Skull Base Fracture or Abuse Suspicion Based on Intraorbital Lymphangioma Secondary to Periorbital Hematoma.

Intraorbital lymphangiomas are among the orbital tumors that can cause sudden eye protrusion in children. In children with periorbital hematoma (panda eye sign), a skull fracture or abuse is likely first considered as the differential diagnosis. A 7-month-old boy presented to the ophthalmologist with complaints of swelling of the right upper eyelid, subconjunctival hemorrhage on the right ear side, and periorbital subcutaneous hemorrhage, which had appeared since the morning of the day before the visit. The eyeball did not protrude. Based on the interview and clinical findings, right eyeball contusion was suspected. The patient was then followed up for observation. Later, during the physical examination, the abovementioned symptoms were noted. Hence, the patient was admitted for a close examination based on the suspicion of skull base fracture and abuse. Contrast-enhanced magnetic resonance imaging (MRI) after admission revealed a multifocal cystic structure within the right intraorbital muscular cone. Thus, he was diagnosed with right intraorbital lymphangioma. Intraorbital lymphangioma may not show ocular protrusion, and this disease should be considered in cases where abuse is suspected, considering the periorbital subcutaneous hemorrhage.

A Boy Presenting with a Fever and Pancytopenia Diagnosed with Systemic Lupus Erythematosus without a Positive Anti-ds-DNA Antibody Result or Hypocomplementemia: A Case Report.

BACKGROUND: Hematological involvement, including anemia, leukopenia, lymphopenia, and thrombocytopenia, is one of the most common manifestations of childhood-onset systemic lupus erythematosus (cSLE). Specifically, relatively severe forms of hematological involvement, such as macrophage activation syndrome (MAS) and thrombotic microangiopathy, occur in the course of the disease. Positivity for anti-double stranded-DNA (ds-DNA) antibody and hypocomplementemia are important as not only criteria of diagnosing cSLE but also in the determination of the disease activity. CASE REPORT: A 13-year-old boy without pre-existing disease was referred to our hospital chiefly complaining of a fever for > 7 days, long-lasting malaise, nausea, and non-malar face rash. His blood examination showed pancytopenia and hyperferritinemia, but positive results for anti-ds-DNA antibody and hypocomplementemia were not recognized. Bone marrow aspiration revealed no evidence of malignant diseases, hemophagocytic lymphohistiocytosis, or MAS. A renal biopsy for the differential diagnosis of proteinuria and hematuria revealed class IIIa +V lupus nephritis, leading to the diagnosis of cSLE. CONCLUSIONS: It is important for cSLE to be considered in patients with pancytopenia, even those without positive anti-ds-DNA antibody findings or hypocomplementemia, and for aggressive approaches to be adopted for the differential diagnosis, including a renal biopsy.

Associations of complementation group, ALDH2 genotype, and clonal abnormalities with hematological outcome in Japanese patients with Fanconi anemia.

Fanconi anemia (FA) is a genetically and clinically heterogeneous disorder that predisposes patients to bone marrow failure (BMF), myelodysplastic syndromes (MDS), and acute myeloid leukemia (AML). To study which genetic and phenotypic factors predict clinical outcomes for Japanese FA patients, we examined the FA genes, bone marrow karyotype, and aldehyde dehydrogenase-2 (ALDH2) genotype; variants of which are associated with accelerated progression of BMF in FA. In 88 patients, we found morphologic MDS/AML in 33 patients, including refractory cytopenia in 16, refractory anemia with excess blasts (RAEB) in 7, and AML in 10. The major mutated FA genes observed in this study were FANCA (n = 52) and FANCG (n = 23). The distribution of the ALDH2 variant alleles did not differ significantly between patients with mutations in FANCA and FANCG. However, patients with FANCG mutations had inferior BMF-free survival and received hematopoietic stem cell transplantation (HSCT) at a younger age than those with FANCA mutations. In FANCA, patients with the c.2546delC mutation (n = 24) related to poorer MDS/AML-free survival and a younger age at HSCT than those without this mutation. All patients with RAEB/AML had an abnormal karyotype and poorer prognosis after HSCT; specifically, the presence of a structurally complex karyotype with a monosomy (n = 6) was associated with dismal prognosis. In conclusion, the best practice for a clinician may be to integrate the morphological, cytogenetic, and genetic data to optimize HSCT timing in Japanese FA patients.

