Postoperative early weight-bearing using double plating for periprosthetic, interprosthetic, and interimplant distal femur fractures following total knee arthroplasty: A report of three cases.

Background: Distal femur fractures (DFFs) following total knee arthroplasty (TKA) in older patients often require prolonged non-weight-bearing, thereby decreasing their activities of daily living (ADL) and increasing mortality. This report clarifies early weight-bearing safety and utility by using double-plate fixation on medial and lateral sides (LM180 double-plate fixation) for DFFs following TKA. Case presentation: Three cases of Su Type III periprosthetic, interprosthetic, and interimplant DFFs following TKA, where bone stock was limited, were treated with LM180 double-plate fixation using locking plates through medial and lateral incisions on the distal femur. In interprosthetic and interimplant DFF cases, the proximal section was secured by overlapping the lateral plate +/- medial plate with the proximal femur stem of the intramedullary nail by using monocortical screws and cerclage wires. Early postoperative partial weight-bearing was recommended, and full weight-bearing was allowed 4-5 weeks postoperation. All cases regained independent walking without hardware failure. Average ADL scores, namely, Barthel index (BI) and functional independence measure (FIM), were recovered to 85/100 and 114.7/126, respectively, approaching near-normal values. Conclusion: LM180 double-plate fixation for DFFs such as Su Type III periprosthetic, Vancouver type C interprosthetic, and interimplant DFFs following TKA with limited bone stock can be used to achieve early weight-bearing without fixation failure and help maintain ADL.

Activation of STING in pancreatic cancer-associated fibroblasts exerts an antitumor effect by enhancing tumor immunity.

Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate; therefore, the development of effective treatments is a priority. The stimulator of interferon genes (STING) pathway enhances tumor immunity by inducing the production of type 1 interferon (IFN) and proinflammatory cytokines and chemokines and promoting the infiltration of cytotoxic T cells. To assess the function of STING on pancreatic tumorigenesis, Ptf1aER-Cre/+ LSL-KrasG12D/+ p53loxP/loxP mice (KPC mice) and Ptf1aER-Cre/+ LSL-KrasG12D/+ p53loxP/loxP/STING-/- mice (KPCS mice) were generated. However, STING deletion did not affect pancreatic tumorigenesis in mice. Because STING is expressed not only in immune cells but also in cancer-associated fibroblasts (CAFs), we evaluated the STING function in PDAC CAFs. A mouse STING agonist 5,6-Dimethyl-9-oxo-9H-xanthene-4-acetic acid (DMXAA) was administered to KPC mice and CAFs from KPC mice and the resulting immune response was evaluated. DMXAA activated STING in PDAC CAFs in KPC mice, promoting cytotoxic T cell infiltration by secreting proinflammatory cytokines and enhancing tumor immunity. We next generated STING-deficient PDAC cells and subcutaneous tumors in which STING was expressed only in CAFs by performing bone marrow transplantation and assessed the antitumor effect of STING-activated CAFs. The administration of DMXAA to subcutaneous tumors expressing STING only in CAFs sustained the antitumor effect of DMXAA. About half of human PDACs lacked STING expression in the cancer stroma, suggesting that STING activation in PDAC CAFs exerts an antitumor effect, and STING agonists can be more effective in tumors with high than in those with low STING expression in the stroma.

A Novel Characteristic Gastric Mucus Named "Web-like Mucus" Potentially Induced by Vonoprazan.

Background: In the absence of Helicobacter pylori (HP) infection, a characteristic gastric mucus adhesion may appear during the use of vonoprazan. We named this novel characteristic mucus "web-like mucus" (WLM). This study aimed to determine the incidence and risk factors for WLM. Methods: Between January 2017 and January 2022, 5665 patients were enrolled in this study. The patients were divided into a proton-pump inhibitor (PPI)-prescribed group (n = 2000), a vonoprazan-prescribed group (n = 268), and a no-PPI/vonoprazan-prescribed (n = 3397) group, and the presence of WLM was examined. After excluding four patients with autoimmune gastritis, the remaining 264 patients in the vonoprazan group were divided into WLM and non-WLM groups, and their clinical features were analyzed. Results: A total of 55 (21%) patients had WLM, all in the vonoprazan-prescribed group. There were no significant differences in factors such as, sex, age, chronic kidney disease, diabetes mellitus, HP eradication history, smoking, or alcohol consumption between the WLM and non-WLM groups. The median duration from the start of vonoprazan administration to the endoscopic detection of WLM was 2 (1-24) months. Conclusions: WLM appears to be a characteristic feature in patients treated with vonoprazan.

