year DFS, DSS and OS did not differ significantly between the two groups. Considering the benefits of LSNNS on postoperative quality of life, LSNNS could be recommended as an alternative treatment option for EGC.

Feasibility of Regional Lymphadenectomy for Stomach-Preserving Surgery in Early Gastric Cancer Omitting Sentinel Node Navigation: A Post Hoc Analysis of the SENORITA Trial.

BACKGROUND: Sentinel node navigation (SNN) has been known as the effective treatment for stomach-preserving surgery in early gastric cancer; however, SNN presents several technical difficulties in real practice. OBJECTIVE: This study aimed to evaluate the feasibility of regional lymphadenectomy omitting SNN, using the post hoc analysis of a randomized controlled trial. METHODS: Using data from the SENORITA trial that compared laparoscopic standard gastrectomy with lymphadenectomy and laparoscopic SNN, 237 patients who underwent SNN were included in this study. Tumor location was divided into longitudinal and circumferential directions. According to the location of the tumor, the presence or absence of lymph node (LN) metastases between sentinel and non-sentinel basins were analyzed. Proposed regional LN stations were defined as the closest area to the primary tumor. Sensitivities, specificities, positive predictive values, and negative predictive values (NPV) of SNN and regional lymphadenectomy were compared. RESULTS: Metastasis to non-sentinel basins with tumor-free in sentinel basins was observed in one patient (0.4%). The rate of LN metastasis to non-regional LN stations without regional LN metastasis was 2.5% (6/237). The sensitivity and NPV of SNN were found to be significantly higher than those of regional lymphadenectomy (96.8% vs. 80.6% [p = 0.016] and 99.5% vs. 97.2% [p = 0.021], respectively). CONCLUSIONS: This study showed that regional lymphadenectomy for stomach-preserving surgery, omitting SNN, was insufficient; therefore, SNN is required in stomach-preserving surgery.

Finely tuned ionizable lipid nanoparticles for CRISPR/Cas9 ribonucleoprotein delivery and gene editing.

Nonviral delivery of the CRISPR/Cas9 system provides great benefits for in vivo gene therapy due to the low risk of side effects. However, in vivo gene editing by delivering the Cas9 ribonucleoprotein (RNP) is challenging due to the poor delivery into target tissues and cells. Here, we introduce an effective delivery method for the CRISPR/Cas9 RNPs by finely tuning the formulation of ionizable lipid nanoparticles. The LNPs delivering CRISPR/Cas9 RNPs (CrLNPs) are demonstrated to induce gene editing with high efficiencies in various cancer cell lines in vitro. Furthermore, we show that CrLNPs can be delivered into tumor tissues with high efficiency, as well as induce significant gene editing in vivo. The current study presents an effective platform for nonviral delivery of the CRISPR/Cas9 system that can be applied as an in vivo gene editing therapeutic for treating various diseases such as cancer and genetic disorders.

Identification of Cellular Isoschaftoside-Mediated Anti-Senescence Mechanism in RAC2 and LINC00294.

As cellular senescence, reactive oxygen species (ROS) accumulate excessively, causing cellular damage. Flavonoids derived from natural products are known for their antioxidant effects and their ability to delay cellular senescence. Previous studies have attempted to mitigate cellular senescence using flavonoids from natural sources. However, the detailed mechanisms and regulatory targets of some flavonoids exhibiting antioxidant effects have not been fully elucidated. Therefore, we screened a library of flavonoids for antioxidant properties. Isoschaftoside, a glycosidic flavonoid, significantly reduced ROS levels in senescent cells. It was found that mitochondrial function was restored, and dependence on glycolysis was reduced in senescent cells treated with isoschaftoside. Additionally, we identified that isoschaftoside suppresses ROS by reducing the expression of RAC2 and LINC00294 in senescent cells. Taken together, this study establishes a novel mechanism for ROS inhibition and the regulation of cellular senescence by isoschaftoside. Our findings contribute important insights to antioxidant and anti-senescence research.

Safety and efficacy of a novel anti-CD19 chimeric antigen receptor T cell product targeting a membrane-proximal domain of CD19 with fast on- and off-rates against non-Hodgkin lymphoma: a first-in-human study.

