[Severe consciousness disturbance after cord blood transplantation for relapsed T lymphoblastic lymphoma].

T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has a poor prognosis. Nelarabine has recently shown relatively good results in patients with relapsed or refractory T-ALL/LBL, but requires careful monitoring for neurological complications. A 50-year-old man with early recurrence of T-LBL after allogenic peripheral blood stem cell transplantation received nelarabine monotherapy and achieved complete remission after 1 cycle. He then received umbilical cord blood transplantation, and experienced sustained disturbance of consciousness. He later died of multiple organ failure, and autopsy suggested that nelarabine-induced leukoencephalopathy had caused the disturbance of consciousness. This case suggests that physicians should carefully monitor patients for neurological complications and consider imaging follow-up and consultation with a neurologist.

Targeted Metabolomic Profiling of Plasma Samples in Gastric Cancer by Liquid Chromatography-Mass Spectrometry.

INTRODUCTION: As the high mortality rate of gastric cancer (GC) is due to delayed diagnosis, early detection is vital for improved patient outcomes. Metabolic deregulation plays an important role in GC. Although various metabolite-level biomarkers for early detection have been assessed, there is still no unified early detection method. We conducted a plasma metabolome study to assess metabolites that may distinguish GC samples from non-GC samples. METHODS: Blood samples were collected from 72 GC patients and 29 control participants (non-GC group) at the Tokyo Medical University Hospital between March 2020 and November 2020. Hydrophilic metabolites were identified and quantified using liquid chromatography-time-of-flight mass spectrometry. Differences in metabolite concentrations between the GC and non-GC groups were evaluated using the Mann-Whitney test. The discrimination ability of each metabolite was evaluated by the area under the receiver operating characteristic curve. A radial basis function (RBF) kernel-based support vector machine (SVM) model was developed to assess the discrimination ability of multiple metabolites. The selection of variables used for the SVM utilized a step-wise regression method. RESULTS: Of the 96 quantified metabolites, 8 were significantly different between the GC and non-GC groups. Of these, N1-acetylspermine, succinate, and histidine were used in the RBF-SVM model to discriminate GC samples from non-GC samples. The area under the curve (AUC) of the RBF-SVM model was higher (0.915; 95% CI: 0.865-0.965, p < 0.0001), indicating good performance of the RBF-SVM model. The application of this RBF-SVM to the validation dataset resulted from the AUC of the RBF-SVM model was (0.885; 95% CI: 0.797-0.973, p < 0.0001), indicating the good performance of the RBF-SVM model. The sensitivity of the RBF-SVM model was better (69.0%) than those of the common tumor markers carcinoembryonic antigen (CEA) (10.5%) and carbohydrate antigen 19-9 (CA19-9) (2.86%). The RBF-SVM showed a low correlation with CEA and CA19-9, indicating its independence. CONCLUSION: We analyzed plasma metabolomics, and a combination of the quantified metabolites showed high sensitivity for the detection of GC. The independence of the RBF-SVM from tumor markers suggested that their complementary use would be helpful for GC screening.

A Case of Biphenotypic Adnexal Carcinoma With Bowenoid and Basaloid Features: Focus on the Expression of SOX9 and Wnt Signaling Pathway Molecules, Including CDX2.

ABSTRACT: An 87-year-old woman presented with a pedunculated nodule of 1.2 × 1.2 × 0.6 cm on her left cheek. Microscopic examination of the lesion revealed bowenoid and rosette-like basaloid components, resembling Bowen disease and neuroendocrine carcinoma, respectively. Immunohistochemically, both components were positive for Wnt signaling pathway molecules-nuclear/cytoplasmic beta-catenin, lymphoid enhancer binding factor 1 (LEF1), and caudal type homeobox 2 (CDX2)-and the adnexal marker SRY-box transcription factor 9 (SOX9). Unlike neuroendocrine tumors and basal cell carcinomas, the basaloid component in the present case was negative for chromogranin A, INSM1, synaptophysin, and p40. Previously reported cases of similar CDX2-positive lesions were diagnosed as squamous cell carcinoma with enteric adenocarcinomatous differentiation and basaloid cutaneous carcinoma with a primitive cytomorphology. However, the lesion in the present case was simultaneously positive for SOX9, indicating adnexal differentiation. In particular, the expression of multiple Wnt signaling pathway molecules indicates follicular differentiation despite the absence of morphological follicular features, such as shadow cells. Moreover, shared immunopositivity for SOX9, CDX2, nuclear/cytoplasmic beta-catenin, and LEF1 by both bowenoid and basaloid components indicated that the bowenoid component did not represent Bowen disease but a part of the adnexal tumor, and that the basaloid component was not a tumor-to-tumor metastasis. After complete excision, no recurrence has been observed for 5 months. The findings of the present case expand the histological spectrum of cutaneous adnexal tumors with follicular immunophenotypic differentiation.

