Second allogeneic hematopoietic SCT for relapsed ALL in children

A second SCT is generally accepted as the only potentially curative approach for ALL patients that relapse after SCT, but the role of second SCT for pediatric ALL is not fully understood. We performed a retrospective analysis of 171 pediatric patients who received a second allo-SCT for relapsed ALL after allo-SCT. OS at 2 years was 29.4±3.7%, the cumulative incidence of relapse was 44.1±4.0% and non-relapse mortality was 18.8±3.5%. Relapse occurred faster after the second SCT than after the first SCT (117 days vs 164 days, P=0.04). Younger age (9 years or less), late relapse (180 days or more after first SCT), CR at the second SCT, and myeloablative conditioning were found to be related to longer survival. Neither acute GVHD nor the type of donor influenced the outcome of second SCT. Multivariate analysis showed that younger age and late relapse were associated with better outcomes. Our analysis suggests that second SCT for relapsed pediatric ALL is an appropriate treatment option for patients that have achieved CR, which is associated with late relapse after the first SCT.     

Transfusion-transmitted malaria: case report of asymptomatic donor harboring Plasmodium malariae

Malaria in Brazil is endemic in the Amazon region, but autochthonous cases with low parasitaemia occur in the Atlantic Forest area of the country. According to Brazilian legislation no test is mandatory for blood donors from non-endemic areas. However if they have traveled to malaria transmission regions they are deferred for six months before they can donate. This report describes a transfusion-transmitted malaria case in Sao Paulo, Brazil, where one recipient received infected blood and developed the disease. He lived in Sao Paulo and had no previous transfusion or trips to endemic areas, including those of low endemicity, such as Atlantic Forest. Thick blood smears confirmed Plasmodium malariae. All donors lived in Sao Paulo and one of them (Donor 045-0) showed positive hemoscopy and PCR. This asymptomatic donor had traveled to Juquia, in the Atlantic Forest area of S ao Paulo State, where sporadic cases of autochthonous malaria are described. DNA assay revealed P. malariae in the donor's (Donor 045-0) blood. Serum archives of the recipient and of all blood donors were analyzed by ELISA using both P. vivax and P. falciparum antigens, and IFAT with P. malariae. Donor 045-0's serum was P. malariae IFAT positive and the P. vivax ELISA was reactive. In addition, two out of 44 donors' archive sera were also P. vivax ELISA reactive. All sera were P. falciparum ELISA negative. This case suggests the need of reviewing donor selection criteria and deferral strategies to prevent possible cases of transfusion-transmitted malaria.     

Alpha‐actinin‐4 (ACTN4) gene amplification is a predictive biomarker for adjuvant chemotherapy with tegafur/uracil in stage I lung adenocarcinomas

Although adjuvant tegafur/uracil (UFT) is recommended for patients with completely resected stage I non‐small‐cell lung cancer (NSCLC) in Japan, only one‐third of cases has received adjuvant chemotherapy (ADJ) according to real‐world data. Therefore, robust predictive biomarkers for selecting ADJ or observation (OBS) without ADJ are needed. Patients who underwent complete resection of stage I lung adenocarcinoma with or without adjuvant UFT were enrolled. The status of ACTN4 gene amplification was analyzed by FISH. Statistical analyses to determine whether the status of ACTN4 gene amplification affected recurrence‐free survival (RFS) were carried out. Formalin‐fixed, paraffin‐embedded samples from 1136 lung adenocarcinomas were submitted for analysis of ACTN4 gene amplification. Ninety‐nine (8.9%) of 1114 cases were positive for ACTN4 gene amplification. In the subgroup analysis of patients aged 65 years or older, the ADJ group had better RFS than the OBS group in the ACTN4‐positive cohort (hazard ratio [HR], 0.084, 95% confidence interval [CI], 0.009‐0.806; P = .032). The difference in RFS between the ADJ group and the OBS group was not significant in ACTN4‐negative cases (all ages: HR, 1.214; 95% CI, 0.848‐1.738; P = .289). Analyses of ACTN4 gene amplification contributed to the decision regarding postoperative ADJ for stage I lung adenocarcinomas, preventing recurrence, improving the quality of medical care, preventing the unnecessary side‐effects of ADJ, and saving medical costs.     

