[A Case of Long-Term Response to Chemotherapy in Mucinous Carcinoma of the Duodenum with Multiple Distant Metastases].

Primary carcinoma of the duodenum, especially mucinous carcinoma of the duodenum, is extremely rare. We present a case of a long-term response to chemotherapy in mucinous carcinoma of the duodenum with multiple distant metastases. A 60-year-old man was admitted to our hospital with epigastric pain and jaundice. CT showed a thickening of the duodenal wall; extensive lymphadenopathy around the head of the pancreas, in the para-aortic region and the mediastinum; suspected peritoneal dissemination; lung metastases; and bone metastases. An upper gastrointestinal endoscopy revealed a duodenal stenosis in the descending limb with irregular mucosa, and a diagnosis of mucinous carcinoma of the duodenum was made on the basis of the histological analysis of the biopsy sample. Double bypass surgery involving a choledochojejunostomy and gastrojejunostomy were performed for obstruction of the duodenum and common bile duct. After FOLFOXIRI therapy was initiated, the tumors were reduced markedly. Despite withdrawal after 28 courses of chemotherapy, the patient achieved a long-term response for 10 years after the initiation of chemotherapy.

A Case Report: Ovarian Fibrothecoma with Minor Sex Cord Elements.

Introduction: Ovarian stromal tumors with minor sex cord elements are rare, and there are not specific imaging features to help in making the diagnosis. Case Presentation: We report a case of this tumor in an 81-year-old woman who was referred to our hospital for constipation and a pelvic mass. Magnetic resonance imaging demonstrated a well-circumscribed mass and isointensity compared to the skeletal muscle on T1-weighted imaging (T1WI) and low signal intensity mixed with high signal ranges on T2-weighted imaging. Dynamic gadolinium-enhanced fat-suppressed T1WI revealed mild and increased enhancement of the peripheral area in the early and delayed phases, respectively. On diffusion-weighted imaging (DWI), a heterogeneously high signal intensity corresponding to the peripheral enhanced area was observed, and the apparent diffusion coefficient values of the high-intensity areas on DWI were low. Malignancy could be suspected, so the mass was surgically removed. Pathological assessment revealed a fibrothecoma with minor sex cord elements. Conclusion: The tumor's preoperative diagnosis is difficult, although the possibility of this rare tumor from atypical findings on DWI and/or dynamic contrast enhancement studies should be considered.

Survival outcomes of lung metastases from colorectal cancer treated with pulmonary metastasectomy or modern systemic chemotherapy: a single institution experience.

BACKGROUND: Although pulmonary metastasectomy is an accepted treatment strategy for resectable lung metastases (LM) from colorectal cancer (CRC), its survival benefits are controversial. In contrast, recent advancements in chemotherapy have significantly improved metastatic CRC prognosis. This study aimed to evaluate survival outcome of LM from CRC in the age of newly developed chemotherapy. METHODS: We retrospectively reviewed 50 patients who underwent complete resection and 22 patients who received chemotherapy as definitive treatment for LM from resected CRC at our hospital. The present study was limited to patients who started treatment for isolated LM after molecular targeted drugs became available in Japan. RESULTS: Overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS) rates after pulmonary resection were 64.5%, 66.4%, and 32.6% at five years, respectively. OS and CSS rates of chemotherapy patients were 26.8% and 28.3% at five years, with a median progression-free survival time of 10.0 months. When compared the characteristics of surgical and chemotherapy patients, patients with pN factors of CRC (p = 0.013), smaller size (p < 0.001), larger number (p < 0.001), and bilateral (p < 0.001) LM received chemotherapy. Univariate analysis showed that multiple LM and rectal lesions were poor prognostic factors for OS (p = 0.012) and DFS (p = 0.017) in surgical patients, and rectal lesions were a poor prognostic factor for OS (p = 0.013) in chemotherapy patients. CONCLUSIONS: Pulmonary metastasectomy showed a favorable survival in patients with LM from CRC. Despite the high recurrence rate after metastasectomy and recent advances in chemotherapy, surgical resection could still be considered as a valid option among multidisciplinary treatments. TRIAL REGISTRATION: The research plan was approved by the Institutional Review Board of Shinko Hospital (No. 2142) on February 7, 2022.