BACKGROUND: Commercial anti-CD19 chimeric antigen receptor T-cell therapies (CART19) are efficacious against advanced B-cell non-Hodgkin lymphoma (NHL); however, most patients ultimately relapse. Several mechanisms contribute to this failure, including CD19-negative escape and CAR T dysfunction. All four commercial CART19 products utilize the FMC63 single-chain variable fragment (scFv) specific to a CD19 membrane-distal epitope and characterized by slow association (on) and dissociation (off) rates. We hypothesized that a novel anti-CD19 scFv that engages an alternative CD19 membrane-proximal epitope independent of FMC63 and that is characterized by faster on- and off-rates could mitigate CART19 failure and improve clinical efficacy. METHODS: We developed an autologous CART19 product with 4-1BB co-stimulation using a novel humanized chicken antibody (h1218). This antibody is specific to a membrane-proximal CD19 epitope and harbors faster on/off rates compared to FMC63. We tested h1218-CART19 in vitro and in vivo using FMC63-CART19-resistant models. We conducted a first-in-human multi-center phase I clinical trial to test AT101 (clinical-grade h1218-CART19) in patients with relapsed or refractory (r/r) NHL. RESULTS: Preclinically, h1218- but not FMC63-CART19 were able to effectively eradicate lymphomas expressing CD19 point mutations (L174V and R163L) or co-expressing FMC63-CAR19 as found in patients relapsing after FMC63-CART19. Furthermore, h1218-CART19 exhibited enhanced killing of B-cell malignancies in vitro and in vivo compared with FMC63-CART19. Mechanistically, we found that h1218-CART19 had reduced activation-induced cell death (AICD) and enhanced expansion compared to FMC63-CART19 owing to faster on- and off-rates. Based on these preclinical results, we performed a phase I dose-escalation trial, testing three dose levels (DL) of AT101 (the GMP version of h1218) using a 3 + 3 design. In 12 treated patients (7 DLBCL, 3 FL, 1 MCL, and 1 MZL), AT101 showed a promising safety profile with 8.3% grade 3 CRS (n = 1) and 8.3% grade 4 ICANS (n = 1). In the whole cohort, the overall response rate was 91.7%, with a complete response rate of 75.0%, which improved to 100% in DL-2 and -3. AT101 expansion correlates with CR and B-cell aplasia. CONCLUSIONS: We developed a novel, safe, and potent CART19 product that recognizes a membrane-proximal domain of CD19 with fast on- and off-rates and showed significant efficacy and promising safety in patients with relapsed B-cell NHL. TRIAL REGISTRATION: NCT05338931; Date: 2022-04-01.

A Proteomic Approach to Understand the Clinical Significance of Acute Myeloid Leukemia-Derived Extracellular Vesicles Reflecting Essential Characteristics of Leukemia.

Extracellular vesicle (EV) proteins from acute myeloid leukemia (AML) cell lines were analyzed using mass spectrometry. The analyses identified 2450 proteins, including 461 differentially expressed proteins (290 upregulated and 171 downregulated). CD53 and CD47 were upregulated and were selected as candidate biomarkers. The association between survival of patients with AML and the expression levels of CD53 and CD47 at diagnosis was analyzed using mRNA expression data from The Cancer Genome Atlas database. Patients with higher expression levels showed significantly inferior survival than those with lower expression levels. ELISA results of the expression levels of CD53 and CD47 from EVs in the bone marrow of patients with AML at diagnosis and at the time of complete remission with induction chemotherapy revealed that patients with downregulated CD53 and CD47 expression appeared to relapse less frequently. Network model analysis of EV proteins revealed several upregulated kinases, including LYN, CSNK2A1, SYK, CSK, and PTK2B. The potential cytotoxicity of several clinically applicable drugs that inhibit these kinases was tested in AML cell lines. The drugs lowered the viability of AML cells. The collective data suggest that AML cell-derived EVs could reflect essential leukemia biology.

Medial Arterial Calcification and the Risk of Amputation of Diabetic Foot Ulcer in Patients With Diabetic Kidney Disease.