Safety and Applicability of Continuous Retrograde Cardioplegia in Minimally Invasive Aortic Valve Replacement: New Approaches

Purpose: To discuss minimally invasive cardiac surgery aortic valve replacement (MICS-AVR) approach via anterior thoracotomy using continuous retrograde cardioplegia. Continuous retrograde cardioplegia facilitates excellent continuous homogeneous cooling of the heart during cardiac arrest.Methods: We performed AVR using the proposed method in nine patients between June 2018 and September 2019. The median age of the patients was 73 (range: 43–84) years. The pleural space was entered via anterior thoracotomy. After opening of the right atrium, a retrograde cardioplegic cannula was inserted into the coronary sinus with a purse-string suture. Continuous cold blood retrograde cardioplegia was initiated at 700 mL/h.Results: Extubation in the operating room was performed in five (56%) patients. No new decreased function of the left and right ventricles was observed in intraoperative transesophageal echography or transthoracic echocardiogram.Conclusion: MICA-AVR through continuous retrograde cardioplegia is a safe technique.     

Ultraviolet B irradiation of the mouse eye induces pigmentation of the skin more strongly than does stress loading,by increasing the levels of prohormone convertase 2 and α‐melanocyte‐stimulating hormone

Background. In previous studies, we made the unexpected finding that in mice, ultraviolet (UV)B irradiation of the eye increased the concentration of α‐melanocyte‐stimulating hormone (α‐MSH) in plasma, and systemically stimulated epidermal melanocytes. Aims. To compare the extent of the pigmentation induced by social and restraint stress (which activate the hippocampus–pituitary system) with that induced by UVB irradiation. Methods. DBA/2 and sham‐operated or hypophysectomized DBA/2 mice were subjected to local UVB exposure using a sunlamp directed at the eye, and two types of stress (social and restraint) were imposed. Results. UVB irradiation of the eye or exposure to stress loading both increased the number of Dopa‐positive melanocytes in the epidermis, and hypophysectomy strongly inhibited the UVB‐induced and stress‐induced stimulation of melanocytes. Irradiation of the eye caused a much greater increase in dopamine than did the stress load. Both UVB eye irradiation and stress increased the blood levels of α‐MSH and adrenocorticotropic hormone (ACTH). In addition, the increase in plasma α‐MSH was greater in animals subjected to UVB eye irradiation than in those subjected to stress loading, whereas the reverse occurred for plasma ACTH. UVB irradiation to the eye and stress loading increased the expression of prohormone convertase (PC)1/3 and PC2 in the pituitary gland. The increase in expression of pituitary PC2 was greater in animals subjected to UVB eye irradiation than to stress, whereas no difference was seen between the two groups for the increase in PC1/3. Conclusions. UVB eye irradiation exerts a stronger effect on pigmentation than stress loading, and is related to increased levels of α‐MSH and PC2.     

Orthotopic sigmoid vs. ileal neobladders in Japanese patients: A comparative assessment of complications,functional outcomes,and quality of life

ObjectivesTo compare the clinical outcomes of sigmoid and ileal neobladders (NBs) created following radical cystectomy.Materials and methodsThis study included 90 and 144 Japanese patients undergoing radical cystectomy and orthotopic NB reconstruction with a sigmoid and ileal segment, respectively. Postoperative clinical outcomes between the sigmoid and ileal NB groups (SNBG and INBG) were compared.ResultsIn this series, 110 early and 51 late complications occurred in 71 and 41 patients, respectively; however, there was no significant difference in the incidence of complications between SNBG and INBG. At 1 year postoperatively, there were no significant differences in the proportion of spontaneous voiders and the continence status between these 2 groups; however, despite the lack of significant differences in the maximal flow rate and voided volume, the post-void residual in SNBG was significantly smaller than that in INBG. Voiding functional outcomes at 5 years postoperatively were also obtained from 28 and 49 in SNBG and INBG, respectively. Although there were no significant changes in the functional outcomes in SNBG, the proportion of spontaneous voiders and post-void residual in INBG at 5 years postoperatively were significantly poorer than those at 1 year postoperatively. Furthermore, the postoperative health-related quality of life assessed by a Short-Form 36 survey did not show any significant differences in all 8 scores between these 2 groups.ConclusionsBoth types of NB reconstruction resulted in comparatively satisfactory outcomes; however, the voiding function, particularly that on long-term follow-up, in SNBG appeared to be more favorable than that in INBG.     

