Risk factors for intraoperative and delayed perforation related with gastric endoscopic submucosal dissection.

BACKGROUND AND AIM: Perforation is one of the most important complications of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). Several studies have examined risk factors for intraoperative and delayed perforations, but most were retrospective analyses with small numbers of patients. METHODS: This study represents a secondary analysis of a Japanese multicenter prospective cohort study. We investigated the factors associated with each type of perforation using 9015 patients with 9975 EGCs undergoing ESD between July 2010 and June 2012. RESULTS: Intraoperative perforation occurred in 198 patients (2.2%) with 203 lesions (2.0%), necessitating emergency surgery for four lesions (0.04% [2.0%, 4/203]). Delayed perforation occurred in another 37 patients (0.4%) with 42 lesions (0.4%), requiring emergency surgery for 12 lesions (0.12% [28.6%, 12/42]). Factors showing significant independent correlations with intraoperative perforation were upper or middle third of the stomach; remnant stomach or gastric tube; procedure time ≥100 min; tumor size >35 mm; body mass index (BMI) < 18.5 kg/m2; and ≥72 years. Factors showing significant independent correlations with delayed perforation were procedure time ≥60 min; BMI < 18.5 kg/m2; ≥75 years; ulceration; and tumor size >20 mm. Intraoperative perforation occurred most frequently at the greater curvature in the upper third of the stomach (7.9%), whereas delayed perforation occurred most frequently at the greater curvature in the middle third (1.2%). CONCLUSION: This multicenter prospective cohort study clarified the risk and risk factors of intraoperative and delayed perforation related to ESD for EGCs, providing information to help endoscopists reduce perforation.

Methylation analysis of DCC gene in saliva samples is an efficient method for non-invasive detection of superficial hypopharyngeal cancer.

BACKGROUND: Advances in upper gastrointestinal endoscopic technology have enabled early detection and treatment of hypopharyngeal cancer. However, in-depth pharyngeal observations require sedation and are invasive. It is important to establish a minimally invasive and simple evaluation method to identify high-risk patients. METHODS: Eighty-seven patients with superficial hypopharyngeal cancer and 51 healthy controls were recruited. We assessed the methylation status of DCC, PTGDR1, EDNRB, and ECAD, in tissue and saliva samples and verified the diagnostic accuracy by methylation analyses of their promoter regions using quantitative methylation-specific PCR. RESULTS: Significant differences between cancer and their surrounding non-cancerous tissues were observed in the methylation values of DCC (p = 0.003), EDNRB (p = 0.001), and ECAD (p = 0.043). Using receiver operating characteristic analyses of the methylation values in saliva samples, DCC showed the highest area under the curve values for the detection of superficial hypopharyngeal cancer (0.917, 95% confidence interval = 0.864-0.970), compared with those for EDNRB (0.680) and ECAD (0.639). When the cutoff for the methylation values of DCC was set at ≥0.163, the sensitivity to detect hypopharyngeal cancer was 82.8% and the specificity was 90.2%. CONCLUSIONS: DCC methylation in saliva samples could be a non-invasive and efficient tool for early detection of hypopharyngeal cancer in high-risk patients.

Potential for expanding indications and curability criteria of endoscopic resection for early gastric cancer in elderly patients: results from a Japanese multicenter prospective cohort study.

BACKGROUND AND AIMS: Evidence for endoscopic resection (ER) in elderly patients with early gastric cancer (EGC) is limited. We assessed its clinical outcomes, and explored new indications and curability criteria. METHODS: We analyzed data from a Japanese multicenter prospective cohort study. Patients aged ≥75 years with EGC treated with ER were included. We classified "eCuraC-2 (corresponding to noncurative ER, defined in the Japanese gastric cancer treatment guidelines)" into "elderly-high (EL-H)" (>10% estimated metastatic risk) and "elderly-low (EL-L)" (≤10%). RESULTS: In total, 3,371 patients with 3,821 EGCs were included; endoscopic submucosal dissection (ESD) was the prominent treatment choice. Among them, 3,586 lesions met the guidelines' ER indications and 235 did not. The proportions of en bloc and R0 resections and perforations were 98.9%, 94.4%, and 0.8%, respectively, in EGCs within the indications. In EGCs beyond the indications, they were 99.5%, 85.4%, and 5.9%, respectively, for lesions diagnosed as ≤3 cm, and 96.0%, 64.0%, and 18.0% for those >3 cm. Curative ER ("eCuraA/B") and EL-L were observed in 83.6% and 6.2% of lesions within the indications, respectively, and in 44.2% and 16.8% of lesions <3 cm beyond the indications, respectively. The 5-year cumulative gastric cancer death rates following eCuraA/B and EL-H were 0.3% (95% CI, 0.2-0.6) and 3.5% (2.0-5.7), respectively. Following EL-L, the rate was 0.9% (0.2-3.5) even without subsequent treatment. CONCLUSIONS: Usefulness of ESD for elderly EGC patients was confirmed by their clinical outcomes. Lesions ≤3 cm and EL-L emerged as new ER indication and curability criterion, respectively.