Hematopoietic stem cell transplantation for inborn errors of metabolism: A report from the Research Committee on Transplantation for Inborn Errors of Metabolism of the Japanese Ministry of Health, Labour and Welfare and the Working Group of the Japan Society for Hematopoietic Cell Transplantation.

A total of 216 patients with IEM were treated by allogeneic HSCT in Japan from 1985 until 2010. The results of UCBT have improved, and the OS rate of UCBT (81.9%) was not different from those of RBMT (87.2%) or UBMT (73.9%) in 2000-2010. However, EFS rates in RBMT (73.2%) and UBMT (62.2%) were better than that in UCBT (49.5%), and the difference between RBMT and UCBT was significant (p = 0.01). The EFS rate of patients conditioned by RIC (74.6%) was comparable or slightly better than in those who underwent MAC with irradiation (57.9%) or without irradiation (54.2%) in 2000-2010. A more pronounced trend was observed toward differential EFS for UCBT in 2000-2010: RIC (62.9%), MAC with irradiation (20.0%), and MAC without irradiation (42.1%). The difference between RIC and MAC with irradiation was significant (p < 0.03). In summary, we report a Japanese registry analysis of HSCT for IEM with improving survival in UCBT. The introduction of RIC after 2000 was considered to contribute to this improvement. UCBT could be recommended for those who lack an HLA-identical sibling donor.

Early diagnosis of asparaginase-associated pancreatitis based on elevated serum elastase-1 levels: Case reports.

L-asparaginase (L-asp) is a well-known anticancer agent used in the treatment of acute lymphoblastic leukemia (ALL) in children. However, it is also known to induce several acute complications, such as acute pancreatitis. This is a presentation of two pediatric acute lymphoblastic leukemia (ALL) cases of asparaginase-associated pancreatitis (AAP) diagnosed at an early stage based on elevated serum elastase-1 levels, in the presence of normal serum amylase levels. Early diagnosis and treatment of AAP, although imperative, is occasionally difficult if only standard diagnostic procedures are followed. Elastase-1 is a potentially useful marker for the early diagnosis of AAP. Therefore, the measurement of elastase-1 levels, in addition to amylase and lipase levels, is recommended in L-asp-treated patients.

Long-term efficacy of hematopoietic stem cell transplantation on brain involvement in patients with mucopolysaccharidosis type II: a nationwide survey in Japan.

Hematopoietic stem cell transplantation (HSCT) has not been indicated for patients with mucopolysaccharidosis II (MPS II, Hunter syndrome), while it is indicated for mucopolysaccharidosis I (MPS I) patients <2 years of age and an intelligence quotient (IQ) of ≥ 70. Even after the approval of enzyme replacement therapy for both of MPS I and II, HSCT is still indicated for patients with MPS I severe form (Hurler syndrome). To evaluate the efficacy and benefit of HSCT in MPS II patients, we carried out a nationwide retrospective study in Japan. Activities of daily living (ADL), IQ, brain magnetic resonance image (MRI) lesions, cardiac valvular regurgitation, and urinary glycosaminoglycan (GAG) were analyzed at baseline and at the most recent visit. We also performed a questionnaire analysis about ADL for an HSCT-treated cohort and an untreated cohort (natural history). Records of 21 patients were collected from eight hospitals. The follow-up period in the retrospective study was 9.6 ± 3.5 years. ADL was maintained around baseline levels. Cribriform changes and ventricular dilatation on brain MRI were improved in 9/17 and 4/17 patients, respectively. Stabilization of brain atrophy was shown in 11/17 patients. Cardiac valvular regurgitation was diminished in 20/63 valves. Urinary GAG concentration was remarkably lower in HSCT-treated patients than age-matched untreated patients. In the questionnaire analysis, speech deterioration was observed in 12/19 patients in the untreated cohort and 1/7 patient in HSCT-treated cohort. HSCT showed effectiveness towards brain or heart involvement, when performed before signs of brain atrophy or valvular regurgitation appear. We consider HSCT is worthwhile in early stages of the disease for patients with MPS II.