We assessed the risk factors for major amputation of diabetic foot ulcers (DFUs) in patients with diabetic kidney disease (DKD) stages 3b-5. For DFU assessment, in addition to DFU location and presence of infection, ischemia, and neuropathy, vascular calcification was assessed using the medial arterial calcification (MAC) score. Of 210 patients, 26 (12.4%) underwent major amputations. Only the location and extension of DFU, represented by Texas grade differed between the minor and major amputation groups. However, after adjusting for covariates, ulcer location of mid- or hindfoot (vs. forefoot, odds ratio [OR] = 3.27), Texas grades 2 or 3 (vs. grade 0, OR = 5.78), and severe MAC (vs. no MAC, OR = 4.46) was an independent risk factor for major amputation (all P < 0.05). The current use of antiplatelets was a possible protective factor for major amputations (OR = 0.37, P = 0.055). In conclusion, DFU with severe MAC is associated with major amputation in patients with DKD.

WFDC2 Promotes Spasmolytic Polypeptide-Expressing Metaplasia Through the Up-Regulation of IL33 in Response to Injury.

BACKGROUND & AIMS: WAP 4-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4, is a small secretory protein that is highly expressed in fibrosis and human cancers, particularly in the ovaries, lungs, and stomach. However, the role of WFDC2 in carcinogenesis is not fully understood. The present study aimed to investigate the role of WFDC2 in gastric carcinogenesis with the use of preneoplastic metaplasia models. METHODS: Three spasmolytic polypeptide-expressing metaplasia (SPEM) models were established in both wild-type and Wfdc2-knockout mice with DMP-777, L635, and high-dose tamoxifen, respectively. To reveal the functional role of WFDC2, we performed transcriptomic analysis with DMP-777-treated gastric corpus specimens. RESULTS: Wfdc2-knockout mice exhibited remarkable resistance against oxyntic atrophy, SPEM emergence, and accumulation of M2-type macrophages in all 3 SPEM models. Transcriptomic analysis revealed that Wfdc2-knockout prevented the up-regulation of interleukin-33 (IL33) expression in the injured mucosal region of SPEM models. Notably, supplementation of recombinant WFDC2 induced IL33 production and M2 macrophage polarization, and ultimately promoted SPEM development. Moreover, long-term treatment with recombinant WFDC2 was able to induce SPEM development. CONCLUSIONS: WFDC2 expressed in response to gastric injury promotes SPEM through the up-regulation of IL33 expression. These findings provide novel insights into the role of WFDC2 in gastric carcinogenesis.

Estimation error of the body surface area in psoriasis: a comparative study of physician and computer-assisted image analysis (ImageJ).

BACKGROUND: Assessing the area involved in a skin disease, i.e. the body surface area (BSA), is essential in diagnosing disease severity, including in psoriasis. However, in psoriasis, BSA tends to be overestimated by physicians and has shown high inter-rater and intrarater variability. Furthermore, there are no reports suggesting the cause and clinical significance of overestimating BSA in psoriasiss. AIM: To investigate the errors in estimating BSA in psoriasis by comparing physicians' results with those of computer-assisted image analysis (CAIA) and to provide suggestions regarding the clinical implications of such errors. METHODS: Using 43 images, 36 physicians visually estimated BSA in psoriasis, and subsequently, the images were evaluated using a CAIA program (ImageJ); the BSA values determined by the physicians and CAIA were then compared and matched. The BSA percentage was also graded on a scale from 0 to 6, as follows: Grade 0 = no lesion, Grade 1 = 1%-9%, Grade 2 = 10%-29%, Grade 3 = 30%-49%, Grade 4 = 50%-69%, Grade 5 = 70%-89% and Grade 6 = 90%-100%. Each grade range was divided, with the bottom and top 50% defined as the 'first half' and 'second half,' respectively. RESULTS: The mean proportion of correct assessments by physicians was 49.4%. Physicians tended to overestimate the BSA of psoriatic lesions by 8.76% ± 8.82% compared with CAIA. The largest estimation error (proportion incorrect 75.7%) was observed in Grade 3 (30%-49% involvement). Estimates in the second half of the range demonstrated a higher proportion of inaccuracies compared with those in the first half. An overestimating error occurred in certain morphological characteristics of the psoriatic lesions. CONCLUSIONS: The inaccuracy of BSA estimation by physicians may be related to the fact that information from the human eye is perceived to be exaggerated compared with the actual size. Further research into using artificial intelligence technology is needed to reduce quantification error and develop an ideal BSA assessment system. Additionally, education and training are needed for physicians to measure BSA accurately.