Single-Arm, Prospective, Interventional Study of Helicobacter pylori Eradication Rescue Therapy with Rifabutin, Metronidazole, and Vonoprazan.

Background and Objective: Rescue Helicobacter pylori eradication can be challenging. Rifabutin (RBT) demonstrates high activity against Helicobacter pylori and is incorporated into various rescue eradication regimens. This exploratory study was performed to evaluate the efficacy and safety of a rescue regimen comprising RBT, metronidazole (MNZ), and vonoprazan (VPZ). Methods: This prospective, single-center, single-arm, interventional study was performed in Japan. Eligible patients were those who underwent failed primary eradication treatment (7-day treatment with three drugs: VPZ or a proton pump inhibitor [PPI], amoxicillin [AMPC], and clarithromycin) and secondary eradication treatment (7-day treatment with three drugs: VPZ or a PPI, AMPC, and MNZ) and those who were unable to receive first- and second-line therapy because of penicillin allergy. Twenty Helicobacter pylori-positive patients were treated with RBT (150 mg twice daily), MNZ (250 mg twice daily), and VPZ (20 mg twice daily) for 10 days (RBT-MNZ-VPZ therapy). Eradication success was evaluated using the urea breath test. Drug susceptibility test results were available in 16 patients. This study is registered in the Japan Registry of Clinical Trials (jRCT031220504). Results: The intention-to-treat (ITT) and per-protocol (PP) eradication rates of RBT-MNZ-VPZ therapy were 70% (90% confidence interval [CI]: 49.2%-86.0%) and 72.2% (95% CI: 50.2%-88.4%), respectively. In the MNZ-susceptible subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were 100% (90% CI: 68.8%-100%) and 100% (90% CI: 65.2%-100%). In the MNZ-resistant subgroup, the ITT (n = 8) and PP (n = 7) eradication rates were both 62.5% (90% CI: 28.9%-88.9%). All infections were RBT-susceptible. Conclusions: These findings suggest that RBT-MNZ-VPZ therapy may be a promising rescue regimen, especially in MNZ- and RBT-susceptible infections or patients with penicillin allergy.

Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature.

Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

The usefulness of texture and color enhancement imaging to identify the minor papilla orifice.

In clinical cases of pancreas divisum, endoscopic retrograde cholangiopancreatography often necessitates cannulation of the pancreatic duct through the minor papilla. Nevertheless, this procedure can be challenging because of the small size of the minor papilla and the difficulty in visualizing the ductal orifice. A new image-enhanced endoscopy technique called texture and color enhancement imaging (TXI) has been developed, which enhances texture, brightness, and color compared with white-light imaging, resulting in subtle differences in the surface mucosa. Herein, we describe the case of a 73-year-old man with pancreas divisum in whom TXI was useful in identifying the orifice of the minor papilla. He was referred to our hospital with repetitive acute exacerbation of chronic pancreatitis. Since contrast-enhanced computed tomography revealed a pancreatic stone in the main pancreatic duct, endoscopic retrograde cholangoepancreatography was performed as a therapeutic intervention. Despite the initial difficulty in identifying the orifice of the minor papilla on white-light imaging, TXI enhanced its visibility successfully, enabling dorsal pancreatic duct cannulation via the minor papilla. Subsequently, endoscopic pancreatic sphincterotomy was performed and a 6Fr plastic stent was placed. Post-endoscopic therapy, the patient's abdominal pain was relieved. TXI was useful in identifying the minor papilla orifice and led to successful cannulation.

Phenotypes for general behavior, activity, and body temperature in 3q29 deletion model mice.

