Primary ileal myeloid sarcoma presenting with bowel obstruction: a case report.

BACKGROUND: Myeloid sarcoma (MS) is an extramedullary tumor constituted by myeloid blasts or immature myeloid cells. It frequently occurs in conjunction with acute myeloid leukemia (AML); however, it can exceptionally manifest in patients without leukemia. Here, we present a rare case of primary MS originating in the small bowel without evidence of bone marrow involvement. CASE REPRESENTATION: A 33 year-old female with no relevant medical history was admitted to our hospital with recurrent abdominal pain. Computed tomography (CT) revealed bowel obstruction due to thickening of the ileum wall, which was suspected to be an ileal tumor. Initially, ectopic endometriosis was suspected because of abdominal pain associated with the menstrual cycle and changes observed on a follow-up CT scan. The lesion could not be detected by double-balloon endoscopy. Despite conservative treatment, the obstruction persisted, and laparoscopic partial ileal resection was performed, which revealed extensive involvement of the ileum and mesentery. Additionally, the mesentery of the resected ileum was extremely thickened. Histopathological and immunohistochemical examinations of the surgical specimen indicated ileal MS. Bone marrow aspiration after discharge was negative for cytological findings of leukemia, leading to a final diagnosis of primary ileal MS. Her postoperative course was uneventful, and she is currently undergoing systemic chemotherapy tailored to AML at another hospital. CONCLUSIONS: Even though MS of the small bowel is rare and may not be considered preoperatively, similar surgical treatment to that of other small bowel malignancies can ensure proper postoperative diagnosis and appropriate chemotherapy. Given the potential need for chemotherapy, ensuring surgical safety that allows for its rapid initiation is critical.

Impact of acute coronary syndrome on early in-stent neoatherosclerosis as shown by optical coherence tomography.

Background: Patients with acute coronary syndrome (ACS) have a higher risk of requiring target vessel revascularisation after percutaneous coronary intervention (PCI) than patients with stable angina. Neoatherosclerosis is a significant risk factor for very late stent thrombosis, and the presence of neoatherosclerosis is independently associated with major adverse cardiac events. Aims: In this study, we used optical coherence tomography (OCT) to investigate the impact of ACS on neoatherosclerosis within 1 year after PCI. Methods: We investigated 102 patients (122 lesions) who had undergone PCI using a second-generation drug-eluting stent (DES) from March 2017 to November 2020 and were followed up with OCT within 1 year. The patients were categorised into the ACS group or non-ACS group according to their clinical findings at the time of target lesion treatment. We used OCT to investigate the presence of neoatherosclerosis. Results: The ACS group comprised 23 (22.5%) patients. There were no differences in the patients' clinical characteristics between the groups. The total stent length tended to be shorter in the ACS group than in the non-ACS group (24 mm vs 32 mm, respectively; p=0.09), but this difference was not statistically significant. The median duration from PCI was 290 days. Neoatherosclerosis was more frequent in ACS lesions (39% vs 4%; p<0.01), and implantation of a DES in ACS lesions was an independent predictor of neoatherosclerosis occurrence (odds ratio 9.70; p<0.01). Conclusions: This observational study using OCT indicates that stenting for ACS lesions is associated with early in-stent neoatherosclerosis.

p53-armed oncolytic virotherapy induces abscopal effect in osteosarcoma by promoting immunogenic cell death.