Prevention of Petersen's hernia using jejunal mesentery fixing (Mefix).

BACKGROUND: The aim of this study was to compare the 1 year incidence of Petersen's hernia between individuals who were treated with the jejunal mesentery fixing (Mefix) method and those with the closure of Petersen's space method. MATERIAL AND METHODS: We retrospectively collected clinical data of patients who underwent gastrectomy for gastric cancers with the closure of Petersen's space defect (N = 49) and Mefix (N = 26). The Mefix method was performed by fixing the jejunal mesentery (jejunojejunostomy below 30 cm) to the transverse mesocolon using nonabsorbable barbed sutures. RESULTS: The procedure time for mesentery fixing (3.7 ± 1.1 mins) was significantly shorter than that for Petersen's space closure (7.5 ± 1.5 mins) (p < .001) although the operation times were similar between the two groups. There was no incidence of Petersen's hernias postoperatively in both groups. One case of reoperation was reported in the closure group due to small bowel obstruction by kinking of the jejunojejunostomy. CONCLUSION: We found no occurrence of Petersen's hernias postoperatively in either group. We also found that the Mefix method was faster and easier to perform than the closure method. The Mefix method is an excellent alternative method to prevent the occurrence of Petersen's hernia after B-II or Roux-en-Y reconstruction.

Distinct handedness of spin wave across the compensation temperatures of ferrimagnets.

Antiferromagnetic spin waves have been predicted to offer substantial functionalities for magnonic applications due to the existence of two distinct polarizations, the right-handed and left-handed modes, as well as their ultrafast dynamics. However, experimental investigations have been hampered by the field-immunity of antiferromagnets. Ferrimagnets have been shown to be an alternative platform to study antiferromagnetic spin dynamics. Here we investigate thermally excited spin waves in ferrimagnets across the magnetization compensation and angular momentum compensation temperatures using Brillouin light scattering. Our results show that right-handed and left-handed modes intersect at the angular momentum compensation temperature where pure antiferromagnetic spin waves are expected. A field-induced shift of the mode-crossing point from the angular momentum compensation temperature and the gyromagnetic reversal reveal hitherto unrecognized properties of ferrimagnetic dynamics. We also provide a theoretical understanding of our experimental results. Our work demonstrates important aspects of the physics of ferrimagnetic spin waves and opens up the attractive possibility of ferrimagnet-based magnonic devices.

Publisher Correction: Distinct handedness of spin wave across the compensation temperatures of ferrimagnets.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Nanomedicine for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that results in severe inflammatory microenvironments in the joint tissues. In clinics, disease-modifying antirheumatic drugs (DMARDs) are generally prescribed to patients with RA, but their long-term use often shows toxicity in some organs such as the gastrointestinal system, skin, and kidneys and immunosuppression-mediated infection. Nanomedicine has emerged as a new therapeutic strategy to efficiently localize the drugs in inflamed joints for the treatment of RA. In this Review, we introduce recent research in the area of nanomedicine for the treatment of RA and discuss how the nanomedicine can be used to deliver therapeutic agents to the inflamed joints and manage the progression of RA, particularly focusing on targeted delivery, controlled drug release, and immune modulation.

A comparison of postoperative outcomes after open and laparoscopic reduction of Petersen's Hernia: a multicenter observational cohort study.

BACKGROUND: The aim of this multicenter cohort study was to compare the clinical courses between open and laparoscopic Petersen's hernia (PH) reduction. METHOD: We retrospectively collected the clinical data of patients who underwent PH repair surgery after gastrectomy for gastric cancer from 2015-2018. Forty patients underwent PH reduction operations that were performed by six surgeons at four hospitals. Among the 40 patients, 15 underwent laparoscopic PH reduction (LPH), and 25 underwent open PH reduction (OPH), including 4 patients who underwent LPH but required conversion to OPH. RESULTS: We compared the clinical factors between the LPH and OPH groups. In the clinical course, we found no differences in operation times or intraoperative bowel injury, morbidity, or mortality rates between the two groups (p > 0.05). However, the number of days on a soft fluid diet (OPH vs. LPH; 5.8 vs. 3.7 days, p = 0.03) and length of hospital stay (12.6 vs. 8.2 days, p = 0.04) were significantly less in the LPH group than the OPH group. Regarding postoperative complications, the OPH group had a case of pneumonia and sepsis with multi-organ failure, which resulted in mortality. In the LPH group, one patient experienced recurrence and required reoperation for PH. CONCLUSION: Laparoscopic PH reduction was associated with a faster postoperative recovery period than open PH reduction, with a similar incidence of complications. The laparoscopic approach should be considered an appropriate strategy for PH reduction in selected cases.

