The histone methyltransferase KMT2D is essential for embryo implantation via regulating precise differentiation of endometrial cells.

Embryo implantation failures are a major challenge in reproductive medicine, but the underlying mechanism remains poorly understood. Successful implantation requires dynamic remodeling of the endometrium through integrated proliferation and differentiation of endometrial cells including luminal epithelial, glandular epithelial, and stromal cells. Conversely, their disruption causes infertility. Spatiotemporal control of transcription is required for these processes; however, the underlying epigenetic regulation is largely unknown. In this study, we examined expression data from the human endometrium during implantation and discovered that expression of the histone lysine methyltransferase KMT2D was significantly suppressed in patients with recurrent implantation failure. Further study revealed that uterine deletion of Kmt2d in mice caused infertility due to implantation failure. Morphological analysis discovered a reduction in the number of uterine glands and aberrant differentiation of the luminal and glandular epithelium into stratified phenotypes in Kmt2d knockout uteri. Administration of leukemia inhibitory factor protein, which is expressed in uterine glands and is essential for implantation, did not rescue implantation failure in Kmt2d knockout mice, suggesting that infertility was not solely due to uterine gland dysfunction. RNA sequencing analysis revealed that Kmt2d knockout uteri displayed suppressed expression of genes involved in ion homeostasis, which may affect the uterine luminal morphology. Our study suggests that KMT2D plays an essential role in facilitating successful embryo implantation by regulating the coordinated differentiation of endometrial cells, providing valuable insights into unexplained implantation failures in women.

Clinical course of small gastric subepithelial lesion less than 20 mm diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

BACKGROUND AND AIM: Gastrointestinal stromal tumors (GISTs) are treated as malignant gastric subepithelial lesions (SELs), and resection is recommended. However, small gastric SELs < 20 mm with no malignant features are monitored without histopathological examination, and the frequency of malignancy is unknown. This study aimed to clarify the clinicopathological findings and clinical course of gastric SELs < 20 mm measured by endoscopic ultrasound (EUS). METHODS: This retrospective cohort study included consecutive patients with small gastric SELs < 20 mm diagnosed using EUS at a tertiary referral center between 2009 and 2021. The clinical course after diagnosis using EUS-guided fine-needle aspiration (EUS-FNA) was reviewed. RESULTS: Among 333 patients with small gastric SELs, 104 patients with 105 lesions underwent EUS-FNA. The pathological diagnosis was confirmed in 87 patients. GISTs were the most common pathology (47%). Among the 87 patients, 43 underwent therapeutic interventions, including tumor resection and chemotherapy. In groups of tumor resection, the pathological tumor size on the resected specimen was significantly larger than the size measured by EUS (19.5 mm vs 15.0 mm, P < 0.001), and 37% of resected SELs were 20 mm or over. No recurrence was observed after tumor resection during a mean follow-up period of 40 months. CONCLUSIONS: Approximately 40% of small gastric SELs were malignant tumors, such as GIST, with most of them requiring treatment. Additionally, considering that the EUS measurement is 5 mm smaller than the pathological tumor diameter, further examinations, such as systematic EUS-FNA, may be required for SEL, including those smaller than 20 mm.

Improving cell-specific recombination using AAV vectors in the murine CNS by capsid and expression cassette optimization.

The production of cell-type- and age-specific genetically modified mice is a powerful approach for unraveling unknown gene functions. Here, we present a simple and timesaving method that enables adeno-associated virus (AAV)-mediated cell-type- and age-specific recombination in floxed mice. To achieve astrocyte-specific recombination in floxed Ai14 reporter mice, we intravenously injected blood-brain barrier-penetrating AAV-PHP.eB vectors expressing Cre recombinase (Cre) using the astrocyte-specific mouse glial fibrillary acidic protein (mGfaABC1D) promoter. However, we observed nonspecific neuron-predominant transduction despite the use of an astrocyte-specific promoter. We speculated that subtle but continuous Cre expression in nonastrocytic cells triggers recombination, and that excess production of Cre in astrocytes inhibits recombination by forming Cre-DNA aggregates. Here, we resolved this paradoxical event by dividing a single AAV into two mGfaABC1D-promoter-driven AAV vectors, one expressing codon-optimized flippase (FlpO) and another expressing flippase recognition target-flanked rapidly degrading Cre (dCre), together with switching the neuron-tropic PHP.eB capsid to astrocyte-tropic AAV-F. Moreover, we found that the FlpO-dCre system with a target cell-tropic capsid can also function in neuron-targeting recombination in floxed mice.