Osteosarcoma (OS), the most frequent primary malignant tumor of bone in children and adolescents, is refractory to immune checkpoint inhibitors due to its poor antitumor immune response. Chemotherapy and virotherapy induce immunogenic cell death (ICD) and antitumor immune responses, leading to the abscopal effect in untreated tumors. We previously demonstrated the antitumor activity of the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 in human OS cells. Here, we show the therapeutic potential of chemotherapeutic drugs (doxorubicin, cisplatin) and telomerase-specific oncolytic adenoviruses (OBP-301, p53-armed OBP-702) to induce ICD in human OS cells (U2OS, MNNG/HOS, SaOS-2) and murine OS cells (NHOS). OBP-702 induced more profound ICD via the secretion of adenosine triphosphate (ATP) and high-mobility group box protein B1 (HMGB1) compared with chemotherapy and OBP-301 in human OS cells. Murine NHOS cells were also more sensitive to OBP-702 than OBP-301. Subcutaneous NHOS tumor models demonstrated that intratumoral injection of OBP-702 significantly increased the tumor infiltration of cytotoxic CD8+ T cells and induced the abscopal effect against non-treated tumors compared with OBP-301. Our results suggest that OBP-702 is a promising antitumor reagent to induce ICD with secretion of ATP and HMGB1 and the abscopal effect against OS.

BRAF-mutant microsatellite-stable rectal cancer with acquired KRAS mutation leading to drug resistance in liver metastasis.

BRAF-mutant microsatellite-stable colorectal cancer (CRC), metastasized to distant sites, is associated with a poor prognosis. However, the BEACON CRC regimen, comprising a BRAF inhibitor, MEK inhibitor, and anti-EGFR antibody, offered a prolonged prognosis. Nonetheless, resistance to this regimen may occur, as observed in our reported case of CRC, where a KRAS mutation was identified in addition to the BRAF V600E mutation. Here, we present a case of 74-year-old woman with rectal cancer (pT4bN1bM0 Stage IIIc) harboring the BRAF V600E mutation. After resection of the primary tumor and during adjuvant chemotherapy using CAPOX (capecitabine and oxaliplatin), liver and lung metastases became apparent, and a companion diagnosis test revealed the presence of a BRAF V600E mutation. The new lesions were deemed resistant to the CAPOX regimen, and we decided to introduce encorafenib and cetuximab. After resection of liver metastases, encorafenib and cetuximab were reintroduced, but a new lesion appeared in hepatic S7, indicating resistance to the encorafenib and cetuximab regimen. The resistant liver metastasis was subsequently resected. To elucidate the resistance mechanism, we conducted a comprehensive analysis using the FoundationOne CDx cancer gene panel test, revealing the presence of a KRAS Q61H mutation alongside the BRAF V600E mutation. Subsequent liquid biopsy after liver recurrence confirmed the persistence of the KRAS Q61H mutation. Our results highlight the significance of cancer genome profiling tests (CGP tests) and liquid biopsies in guiding treatment strategies for BRAF-mutant colorectal cancer. Therefore, CGP testing offers valuable information for treatment, even if it does not lead to new drug administrations.

Senescent Fibroblasts Potentiate Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells via IL-8-mediated Crosstalk.

BACKGROUND/AIM: Diffuse-type gastric cancer (DGC) often forms peritoneal metastases, leading to poor prognosis. However, the underlying mechanism of DGC-mediated peritoneal metastasis is poorly understood. DGC is characterized by desmoplastic stroma, in which heterogeneous cancer-associated fibroblasts (CAFs), including myofibroblastic CAFs (myCAFs) and senescent CAFs (sCAFs), play a crucial role during tumor progression. This study investigated the CAF subtypes induced by GC cells and the role of sCAFs in peritoneal metastasis of DGC cells. MATERIALS AND METHODS: Conditioned medium of human DGC cells (KATOIII, NUGC-4) and human intestinal-type GC (IGC) cells (MKN-7, N87) was used to induce CAFs. CAF subtypes were evaluated by analyzing the expression of α-smooth muscle actin (α-SMA), senescence-associated ß-galactosidase (SA-ß-gal), and p16 in human normal fibroblasts (GF, FEF-3). A cytokine array was used to explore the underlying mechanism of GC-induced CAF subtype development. The role of sCAFs in peritoneal metastasis of DGC cells was analyzed using a peritoneally metastatic DGC tumor model. The relationships between GC subtypes and CAF-related markers were evaluated using publicly available datasets. RESULTS: IGC cells significantly induced α-SMA+ myCAFs by secreting transforming growth factor-ß, whereas DGC cells induced SA-ß-gal+/p16+ sCAFs by secreting interleukin (IL)-8. sCAFs further secreted IL-8 to promote DGC cell migration. In vivo experiments demonstrated that co-inoculation of sCAFs significantly enhanced peritoneal metastasis of NUGC-4 cells, which was attenuated by administration of the IL-8 receptor antagonist navarixin. p16 and IL-8 expression was significantly associated with poor prognosis of DGC patients. CONCLUSION: sCAFs promote peritoneal metastasis of DGC via IL-8-mediated crosstalk.