Dynamic changes of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio predicts breast cancer prognosis.

BACKGROUND: We aimed to identify whether neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are more useful predictors after initial intention to treat than at the time of diagnosis. METHODS: We collected the medical data of 533 patients. The results of the peripheral blood sampling before the primary treatments were labeled as initial cohort, and those obtained between 24 and 36 months after initial treatment were defined as the 2nd cohort. Delayed metastasis has been defined as distant metastasis 2 years after treatment, and survival outcome was estimated and compared across groups. RESULTS: Median follow-up duration was 74 months (24-162 months), and 53 patients experienced delayed metastasis. In univariate analysis, metastasis-free survival, patient age at diagnosis, tumor size, axillary lymph node metastasis, HER-2 status, initial NLR and PLR, and 2nd NLR and PLR were found to be significantly associated with delayed metastasis. However, in multivariate analysis, only the 2nd NLR and PLR were found to be significantly associated with delayed metastasis, excluding initial NLR and PLR. Metastasis-free survival was analyzed through the pattern changes of NLR or PLR. The results revealed that patients with continued low NLR and PLR values at pre- and post-treatment (low initial values and 2nd values) showed a significantly better prognosis than those with a change in value or continued high NLR and PLR. CONCLUSIONS: We identified that patients with persistent high NLR and PLR after initial treatment have significant worse prognosis in terms of late metastasis. Therefore, these results suggest that NLR and PLR are more useful in predicting prognosis post-treatment.

Safety and location analysis of transumbilical endoscopic submucosal dissection with single-basin lymph node dissection in the upper gastric body: a porcine model.

BACKGROUND: In our previous study, transumbilical endoscopic submucosal dissection (TU-ESD) was revealed to be feasible, but delayed gastric perforation was observed in 30% of ESD sites. In this study, we aimed to verify locations at which it is feasible to perform TU-ESD in the upper gastric body and to demonstrate the safety of TU-ESD in single-basin lymph node dissection (SBLND). METHODS: In vitro, TU-ESD was performed at three lesion sites (anterior wall, AW; posterior wall, PW; and lesser curvature, LC) in each porcine stomach using an EASIE-R tray (cases = 10). In vivo, TU-ESD was performed with SBLND in 9 pigs. Seven days after the operation, the pigs were sacrificed and examined. RESULTS: In the in vitro feasibility study, the TU-ESD time was significantly faster in the PW group (5.9 ± 2.0 min) than in the LC group (8.5 ± 1.5 min) (p < 0.05) in all 10 cases. In the in vivo survival study, TU-ESD with SBLND was successfully performed without any complications (N = 9). There were no cases of delayed perforation, and healing ulcers were found in all pigs 7 days after the operation. Ulcer size (5.2 ± 3.5 cm2) was approximately 36% smaller than that observed at the ESD operation site (8.1 ± 1.9 cm2) (p = 0.05). Epithelialization in the margin and healing of the gastric ulcers were confirmed by microscopy. CONCLUSIONS: TU-ESD with SBLND is a feasible and safe method. The upper posterior gastric body could be the most feasible location for performing TU-ESD, perhaps because of the difference in the subcutaneous dissection time.

Safety and efficacy of post-anastomotic intraoperative endoscopy to avoid early anastomotic complications during gastrectomy for gastric cancer.