Matched sibling donor stem cell transplantation for Fanconi anemia patients with T-cell somatic mosaicism.

SCT from HLA-identical sibling donors is generally associated with an excellent survival in FA patients if performed prior to the development of MDS or leukemia. However, the optimal conditioning regimen has not been defined. We report here our experience with 15 Japanese FA patients who underwent HLA-matched sibling donor SCT. The aim of this study is to compare radiation-based conditioning to Flu-based conditioning for FA patients in a Japanese population where the T-cell somatic mosaicism is higher than in the Caucasian population. Eight patients (a-group) received a radiation-based conditioning (500-600 cGy of thoracoabdominal/TBI) with CY dose modification (20-120 mg/kg), and ATG; two patients exhibited rejection. Seven patients (b-group) received CY (40 mg/kg), 150-180 mg/m(2) of Flu, and ATG. Durable engraftment was demonstrated in all patients. In FA patients, Flu-based conditioning may allow stable engraftment in matched sibling donor transplantation without radiation, even in patients with T-cell somatic mosaicism.

Decreased serum testosterone levels in long-term adult survivors with fatty liver after childhood stem cell transplantation.

Fatty liver and male gonadal dysfunction are potential late effects of therapy in adult survivors treated with stem cell transplantation (SCT) in childhood. Obesity and metabolic syndrome also are associated with low serum testosterone levels in the general population. However, the relationship between the degree of fatty liver and changes in serum testosterone levels in adult survivors has not been fully studied. We reviewed the clinical records of 34 male patients who received allogeneic SCT in childhood or adolescence. The median age at SCT was 10.0 years, and the median follow-up after SCT was 15.9 years. All but one patient showed no tendency toward overweight/obesity during the follow-up period. Fatty liver was diagnosed by ultrasound in 15 patients at 4 to 20 years after SCT. Patients who received cranial radiation therapy before SCT were more likely to develop fatty liver and insulin resistance. Moreover, fatty liver was statistically associated with decreased serum testosterone levels, whereas nonfatty liver was not (median, 527 ng/dL [range, 168-944 ng/dL] versus 302 ng/dL [165-698 ng/dL]; P < .0001). Changes in testosterone levels after SCT are affected not only by primary gonadal dysfunction but also by subsequent development or exacerbation of fatty liver.

High incidence of radiation-induced cavernous hemangioma in long-term survivors who underwent hematopoietic stem cell transplantation with radiation therapy during childhood or adolescence.

Radiation-induced cavernous hemangioma (RICH) is a late complication of cerebral radiation therapy. Long-term survivors of hematopoietic stem cell transplantation (HSCT) who underwent radiation therapy could be at increased risk for RICH. We investigated records of 68 patients who underwent HSCT during childhood or adolescence and were assessed by magnetic resonance imaging (MRI), including T2*-weighted imaging of the brain, annually for 5 years over a range of 6 to 29 years after HSCT. We developed a scoring and grading system for RICH to monitor the process and the progress of radiologic changes. Among the 68 patients investigated, 28 (41.2%) were diagnosed with CH. All 28 patients had received total body irradiation as a conditioning treatment for HSCT and/or cranial radiation therapy before HSCT as part of the treatment of their primary disease. RICH was diagnosed in none of the patients who did not receive radiation (n = 19), in 46.2% of those who received 6 to 12 Gy (n = 39), and in all of those who received 18 to 36 Gy (n = 10). Total RICH scores were correlated with higher radiation doses. Careful and long-term evaluation with MRI, including T2*-weighted imaging, is necessary for HSCT recipients who received radiation therapy before and/or during HSCT.

Cryosurgical left-sided maze procedure in patients with valvular heart disease: medium-term results.