Factors associated with long-term efficacy of lubiprostone for chronic constipation.

The prevalence of chronic constipation in Japan is increasing, and is presently almost 1 in 5 people. Because constipation is common, especially in older patients, to avoid adverse events and polypharmacy, simple treatments at low doses are generally desired. Although the chloride channel activator lubiprostone is candidate drug that may solve these problems, factors associated with the long-term efficacy of lubiprostone monotherapy for chronic constipation in treatment-naive patients remain unclear. We here retrospectively investigated the clinical characteristics and factors of patients who achieved long-term constipation improvement with lubiprostone monotherapy. Seventy-four patients with chronic constipation treated with lubiprostone monotherapy (24 or 48 µg/day) from January 2017 to August 2018 were reviewed. Patient characteristics and clinical time-courses were compared between those who sustained improvement for 6 months, and those who became refractory to treatment. In 54 patients (76.1%), constipation improved by lubiprostone administration for 6 months. On multivariate analysis, a significant clinical factor associated with sustained improvement was a starting lubiprostone dose of 24 µg/day (odds ratio: 5.791; 95% confidence interval: 1.032-32.498; p = 0.046). A starting lubiprostone dose of 24 µg/day has efficacy to improve chronic constipation and to prevent adverse events of nausea and diarrhea in Japanese patients.

Validation of the BEST-J score, a prediction model for bleeding after endoscopic submucosal dissection for early gastric cancer: a multicenter retrospective observational study.

BACKGROUND: A new scoring system, the BEST-J score, using ten risk factors to assign cases to different post-endoscopic submucosal dissection (ESD) risk groups for bleeding, has been shown to be accurate for risk stratification. We first aimed to validate the BEST-J score at four hospitals not specialized in performing ESD and then aimed to identify other risk factors for post-ESD bleeding. METHODS: We evaluated the incidence of post-ESD bleeding in 791 cases of early gastric cancer (EGC) between October 2013 and December 2020 as a retrospective, multi-center observational study conducted at four hospitals. Multivariate logistic regression models to examine the effect of independent variables on post-ESD bleeding firstly included ten possible factors raised by the BEST-J score and secondly included statistically significant (p < 0.01) in univariate analysis. The prediction accuracy of the model was evaluated by receiver-operating characteristic analysis and the areas under the curve (AUC). RESULTS: The incidence of post-ESD bleeding was 4.8% (38/791, 95% confidence interval [CI] 3.4-6.5%). On multivariate analysis, the risk factors were P2Y12 receptor antagonist (odds ratio [OR]: 5.870, 95% CI 1.624-21.219), warfarin (8.382, 1.658-42.322), direct oral anticoagulant (DOAC) (8.980, 1.603-50.322), and tumor location in lower third of stomach (2.151, 1.012-4.571), respectively. When we categorized cases into low-risk by BEST-J score, intermediate-risk, high-risk, and very high-risk groups, the bleeding rates were 2.8%, 7.3%, 12.8%, and 19.0%, respectively. The AUC for our cohort was 0.713 (95% CI 0.625-0.802) for the BEST-J score. In the multivariate analysis in our cohort, the risks were age, body mass index, P2Y12 receptor antagonist, warfarin, DOAC, respectively. DISCUSSION: The BEST-J score is equally accurate in risk stratification of patients with EGC for post-ESD bleeding at non-specialized facilities for ESD as in specialized hospitals. BMI and age may be helpful additional risk factors at hospitals not specialized.

Diagnostic efficacy of the Japan NBI Expert Team classification with dual-focus magnification for colorectal tumors.

