Sirolimus treatment for intractable lymphatic anomalies: an open-label, single-arm, multicenter, prospective trial.

Introduction: Intractable lymphatic anomalies (LAs) include cystic lymphatic malformation (LM; macrocystic, microcystic, or mixed), generalized lymphatic anomaly, and Gorham-Stout disease. LAs can present with severe symptoms and poor prognosis. Thus, prospective studies for treatments are warranted. We conducted a prospective clinical trial of sirolimus for intractable LAs. Methods: This was an open-label, single-arm, multicenter, prospective trial involving five institutions in Japan. All patients with LAs received oral sirolimus once daily, and the dose was adjusted to ensure that the trough concentration remained within 5-15 ng/mL. We prospectively assessed the drug response (response rate for radiological volumetric change in target lesion), performance state, change in respiratory function, visceral impairment (pleural effusion, ascites, bleeding, pain), laboratory examination data, quality of life (QOL), and safety at 12, 24, and 52 weeks of administration. Results: Eleven patients with LAs (9 generalized lymphatic anomaly, 1 cystic LM, 1 Gorham-Stout disease) were treated with sirolimus, of whom 6 (54.5%; 95% confidence interval: 23.4-83.3%) demonstrated a partial response on radiological examination at 52 weeks of administration. No patients achieved a complete response. At 12 and 24 weeks of administration, 8 patients (72.7%) already showed a partial response. However, patients with stable disease showed minor or no reduction after 12 weeks. Adverse events, such as stomatitis, acneiform dermatitis, diarrhea, and fever, were common with sirolimus. Sirolimus was safe and tolerable. Conclusion: Sirolimus can reduce the lymphatic tissue volume in LAs and may lead to improvements in clinical symptoms and QOL.

Surgical outcome and prognosis of pediatric solid-pseudopapillary neoplasm.

BACKGROUND: The aim of this study was to clarify the characteristics and outcomes of pediatric patients with solid pseudopapillary neoplasms (SPNs) who underwent pancreatectomy. METHODS: Pediatric patients with SPNs who underwent pancreatectomy at our institution between 1995 and 2020 were included in the study. RESULTS: During the period under review, 12 patients underwent pancreatectomy for SPNs (median age: 10 years; range: 6-15 years). The surgical procedures included pancreatoduodenectomy (n = 2; 16.6%), distal pancreatectomy (n = 3; 25%), and enucleation (n = 7; 58.3%). The most common postoperative complication was postoperative pancreatic fistula (n = 6; 50%). Patients who underwent enucleation tended to have higher postoperative complication rates compared with those who underwent other procedures. All patients were alive without recurrence at the end of the study period. CONCLUSIONS: SPN is associated with a good prognosis, regardless of the surgical procedure. If surgeons select enucleation for pediatric SPNs, they should bear in mind that it is associated with a higher complication rate.

Effects of changes in skeletal muscle mass on the prognosis of pediatric malignant solid tumors.

PURPOSE: This study aims to clarify the relationship between changes in skeletal muscle mass during treatment and prognosis of pediatric malignant solid tumors. METHODS: Patients with pediatric malignant solid tumors who were treated at Kyushu University Hospital from 2007 to 2017 were divided into two groups: the progression-free survival (PFS) group and the relapse/death (R/D) group; the psoas major muscle volume (PMV) was then compared. We also measured the PMV and psoas muscle area (PMA) of pediatric patients with no complications who underwent surgery for acute appendicitis (control) and compared the values with those of patients with malignant tumors. RESULTS: No significant differences were observed in the PMV and PMA between patients with appendicitis and those with malignant tumors. Significant differences were found in the rate of change in PMV between the PFS (1.424) and R/D groups (1.071) (P = 0.0024). When the cut-off value of the rate of change in the PMV was 1.20, patients whose rate of change in PMV was ≥ 1.20 had longer PFS (P = 0.0231) and overall survival (P = 0.0229) than those whose rate of change was < 1.20. CONCLUSION: Pediatric patients with malignant solid tumors and increased skeletal muscle mass during treatment have a good prognosis.

Feasibility of Real-Time Central Surgical Review for Patients with Advanced-Stage Hepatoblastoma in the JPLT3 Trial.