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters.

The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain-containing ion transport regulator 3 (FXYD3), a component of the Na+/K+ pump. Accordingly, FXYD3+ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3+ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3+ CSCs were sensitive to senolytic Na+/K+ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3+ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na+/K+ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis.

On-top-plasty reconstruction for thumb triplication.

Thumb triplication is a very rare pattern of radial polydactyly that presents as a more complicated form of thumb. Because of its morphological complexity, treatment often requires surgical ingenuity in addition to the conventional surgical treatment algorithms for duplication. We report the case of thumb triplication on the right hand of a 17-month-old boy. We performed on-top-plasty of the ulnar thumb over the intermediate thumb, and achieved a functional and aesthetic thumb. The technique of on-top-plasty is effective for finger reconstruction that maximizes the use of limited tissue and is widely used for treating hand trauma and congenital hand anomalies. In the present case, on-top-plasty contributed most effectively to creating a sufficiently sized thumb, achieving interphalangeal optimization by joining the extra middle phalanx with the proximal phalanx, and securing the first web space by moving the ulnar thumb laterally.

THBS1-producing tumor-infiltrating monocyte-like cells contribute to immunosuppression and metastasis in colorectal cancer.

Mesenchymal activation, characterized by dense stromal infiltration of immune and mesenchymal cells, fuels the aggressiveness of colorectal cancers (CRC), driving progression and metastasis. Targetable molecules in the tumor microenvironment (TME) need to be identified to improve the outcome in CRC patients with this aggressive phenotype. This study reports a positive link between high thrombospondin-1 (THBS1) expression and mesenchymal characteristics, immunosuppression, and unfavorable CRC prognosis. Bone marrow-derived monocyte-like cells recruited by CXCL12 are the primary source of THBS1, which contributes to the development of metastasis by inducing cytotoxic T-cell exhaustion and impairing vascularization. Furthermore, in orthotopically generated CRC models in male mice, THBS1 loss in the TME renders tumors partially sensitive to immune checkpoint inhibitors and anti-cancer drugs. Our study establishes THBS1 as a potential biomarker for identifying mesenchymal CRC and as a critical suppressor of antitumor immunity that contributes to the progression of this malignancy with a poor prognosis.

First Branchial Cleft Fistula Piercing through the Main Trunk of the Facial Nerve.

First branchial cleft fistulas are congenital malformations that result from the incomplete closure of the ectodermal portion of the first branchial cleft. These fistulas typically appear as small pits or subcutaneous masses in the upper neck and cheek and can cause pain due to infection and inflammation. Surgical excision is the most effective treatment, but special attention is necessary to avoid facial nerve injury due to the proximity of the lesion to the nerve and variations in their arrangement. Here, we report the successful treatment of a first branchial cleft fistula piercing through the main trunk of the facial nerve in a 3-year-old girl. Intraoperative findings revealed that the fistula in the parotid gland opened into the cheek area from the ear canal. Identification of the facial nerve trunk was challenging due to the malformation of the lower end of the auricular cartilage, which is an anatomical landmark of the facial nerve. The trunk of the facial nerve was divided proximally by the fistula and merged just past the fistula. Preoperative magnetic resonance is important for determining the fistula location, surrounding anatomical variations, and fistula-facial nerve arrangement. Furthermore, early surgical treatment should be considered to prevent tissue scarring and adhesion due to infection, which can lead to facial nerve injury.

Summary of Japanese clinical practice guidelines for head and neck cancer - 2022 update edited by the Japan society for head and neck cancer.