BACKGROUND AND AIMS: The Japan NBI Expert Team (JNET) classification is the first unified classification criteria for colorectal tumors using magnifying narrow-band imaging (NBI) in Japan. However, the diagnostic stratification ability of the JNET classification with dual-focus magnifying NBI (DF-JNET) has remained obscure. The aim of this study was to validate the diagnostic stratification ability of DF-JNET for colorectal tumors in two Japanese referral centers. METHODS: A multicenter retrospective image evaluation study was conducted by three experienced endoscopists, including an original JNET member who was also involved in establishing the diagnostic criteria. A total of two images, namely, one representative non-magnified white light image and one representative DF-NBI image for each of the 557 consecutive lesions were used in the evaluation study. The diagnostic value of DF-JNET was calculated based on the evaluation data. RESULTS: The sensitivity, specificity, positive and negative predictive values, and accuracy of DF-JNET Type 1 for differentiating between non-neoplastic and neoplastic lesions were 78.1%, 98.6%, 89.1%, 96.8%, and 95.9%, respectively; of Type 2A lesions for differentiating low-grade dysplasia from others were 98.0%, 76.5%, 94.9%, 89.7%, and 94.1%, respectively; of Type 2B lesions for differentiating high-grade dysplasia and shallow submucosal invasive carcinoma from others were 43.5%, 99.1%, 66.7%, 97.6%, and 96.8%, respectively; and of Type 3 lesions for differentiating deep submucosal invasive carcinoma from others were 83.3%, 99.5%, 62.5%, 99.8%, and 99.3%, respectively. CONCLUSIONS: All DF-JNET types had an over 90% diagnostic accuracy for the histological prediction of colorectal tumors. DF-JNET might contribute to appropriate treatment choices, such as endoscopic resection or surgery, not only in Japan but also in Western countries in which the use of optical zoom endoscopy is limited.

Efficacy of endoscopic clip closure for nonperforated muscle layer exposure during esophageal endoscopic submucosal dissection.

Exposure of the muscle layer during endoscopic submucosal dissection (ESD) in the esophagus can lead to complications such as fever and pain. Although closure with endoscopic clips is widely used when perforation is a major complication, its value when the exposed muscle layer is not perforated is unclear. Data for 104 lesions in 104 patients who underwent esophageal ESD between 2008 and 2020 were retrospectively analyzed. Patients with multiple tumors, those who experienced procedure-related adverse events such as aspiration pneumonitis, perforation during ESD, or delayed bleeding, and those in whom the muscle layer was not exposed were excluded. The clinical course of inflammation after ESD in patients in whom the muscle layer was exposed was examined according to whether endoscopic clips were used for closure. A significantly greater number of patients had a temperature ≤ 37.5°C in the clip closure group than in the nonclip closure group (≤37.5°C/≥37.6°C, 47/14 vs. 25/18, respectively, P = 0.040). Furthermore, significantly more patients in the clip closure group had a white blood cell count ≤10,000/µL (≤10,000/µL/>10,000/µL, 51/10 vs. 21/22, P < 0.001) and a C-reactive protein level < 1.0 mg/dL (<1.0 mg/dL/≥1.0 mg/dL, 40/21 vs. 36/7, P = 0.040) in the 24 hour post-ESD. The results were not changed after propensity score matching. Closure with endoscopic clips reduces inflammation after esophageal ESD with nonperforated muscle layer exposure. Even if there is no obvious perforation during ESD, closure of the exposed muscle layer with endoscopic clips may contribute to the clinical course post-ESD.

[A case of colon cancer manifesting as intussusception in pregnancy].

This is the case of a 40-year-old, 34-week pregnant woman, who had bloody stools and abdominal pain from 20 weeks gestation. She presented to our department as she noted an exacerbation in her abdominal pain, and was admitted. Sonography and magnetic resonance imaging displayed a mass with an appearance consistent with intussusception, hence intussusception was diagnosed. The patient underwent a cesarean section and concurrent partial colectomy, which showed that she had a colon cancer. There were no postoperative complications. Colon cancer as a complication of pregnancy is rare. We encountered a case of a patient with colorectal cancer that caused intussusception in the latter half of pregnancy, and report it here with a review of the literature.