BACKGROUND: Anastomotic complications such as leaks, bleeding, and stricture remain the most serious complications of surgery for gastric cancer. No perfect method exists for an accurate and reliable prevention of these complications. This study investigated the safety and efficacy of post-anastomotic intraoperative endoscopy (PAIOE) for avoidance of early anastomotic complications during gastrectomy in gastric cancer. METHODS: This retrospective case-control study enrolled patients from a tertiary care, academic medical center. Routine PAIOE was performed on 319 patients undergoing gastrectomy for gastric cancer between 2015 and 2016. As controls, without PAIOE 270 patients from 2013 to 2014 were used for comparison. Early anastomotic complications and outcomes after PAIOE were determined. RESULTS: Although there were no differences between the PAIOE and non-PAIOE group in terms of overall complication rates (20.1% vs 26.7%; P > 0.05), there were fewer complications related to anastomosis (3.4% vs 8.9%; P < 0.01) in the PAIOE group. The PAIOE group had rates of 2.5% for anastomotic leakage, 0.9% for intra-luminal bleeding, and 0% for anastomotic stenosis, while the non-PAIOE group exhibited rates of 5.6%, 2.6%, and 0.7%, respectively. Thirty-one abnormalities were detected in 26 PAIOE patients (9.71%) (20 venous bleeding, 7 mucosal tearing, 2 air leaks, 1 arterial bleeding, and 1 anastomotic stricture). All abnormalities were corrected by proper interventions (13 reinforced additional suture, 13 endoscopic hemostasis, and 2 re-anastomosis). There were no morbidities associated with PAIOE. CONCLUSIONS: PAIOE appears to be a safe and reliable procedure to evaluate the stability of gastrointestinal anastomosis for gastric cancer patients. Further data collection and a well-designed prospective study are needed to confirm the validity of PAIOE.

Levels of Extracellular Vesicles in Pulmonary and Peripheral Blood Correlate with Stages of Lung Cancer Patients.

BACKGROUND: The extracellular vesicle (EV) concentration is known to be higher in cancer patients than in healthy individuals. Herein, we report that EV levels differ in the tumor-draining pulmonary vein blood and the peripheral blood of animal models and human subjects at different pathological stages of lung cancer. METHODS: Ten rabbits and 40 humans formed the study cohorts. Blood was collected from the peripheral vein of members of all groups. Pulmonary blood was collected intraoperatively from all groups except for the healthy human controls. Quantitative analysis of EV levels was performed using a nanoparticle tracking assay, a CD63 enzyme-linked immunosorbent assay, and western blotting. RESULTS: The EV levels in the peripheral blood of animals and patients with lung cancer were higher than those in the peripheral blood of healthy controls (p < 0.01 and p < 0.001, respectively). Moreover, for both animals and patients with lung cancer, the EV levels in the pulmonary blood were significantly higher than those in the preoperative peripheral blood (p < 0.01 and p < 0.0001, respectively). In patients, the pathological stages of lung cancer showed a higher correlation with the pulmonary EV levels than the peripheral EV levels. CONCLUSIONS: EV levels increased with increasing lung cancer grade, and this trend was more prominent in the pulmonary blood than in the peripheral blood.

Prediction of Postoperative Mortality in Patients with Organ Failure After Gastric Cancer Surgery.

BACKGROUND: Scarce data are available on the characteristics of postoperative organ failure (POF) and mortality after gastrectomy. We aimed to describe the causes of organ failure and mortality related to gastrectomy for gastric cancer and to identify patients with POF who are at a risk of failure to rescue (FTR). METHODS: The study examined patients with POF or in-hospital mortality in Seoul National University Hospital between 2005 and 2014. We identified patients at a high risk of FTR by analyzing laboratory findings, complication data, intensive care unit records, and risk scoring including Acute Physiology and Chronic Health Evaluation (APACHE) IV, Sequential Organ Failure Assessment (SOFA) score, and Simplified Acute Physiology Score (SAPS) 3 at ICU admission. RESULTS: Among the 7304 patients who underwent gastrectomy, 80 (1.1%) were identified with Clavien-Dindo classification (CDC) grade ≥ IVa. The numbers of patients with CDC grade IVa, IVb, and V were 48 (0.66%), 11 (0.15%), and 21 (0.29%), respectively. Pulmonary failure (43.8%), surgical site complication (27.5%), and cardiac failure (13.8%) were the most common causes of POF and mortality. Cancer progression (100%) and cardiac events (45.5%) showed high FTR rates. In univariate analysis, acidosis, hypoalbuminemia, SOFA, APACHE IV, and SAPS 3 were identified as risk factors for FTR (P < 0.05). Finally, SAPS 3 was identified as an independent predictive factor for FTR. CONCLUSIONS: Cancer progression and acute cardiac failure were the most lethal causes of FTR. SAPS 3 is an independent predictor of FTR among POF patients after gastrectomy.