[Hemophagocytic lymphohistiocytosis following mRNA-1273 COVID-19 vaccination].

A 34-year-old man with no medical history presented with fever 4 days after receiving the first dose of mRNA-1273 coronavirus disease 2019 (COVID-19) vaccine. He had no prior clinical evidence of severe acute respiratory syndrome coronavirus 2 infection and was negative for serial polymerase chain reaction testing. Ten days after vaccination, he was referred to our hospital because of no response to antibiotics and the emergence of neutropenia, thrombocytopenia, and liver dysfunction. Blood tests also showed elevated serum ferritin and plasma soluble interleukin-2 receptors. Serological and PCR testing excluded active infections of cytomegalovirus, Epstein-Barr virus, and hepatitis viruses. Blood culture yielded no growth. Computed tomography revealed mild hepatosplenomegaly and porta hepatis lymphadenopathy but no focus on infection. Bone marrow aspiration demonstrated hemophagocytosis but no infiltrating lymphoma cells. Immediately, 2-mg/kg intravenous methylprednisolone was commenced based on the presumptive diagnosis of hemophagocytic lymphohistiocytosis (HLH), leading to the rapid and durable improvement of his symptoms and laboratory data. Later, without other causes triggering hemophagocytosis, and with the close link between vaccination and disease onset, the final diagnosis of vaccination-induced secondary HLH was made. HLH after COVID-19 vaccination, though extremely rare, can occur regardless of the vaccine type. Therefore, clinicians should recognize and deal with this occasionally fatal adverse event.

A vaginal fibroepithelial stromal polyp: a case report with magnetic resonance images.

A fibroepithelial stromal polyp is a benign soft tissue tumour that can occur in the vagina, vulva and uterine cervix. Magnetic resonance imaging (MRI) findings have been reported in patients with vulvar fibroepithelial stromal polyps, not in those with vaginal polyps. We present MRI findings of vaginal fibroepithelial stromal polyp in a postmenopausal female. A 1 to 2 cm firm vaginal mass arising from the left side of the vaginal wall with hypointense signal changes on T1W MRI was identified. A well-defined vaginal mass (1 cm diameter) was detected with inhomogeneous signal intensity on T2W images. However, a major portion had high signal intensity on diffusion-weighted images. A benign vaginal lesion with oedematous changes or myxoid degeneration was suspected. Vaginal resection was performed, and fibroepithelial stromal polyp was pathologically diagnosed. MRI may be a useful non-invasive modality for preoperatively diagnosing vaginal fibroepithelial stromal polyps.

Dysmegakaryopoiesis and Transient Mild Increase in Bone Marrow Blasts in Patients With Aplastic Anemia Treated With Eltrombopag May Be Signs of Hematologic Improvement and Not Portend Clonal Evolution.

OBJECTIVES: Eltrombopag, a thrombopoietin-receptor agonist, stimulates hematopoiesis in patients with acquired aplastic anemia (AA). Cytomorphologic changes in bone marrow after eltrombopag administration are still unclear. This study examined the effect of eltrombopag on cytomorphologic findings using data from prior phase 2 studies (E1201 and E1202). METHODS: Microscopic examinations were performed in 31 patients with AA (E1201 [n = 21], E1202 [n = 10]). The relationship between hematologic improvement and morphologic findings was also investigated. RESULTS: In 5 patients (E1201 [n = 3], E1202 [n = 2]), the bone marrow blast count increased after initiation of eltrombopag treatment compared with screening values. The blast count was less than 5%, and the increase in bone marrow blasts was transient in all 4 patients who had bone marrow examinations at follow-up. In 8 patients (E1201 [n = 5], E1202 [n = 3]), dysplastic forms of megakaryocytes were found in the bone marrow following treatment initiation. Dysmegakaryopoiesis of 10% or more was found in 3 patients. None of the patients revealed micromegakaryocytes. Ten patients showed an increase in bone marrow blasts and/or dysmegakaryopoiesis following treatment initiation. Nine of 10 patients showed hematologic improvement in 1 or more lineages. CONCLUSIONS: Dysmegakaryopoiesis without micromegakaryocytes and a transient increase of less than 5% in bone marrow blast count may be signs of hematologic improvement with eltrombopag for patients with AA.

Termination-of-resuscitation rule in the emergency department for patients with refractory out-of-hospital cardiac arrest: a nationwide, population-based observational study.