Predictive Factors of Postendoscopic Submucosal Dissection Electrocoagulation Syndrome and the Utility of Computed Tomography Scan after Esophageal Endoscopic Submucosal Dissection.

BACKGROUND/AIMS: Recently, postendoscopic submucosal dissection electrocoagulation syndrome (PEECS) has attracted attention. However, the criteria for computed tomography (CT) scanning following esophageal endoscopic submucosal dissection (ESD) are unclear. In this study, we aimed to identify the predictive factors of PEECS and the usefulness of CT scanning after esophageal ESD. METHODS: A total of 245 lesions in 223 patients who underwent esophageal ESD between February 2008 and October 2018 were retrospectively analyzed. Patients with double cancers, those who experienced procedural accidents, such as aspiration pneumonitis or perforation, and those who were unable to undergo CT were excluded from the study. PEECS evaluation items included body temperature (≤37.7°C = 1 point, ≥37.8°C = 2 points), white blood cell count (<10,800/µL = 1 point, ≥10,800/µL = 2 points), and chest pain (numerical rating scale [NRS] ≤4 = 1 point, NRS ≥5 = 2 points). Scores of ≥5 points were categorized as the PEECS-positive group, and scores of ≤4 points were categorized as the PEECS-negative group. The degree of mediastinal emphysema on CT was stratified into 5 grades, in which grades 0 and 1 were considered as the "low-grade" group, and grades 2, 3, and 4 were considered as the "high-grade" group. We analyzed the prognostic factors of high-grade mediastinal emphysema, including the presence or absence of PEECS. RESULTS: The PEECS-positive group comprised 18 out of the 163 patients (11.0%), and mediastinal emphysema was stratified into grades 0 (94), 1 (51), 2 (12), 3 (5), and 4 (1 patient). Three independent risk factors for the onset of PEECS were identified, as follows: resected area ≥750 mm2 (OR 7.28, 95% CI 1.42-37.33, p = 0.017), treatment duration ≥75 min (OR 10.26, 95% CI 1.20-87.77, p = 0.034), and muscle layer exposure (OR 10.92, 95% CI 2.22-53.74, p = 0.003). Two independent predictive factors of high-grade mediastinal emphysema were identified, which were PEECS positivity (OR 4.31, 95% CI 1.29-14.41, p = 0.018), and muscle layer exposure (OR 4.08, 95% CI 1.18-14.06, p = 0.026). CONCLUSIONS: A large resected area, prolonged treatment duration, and muscle layer exposure are risk factors for the onset of PEECS. Mediastinal emphysema was observed in 43% of patients following ESD. When marked clinical symptoms of PEECS appear, high-grade mediastinal emphysema may be observed, and therefore CT should be performed in these cases.

[Intra-abdominal bleeding caused after esophagogastroduodenoscopy: a case report].

An 86-year-old man was transferred to the Tokyo Medical University Hospital because of a temporary loss of consciousness and melena. We performed upper gastrointestinal endoscopy, which revealed Mallory-Weiss syndrome caused by a strong vomiting reflex. After an examination, he complained of abdominal pain, and his blood pressure decreased. Abdominal contrast-enhanced computed tomography showed fresh intra-abdominal hemorrhage. We performed transcatheter arterial embolization by using N-butyl-2-cyanoacrylate to control the bleeding from the right gastroepiploic artery. Intra-abdominal hemorrhage after upper gastrointestinal endoscopy is rare, and we report this case with the literature review.

Possible Involvement of Human Mast Cells in the Establishment of Pregnancy via Killer Cell Ig-Like Receptor 2DL4.

The involvement of mast cells in the establishment of pregnancy is unclear. Herein, we found that human mast cells are present in the decidual tissues of parous women and expressed a human-specific protein killer cell Ig-like receptor (KIR) 2DL4, a receptor for human leukocyte antigen G expressed on human trophoblasts. In contrast, decreased numbers of decidual mast cells and reduced KIR2DL4 expression were observed in these cells of infertile women who had undergone long-term corticosteroid treatment. Co-culture of the human mast cell line, LAD2, and human trophoblast cell line, HTR-8/SVneo, accelerated the migration and tube formation of HTR-8/SVneo cells in a KIR2DL4-dependent manner. These observations suggest the possible involvement of human mast cells in the establishment of pregnancy via KIR2DL4 and that long-term corticosteroid treatment may cause infertility by influencing the phenotypes of decidual mast cells.