A multi-center, prospective, clinical study to evaluate the anti-reflux efficacy of laparoscopic double-flap technique (lD-FLAP Study).

Background: Double-flap technique (DFT) is a reconstruction procedure after proximal gastrectomy (PG). We previously reported a multi-center, retrospective study in which the incidence of reflux esophagitis (RE) (Los Angeles Classification ≥Grade B [LA-B]) 1 year after surgery was 6.0%. There have been many reports, but all of them were retrospective. Thus, a multi-center, prospective study was conducted. Methods: Laparoscopic PG + DFT was performed for cT1N0 upper gastric cancer patients. The primary endpoint was the incidence of RE (≥LA-B) 1 year after surgery. The planned sample size was 40, based on an estimated incidence of 6.0% and an upper threshold of 20%. Results: Forty patients were recruited, and 39, excluding one with conversion to total gastrectomy, received protocol treatment. Anastomotic leakage (Clavien-Dindo ≥Grade III) was observed in one patient (2.6%). In 38 patients, excluding one case of postoperative mortality, RE (≥LA-B) was observed in two patients (5.3%) 1 year after surgery, and the upper limit of the 95% confidence interval was 17.3%, lower than the 20% threshold. Anastomotic stricture requiring dilatation was observed in two patients (5.3%). One year after surgery, body weight change was 88.9 ± 7.0%, and PNI <40 and CONUT ≥5, indicating malnutrition, were observed in only one patient (2.6%) each. In the quality of life survey using the PGSAS-45 questionnaire, the esophageal reflux subscale score was 1.4 ± 0.6, significantly better than the public data (2.0 ± 1.0; p = 0.001). Conclusion: Laparoscopic DFT showed anti-reflux efficacy. Taken together with the acceptable incidence of anastomotic stricture, DFT can be an option for reconstruction procedure after PG.

Functional remodeling of intraperitoneal macrophages by oncolytic adenovirus restores anti-tumor immunity for peritoneal metastasis of gastric cancer.

Intraperitoneal tumor-associated macrophages (TAMs) are involved in evading anti-tumor immunity and promoting the peritoneal metastasis (PM) of gastric cancer (GC). Oncolytic viruses are known to induce the activation of host anti-tumor immunity in addition to tumor lysis. This study investigated whether a wild-type p53-loading telomerase-specific oncolytic adenovirus (OBP-702) could elicit the remodeling of intraperitoneal macrophages and enhance the efficacy of immune therapy. Increased numbers of CD163 TAMs and few CD8+ lymphocytes were immunohistochemically observed in clinical samples with PM, which suggested that TAMs were associated with the suppression of anti-tumor immunity. OBP-702 induced immunogenic cell death and upregulated PD-L1 expression in human and murine GC cell lines. Intraperitoneal administration of OBP-702 increased recruitment of CD8+ lymphocytes into the PM via the functional remodeling of intraperitoneal macrophages from TAM toward a pro-inflammatory phenotype, resulting in significantly suppressed tumor growth for the in vivo model. Furthermore, the combination of intraperitoneal OBP-702 with anti-programmed cell death-1 antibody enhanced anti-tumor immunity and prolonged the survival of mice bearing PM. Intraperitoneal immunotherapy using OBP-702 restores anti-tumor immunity via the remodeling of intraperitoneal macrophages in addition to direct tumor lysis and cooperates with immune checkpoint inhibitors to suppress PM in GC.