Impact of endoscopy intervals on metachronous gastric cancer after endoscopic submucosal dissection: Comparison between 1 year and half-a-year.

OBJECTIVES: Japanese guidelines recommend posttreatment endoscopy once or twice a year after endoscopic submucosal dissection (ESD) for early gastric cancer. However, the impact of endoscopy intervals on metachronous gastric cancer (MGC) remains unclear, especially the difference between 1-year and half-a-year intervals. We aimed to investigate this difference. METHODS: This study retrospectively investigated 2429 patients who underwent gastric ESD between May 2001 and June 2019 at our hospital. Patients who developed MGC were classified based on those who underwent the previous endoscopy within at least 7 months (short-interval group) and within 8-13 months (regular-interval group). Propensity score matching (PSM) was used to adjust for possible confounders. The primary outcome was the proportion of MGC beyond curative ESD criteria established in the guidelines. RESULTS: A total of 216 eligible patients developed MGC. The short- and regular-interval groups included 43 and 173 patients, respectively. Overall, no patients in the short-interval group had MGC beyond curative ESD criteria, while 27 patients in the regular-interval group did. The proportion of MGC beyond curative ESD criteria was significantly lower in the short-interval group than in the regular-interval group before (P = 0.003) and after (P = 0.028) PSM. Although not significant, the short-interval group tended to have a higher stomach preservation rate than the regular-interval group (P = 0.093). CONCLUSION: Our study indicated a possible benefit of biannual surveillance endoscopy in the early post-ESD period.

Predictors of severe submucosal fibrosis during endoscopic submucosal dissection in patients with ulcerative colitis: Retrospective cohort study.

OBJECTIVES: Severe submucosal fibrosis is a crucial technical difficulty encountered during endoscopic submucosal dissection (ESD) in patients with ulcerative colitis (UC). We aimed to identify predictors of severe submucosal fibrosis in patients with UC. METHODS: We retrospectively included 55 tumors resected using ESD from 48 consecutive patients with UC. We analyzed the clinicopathological characteristics and treatment outcomes between the F0/1 (none to mild submucosal fibrosis) group (n = 28) and F2 (severe submucosal fibrosis) group (n = 27). RESULTS: No significant difference was found between the F0/1 and F2 groups in en bloc resection rate (100% vs. 96%, P = 0.49), the R0 resection rate (100% vs. 93%, P = 0.24), and the dissection speed (0.18 vs. 0.13 cm2 /min, P = 0.07). Intraoperative perforation was more common in the F2 group (30%) than in the F0/1 group (8%; P = 0.01). Multivariable analysis showed that a longer duration of UC (≥10 years; odds ratio [OR] 6.11; 95% confidence interval [CI] 1.20-31.03; P = 0.03) and scarring of background mucosa of the tumor (OR 39.61; 95% CI 3.91-400.78; P < 0.01) were independent predictors of severe submucosal fibrosis. CONCLUSION: Long UC duration and scarring background mucosa were predictors of severe submucosal fibrosis associated with perforation during ESD.

Aberrant activation of estrogen receptor-α signaling in Mettl14-deficient uteri impairs embryo implantation.