SLAM family member 8 is involved in oncogenic KIT-mediated signalling in human mastocytosis.

The signalling lymphocytic activation molecule family member 8 (SLAMF8)/CD353 is a member of the CD2 family of proteins. Its ligand has not been identified. SLAMF8 is expressed by macrophages and suppresses cellular functions. No study has yet explored SLAMF8 expression or function in human mastocytosis, which features oncogenic KIT-mediated proliferation of human mast cells. SLAMF8 protein was expressed in human mastocytosis cells, immunohistochemically. SLAMF8 expression was also evident in the human mast cell lines, HMC1.2 (expressing oncogenic KIT) and LAD2 (expressing wild-type KIT) cells. SLAMF8 knock-down significantly reduced the KIT-mediated growth of HMC1.2 cells but not that of LAD2 cells. SLAMF8 knock-down HMC1.2 cells exhibited significant attenuation of SHP-2 activation and oncogenic KIT-mediated RAS-RAF-ERK signalling. An interaction between SLAMF8 and SHP-2 was confirmed in HMC1.2 cells and all pathological mastocytosis specimens examined (19 of 19 cases, 100%). Thus, SLAMF8 is involved in oncogenic KIT-mediated RAS-RAF-ERK signalling and the subsequent growth of human neoplastic mast cells mediated by SHP-2. SLAMF8 is a possible therapeutic target in human mastocytosis patients.

Gingival Hyperplasia Masquerading as Tumor Lesion, Possibly Linked to Amlodipine Use.

ABSTRACT: A 70-year-old woman under amlodipine treatment for hypertension presented with a hemorrhagic mass in the mandibular gingiva. Imaging studies revealed high signal intensity in T2-weighted MRI and moderate 18F-FDG accumulation at the lesion's periphery. Although no malignancy was detected, the lesion continuously grew, prompting excision. Histopathological examination confirmed gingival hyperplasia attributed to amlodipine use. Drug-induced gingival hyperplasia typically presents as diffuse swelling; however, this lesion manifested as a polyp, posing diagnostic challenges. Reports on imaging findings for drug-induced gingival hyperplasia are limited. Understanding imaging patterns alongside clinical history aids in accurate diagnosis.

SMARCA4-Deficient Poorly Differentiated Adenocarcinoma of the Gallbladder.

ABSTRACT: A 64-year-old woman presented with chest pain while eating and was referred to our hospital. Physical examination revealed abdominal distension, tenderness, and lower-extremity edema. Imaging revealed a large gallbladder tumor infiltrating the liver, with ascites and pleural effusion. A biopsy confirmed a poorly differentiated adenocarcinoma with SMARCA4 deficiency (cT3N2M1, cStage IV). Chemotherapy was ineffective and led to tumor progression. The patient died 9 months later. Recently, attention has been paid to SMARCA4 deficiency, which is a genetic mutation found in tumors. Here, we report on poorly differentiated adenocarcinomas of the gallbladder based on imaging findings, including FDG PET.

Hyalinizing Clear Cell Carcinoma in the Sphenoid Sinus.

ABSTRACT: A 39-year-old man presented with a 1-month history of headaches. Imaging revealed a mass with extensive destruction. T2-weighted imaging displayed mixture of low and sponge-like high intensities and also dark area, with FDG PET/CT showing uneven but intense accumulation. Biopsy confirmed EWSR1 rearrangement, and hyalinizing clear cell carcinoma (HCCC) was diagnosed. HCCC, recently renamed from clear cell carcinoma in the fifth edition of the World Health Organization Classification of Head and Neck Tumors, is a rare tumor. This case describes the features of T2-weighted imaging and FDG PET patterns in HCCC, possibly contributing to their consideration in the differential diagnosis.

Appendiceal neoplasms derived from appendiceal tip remnants following appendectomy: a report of two cases.