Whole genome analysis has identified rare copy number variations (CNV) that are strongly involved in the pathogenesis of psychiatric disorders, and 3q29 deletion has been found to have the largest effect size. The 3q29 deletion mice model (3q29-del mice) has been established as a good pathological model for schizophrenia based on phenotypic analysis; however, circadian rhythm and sleep, which are also closely related to neuropsychiatric disorders, have not been investigated. In this study, our aims were to reevaluate the pathogenesis of 3q29-del by recreating model mice and analyzing their behavior and to identify novel new insights into the temporal activity and temperature fluctuations of the mouse model using a recently developed small implantable accelerometer chip, Nano-tag. We generated 3q29-del mice using genome editing technology and reevaluated common behavioral phenotypes. We next implanted Nano-tag in the abdominal cavity of mice for continuous measurements of long-time activity and body temperature. Our model mice exhibited weight loss similar to that of other mice reported previously. A general behavioral battery test in the model mice revealed phenotypes similar to those observed in mouse models of schizophrenia, including increased rearing frequency. Intraperitoneal implantation of Nano-tag, a miniature acceleration sensor, resulted in hypersensitive and rapid increases in the activity and body temperature of 3q29-del mice upon switching to lights-off condition. Similar to the 3q29-del mice reported previously, these mice are a promising model animals for schizophrenia. Successive quantitative analysis may provide results that could help in treating sleep disorders closely associated with neuropsychiatric disorders.

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.

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.

Risk assessment of metachronous gastric cancer after endoscopic submucosal dissection based on endoscopic intestinal metaplasia.

Background and Aim: The incidence of metachronous gastric cancer (MGC) after endoscopic treatment for early gastric cancer (EGC) is high, but a method of risk assessment for MGC based on endoscopic findings has not been established. In this study, we focused on endoscopic intestinal metaplasia (IM) and investigated the risk for MGC after endoscopic submucosal dissection (ESD) for EGC. Methods: This retrospective observational study involved patients who underwent curative ESD for EGC from April 2015 to January 2021. We assessed endoscopic IM using the pretreatment endoscopic examination images. The severity of endoscopic IM was classified into four levels: 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Four different gastric areas were evaluated. We divided the patients into a low-score group and a high-score group, and compared the cumulative incidence of MGC. Results: In total, 156 patients who met the inclusion criteria were followed up for at least 12 months after ESD, and MGC developed in 14 patients during a mean period oof 41.5 months. The endoscopic IM scores in the lesser curvature of the antrum, lesser curvature of the corpus, and greater curvature of the corpus were higher in patients with MGC than in those without MGC. In the corpus, the 5-year cumulative incidence of MGC was significantly higher in the high-score group than in the low-score group (29.8% vs 10.0%, P = 0.004). Conclusion: The severity of endoscopic corpus IM was associated with MGC. Thus, patients with severe corpus IM at the time of ESD require careful examination and intensive follow-up.

Cervical esophageal adenocarcinoma of intestinal type in ectopic gastric mucosa.

A 45-year-old man underwent esophagogastroduodenoscopy because of symptoms of laryngopharyngeal discomfort. We found a protruded reddish lesion adjacent to the ectopic gastric mucosa (EGM) in the cervical esophagus, and a biopsy revealed that it was a tubular adenocarcinoma. We diagnosed the patient with intramucosal cancer and performed endoscopic submucosal dissection. Esophageal endoscopic submucosal dissection was performed under general anesthesia using a conventional procedure. The resected tumor measured 23 × 14 mm and was adjacent to the EGM. Histologically, the tumor cells showed moderately well-differentiated adenocarcinoma confined to the muscularis mucosa with no lymphovascular infiltration. Immunohistochemically, the tumor cells were positive for intestinal markers, namely MUC2 and CD10, and negative for gastric markers, namely MUC5AC and MUC6. The patient had no post-endoscopy submucosal dissection stenosis and remained disease-free without local recurrence. EGM of the cervical esophagus develops from the columnar epithelium during embryonic development. There are few reports on endoscopic submucosal dissection for mucosal cancer. Of these, immunostaining was performed in three cases. All were positive for MUC5AC and MUC6 and negative for MUC2 and CD10. Usually, EGM shows gastric type epithelium, but occasional cases with intestinal metaplasia, which show positivity for MUC2 and CD10, have been reported. Therefore, we consider this to be an extremely rare case of esophageal adenocarcinoma arising from intestinal metaplasia within the EGM.