The aim of the "Japanese Clinical Practice Guidelines for Head and Neck Cancer - 2022 Update" is to review the latest evidence regarding head and neck cancer and to present the current standard approaches for diagnosis and treatment. These evidence-based recommendations were created with the consensus of the Guideline Committee, which is composed of otorhinolaryngologists and head and neck surgeons, together with radiologists, radiation oncologists, medical oncologists, plastic surgeons, dentists, palliative care physicians, and rehabilitation physicians. These guidelines were created by the Clinical Practice Guideline Committee of the Japan Society for Head and Neck Cancer based on the "Head and Neck Cancer Treatment Guidelines 2018 Edition," and the revised draft was compiled after evaluation by the Assessment Committee and public comments. The 'Clinical questions and recommendations' section consists of 13 categories, and 59 clinical questions are described in total. Here we describe 6 clinical questions specific to other sets of guidelines with recommendations and comments.

Fat Necrosis Mimicking Local Recurrence With Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Positivity After Partial Nephrectomy for Renal Cell Carcinoma.

We report a case of fat necrosis with positive results on fluorodeoxyglucose positron emission tomography (FDG-PET)-CT imaging after partial nephrectomy. A 77-year-old man underwent a partial nephrectomy for a right renal mass. The histopathological results showed clear cell renal cell carcinoma, G1>G2, pT1a. Four and a half years after surgery, a nodule appeared in the retroperitoneal space on CT. FDG-PET CT showed increased uptake in the nodule, indicating local recurrence of carcinoma. A right nephrectomy was performed. The histopathological diagnosis was fat necrosis.

Perioperative Factors Aggravating Pharyngocutaneous Fistula After Total Laryngectomy: A Single-Center Retrospective Analysis Using the Clavien-Dindo Classification.

BACKGROUND: Pharyngocutaneous fistula formation represents a major postoperative complication following total laryngectomy. We aimed to investigate the risk factors for pharyngocutaneous fistula development after total laryngectomy and to identify factors that lead to severe cases of pharyngocutaneous fistula. METHODS: Patients who underwent total laryngectomy between January 2013 and February 2021 were included in the study and were divided into 2 groups: Those with and without pharyngocutaneous fistula. The severity of pharyngocutaneous fistula was graded using the Clavien-Dindo classification. RESULTS: Patients with pharyngocutaneous fistula experienced longer operative time, greater intraoperative blood loss, greater decrease in perioperative hemoglobin level, and longer postoperative hospitalization. Unlike in lower-severity cases, patients with grade IIIb pharyngocutaneous fistula underwent preoperative radiotherapy or chemoradiotherapy; preoperative treatment was thus a risk factor for higher severity of pharyngocutaneous fistula (odds ratio, 35; P = 0.004). CONCLUSION: Salvage laryngectomy was found to be a predictor of severe pharyngocutaneous fistula development. Prolonged operative time, increased intraoperative blood loss, and decreased postoperative hemoglobin level were found to be predictors of postlaryngectomy pharyngocutaneous fistula formation.

Evolutionary histories of breast cancer and related clones.

Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1-3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient's early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves.

Lesion size, elevated morphology, and non or closed-type atrophy are predictive factors for gastric adenocarcinoma of the fundic gland type rather than oxyntic gland adenoma.

Background: An oxyntic gland neoplasm confined to the mucosal layer (T1a) is classified as an oxyntic gland adenoma, whereas that with submucosal invasion (T1b) is defined as gastric adenocarcinoma of the fundic gland type (GA-FG). Methods: To reveal the differences in clinical features between them, we retrospectively investigated 136 patients with 150 oxyntic gland adenoma and GA-FG lesions. Results: The univariate analysis revealed that the mean size (GA-FG vs. oxyntic gland adenoma, 7.7±5.4 vs. 5.5±3.1 mm), the prevalence of elevated morphology (79.1% vs. 51.8%), black pigmentation within the lesion (23.9% vs. 9.6%), and non or closed-type atrophy (81.2% vs. 65.1%) were different between the two groups. A multivariate logistic regression analysis revealed that ≥5 mm lesion size (odds ratio, 2.96; 95% confidence interval: 1.21-7.23), elevated morphology (odds ratio, 2.40; 95% confidence interval: 1.06-5.45), and no or closed-type atrophy (odds ratio, 2.49; 95% confidence interval: 1.07-5.80) were factors in distinguishing GA-FG from oxyntic gland adenoma. When oxyntic gland neoplasms with no or one feature were judged as oxyntic gland adenomas and those with two or three features were judged as GA-FG, the sensitivity and specificity were 85.1% and 43.4% for GA-FG, respectively. Conclusions: We identified three possible distinctive features of GA-FG compared to oxyntic gland adenoma: lesion size ≥5 mm, elevated morphology, and no or closed-type atrophy.