The precise control of endometrial receptivity is crucial for successful embryo implantation, which is strictly regulated by the ovarian steroid hormones estrogen and progesterone. Despite our improved understanding of the genetic regulation of implantation downstream of the action of hormones, we do not know much about the epigenetic regulation that occurs during early pregnancy. To investigate the role of the N6-methyladenosine (m6A) RNA modification in embryo implantation, we generated mice with conditional deletion of Mettl14, a core component of the m6A writer complex, in the uterus. These mice were infertile due to implantation failure. We showed that Mettl14-deficient uteri had aberrant upregulation of estrogen receptor α (ERα) signaling and ERα phosphorylation, but progesterone receptor (PGR) signaling was largely unaffected. Additionally, Mettl14 deletion led to abnormal activation of the innate immune pathway in Mettl14-deficient uteri. This effect was accompanied by the infiltration of immune cells, such as macrophages and dendritic cells, into the basal region of the endometrial epithelium. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) showed that genes involved in the innate immune response had decreased m6A peaks in Mettl14-deficient mice. These results suggest that Mettl14 plays a crucial role in successful implantation by precisely regulating both ERα signaling and innate immunity in the uterus.

Gene-Modified Blister Fluid-Derived Mesenchymal Stromal Cells for Treating Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa (RDEB) is a genodermatosis caused by variants in COL7A1-encoded type VII collagen, a major component of anchoring fibrils. In this study, we developed an ex vivo gene therapy for RDEB using autologous mesenchymal stromal cells (MSCs). On the basis of our previous studies, we first attempted to isolate MSCs from the blister fluid of patients with RDEB and succeeded in obtaining cells with a set of MSC characteristics from all 10 patients. We termed these cells blister fluid-derived MSCs. Blister fluid-derived MSCs were genetically modified and injected into skins of type VII collagen-deficient neonatal mice transplanted onto immunodeficient mice, resulting in continuous and widespread expression of type VII collagen at the dermal-epidermal junction, particularly when administered into blisters. When injected intradermally, the efforts were not successful. The gene-modified blister fluid-derived MSCs could be cultured as cell sheets and applied to the dermis with an efficacy equivalent to that of intrablister administration. In conclusion, we successfully developed a minimally invasive and highly efficient ex vivo gene therapy for RDEB. This study shows the successful application of gene therapy in the RDEB mouse model for both early blistering skin and advanced ulcerative lesions.

Multiplexed genome editing by in vivo electroporation of Cas9 ribonucleoproteins effectively induces endometrial carcinoma in mice.

Synergistic effects among multiple gene mutations are involved in cancer development and progression. However, developing genetically modified mouse models to analyze various combinations of mutations is extremely labor-intensive and time-consuming. To address these problems, we developed a novel method for in vivo multiplexed genome editing of the murine uterus to model human endometrial carcinoma (EMC). To do this, we injected a CRISPR-Cas9 ribonucleoprotein complex into the uterine cavity of adult female mice, followed by electroporation. Evaluation of reporter mice demonstrated that genome editing occurred specifically in uterine epithelial cells, which are the origin of EMCs. Simultaneous targeting of Pten/Trp53/Lkb1, or targeting of Pten/Lkb1 along with the Ctnnb1ΔEx3 mutation, resulted in efficient generation of invasive tumors in wild-type females within 3 months. This novel method will enable rapid and easy validation of many combinations of gene mutations that lead to endometrial carcinogenesis.

Endoscopic resection is feasible for high-grade dysplasia in patients with ulcerative colitis.

BACKGROUND: Endoscopic resection (ER) is feasible for treating well-circumscribed dysplasia in patients with ulcerative colitis (UC). However, long-term prognosis of ER for high-grade dysplasia (HGD) in patients with UC remains unclear. We aimed to evaluate the long-term prognoses of ER for HGD compared with low-grade dysplasia (LGD) and verify the feasibility of ER and follow-up with surveillance colonoscopy for HGD. METHODS: An observational, single-center retrospective study included 38 and 22 patients with LGD and HGD who were followed-up with surveillance colonoscopy after ER. We evaluated the cumulative incidence rate of metachronous HGD or colorectal cancer (CRC) and identified the characteristics of metachronous dysplasia. RESULTS: The median follow-up period was 56 months, and surveillance colonoscopies were performed 3.6 times (mean). The 5-year cumulative incidence rate of HGD/CRC was relatively high in HGD (24.6%) than in LGD (13.7%), but the difference was not significant (p = .16). In HGD cases, six metachronous dysplasia lesions (two LGD and four HGD) were detected 11.6-40.5 months after ER. However, these patients did not progress to CRC. All metachronous lesions were well-circumscribed and with no invisible dysplasia surrounding them; they were 'endoscopically resectable' lesions. Two of the four metachronous HGD lesions were treated endoscopically and two, by colectomy. No synchronous HGD or CRC was detected in the colectomy specimens. CONCLUSIONS: Our results suggest that ER and follow-up with surveillance colonoscopy is feasible in patients with HGD when histological complete resection is achieved.