BACKGROUND: Neoplasms derived from remnant appendix are rarely described, with most cases arising from the appendiceal "stump". Here, we present two surgical cases of appendiceal neoplasms derived from appendiceal "tip" remnants. CASE PRESENTATION: The first patient was a 71-year-old man who had undergone laparoscopic appendectomy for acute appendicitis 12 years prior. During appendectomy, the appendiceal root was ligated, but the appendix was not completely removed due to severe inflammation. At the most recent presentation, computed tomography (CT) was performed to examine choledocholithiasis, which incidentally revealed a cystic lesion of approximately 90 mm adjacent to the cecum. A retrospective review revealed that the cystic lesion had increased in size over time, and laparoscopic ileocecal resection was performed. Pathology revealed no continuity from the appendiceal orifice to the cyst, and a diagnosis of low-grade appendiceal mucinous neoplasm (LAMN) was made from the appendiceal tip remnant. The patient was discharged without complications. The second patient was a 65-year-old man who had undergone surgery for peritonitis due to severe appendicitis 21 years prior. During this operation, the appendix could not be clearly identified due to severe inflammation; consequently, cecal resection was performed. He was referred to our department with a chief complaint of general fatigue and loss of appetite and a cystic lesion of approximately 85 mm close to the cecum that had increased over time. CT showed irregular wall thickening, and malignancy could not be ruled out; therefore, laparoscopic ileocecal resection with D3 lymph node dissection was performed. The pathological diagnosis revealed mucinous adenocarcinoma (TXN0M0) arising from the remnant appendiceal tip. The patient is undergoing follow-up without postoperative adjuvant chemotherapy, with no evidence of pseudomyxoma peritonei or cancer recurrence for 32 months postoperatively. CONCLUSIONS: If appendicitis-associated inflammation is sufficiently severe that accurate identification of the appendix is difficult, it may remain on the apical side of the appendix, even if the root of the appendix is ligated and removed. If the appendectomy is terminated incompletely, it is necessary to check for the presence of a residual appendix postoperatively and provide appropriate follow-up.

Rebleeding Risk of Acute Hemorrhagic Rectal Ulcer: A Multicenter Retrospective Study.

Objective Acute hemorrhagic rectal ulcer (AHRU) is characterized by sudden, painless, and massive bleeding from rectal ulcers. To date, few studies have analyzed the risk factors for AHRU rebleeding. In this study, we clarified the risk factors of rebleeding after initial hemostasis of AHRU through a multicenter study. Methods A total of 149 patients diagnosed with AHRU between January 2015 and May 2020 at 3 medical centers were enrolled. We retrospectively investigated the following factors: age, sex, body mass index (BMI), performance status (PS), Charlson comorbidity index (CCI), comorbidities, medications, laboratory examinations, endoscopic findings, view of the entire rectum on endoscopy, hemostasis method, blood transfusion history, shock, instructions for posture change after initial hemostasis, and clinical course. Results Rebleeding was observed in 35 (23%) of 149 patients. A multivariate analysis showed that significant factors for rebleeding were PS 4 [odds ratio (OR), 5.23; 95% confidence interval (CI)], 1.97-13.9; p=0.001], a blood transfusion history (OR, 3.66; 95% CI, 1.41-9.51; p=0.008), low an estimated glomerular filtration rate (eGFR) levels (OR, 0.98; 95% CI, 0.97-0.99; p=0.001), poor view of the whole rectum on endoscopy (OR, 0.33; 95% CI, 0.12-0.90; p=0.030), and use of monopolar hemostatic forceps (OR, 4.89; 95% CI, 1.37-17.4; p=0.014). Conclusion Factors associated with rebleeding of AHRU were a poor PS (PS4), blood transfusion, a low eGFR, poor view of the whole rectum on endoscopy, and the use of monopolar hemostatic forceps.

Inverted FDG Uptake Pattern in Subcutaneous Panniculitis-Like T-Cell Lymphoma.

ABSTRACT: A 47-year-old woman presented with a 2-month history of subcutaneous nodules, erythema, and fever. 18F-FDG PET images demonstrated inverted FDG uptake pattern corresponding to the subcutaneous lesion against lymph nodes. The specimen of the inguinal lesion showed massive infiltration of small lymphocytes in the adipose tissue with rimming adipocytes, whereas very few tumor cells infiltrated the lymph nodes. Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) was diagnosed. SPTCL normally shows quite interesting distribution of tumor cells, that is, lymph node involvement is usually absent. Therefore, this case highlighted the importance of the inverted accumulation pattern on FDG PET to suspect SPTCL.