BACKGROUND: In Japan, emergency medical service (EMS) providers are prohibited from field termination-of-resuscitation (TOR) in out-of-hospital cardiac arrest (OHCA) patients. In 2013, we developed a TOR rule for emergency department physicians (Goto's TOR rule) immediately after hospital arrival. However, this rule is subject to flaws, and there is a need for revision owing to its relatively low specificity for predicting mortality compared with other TOR rules in the emergency department. Therefore, this study aimed to develop and validate a modified Goto's TOR rule by considering prehospital EMS cardiopulmonary resuscitation (CPR) duration. METHODS: We analysed the records of 465,657 adult patients with OHCA from the All-Japan Utstein registry from 2016 to 2019 and divided them into two groups: development (n = 231,363) and validation (n = 234,294). The primary outcome measures were specificity, false-positive rate (FPR), and positive predictive value (PPV) of the revised TOR rule in the emergency department for predicting 1-month mortality. RESULTS: Recursive partitioning analysis for the development group in predicting 1-month mortality revealed that a modified Goto's TOR rule could be defined if patients with OHCA met the following four criteria: (1) initial asystole, (2) unwitnessed arrest by any laypersons, (3) EMS-CPR duration > 20 min, and (4) no prehospital return of spontaneous circulation (ROSC). The specificity, FPR, and PPV of the rule for predicting 1-month mortality were 99.2% (95% confidence interval [CI], 99.0-99.4%), 0.8% (0.6-1.0%), and 99.8% (99.8-99.9%), respectively. The proportion of patients who fulfilled the rule and the area under the receiver operating curve (AUC) was 27.5% (95% CI 27.3-27.7%) and 0.904 (0.902-0.905), respectively. In the validation group, the specificity, FPR, PPV, proportion of patients who met the rule, and AUC were 99.1% (95% CI 98.9-99.2%), 0.9% (0.8-1.1%), 99.8% (99.8-99.8%), 27.8% (27.6-28.0%), and 0.889 (0.887-0.891), respectively. CONCLUSION: The modified Goto's TOR rule (which includes the following four criteria: initial asystole, unwitnessed arrest, EMS-CPR duration > 20 min, and no prehospital ROSC) with a > 99% predictor of 1-month mortality is a reliable tool for physicians treating refractory OHCAs immediately after hospital arrival.

Epithelioid leiomyoma of the uterus: A case report with magnetic resonance imaging findings.

Epithelioid leiomyoma of the uterus is rare, and its prognostic factors have not been well established. Moreover, radiologic findings of this disease have not been previously documented. This is a case of a 49-year-old woman with epithelioid leiomyoma of the uterus. Magnetic resonance imaging (MRI) revealed a heterogeneous high-intensity mass with multiple ordinary uterine leiomyomas. The mass showed a slightly diffusion-restricted site. Since benign tumors could not be confidently diagnosed using these MRI findings, total abdominal hysterectomy with bilateral salpingectomy was performed, and a pathological diagnosis of epithelioid leiomyoma of the uterus was established. Microscopically, this lesion showed edematous changes and cyst formation, causing a heterogeneous appearance on T2-weighted images. In addition, the diffusion-restricted site is considered to be consistent with areas of solid and dense proliferation of tumor cells. The patient survived and was well 10 months after the surgery. It is important to recognize this benign variant of leiomyoma with an unusual appearance, to provide appropriate therapeutic management.

Autoimmune-mediated thrombocytopenia after allogeneic hematopoietic stem cell transplantation: significance of detecting reticulated platelets and glycoprotein-specific platelet autoantibodies.

Autoimmune hematological disorders are rare complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis of immune thrombocytopenia (ITP) is challenging, especially after allo-HSCT, because various complications such as graft-versus-host disease, disease relapse, viral infection, thrombotic microangiopathy, and drug side effects can also cause thrombocytopenia. Assessment of reticulated platelets (RP) and plasma thrombopoietin (TPO) levels may be useful to distinguish between ITP and hypoplastic thrombocytopenia. ITP is generally characterized by an increased percentage of RP, and a normal or slightly increased plasma TPO level. We now report three cases of thrombocytopenia after allo-HSCT. RP% was elevated in these patients, as it is in primary ITP. However, in contrast to primary ITP, plasma TPO levels were high in two of three patients. Anti-αIIbß3 and anti-GPIb/IX-specific direct IgG antibodies were detected as well, suggesting occurrence of immune-mediated platelet destruction in addition to bone marrow suppression in two patients. All three patients were successfully treated with corticosteroids and/or thrombopoietin receptor agonists (TPO-RAs). These results suggest that increased RP% and detection of glycoprotein-specific platelet autoantibodies are useful for the diagnosis of ITP after HSCT.