Perioperative and Postoperative Continuous Nutritional Counseling Improves Quality of Life of Gastric Cancer Patient Undergoing Gastrectomy.

Post-gastrectomy syndrome (PGS) and body weight loss (BWL) decrease quality of life (QOL) and survival of the patient undergoing gastrectomy. We have introduced perioperative and post-discharge continuous nutritional counseling (CNC) to prevent BWL and improve QOL after gastrectomy. In the present study, we evaluated the effect of CNC on QOL using the Post-gastrectomy Syndrome Assessment Scale-45 (PGSAS-45). Eighty-three patients with gastric cancer (GC) who underwent curative gastrectomy between March 2018 and July 2019 were retrospectively analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 45) or CNC (CNC group, n = 38) after gastrectomy. QOL at 12 months after gastrectomy was compared between the two groups. In QOL assessment, change in body weight (-7.98% vs. -12.77%, p = 0.0057), ingested amount of food per meal (7.00 vs. 6.07, p = 0.042) and ability for working (1.89 vs. 2.36, p = 0.049) were significantly better in CNC group than control group. Multiple regression analysis showed that CNC was a significantly beneficial factor for abdominal pain subscale (p = 0.028), diarrhea subscale (p = 0.047), ingested amount of food per meal (p = 0.012), Ability for working (p = 0.031) and dissatisfaction at the meal (p = 0.047). Perioperative and postoperative CNC could improve QOL in the patient undergoing gastrectomy in addition to preventing postoperative BWL.

p53-Armed Oncolytic Virotherapy Improves Radiosensitivity in Soft-Tissue Sarcoma by Suppressing BCL-xL Expression.

Soft-tissue sarcoma (STS) is a heterogeneous group of rare tumors originating predominantly from the embryonic mesoderm. Despite the development of combined modalities including radiotherapy, STSs are often refractory to antitumor modalities, and novel strategies that improve the prognosis of STS patients are needed. We previously demonstrated the therapeutic potential of two telomerase-specific replication-competent oncolytic adenoviruses, OBP-301 and tumor suppressor p53-armed OBP-702, in human STS cells. Here, we demonstrate in vitro and in vivo antitumor effects of OBP-702 in combination with ionizing radiation against human STS cells (HT1080, NMS-2, SYO-1). OBP-702 synergistically promoted the antitumor effect of ionizing radiation in the STS cells by suppressing the expression of B-cell lymphoma-X large (BCL-xL) and enhancing ionizing radiation-induced apoptosis. The in vivo experiments demonstrated that this combination therapy significantly suppressed STS tumors' growth. Our results suggest that OBP-702 is a promising antitumor reagent for promoting the radiosensitivity of STS tumors.

Long-term activation of anti-tumor immunity in pancreatic cancer by a p53-expressing telomerase-specific oncolytic adenovirus.

BACKGROUND: Pancreatic cancer is an aggressive, immunologically "cold" tumor. Oncolytic virotherapy is a promising treatment to overcome this problem. We developed a telomerase-specific oncolytic adenovirus armed with p53 gene (OBP-702). METHODS: We investigated the efficacy of OBP-702 for pancreatic cancer, focusing on its long-term effects via long-lived memory CD8 + T cells including tissue-resident memory T cells (TRMs) and effector memory T cells (TEMs) differentiated from effector memory precursor cells (TEMps). RESULTS: First, in vitro, OBP-702 significantly induced adenosine triphosphate (ATP), which is important for memory T cell establishment. Next, in vivo, OBP-702 local treatment to murine pancreatic PAN02 tumors increased TEMps via ATP induction from tumors and IL-15Rα induction from macrophages, leading to TRM and TEM induction. Activation of these memory T cells by OBP-702 was also maintained in combination with gemcitabine+nab-paclitaxel (GN) in a PAN02 bilateral tumor model, and GN + OBP-702 showed significant anti-tumor effects and increased TRMs in OBP-702-uninjected tumors. Finally, in a neoadjuvant model, in which PAN02 cells were re-inoculated after resection of treated-PAN02 tumors, GN + OBP-702 provided long-term anti-tumor effects even after tumor resection. CONCLUSION: OBP-702 can be a long-term immunostimulant with sustained anti-tumor effects on immunologically cold pancreatic cancer.