Outpatient flexible endoscopic diverticulotomy for the management of Zenker's diverticulum: a retrospective analysis of a large single-center cohort.

BACKGROUNDS AND AIMS: Flexible endoscopic Zenker's diverticulotomy (EZD) is well established as a safe and effective technique. Because of rare but concerning adverse events, most centers admit patients for observation and barium swallow study. Our center routinely performs EZD as a day procedure, discharging appropriate patients on the same day after clinical review. This study evaluates outcomes of this cohort compared with previously published studies where patients are admitted for observation. METHODS: A retrospective analysis was performed of EZD procedures done at our center using a flexible endoscope and, in most cases, a diverticulotomy overtube with patients under moderate sedation or general anesthesia. Patients were observed for 2 hours and discharged if no clinical concerns were found. Patient comorbidities, American Society of Anesthesiologists physical status, and endoscopic adverse events were recorded against the American Society for Gastrointestinal Endoscopy severity grading system. RESULTS: Two hundred forty EZD procedures were performed between January 2015 and February 2021. Eleven (4.6%) intraprocedural adverse events occurred: 4 perforations, 4 bleeds, and 1 each postprocedural pain, delirium, and vomiting, respectively. All were recognized within the 2-hour observation period and were managed conservatively, except 1 patient who required surgery. Six patients (2.5%) presented with delayed adverse events: 2 bleeds, 2 perforations, and 2 postprocedural pain. All patients recovered uneventfully with supportive care. CONCLUSIONS: All significant adverse events requiring endoscopic or surgical intervention were identified before discharge. Delayed adverse events occurred in 2.5% of cases, all of which were managed supportively. Our data are comparable with published cohorts of admitted patients, demonstrating that appropriately selected patients may be managed as outpatients while maintaining similar safety outcomes.

The N6-methyladenosine methyltransferase METTL16 enables erythropoiesis through safeguarding genome integrity.

During erythroid differentiation, the maintenance of genome integrity is key for the success of multiple rounds of cell division. However, molecular mechanisms coordinating the expression of DNA repair machinery in erythroid progenitors are poorly understood. Here, we discover that an RNA N6-methyladenosine (m6A) methyltransferase, METTL16, plays an essential role in proper erythropoiesis by safeguarding genome integrity via the control of DNA-repair-related genes. METTL16-deficient erythroblasts exhibit defective differentiation capacity, DNA damage and activation of the apoptotic program. Mechanistically, METTL16 controls m6A deposition at the structured motifs in DNA-repair-related transcripts including Brca2 and Fancm mRNAs, thereby upregulating their expression. Furthermore, a pairwise CRISPRi screen revealed that the MTR4-nuclear RNA exosome complex is involved in the regulation of METTL16 substrate mRNAs in erythroblasts. Collectively, our study uncovers that METTL16 and the MTR4-nuclear RNA exosome act as essential regulatory machinery to maintain genome integrity and erythropoiesis.

Learning curve analysis for duodenal endoscopic submucosal dissection: A single-operator experience.