PURPOSE: We evaluated medium-term results of the left-sided maze procedure using cryoablation in patients with valvular heart disease. METHODS: We retrospectively evaluated 111 patients with valvular heart disease who underwent the cryosurgical left-sided maze procedure. The mean follow-up period was 36.8 ± 24.9 months, and the mean duration of atrial fibrillation was 5.6 ± 6.0 years. The primary surgical procedure was mitral valve replacement in 42 patients, mitral valve plasty in 28, aortic valve replacement in 25, and combined aortic and mitral replacement or plasty in 16. RESULTS: The 7-year actuarial survival rate was 82.9 ± 11.4% for patients in sinus rhythm and 87.0 ± 7.0% for patients with atrial fibrillation, showing no difference between the two groups (p = 0.236). At final follow-up, 86 out of 111 patients (77.5%) remained free from atrial fibrillation. Sinus rhythm was maintained in 26 of 42 patients (61.9%) in the mitral valve replacement group, 26 of 28 patients (92.9%) in the mitral valve plasty group, 15 of 17 patients (88.2%) in the aortic valve replacement group, and 18 of 24 patients (75.0%) in the combined aortic and mitral replacement or plasty group. The overall actuarial rate of freedom from atrial fibrillation at 5 years after surgery was 70.4 ± 6.0%. CONCLUSION: The cryosurgical left-sided maze procedure is a safe, simple, and excellent operation for medically refractory atrial fibrillation.

Electron beam cine CT-based evaluation of left atrial function after the maze procedure for mitral valve regurgitation.

OBJECTIVE: There has been little investigation of whether atrial function is equally restored by surgery in patients with mitral regurgitation (MR) and atrial fibrillation (AF) compared to patients in sinus rhythm (SR). PATIENTS AND METHODS: We evaluated left atrium (LA) volume-time curves obtained from electron beam tomography. The study involved 33 patients who had surgical treatment for MR with or without AF and 11 control patients. RESULTS: (1) In patients with SR, LA volume decreased significantly along with a resolution of early regurgitation postoperatively, and the reserve function was well maintained. The LA booster pump function was also well maintained before and after surgery. (2) In patients with AF that resolved after maze surgery, the LA volume was larger than that of the sinus group immediately after surgery, and it did not improve in postoperative periods. These patients had a lower reserve function and a much lower booster pump function despite restoration of SR. CONCLUSIONS: The maze procedure is suggested to be unlikely to achieve restoration of atrial function in patients with MR accompanied by AF, even if SR returns postoperatively. Because patients with SR demonstrated the same LA function as the control postoperatively, surgical indication should be considered for patients with severe MR while their atrial function and SR are maintained.

Prevalence and avoidance of patient-prosthesis mismatch in aortic valve replacement in small adults.

BACKGROUND: It is still controversial as to whether a small prosthesis should be inserted or a small aortic annulus should be enlarged to minimize patient-prosthesis mismatch (PPM). This retrospective study reviewed our strategy for avoiding PPM. METHODS: Isolated or combined aortic valve replacement was performed in 181 patients, including 24 patients (13.3%) aged less than 65 years with a small aortic annulus (< or = 21 mm) who underwent enlargement of the annulus by the Manouguian (n = 18) or Nicks (n = 6) procedure. In patients aged 65 years or more, a Carpentier-Edwards Perimount pericardial (CEP) valve was implanted with few exceptions. We assessed our strategy for avoiding PPM by comparison with published normal reference values for the indexed effective orifice area. RESULTS: A CEP valve was implanted in 53 patients, and St. Jude Medical (SJM) mechanical valves were used in 128 patients. A standard 21-mm SJM valve was only used in 4 patients and no 19-mm valves were employed. However, 19-mm CEP valves were used in 12 older patients with a small body surface area (1.43 +/- 0.14 m2). No patient receiving an SJM valve had an indexed effective orifice area of 0.85 cm2/m2 or less, and PPM developed in only 2 (3.8%) of 53 patients receiving CEP valves. Consequently, the prevalence of PPM was 1.1%. The 10-year survival rates of patients receiving CEP or SJM valves with or without annular enlargement were similar. CONCLUSIONS: The prevalence of PPM was low in patients more than 65 years old with a relatively small body size who received bioprosthetic valves. In patients less than 65 years old with a small annulus, the method of first choice for avoiding PPM is aortic annular enlargement.

A technique for the prevention of hoarseness during surgery for distal aortic arch aneurysm.

Hoarseness occurs frequently after surgery to repair distal aortic arch aneurysms when using only a median sternotomy approach. We describe a useful technique which protects the left recurrent laryngeal nerve during this procedure and reduces the incidence of postoperative hoarseness.