In the JPLT3 study, a real-time central surgical reviewing (CSR) system was employed aimed at facilitating early referral of candidates for liver transplantation (LTx) to centers with pediatric LTx services. The expected consequence was surgery, including LTx, conducted at the appropriate time in all cases. This study aimed to review the effect of CSR on institutional surgical decisions in cases enrolled in the JPLT3 study. Real-time CSR was performed in cases in which complex surgeries were expected, using images obtained after two courses of preoperative chemotherapy. Using the cloud-based remote image viewing system, an expert panel consisting of pediatric and transplant surgeons reviewed the images and commented on the expected surgical strategy or the necessity of transferring the patient to a transplant unit. The results were summarized and reported to the treating institutions. A total of 41 reviews were conducted for 35 patients, and 16 cases were evaluated as possible candidates for LTx, with the treating institutions being advised to consult a transplant center. Most of the reviewed cases promptly underwent definitive liver surgeries, including LTx per protocol.

Laparoscopic approach for abdominal neuroblastoma in Japan: results from nationwide multicenter survey.

BACKGROUND: Some neuroblastoma (NB) cases are suitable for minimally invasive surgery (MIS), but indication and technical issue are unclear. We assessed the current status of MIS for abdominal NB after mass screening period in Japan. METHODS: Preliminary questionnaires requesting the numbers of NB cases that underwent MIS from 2004 to 2016 were sent to 159 Japanese institutes of pediatric surgery. The secondary questionnaires were then sent to the institutions that reported MIS cases of NB in order to collect detailed data. RESULTS: One hundred and thirty-four (84.2%) institutions responded to the preliminary questionnaires, and 83 (52.2%) reported managing operative cases. The total number of operative cases was 1496. MIS was performed for 175 (11.6%) cases, of which the completed forms of 140 patients were returned, including 100 abdominal NB cases. The male/female ratio was 51/49. Forty-seven cases underwent a laparoscopic biopsy, and 2 (4.3%) cases were converted to laparotomy due to bleeding. Sixty-five cases underwent MIS for radical resection, and 7 (10.8%) were converted to laparotomy. The reasons for open conversion were bleeding and severe adhesion. Regarding open conversion, there were no significant relationships between conversion and neo-adjuvant chemotherapy, biopsies, stage, size, or MYCN amplification. We found no relationship between resectability and vascular encasement in this study. There was relationship between the resected tumor size and the patients' height, which was expressed using the following formula: [Formula: see text] (x, patients height, y, tumor size; p = 0.004219, SE: 1.55566). Postoperative complications after radical resection were recognized in 7 (10.8%) cases. CONCLUSIONS: MIS was performed in limited cases of abdominal NB. A laparoscopic biopsy with careful attention to bleeding is feasible. The resected tumor size was shown to correlate with the patients' height. Tumor size within 6 cm of maximum diameter can be resected safely.

Endoscopic Surgical Approach for Pediatric Solid Tumors That Permits Complete Curability and Exhibits Cosmetic Advantages.

Background: We actively use novel endoscopic surgical approaches with complete curability and good cosmetic outcomes to facilitate the removal of resected tumors from the body via a small incision. Patients and Methods: This retrospective study reviewed the medical records of patients who underwent endoscopic surgery for treating solid tumors in the abdominal, thoracic, and urogenital regions between April 2013 and March 2020. Results: At our institution, minimally invasive surgery (MIS) is performed for malignant tumors with a maximum diameter of ≤5 cm and nonmalignant tumors without diameter restrictions, although both need to have no vascular encasement. In total, 135 pediatric solid tumor resections were performed at our institution during the aforementioned period, among whom 37 patients satisfied the MIS criteria. Among them, 28 patients underwent endoscopic surgeries, whereas 9 underwent open surgeries. The median surgical durations were 192 and 138 minutes in the MIS and open groups, respectively (P = .096). The median volume of blood loss was 1 and 8 mL in the MIS and open groups, respectively (P = .086). The median lengths of hospital stay were 8 and 7 days in the MIS and open groups, respectively (P = .178). One patient in each group had Clavien-Dindo grade ≥Ⅲ complications. However, there was no surgery-related death. All patients receiving MIS had satisfactory operative scarring, early recovery, and good cosmetic outcomes. Conclusion: MIS can be used for pediatric solid tumors, considering the patient's quality of life while allowing complete curability and providing endoscopic surgical advantages.