BACKGROUND AND AIMS: Superficial duodenal epithelial tumors are emerging targets for endoscopic submucosal dissection (ESD). However, it is unknown how competence is achieved in duodenal ESD. This study aimed to elucidate the learning curve for duodenal ESD. METHODS: This retrospective observational study included 100 consecutive patients who underwent duodenal ESD by a single endoscopist between March 2014 and September 2021. The primary outcome was to define the learning curve for duodenal ESD by an endoscopist with sufficient non-duodenal ESD experience. Cumulative sum (CUSUM) curve analysis was used to assess the learning curve in terms of procedural speed. Comparative analyses of phases identified using the CUSUM method were performed. RESULTS: In total, 98 patients were included in the analysis. Evaluation of the cumulative sum curve revealed four distinct phases in the graph: phase I, cases 1-25 (learning phase); phase II, cases 26-47 (proficiency phase); phase III, cases 48-72 (mastery phase); and phase IV, cases 73-98 (after introduction of general anesthesia). The median procedural speed was significantly faster in phase II than in phase I (11.1 mm2 /min vs 7.0 mm2 /min, P = .002). Clinically significant intraoperative perforation tended to decrease through phase II to phase IV (22.7%, 12.0%, and 3.8% in phases II, III, and IV, respectively). Delayed perforation occurred only in phases I and II. CONCLUSIONS: Duodenal ESD requires 25 cases to gain proficiency and 50 to achieve mastery even for an endoscopist with extensive non-duodenal ESD experience.

Magnifying endoscopy is useful for tumor border diagnosis in ulcerative colitis patients.

BACKGROUND AND AIMS: Endoscopic resection (ER) is feasible for well-circumscribed tumors in patients with ulcerative colitis (UC); however, the specific manner for diagnosis of the tumor border is unclear. We evaluated the efficacy of magnifying endoscopy (ME) for the diagnosis of tumor borders in UC. METHODS: We analyzed endoscopically or surgically resected tumors in UC patients in whom both chromoendoscopy (CE) and ME were performed, retrospectively. We classified the tumors based on tumor border visibility and evaluated tumor's characteristics and ER outcomes. RESULTS: We examined 100 tumors from 76 UC patients (66 distinct and 34 indistinct on CE). In 22 (65%) indistinct tumors on CE, ME improved the tumor border visibility. Compared with distinct tumors on CE, nonpolypoid and large tumors were more common in indistinct tumors on CE. In indistinct tumors even on ME, flat or depressed morphologies and type V pit were more frequently than in other groups. Sixty-five distinct tumors on CE and 18 distinct tumors on ME alone were treated endoscopically, and their R0 resection rate were 91% and 95% (p > 0.99). CONCLUSIONS: ME can improve the tumor border visibility in UC, and ER is feasible for tumors whose border can be visualized on ME.

Predictors of recurrence of dysplasia or cancer in patients with dysplastic Barrett's esophagus following complete eradication of dysplasia: a single-center retrospective cohort study.

BACKGROUND AND AIMS: Endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) for Barrett's esophagus (BE)-related high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) are considered effective treatments for eradication of BE. Little is known about the impact of achieving complete eradication of intestinal metaplasia (CE-IM) following the complete eradication of neoplasia (CE-N), specifically if CE-IM reduces the risk of recurrent dysplasia. METHODS: Retrospective cohort study of consecutive patients with BE and HGD or intramucosal cancer (IMC)-treated endoscopically at a tertiary referral center between 2001 and 2019. Association between CE-IM and recurrent dysplasia after CE-N was evaluated. RESULTS: A total of 433 patients treated with EMR and/or RFA were included. Of these, 381 (88%) achieved CE-N, of which 345 (80%) had adequate follow-up for inclusion in the analysis. A total of 266 (77%) patients achieved CE-IM; with a median follow-up since initial treatment for HGD/IMC of 45.9 months (IQR 25.9, 93.1); 20 patients (5.8%) had recurrent dysplasia after achieving CE-N. Kaplan Meier survival curves revealed that time free of recurrence in those who achieved CE-IM was significantly higher (p = 0.002). In the multivariable analysis, CE-IM was associated with a significant lower hazard of recurrence (HR 0.2, 95% CI 0.1, 0.6), whereas the number of endoscopic treatments to achieve CE-N was associated with a significant higher hazard of recurrence (HR 1.1, 95% CI 1.0, 1.2). CONCLUSION: Achieving CE-IM following CE-N reduces the risk of recurrent dysplasia and should be considered a treatment target among patients with BE undergoing endoscopic therapies for HGD or EAC.