Association of dispatcher-assisted cardiopulmonary resuscitation with initial shockable rhythm and survival after out-of-hospital cardiac arrest.

BACKGROUND AND IMPORTANCE: Bystander cardiopulmonary resuscitation (CPR) and initial shockable rhythm are crucial predictors of survival after out-of-hospital cardiac arrest (OHCA). However, the relationship between dispatcher-assisted CPR (DA-CPR) and initial shockable rhythm is not completely elucidated. OBJECTIVE: To examine the association of DA-CPR with initial shockable rhythm and outcomes. DESIGN, SETTING AND PARTICIPANTS: This nationwide population-based observational study conducted in Japan included 59 688 patients with witnessed OHCA of cardiac origin after excluding those without bystander CPR. Patients were divided into DA-CPR (n = 42 709) and CPR without dispatcher assistance (unassisted CPR, n = 16 979) groups. OUTCOME MEASURES AND ANALYSIS: The primary outcome measure was initial shockable rhythm, and secondary outcome measures were 1-month survival and neurologically intact survival. A Cox proportional hazards model adjusted for collapse-to-first-rhythm-analysis time and multivariable logistic regression models were used after propensity score (PS) matching to compare the incidence of initial shockable rhythm and outcomes, respectively. MAIN RESULTS: Among all patients (mean age 76.7 years), the rates of initial shockable rhythm, 1-month survival and neurologically intact survival were 20.8, 10.7 and 7.0%, respectively. The incidence of initial shockable rhythm in the DA-CPR group (20.4%, 3462/16 979) was significantly higher than that in the unassisted CPR group (18.5%, 3133/16 979) after PS matching (P < 0.0001). However, no significant differences were found between the two groups with respect to the incidence of initial shockable rhythm in the Cox proportional hazards model [adjusted hazard ratio of DA-CPR for initial shockable rhythm compared with unassisted CPR, 0.99; 95% confidence interval (CI), 0.97-1.02, P = 0.56]. No significant differences were observed in the survival rates in the two groups after PS matching [10.8% (1833/16 979) vs. 10.3% (1752/16 979), P = 0.16] and neurologically intact survival rates [7.3% (1233/16 979) vs. 6.8% (1161/16 979), P = 0.13]. The multivariable logistic regression model showed no significant differences between the groups with regard to survival (adjusted odds ratio of DA-CPR compared with unassisted CPR: 1.00; 95% CI, 0.89-1.13, P = 0.97) and neurologically intact survival (adjusted odds ratio: 1.12; 95% CI, 0.98-1.29, P = 0.14). CONCLUSION: DA-CPR after OHCA had the same independent association with the likelihood of initial shockable rhythm and 1-month meaningful outcome as unassisted CPR.

Dispatcher-assisted conventional cardiopulmonary resuscitation and outcomes for paediatric out-of-hospital cardiac arrests.

AIM: As asphyxial cardiac arrest is more common than cardiac arrest from a primary cardiac event in paediatric cardiac arrest, effective ventilation is important during paediatric cardiopulmonary resuscitation (CPR). We aimed to determine optimal dispatcher-assisted CPR instructions for bystanders after paediatric out-of-hospital cardiac arrest (OHCA). METHODS: We analysed the records of 8172 children who received bystander dispatcher-assisted CPR. Data were obtained from an All-Japan Utstein-style registry from 2005 to 2017. Patients were divided into conventional CPR and compression-only CPR groups. The primary study endpoint was 1-month neurologically intact survival, defined as a Cerebral Performance Category score of 1 or 2 (CPC 1-2). RESULTS: The 1-month CPC 1-2 rate was significantly higher in the dispatcher-assisted conventional CPR group than in the dispatcher-assisted compression-only CPR group (before propensity score matching, 5.7% [175/3077] vs. 3.1% [160/5095], p < 0.0001, adjusted odds ratio 2.48, 95% confidence interval 1.19-3.22; after propensity score matching, 6.0% [156/2618] vs. 2.6% [69/2618], p < 0.0001, adjusted odds ratio 2.42, 95% confidence interval 1.76-3.32). In most subgroup analyses after matching, dispatcher-assisted conventional CPR had a higher CPC 1-2 rate than dispatcher-assisted compression-only CPR; however, CPC 1-2 rates were similar between the two groups for patients with an initial shockable rhythm, those with total prehospital CPR time ≥ 20 min, those receiving public access defibrillation, advanced airway management, or adrenaline administration. CONCLUSION: Within the limitations of this retrospective observational study, dispatcher-assisted conventional CPR was preferable to dispatcher-assisted compression-only CPR as optimal CPR instructions for coaching callers to perform bystander CPR.