Persistent iatrogenic muscular ventricular septal lead perforation after pacemaker implantation using delivery sheath system.

Ventricular septal perforation is a rare complication of pacemaker implantation. Here, we describe the case of a 69-year-old man with complete atrioventricular block and heart failure. The right ventricular pacemaker was implanted with a long pre-shaped delivery sheath. A new systolic murmur appeared after the procedure. Transthoracic echocardiography revealed a ventricular septal perforation, with a Qp/Qs of 1.09, which was a small shunt rate and required no intervention. The persistent ventricular septal perforation was observed, and the shunt rate remained at 8-month follow-up. Learning objective: Ventricular septal lead perforation (VSP) is a rare complication of pacemaker implantation. Although iatrogenic VSP generally close spontaneously without adverse clinical outcomes, clinicians should pay attention to the possibility of its persistence.

Large Tissue Debris Causing Cerebral Embolism After Transcatheter Aortic Valve Replacement.

Cerebral vascular embolism is one of the complications of transcatheter aortic valve replacement (TAVR). Thrombolytic therapy is not expected to be effective when embolic material consists of a large tissue fragment. Instead, mechanical aspiration may be more effective therapy for acute cerebral infarction after TAVR. Here, we describe the case of an 87-year-old woman with aortic valve stenosis and heart failure who underwent TAVR using a self-expandable valve. Acute cerebral infarction with left middle cerebral artery occlusion caused by a large tissue fragment developed after the procedure.

Long-Term Impact of Small Mitral Valve Orifice Area after Transcatheter Edge-to-Edge Mitral Valve Repair on Clinical Outcome: A Three-Dimensional Echocardiography Study.

BACKGROUND: Iatrogenic mitral stenosis is a complication associated with transcatheter edge-to-edge mitral valve repair. Some reports revealed the impact of mean transmitral pressure gradient after procedure on long-term clinical outcomes. However, the association between prognosis and mitral valve orifice area (MVA) after the procedure has been poorly studied. This study aimed to investigate the association between postprocedural small MVA, derived from three-dimensional (3D) transesophageal echocardiography (TEE), and long-term clinical outcomes in 2 cohorts: the degenerative mitral regurgitation (MR) cohort and the functional MR cohort. METHODS: This retrospective study assessed 279 consecutive patients with 3D TEE data during transcatheter edge-to-edge mitral valve repair between January 2010 and December 2016. Mitral valve orifice area after device implantation was measured by 3D planimetry. The patients with degenerative and functional MR were stratified separately into 2 groups according to postprocedural MVA: normal MVA (MVA > 1.5 cm2) group and small MVA (MVA ≤ 1.5 cm2) group. RESULTS: Of the 279 patients, 142 (51%) had degenerative MR and 137 (49%) had functional MR. The number of degenerative MR patients with small MVA was 38, whereas 42 patients were in the functional MR cohort. Patients with small MVA had higher rate of all-cause mortality in the degenerative MR group (log-rank test: P = .01) but not in the functional MR group (log-rank test: P = .52). In multivariate analysis small MVA was independently associated with all-cause mortality but not postprocedural transmitral pressure gradient. Neither small MVA nor transmitral pressure gradient was associated with all-cause mortality in patients with functional MR. CONCLUSION: Small MVA measured by 3D TEE after transcatheter mitral edge-to-edge repair was associated with poor prognosis in patients with degenerative MR.

Clinical Impact of Prehabilitation on Elective Laparoscopic Surgery in Frail Octogenarians With Colorectal Cancer.