Progressive disseminated histoplasmosis in an immunocompetent patient as an underrecognized imported mycosis in Japan

Histoplasmosis caused by Histoplasma capsulatum is found worldwide. Japan is known to be non-endemic area. Progressive disseminated histoplasmosis (PDH) is a severe form of histoplasmosis. We report a case of PDH in a 54-year-old male who was not immunocompromised. His last travel history to an endemic region was 2 years before onset. He was diagnosed as histoplasmosis by 18S rRNA-PCR from serum and ascites and immunodiffusion test. We treated him with parental liposomal amphotericin B for 2 weeks then changed to oral itraconazole, which was continued for 6 months. Rigorous work up, including HIV status, lymphocyte counts, and adrenal function did not reveal any evidence of immunosuppression of the patient. Our case suggests that PDH can occur in immunocompetent patients as previously described, and must be included in the differential diagnoses if presentation is consistent. In addition, the skills of travel history taking are emphasized.     

Relationship between tumor volume and quantitative values calculated using two-dimensional bone scan images

The bone scan index (BSI) is calculated from a whole-body bone scan image; it shows the tumor burden in bone as a percentage of total skeletal mass. It has been used to determine the prognosis and to assess treatment effects; however, little has been reported on whether the BSI calculated using a two-dimensional image can accurately evaluate the three-dimensional spread in tumor volume. We investigated the relationship between tumor volume and BSI using Monte Carlo simulation (MCS). We simulated a gamma camera and constructed a voxel phantom based on an anthropomorphic phantom computed tomography (CT) image and gamma rays emitted from each part according to technetium-99m-labeled methylene diphosphonate (^99mTc-MDP) uptake (bone 1, soft tissue 0.2, tumor 2–32). We constructed bone scan images from the obtained counts and analyzed them using the BSI calculation software. The BSI increased with increased tumor uptake (two- to 32-fold). However, there was not always a significant difference between change in BSI and tumor uptake of eight times or greater than that of bone. When BSI was calculated with a tumor having an uptake of four-to-eight times higher than that of bone, the BSI was consistent with tumor volume, but decreased to about half the tumor volume when tumors were in the thoracic spine (Th-spine) segment. The BSI can be a good indicator of tumor volume in most segments, even though it is affected by the tumor’s ^99mTc-MDP uptake. Nevertheless, values calculated from the Th-spine should be interpreted carefully.     

Brief Questioning by Nursing Staffs before Endoscopic Examination May Not Always Pick Up Clinical Symptoms of Endoscopic Reflux Esophagitis

The clinical features of patients reflux esophagitis without any symptoms have not been clearly demonstrated. This study evaluated the clinical features of patients with endoscopy-positive reflux esophagitis, who did not complain of symptoms, as detected by brief questioning by nursing staffs. Eight thousand and thirty-one patients not taking medication for gastrointestinal disease, were briefly asked about the presence of heartburn, dysphagia, odynophagia and acid regurgitation by nursing staffs before endoscopy for assessment of esophagitis utilizing the Los Angeles Classification. Endoscopically, 1199 (14.9%) patients were classified as positive for reflux esophagitis. The endoscope positive subjects who complain heartburn were 539/1199 (45.0%).The endoscope positive subjects who do not complain symptoms were 465 in 1199 positive reflux esophagitis (38.8%). We compared endoscopic positive subjects without any complain by brief question by nursing staffs to endoscopic positive subjects with heartburn. Male gender, no obesity, absence of hiatus hernia, and low-grade esophagitis were associated with endoscopy-positive patients who do not complain of symptoms. The results of this study indicated correct detection of clinical symptoms of reflux esophagitis might be not easy with brief questioning by nursing staffs before endoscopic examination.