Potential roles of gastroesophageal reflux in patients with superficial esophageal squamous cell carcinoma without major causative risk factors.

BACKGROUND: Cigarette smoking, alcohol consumption, and Lugol-voiding lesions (LVLs) are the major causative risk factors of esophageal squamous cell carcinoma (ESCC); however, reports on ESCC cases unrelated to these risk factors are very limited. Here, we investigated the clinicopathological features and etiology of such cases. METHODS: We retrospectively analyzed 704 consecutive superficial ESCC tumors of 512 patients who were treated with endoscopic submucosal dissection. The enrolled patients were divided into two groups-the very low-risk (VLR)-group and risk (R)-group-based on the presence of the abovementioned risks. Clinical, endoscopic, and pathological characteristics and genetic findings were assessed in both groups. RESULTS: The VLR-group consisted of 21 (4.1%) patients, who were characteristically female. Patients in the VLR-group presented gastroesophageal reflux disease (GERD), hiatal hernia, and non-open-type atrophic gastritis, and were negative for Helicobacter pylori. We found unique endoscopic features-frequently observed in the posterior wall of the middle thoracic esophagus-with a linear shape that closely resembled the erosion-like form of GERD. Additionally, histopathological examination showed that these tumors presented atypical nuclei limited to the basal and parabasal layer, sequential to the surrounding changes that presented pathological chronic inflammation of esophagitis. Evaluation of somatic mutations in cancer-related genes using next-generation sequencing revealed that the positive carcinogenic potential (TP53 mutation) of the tumors was relatively frequent in the VLR-group. CONCLUSIONS: Our study suggests that ESCC without major causative factors is related to GERD, with no remarkable oncogenic difference.

Vaginal mucus in mice: developmental and gene expression features of epithelial mucous cells during pregnancy†.

The vagina is the site of copulation and serves as the birth canal. It also provides protection against external pathogens. In mice, due to the absence of cervical glands, the vaginal epithelium is the main producer of vaginal mucus. The development and differentiation of vaginal epithelium-constituting cells and the molecular characteristics of vaginal mucus have not been thoroughly examined. Here, we characterized vaginal mucous cell development and the expression of mucus-related factors in pregnant mice. The vaginal mucous epithelium layer thickened and became multilayered after Day 12 of pregnancy and secreted increasing amounts of mucus until early postpartum. Using histochemistry and transmission electron microscopy, we found supra-basal mucous cells as probable candidates for precursor cells. In vaginal mucous cells, the expression of TFF1, a stabilizer of mucus, was high, and some members of mucins and antimicrobial peptides (MUC5B and DEFB1) were expressed in a stage-dependent manner. In summary, this study presents the partial characterization of vaginal epithelial mucous cell lineage and expression of genes encoding several peptide substances that may affect vaginal tissue homeostasis and mucosal immunity during pregnancy and parturition.

Safety and efficacy of cell-free and concentrated ascites reinfusion therapy against cirrhotic ascites in comparison with malignancy-related ascites.

BACKGROUND AND AIM: Cell-free and concentrated ascites reinfusion therapy (CART) has been performed against cirrhotic ascites, one of the most common complications seen in patients with decompensated cirrhosis. The aim of this study is to investigate its safety and efficacy, and differences in clinical profiles from CART against malignancy-related ascites with different pathological background. METHODS: The present investigation involved a sub-analysis of data obtained from a prospective observational study of CART performed at 22 centers. The condition of each procedure, therapeutic options, laboratory data, performance status, dietary intake, and abdominal circumference of participants were analyzed. Clinical parameters were compared between before and after CART, with or without albumin infusion, and also primary diseases including cirrhosis and malignant disease. RESULTS: Between January 2014 and January 2015, a total of 48 and 275 CART procedures were performed in patients with cirrhosis and malignancies. In cirrhotic patients, serum albumin concentration increased significantly in groups both with and without concomitant albumin infusion (P = 0.002 and P = 0.023), and no significant difference in CART interval was seen between these groups (P = 0.393). CART interval was not significantly different between cirrhosis and malignancy groups (P = 0.334). Dietary intake significantly improved after CART in both groups (P = 0.043 and P < 0.001). Adverse events were with no clinical significance as observed in patients with malignancies. CONCLUSIONS: Cell-free and concentrated ascites reinfusion therapy was performed safely and effectively in patients with ascites related to decompensated cirrhosis and offers the potential efficacy to maintain plasma colloid osmotic pressure after paracentesis as well as in patients with malignancy.