BACKGROUND/AIM: The aim of the present study was to clarify the clinical impact of prehabilitation by the perioperative management center (PERIO) at our hospital in severely frail octogenarians with colorectal cancer. PATIENTS AND METHODS: We compared the clinicopathological characteristics of octogenarians who underwent surgery for colorectal cancer before the establishment of PERIO intervention (Control group) with those who received prehabilitation (PERIO group). All patients were classified as American Society of Anesthesiologists (ASA) class 3 or higher. The primary outcome was the incidence of postoperative complications. RESULTS: There were 21 patients in the Control group and 19 patients in the PERIO group. Operative time was significantly longer in the PERIO group (Control group, 200 min vs. PERIO group, 230 min; p=0.03) and blood loss was significantly higher in the PERIO group (Control group, 5 ml vs. PERIO group, 30 ml; p=0.02). Postoperative complications occurred in 10 patients (47.6%) in the Control group and 3 patients (15.8%) in the PERIO group and were significantly lower in the PERIO group (p=0.03). Postoperative hospital stay was 13 days (range=7-31 days) in the Control group and 11 days (range=8-70 days) in the PERIO group (p=0.39). The rate of discharge directly to home was 81% in the Control group and 93.3% in the PERIO group (p=0.29). CONCLUSION: In frail octogenarians with colorectal cancer of ASA class 3 or higher, the incidence of postoperative complications was significantly lower after PERIO intervention.

p53-armed oncolytic adenovirus induces autophagy and apoptosis in KRAS and BRAF-mutant colorectal cancer cells.

Colorectal cancer (CRC) cells harboring KRAS or BRAF mutations show a more-malignant phenotype than cells with wild-type KRAS and BRAF. KRAS/BRAF-wild-type CRCs are sensitive to epidermal growth factor receptor (EGFR)-targeting agents, whereas KRAS/BRAF-mutant CRCs are resistant due to constitutive activation of the EGFR-downstream KRAS/BRAF signaling pathway. Novel therapeutic strategies to treat KRAS/BRAF mutant CRC cells are thus needed. We recently demonstrated that the telomerase-specific replication-competent oncolytic adenoviruses OBP-301 and p53-armed OBP-702 exhibit therapeutic potential against KRAS-mutant human pancreatic cancer cells. In this study, we evaluated the therapeutic potential of OBP-301 and OBP-702 against human CRC cells with differing KRAS/BRAF status. Human CRC cells with wild-type KRAS/BRAF (SW48, Colo320DM, CACO-2), mutant KRAS (DLD-1, SW620, HCT116), and mutant BRAF (RKO, HT29, COLO205) were used in this study. The antitumor effect of OBP-301 and OBP-702 against CRC cells was analyzed using the XTT assay. Virus-mediated modulation of apoptosis, autophagy, and the EGFR-MEK-ERK and AKT-mTOR signaling pathways was analyzed by Western blotting. Wild-type and KRAS-mutant CRC cells were sensitive to OBP-301 and OBP-702, whereas BRAF-mutant CRC cells were sensitive to OBP-702 but resistant to OBP-301. Western blot analysis demonstrated that OBP-301 induced autophagy and that OBP-702 induced autophagy and apoptosis in human CRC cells. In BRAF-mutant CRC cells, OBP-301 and OBP-702 suppressed the expression of EGFR, MEK, ERK, and AKT proteins, whereas mTOR expression was suppressed only by OBP-702. Our results suggest that p53-armed oncolytic virotherapy is a viable therapeutic option for treating KRAS/BRAF-mutant CRC cells via induction of autophagy and apoptosis.

[Therapeutic Effect of Oncolytic Adenovirus on Pancreatic Cancer Stroma].

Pancreatic ductal adenocarcinoma(PDAC)is lethal malignancy with abundant stroma. Cancer-associated fibroblasts (CAFs) exist in the PDAC stroma and contribute to progression of malignant transformation, treatment resistance, and recurrence. However, effective treatment to control PDAC stroma has not been established. We have developed tumor suppressor gene p53-armed oncolytic adenovirus(OBP-702), and have clarified therapeutic effects on PDAC cells. In this study, we investigate the therapeutic effect of OBP-702 on PDAC CAF.