A Novel Risk Model for Predicting Dysphagia after Tongue Reconstruction: A Retrospective Multicenter Study in Japan.

BACKGROUND: There is no consensus on the postoperative outcomes of tongue reconstruction. Therefore, the authors developed a novel risk model for predicting dysphagia after tongue reconstruction. METHODS: This retrospective study was conducted by the Oral Pharyngeal Esophageal Operation and Reconstruction Analytical, or OPERA, group across 31 cancer centers and university hospitals in Japan. A total of 532 patients [390 (73.3%) men and 142 (26.7%) women; median age at surgery, 60 years (range, 15 to 88 years)] who were diagnosed with oral tongue squamous cell carcinoma and underwent tongue reconstruction following glossectomy between 2009 and 2013 were included. Independent risk factors were identified using univariate regression analysis and converted to a binary format for multivariate analysis. An integer value was assigned to each risk factor to calculate a total score capable of quantifying the risk of feeding tube dependence. RESULTS: Overall, 54 patients (10.2%) required a feeding tube at the time of evaluation. Predictive factors for feeding tube dependence were advanced age, lower American Society of Anesthesiologists physical status, low body mass index, lower serum albumin, comorbid hypertension and diabetes, extended tongue defect, resection beyond the tongue, laryngeal suspension, postoperative radiation therapy, and no functional teeth. In multivariate logistic regression analysis, age greater than or equal to 58.5 years, postoperative radiation therapy, wider tongue defect, and body mass index less than 21.27 kg/m 2 earned 6, 4, 3, and 2 points, respectively, for a maximum total score of 15. CONCLUSION: The authors' risk model provides a mathematical tool for estimating the individual risk of postoperative feeding tube dependence before tongue reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Postazacitidine clone size predicts long-term outcome of patients with myelodysplastic syndromes and related myeloid neoplasms.

Azacitidine is a mainstay of therapy for myelodysplastic syndrome (MDS)-related diseases. The purpose of our study is to elucidate the effect of gene mutations on hematological response and overall survival (OS), particularly focusing on their posttreatment clone size. We enrolled a total of 449 patients with MDS or related myeloid neoplasms. They were analyzed for gene mutations in pretreatment (n = 449) and posttreatment (n = 289) bone marrow samples using targeted-capture sequencing to assess the impact of gene mutations and their posttreatment clone size on treatment outcomes. In Cox proportional hazard modeling, multihit TP53 mutation (hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.42-2.91; P < .001), EZH2 mutation (HR, 1.71; 95% CI, 1.14-2.54; P = .009), and DDX41 mutation (HR, 0.33; 95% CI, 0.17-0.62; P < .001), together with age, high-risk karyotypes, low platelets, and high blast counts, independently predicted OS. Posttreatment clone size accounting for all drivers significantly correlated with International Working Group (IWG) response (P < .001, using trend test), except for that of DDX41-mutated clones, which did not predict IWG response. Combined, IWG response and posttreatment clone size further improved the prediction of the original model and even that of a recently proposed molecular prediction model, the molecular International Prognostic Scoring System (IPSS-M; c-index, 0.653 vs 0.688; P < .001, using likelihood ratio test). In conclusion, evaluation of posttreatment clone size, together with the pretreatment mutational profile as well as the IWG response play a role in better prognostication of azacitidine-treated patients with myelodysplasia.

Usefulness of Acetic Acid Spray with Narrow-Band Imaging for Identifying the Margin of Sessile Serrated Lesions.