[Chronic myeloid leukemia with an in-frame exon 4 deletion in ABL1 with acute abdomen due to an intrapelvic bulky mass as the initial symptom].

A 23-year-old woman was admitted to our hospital because of rapidly developing lower abdominal pain. Computed tomography revealed ascites, splenomegaly, and a huge mass that occupied the pouch of Douglas and surrounded her uterus. A markedly elevated white blood cell count of 495×109/l and the identification of the BCR-ABL1 fusion gene led to the diagnosis of chronic myeloid leukemia (CML). Although neither an increase in the blast percentage nor any additional chromosomal abnormality was observed in the patient, CML was considered in the blast phase because of extramedullary disease infiltration. Dasatinib was administered with the temporal use of hydroxyurea and VP-16, which resulted in rapid disappearance of her intrapelvic mass and complete hematologic response within 1 month. She refused to undergo allogeneic hematopoietic stem cell transplantation and continued to take dasatinib, achieving complete cytogenetic and major molecular responses within 5 and 11 months, respectively. CML cases initially presenting with extramedullary tumors are rare. Furthermore, in our case, a mutational analysis at diagnosis revealed an in-frame exon 4 deletion in ABL1, which is reported to decrease cell proliferation. This fact is intriguing because her clinical outcome was relatively favorable.

Dispatcher instructions for bystander cardiopulmonary resuscitation and neurologically intact survival after bystander-witnessed out-of-hospital cardiac arrests: a nationwide, population-based observational study.

BACKGROUND: The International Liaison Committee on Resuscitation recommends that dispatchers provide instructions to perform compression-only cardiopulmonary resuscitation (CPR) to callers responding to adults with out-of-hospital cardiac arrest (OHCA). This study aimed to determine the optimal dispatcher-assisted CPR (DA-CPR) instructions for OHCA. METHODS: We analysed the records of 24,947 adult patients (aged ≥ 18 years) who received bystander DA-CPR after bystander-witnessed OHCA. Data were obtained from a prospectively recorded Japanese nationwide Utstein-style database for a 2-year period (2016-2017). Patients were divided into compression-only DA-CPR (n = 22,778) and conventional DA-CPR (with a compression-to-ventilation ratio of 30:2, n = 2169) groups. The primary outcome measure was 1-month neurological intact survival, defined as a cerebral performance category score of 1-2 (CPC 1-2). RESULTS: The 1-month CPC 1-2 rate was significantly higher in the conventional DA-CPR group than in the compression-only DA-CPR group (before propensity score (PS) matching, 7.5% [162/2169] versus 5.8% [1309/22778], p < 0.01; after PS matching, 7.5% (162/2169) versus 5.7% (123/2169), p < 0.05). Compared with compression-only DA-CPR, conventional DA-CPR was associated with increased odds of 1-month CPC 1-2 (before PS matching, adjusted odds ratio 1.39, 95% confidence interval [CI] 1.14-1.70, p < 0.01; after PS matching, adjusted odds ratio 1.34, 95% CI 1.00-1.79, p < 0.05). CONCLUSION: Within the limitations of this retrospective observational study, conventional DA-CPR with a compression-to-ventilation ratio of 30:2 was preferable to compression-only DA-CPR as an optimal DA-CPR instruction for coaching callers to perform bystander CPR for adult patients with bystander-witnessed OHCAs.