Intraperitoneal Administration of p53-armed Oncolytic Adenovirus Inhibits Peritoneal Metastasis of Diffuse-type Gastric Cancer Cells.

BACKGROUND/AIM: Diffuse-type gastric cancer (GC) frequently exhibits peritoneal metastasis, leading to poor prognosis. However, efforts to develop antitumor strategies for preventing the peritoneal metastasis of GC have been unsuccessful. As diffuse-type GC cells often carry a genetic alteration in the tumor suppressor p53 gene, p53 restoration may be a potent strategy for preventing peritoneal metastasis of GC. In this study, we investigated the therapeutic potential of p53-expressing adenoviral vectors against peritoneal metastasis of diffuse-type GC cells. MATERIALS AND METHODS: Three diffuse-type human GC cell types with different p53 statuses (p53-wild type NUGC-4, p53-mutant type GCIY, and p53-null type KATOIII) were used to evaluate the therapeutic potential of p53 activation induced by the p53-expressing, replication-deficient adenovirus Ad-p53 and oncolytic adenovirus OBP-702. Viability, apoptosis, and autophagy of virus-treated GC cells were analyzed under normal and sphere-forming culture conditions using the XTT assay and western blot analysis. The in vivo antitumor effects of OBP-702 and Ad-p53 were assessed using xenograft tumor models involving peritoneal metastasis of NUGC-4 and GCIY cells. RESULTS: Under normal and sphere-forming culture conditions, OBP-702 induced a significantly greater antitumor effect in GC cells compared with Ad-p53 by strongly inducing p53-mediated apoptosis and autophagy and receptor tyrosine kinase suppression. In vivo experiments demonstrated that intraperitoneal administration of OBP-702 significantly suppressed the peritoneal metastasis of NUGC-4 and GCIY cells compared with Ad-p53, leading to prolonged survival of mice. CONCLUSION: Intraperitoneal administration of OBP-702 inhibits the peritoneal metastasis of GC cells by inducing p53-mediated cytopathic activity.

Multidetector Computed Tomography in Patients Who Underwent Transcatheter Mitral Edge-to-Edge Repair.

Multidetector computed tomography (MDCT) can provide valuable information for mitral assessment, but its role in transcatheter mitral edge-to-edge repair (TEER) planning has been poorly elucidated. We aimed to compare MDCT with 3-dimensional transesophageal echocardiography (3D-TEE) for TEER preprocedural evaluation. We analyzed the preprocedural MDCT and 3D-TEE of 108 consecutive patients with mitral regurgitation (MR) who underwent MitraClip implantation. The levels of agreement for the etiology and mechanism of MR, mitral calcification, mitral annulus, and mitral valve orifice area (MVOA) measurements were compared between MDCT and 3D-TEE data. Receiver-operating-characteristic curves were generated for mitral annulus area and MVOA using a low mean transmitral pressure gradient at discharge (<5 mm Hg) as the state variable, and the primary outcome of all-cause mortality or rehospitalization for heart failure at 1 year was compared between MDCT's and 3D-TEE's MVOA <4-cm2 cutoff. Good levels of agreement between MDCT and 3D-TEE were observed for determining the etiology (κ = 0.81) and mechanism (κ = 0.62) of MR but not for grading mitral calcification (κ = 0.31 to 0.35). The correlations between MDCT and 3D-TEE measurements were strong for mitral annulus area (r = 0.90) and good for MVOA (r = 0.73). Furthermore, no significant differences in the area under the receiver-operating-characteristic curve to predict low transmitral pressure gradient at discharge or the primary outcome at 1 year were detected between MDCT- and 3D-TEE-derived parameters (all p >0.05). In conclusion, in patients who underwent TEER with MitraClip, a high degree of agreement for comprehensive evaluation of MR and prediction of clinical outcomes between MDCT and 3D-TEE was observed.