BACKGROUND: Sessile serrated lesions (SSLs) are precursors of colon cancer, especially in cases of large, right colon. However, they are difficult to not only detect, but only clarify the margin of the lesion, which can lead to the poor endoscopic treatment outcomes. AIMS: This study evaluated the usefulness of acetic acid spray with narrow-band imaging (A-NBI) for the better visualization of the margin of SSLs. METHODS: From January 2013 to March 2022, patients with superficial elevated polyps suspected of being SSLs ≥ 10 mm with an endoscopic diagnosis that had been endoscopically resected at Hiroshima City Hiroshima Citizens Hospital were enrolled. Endoscopic images with white-light imaging (WLI), narrow-band imaging (NBI), indigo-carmine (IC), and A-NBI were recorded in each lesion and were randomly arranged and assessed by 10 endoscopists. We compared the visibility score (1 to 4) and color differences (ΔE) between inside and outside of the lesions among WLI, NBI, IC, and A-NBI. RESULTS: Forty-one lesions in 33 cases were included, and a total of 164 images were evaluated. As for the visibility score, most of the lesions were scored as 1 or 2 on WLI, whereas most were scored 4 on A-NBI. The median ΔE of A-NBI was also significantly higher than that of WLI, NBI, or IC (20.5 vs. 8.3 vs. 8.2 vs. 12.3, P < 0.01). A significant correlation was observed between the color difference and visibility score (r = 0.53, P < 0.01). CONCLUSIONS: A-NBI may be a useful modality for identifying the margin of SSLs.

Long-term Survival After Endoscopic Resection For Gastric Cancer: Real-world Evidence From a Multicenter Prospective Cohort.

BACKGROUND & AIMS: We aimed to clarify the long-term outcomes of endoscopic resection (ER) for early gastric cancers (EGCs) based on pathological curability in a multicenter prospective cohort study. METHODS: We analyzed the long-term outcomes of 9054 patients with 10,021 EGCs undergoing ER between July 2010 and June 2012. Primary endpoint was the 5-year overall survival (OS). The hazard ratio for all-cause mortality was calculated using the Cox proportional hazards model. We also compared the 5-year OS with the expected one calculated for the surgically resected patients with EGC. If the lower limit of the 95% confidence interval (CI) of the 5-year OS exceeded the expected 5-year OS minus a margin of 5% (threshold 5-year OS), ER was considered to be effective. Pathological curability was categorized into en bloc resection, negative margins, and negative lymphovascular invasion: differentiated-type, pT1a, ulcer negative, ≤2 cm (Category A1); differentiated-type, pT1a, ulcer negative, >2 cm or ulcer positive, ≤3 cm (Category A2); undifferentiated-type, pT1a, ulcer negative, ≤2 cm (Category A3); differentiated-type, pT1b (SM1), ≤3 cm (Category B); or noncurative resections (Category C). RESULTS: Overall, the 5-year OS was 89.0% (95% CI, 88.3%-89.6%). In a multivariate analysis, no significant differences were observed when the hazard ratio of Categories A2, A3, and B were compared with that of A1. In all the pathological curability categories, the lower limit of the 95% CI for the 5-year OS exceeded the threshold 5-year OS. CONCLUSION: ER can be recommended as a standard treatment for patients with EGCs fulfilling Category A2, A3, and B, as well as A1 (UMIN Clinical Trial Registry, UMIN000005871).

Inhibition of dopamine receptor D1 signaling promotes human bile duct cancer progression via WNT signaling.

Bile duct cancer (BDC) frequently invades the nerve fibers, making complete surgical resection difficult. A single tumor mass contains cells of variable malignancy and cell-differentiation states, with cancer stem cells (CSCs) considered responsible for poor clinical outcomes. This study aimed to investigate the contribution of autosynthesized dopamine to CSC-related properties in BDC. Sphere formation assays using 13 commercially available BDC cell lines demonstrated that blocking dopamine receptor D1 (DRD1) signaling promoted CSC-related anchorage-independent growth. Additionally, we newly established four new BDC patient-derived organoids (PDOs) and found that blocking DRD1 increased resistance to chemotherapy and enabled xenotransplantation in vivo. Single-cell analysis revealed that the BDC PDO cells varied in their cell-differentiation states and responses to dopamine signaling. Further, DRD1 inhibition increased WNT7B expression in cells with bile duct-like phenotype, and it induced proliferation of other cell types expressing Wnt receptors and stem cell-like signatures. Reagents that inhibited Wnt function canceled the effect of DRD1 inhibition and reduced cell proliferation in BDC PDOs. In summary, in BDCs, DRD1 is a crucial protein involved in autonomous CSC proliferation through the regulation of endogenous WNT7B. As such, inhibition of the DRD1 feedback signaling may be a potential treatment strategy for BDC.