Association of subsequent treated shockable rhythm with outcomes after paediatric out-of-hospital cardiac arrests: A nationwide, population-based observational study.

AIM: Among patients with paediatric out-of-hospital cardiac arrests (OHCAs), most have an initial non-shockable rhythm with poor outcomes. There is a subset who developed shockable rhythms. This study aimed to investigate the association between subsequent shock delivery and outcomes after paediatric OHCAs. METHODS: We analysed records of 19,095 children (aged <18 years) with OHCA and initial non-shockable rhythm. Data were obtained from a Japanese nationwide database for 13 years (2005-2017). The primary outcome measure was 1-month neurologically intact survival, defined as cerebral performance category 1-2. RESULTS: Among patients with pulseless electrical activity (PEA, n = 3,326), there was no significant difference between those with subsequent treated shockable rhythm (10.0% [11/109]) and those with sustained non-shockable rhythm (6.0% [192/3,217], p = 0.10) with respect to the neurologically intact survival rate. Among asystole patients (n = 15,769), the neurologically intact survival rate was significantly higher in the subsequent treated shockable rhythm group (4.4% [10/227]) than in the sustained non-shockable rhythm group (0.7% [106/15,542], p < 0.0001). Subsequent treated shockable rhythm with a shock delivery time (time from emergency medical services [EMS]-initiated cardiopulmonary resuscitation [CPR] to shock delivery) ≤9 min was associated with increased odds of neurologically intact survival compared with sustained non-shockable rhythm (PEA, adjusted odds ratio, 2.45 [95% confidence interval, 1.16-5.16], p = 0.018; asystole, 9.77 [4.2-22.5], p < 0.0001). CONCLUSION: After paediatric OHCAs, subsequent treated shockable rhythm was associated with increased odds of 1-month neurologically intact survival regardless of whether the initial rhythm was PEA or asystole, only when the shock was delivered ≤9 min of EMS-initiated CPR.

Time boundaries of the three-phase time-sensitive model for ventricular fibrillation cardiac arrest.

AIM: Ventricular fibrillation (VF) cardiac arrest may consist of three time-sensitive phases: electrical, circulatory, and metabolic. However, the time boundaries of these phases are unclear. We aimed to determine the time boundaries of the three-phase model for VF cardiac arrest. METHODS: We reviewed 20,741 out-of-hospital cardiac arrest cases with initial VF and presumed cardiac origin from the All-Japan Utstein-style registry between 2013 and 2017. The study endpoint was 1-month neurologically intact survival. The collapse-to-shock interval was defined as the time from collapse to the first shock delivery by emergency medical service personnel. The patients were divided into the bystander cardiopulmonary resuscitation (CPR, n = 11,606) and non-bystander CPR (n = 9135) groups. RESULTS: In the bystander CPR group, the collapse-to-shock times that were associated with increased adjusted 1-month neurologically intact survival, compared with those in the non-bystander CPR group, ranged from 7 min (42.9% [244/4999] vs. 26.0% [119/458], adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.44-2.63; P < 0.0001) to 17 min (17.1% [70/410] vs. 7.3% [21/288], aOR, 2.82; 95% CI, 1.62-4.91; P = 0.0002). However, the neurologically intact survival rate of the bystander CPR group was statistically insignificant compared with that of the non-bystander CPR group when the collapse-to-shock time was outside this range. CONCLUSIONS: The time boundaries of the three-phase time-sensitive model for VF cardiac arrest may be defined as follows: electrical phase, from collapse to <7 min; circulatory phase, from 7 to 17 min; and metabolic phase, from >17 min onward.

Temporal trends in neurologically intact survival after paediatric bystander-witnessed out-of-hospital cardiac arrest: A nationwide population-based observational study.