Safety and efficacy of water pressure endoscopic submucosal dissection for colorectal tumors with submucosal fibrosis (with video).

BACKGROUND AND AIMS: Colorectal neoplasms with submucosal fibrosis are the most challenging targets of endoscopic resection. Water pressure endoscopic submucosal dissection (WP-ESD) is a recently introduced procedure that has several advantages over conventional endoscopic submucosal dissection (C-ESD). This study aimed to assess the efficacy and safety of WP-ESD for fibrotic colorectal neoplasms. METHODS: This retrospective observational study investigated 133 colorectal neoplasms expected to have submucosal fibrosis that were resected by WP-ESD or C-ESD between April 2012 and April 2020. Eighty-seven lesions after endoscopic or surgical treatment, 18 with biopsy scar with fold convergence and 28 in patients with ulcerative colitis, were included. The differences in treatment outcomes, including procedure time and adverse event proportions, between the WP-ESD and C-ESD groups were analyzed. The clinical course after perforation using WP-ESD was also evaluated, including postprocedural multidetector CT findings obtained immediately after WP-ESD. RESULTS: Severe submucosal fibrosis was observed in 96 lesions (72.2%). The median procedure time was significantly shorter in the WP-ESD group than in the C-ESD group (43.5 minutes [interquartile range {IQR}, 32.8-73] vs 72 minutes [IQR, 45-105]; P = .0041). The multivariate analysis revealed WP-ESD as an independent factor for a short procedure time (odds ratio, 2.90; 95% confidence interval, 1.28-6.55). The proportions of post-ESD electrocoagulation syndrome (11.6% vs 13.1%) and perforation (20.4% vs 22.8%) were similar between the groups. Four of 11 patients with perforation who underwent WP-ESD showed fluid collection on postprocedural multidetector CT images. CONCLUSIONS: WP-ESD can shorten procedure time for treating fibrotic colorectal neoplasms.

Clinical usefulness of cell-free and concentrated ascites reinfusion therapy (CART) in combination with chemotherapy for malignant ascites: a post-marketing surveillance study.

BACKGROUND: Cell-free and concentrated ascites reinfusion therapy (CART) has been suggested to be able to treat malignant ascites more safely and effectively with chemotherapy because of its ability to retain serum protein and albumin. Although the characteristics of cancer types and CART and the clinical implications of combination therapy with antitumor agents are becoming widespread, there are limited reports on its efficacy and complications. METHODS: In this prospective observational national post-marketing study, 128 patients with malignancies received 300 CART sessions at 22 centers. After excluding other malignancies, the patients were divided into four groups: gynecological malignancies with chemotherapy (GYC+; 18 cases and 36 times) and without chemotherapy (GYC-; 35 cases and 52 times), and gastrointestinal malignancies with chemotherapy (GIC+; 8 cases and 16 times) and without chemotherapy (20 cases and 58 times). RESULTS: There were significant reductions in the body weight in all groups and significant reductions in abdominal circumference and significant improvements in the diet and Eastern Cooperative Oncology Group performance status only in the GYC+ group. The total serum protein and albumin increased significantly in all groups, except for the GIC+ group, before and after CART. There was no significant difference in the presence or absence of antitumor medication. CONCLUSION: With CART, there were differences in the improvement of the clinical symptoms between malignancy groups. The combination of CART and antineoplastic agents may be as safe as CART alone in cases of exudative malignant ascites.