Germ line DDX41 mutations define a unique subtype of myeloid neoplasms.

Germ line DDX41 variants have been implicated in late-onset myeloid neoplasms (MNs). Despite an increasing number of publications, many important features of DDX41-mutated MNs remain to be elucidated. Here we performed a comprehensive characterization of DDX41-mutated MNs, enrolling a total of 346 patients with DDX41 pathogenic/likely-pathogenic (P/LP) germ line variants and/or somatic mutations from 9082 MN patients, together with 525 first-degree relatives of DDX41-mutated and wild-type (WT) patients. P/LP DDX41 germ line variants explained ∼80% of known germ line predisposition to MNs in adults. These risk variants were 10-fold more enriched in Japanese MN cases (n = 4461) compared with the general population of Japan (n = 20 238). This enrichment of DDX41 risk alleles was much more prominent in male than female (20.7 vs 5.0). P/LP DDX41 variants conferred a large risk of developing MNs, which was negligible until 40 years of age but rapidly increased to 49% by 90 years of age. Patients with myelodysplastic syndromes (MDS) along with a DDX41-mutation rapidly progressed to acute myeloid leukemia (AML), which was however, confined to those having truncating variants. Comutation patterns at diagnosis and at progression to AML were substantially different between DDX41-mutated and WT cases, in which none of the comutations affected clinical outcomes. Even TP53 mutations made no exceptions and their dismal effect, including multihit allelic status, on survival was almost completely mitigated by the presence of DDX41 mutations. Finally, outcomes were not affected by the conventional risk stratifications including the revised/molecular International Prognostic Scoring System. Our findings establish that MDS with DDX41-mutation defines a unique subtype of MNs that is distinct from other MNs.

Wearable, wireless, multi-sensor device for monitoring tissue circulation after free-tissue transplantation: a multicentre clinical trial.

Wearable sensors have seen remarkable recent technological developments, and their role in healthcare is expected to expand. Specifically, monitoring tissue circulation in patients who have undergone reconstructive surgery is critical because blood flow deficiencies must be rescued within hours or the transplant will fail due to thrombosis/haematoma within the artery or vein. We design a wearable, wireless, continuous, multipoint sensor to monitor tissue circulation. The system measures pulse waves, skin colour, and tissue temperature to reproduce physician assessment. Data are analysed in real time for patient risk using an algorithm. This multicentre clinical trial involved 73 patients who underwent transplant surgery and had their tissue circulation monitored until postoperative day 7. Herein, we show that the overall agreement rate between physician and sensor findings is 99.2%. In addition, the patient questionnaire results indicate that the device is easy to wear. The sensor demonstrates non-invasive, real-time, continuous, multi-point, wireless, and reliable monitoring for postoperative care. This wearable system can improve the success rate of reconstructive surgeries.

Amplified EPOR/JAK2 Genes Define a Unique Subtype of Acute Erythroid Leukemia.

Acute erythroid leukemia (AEL) is a unique subtype of acute myeloid leukemia characterized by prominent erythroid proliferation whose molecular basis is poorly understood. To elucidate the underlying mechanism of erythroid proliferation, we analyzed 121 AEL using whole-genome, whole-exome, and/or targeted-capture sequencing, together with transcriptome analysis of 21 AEL samples. Combining publicly available sequencing data, we found a high frequency of gains and amplifications involving EPOR/JAK2 in TP53-mutated cases, particularly those having >80% erythroblasts designated as pure erythroid leukemia (10/13). These cases were frequently accompanied by gains and amplifications of ERG/ETS2 and associated with a very poor prognosis, even compared with other TP53-mutated AEL. In addition to activation of the STAT5 pathway, a common feature across all AEL cases, these AEL cases exhibited enhanced cell proliferation and heme metabolism and often showed high sensitivity to ruxolitinib in vitro and in xenograft models, highlighting a potential role of JAK2 inhibition in therapeutics of AEL. SIGNIFICANCE: This study reveals the major role of gains, amplifications, and mutations of EPOR and JAK2 in the pathogenesis of pure erythroleukemia. Their frequent response to ruxolitinib in patient-derived xenograft and cell culture models highlights a possible therapeutic role of JAK2 inhibition for erythroleukemia with EPOR/JAK2-involving lesions. This article is highlighted in the In This Issue feature, p. 369.