AIM: Trends in neurologically intact survival after paediatric out-of-hospital cardiac arrest (OHCA) remain unclear. In the present study, we aimed to determine trends in 1-month neurologically intact survival after paediatric OHCA over time. METHODS: We reviewed the data of 5461 children (aged < 18 years) who experienced bystander-witnessed OHCA and were included in the nationwide Japanese registry from 2005 to 2017. Patients were divided into three groups according to study period: 2005-2010, 2011-2015, and 2016-2017. We analysed the trends in 1-month neurologically intact survival rates over time. RESULTS: The risk-adjusted odds of 1-month neurologically intact survival (odds ratio, 1.86; 95% confidence interval, 1.41-2.44) were significantly improved by 2016-2017 compared with baseline. Similar improvements in 1-month neurologically intact survival rates were observed with both standard bystander cardiopulmonary resuscitation (CPR) with rescue breaths and chest compression-only bystander CPR (P for trend < 0.05 and < 0.001, respectively). In the subgroup analyses by aetiology, the 1-month neurologically intact survival rate in patients with OHCA of non-traumatic origin significantly increased from 11.8%-15.1% to 19.7% (P for trend < 0.001) but not in those with OHCA of traumatic origin (from 4.9% to 3.4% to 4.1%; P for trend = 0.29). CONCLUSION: The 1-month neurologically intact survival rate significantly increased from 2005 to 2017 in Japanese children with bystander-witnessed OHCA, regardless of bystander CPR type; This increase was noted in patients with OHCA of non-traumatic origin but not in those with OHCA of traumatic origin.

White esophagus accompanying multiple circumferential duodenal erosions extending to upper jejunum.

Although white esophagus is an extremely rare disease, careful diagnosis and intensive treatment are required because of a relationship with black esophagus. Further case accumulation including duodenal and jejunum lesion is needed.

High numbers of programmed cell death-1-positive tumor infiltrating lymphocytes correlate with early onset of post-transplant lymphoproliferative disorder.

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of transplantation. In addition to reactivation of Epstein-Barr virus in immunocompromised patients, impaired tumor immunity is suggested to be a risk factor for PTLD. However, it remains unclear whether immune suppressive tumor-infiltrating lymphocytes (TILs) correlate with the occurrence or prognosis of PTLD. We analyzed TILs in 26 patients with PTLD to elucidate the clinicopathological significance of the expression of PD-1 and FoxP3, which are associated with exhausted T-cells and regulatory T-cells (Tregs), respectively. Numbers of PD-1+ TILs in the PTLD specimens were significantly higher in patients who developed PTLD early after transplantation (P = 0.0040), while numbers of FoxP3+ TILs were not (P = 0.184). There was no difference in overall response rate regardless of the expression of PD-1 or FoxP3. FoxP3high patients tended to have a shorter time to progression compared with FoxP3low patients, especially in the case of FoxP3high patients with diffuse large B-cell lymphoma-subtype PTLD (P = 0.011), while PD-1high patients did not. These results suggest that T-cell exhaustion may be mainly associated with PTLD development, while immune suppression by Tregs may be dominant in enhanced progression of PTLD following disease occurrence.

Eltrombopag in Combination with Rabbit Anti-thymocyte Globulin/Cyclosporine A in Immunosuppressive Therapy-naïve Patients with Aplastic Anemia in Japan.

Objective In Japan, immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG), and cyclosporine A (CsA) is the standard of care in patients with aplastic anemia (AA) who are not indicated for stem-cell transplantation, although some patients may experience relapse. This study assessed the efficacy and safety of eltrombopag in combination with rabbit-ATG/CsA in IST-naïve patients with non-severe or severe AA in Japan. Methods In this non-randomized, open-label, single-arm, phase II study, rabbit-ATG/CsA and eltrombopag were initiated on Days 1 and 15 (±3 days), respectively, and continued for ≥26 weeks; rabbit-ATG was given for 5 days (Days 1 to 5). The primary endpoint was the overall response rate (ORR) at Week 26. Patients Patients with AA who were IST-naïve and ≤70 years old or between 71 and 75 years old based on the recommendation of the investigator were enrolled in Japan. Results Of the 11 enrolled patients, 10 started treatment with eltrombopag. The ORRs at Weeks 26 and 52 were 70.0% and 60.0%, respectively. The ORR at Week 26 was 100% (all 3 patients) in patients with non-severe AA and 57.1% (4/7) in patients with severe AA. Among transfusion-dependent patients, 66.7% (4/6) and 62.5% (5/8) became red blood cell- and platelet-transfusion independent, respectively. The most common adverse events were nausea and headache. No deaths or hematologic malignancies were reported. A cytogenetic abnormality was reported in one patient. Conclusion This study confirmed the clinical benefit of eltrombopag plus rabbit-ATG/CsA in IST-naïve patients with non-severe or severe AA in Japan.