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.

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.

Chemoenzymatic Labeling to Visualize Intercellular Contacts Using Lipidated SortaseA.

Methods to label intercellular contact have attracted attention because of their potential in cell biological and medical applications for the analysis of intercellular communications. In this study, a simple and versatile method for chemoenzymatic labeling of intercellularly contacting cells is demonstrated using a cell-surface anchoring reagent of a poly(ethylene glycol)(PEG)-lipid conjugate. The surface of each cell in the cell pairs of interest were decorated with sortase A (SrtA) and triglycine peptide that were lipidated with PEG-lipid. In the mixture of the two-cell populations, the triglycine-modified cells were enzymatically labeled with a fluorescent labeling reagent when in contact with SrtA-modified cells on a substrate. The selective labeling of the contacting cells was confirmed by confocal microscopy. The method is a promising tool for selective visualization of intercellularly contacting cells in cell mixtures for cell-cell communication analysis.

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.

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.

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.

Small intestinal thrombotic microangiopathy following kidney transplantation diagnosed by balloon-assisted enteroscopy.

Thrombotic microangiopathy (TMA) is a serious complication following kidney transplantation. Although intestinal TMA is a major organ injury and causes abdominal pain, diarrhea and bloody stools, the clinical and endoscopic characteristics of small intestinal TMA remain unclear. Here, we report a drug-induced small intestinal TMA, which did not meet the laboratory-defined TMA criteria but was diagnosed by balloon-assisted enteroscopy (BAE). A 32-year-old woman who underwent kidney transplantation at the age of 10 years complained of abdominal pain, diarrhea and bloody stools one month after starting everolimus (EVE) as an immunosuppressant. Although she did not meet the diagnostic criteria for TMA serologically, BAE revealed a circumferential ulcer in the jejunum, and the pathological findings of a biopsy specimen showed microvascular thrombi, compatible with intestinal TMA. Her symptoms improved upon the discontinuation of EVE, demonstrating that EVE can cause drug-induced intestinal TMA. The present case suggests that BAE should be performed when abdominal pain, diarrhea, and bloody stools occur in patients receiving immunosuppressive medication following kidney transplantation, even if there is no evidence of TMA according to the laboratory definition.

Mixed histology poses a greater risk for noncurative endoscopic resection in early gastric cancers regardless of the predominant histologic types.

OBJECTIVES: Clinicopathologic characteristics and treatment outcomes of mixed-histological-type (MT) early gastric cancers (EGCs) treated with endoscopic submucosal dissection (ESD) have not been sufficiently elucidated. We aimed to clarify them in comparison with pure-histological-type EGCs. METHODS: We used 3022 consecutive EGCs in 2281 patients treated with ESD from our prospectively maintained database. Cases were stratified into four groups according to the final diagnosis of the resected specimen are as follows: 2780 pure differentiated-type (DT), 127 DT-predominant MT (D-MT), 87 pure undifferentiated-type (UDT), and 28 UDT-predominant MT (U-MT). Clinicopathologic characteristics and treatment outcome were compared between pure DT and D-MT, and between pure UDT and U-MT separately. Risk factors for deep submucosal invasion, lymphovascular invasion, and a final diagnosis of MT were identified using multivariate analysis. RESULTS: Both D-MT (41.7 vs. 92.0%; P < 0.0001) and U-MT (35.7 vs. 75.9%; P = 0.0002) showed a significantly lower curative resection rate than their pure histologic counterparts. Multivariate analysis revealed that MT was an independent risk factor for deep submucosal (OR 6.55; 95% CI, 4.18-10.14) and lymphovascular (OR 4.74; 95% CI, 2.72-8.29) invasion. Preoperative biopsy results that did not show well-differentiated tubular adenocarcinoma (OR 28.2; 95% CI, 18.9-42.9) were an independent risk factor for a final diagnosis of MT. CONCLUSIONS: MT poses a greater risk for noncurative resection regardless of the predominant histologic types, reflecting more aggressive malignant potential. Although a biopsy examination rarely shows MT, clinicians should consider the possibility of MT when a biopsy examination does not show well-differentiated tubular adenocarcinoma.