Successful management of Wilms tumor accompanied by traumatic renal injury: a case report.

When a tumor and trauma coexist, the treatment strategy must be established while considering their interaction. We herein report a 5-month-old girl with Wilms tumor complicated by blunt renal trauma. She was involved in a traffic accident and had hemorrhagic shock due to renal bleeding. We performed hemostasis by transcatheter arterial embolization. Ten days later, we extirpated the potential malignant tumor and left kidney. We were able to complete the surgery without rupture or major bleeding. Postoperative histopathology confirmed Wilms tumor. In the year since she received postoperative chemotherapy, there has been no recurrence. When we were deciding the treatment strategy, we first had to determine how much the renal trauma had affected the tumor staging. The second issue was when to extirpate the tumor after managing the trauma. There are no standard criteria for such situations at present, so we referred to the criteria concerning the bed rest period in cases of traumatic kidney injury and previous case reports and decided to wait over a week from the injury treatment to perform surgery. As a result, we were able to remove the tumor completely without any rupture or major bleeding.

Current thoracoscopic approach for mediastinal neuroblastoma in Japan-results from nationwide multicenter survey.

BACKGROUND: Minimally invasive surgery (MIS) is appropriate for the treatment of some neuroblastomas (NBs); however, the indications and technical issues are unclear. This study aimed to clarify the current status of MIS for mediastinal NB in Japan. METHODS: Preliminary questionnaires requesting the numbers of neuroblastoma cases in which MIS was performed from 2004 to 2016 were sent to 159 Japanese institutes of pediatric surgery. Secondary questionnaires were sent to institutions with MIS cases to collect detailed data. RESULTS: One hundred thirty-four (84.2%) institutions returned the preliminary questionnaire and 83 institutions (52.2%) reported a total of 1496 operative cases. MIS was performed for 175 (11.6%) cases. Among the 175 cases, completed forms of 140 patients were returned and 40 (male, n = 28; female, n = 12) cases had mediastinal NB. Fourteen patients received thoracoscopic biopsy, none were converted to thoracotomy. Twenty-eight patients received MIS for radical resection, none were converted to thoracotomy. Perioperative complications (Horner's syndrome) were recognized after radical resection in one (2.5%) case. CONCLUSIONS: MIS was performed in a limited number of mediastinal NB cases. A thoracoscopic approach would be feasible for mediastinal NB.

Frequent breakpoints of focal deletion and uniparental disomy in 22q11.1 or 11.2 segmental duplication region reveal distinct tumorigenesis in rhabdoid tumor of the kidney.

SMARCB1 is mutated in most rhabdoid tumors (RTs) developing in the kidney (RTK) and various other organs. Focal deletions found in patients with 22q11.2 deletion syndrome show breakpoints within clusters of segmental duplications (SDs), and those in some RTs show breakpoints in the 22q11-q12 region. SDs are known to cause focal deletion mediated by non-allelic homologous recombination. The present study identified SMARCB1 alterations in all 30 RTKs, using SNP array CGH, MLPA, and sequence analyses. Twenty-eight tumors had a total of 51 breakpoints forming focal 22q deletion and/or uniparental disomy (22qUPD), and the other two had compound mutation with no breakpoints in 22q. Twenty-four (47.1%) of the 51 breakpoints were within SDs, and occurred in 16 (53.3%) of the 30 tumors. The association of breakpoints with SDs was found not only in focal deletion, but also in 22qUPD, indicating that SDs mediate the first and second hits (focal deletion) and the second hit (22qUPD) of SMARCB1 alteration. Of the 51 breakpoints, 14 were recurrent, and 10 of the 14 were within SDs, suggesting the presence of hotspots in the 22q11.2 region. One recurrent breakpoint outside SDs resided in SMARCB1, suggesting inactivation of the gene by out-of-frame fusion. The association between SDs and focal deletion has been reported in two other types of cancer. RTKs may be the third example of SD-associated tumors. Thus, the present study indicated that RTKs exploit genomic instability in the 22q11.1-11.2 SDs region, and 22qUPD caused by mitotic recombination may also be mediated by SDs.

Integrated multiomics analysis of hepatoblastoma unravels its heterogeneity and provides novel druggable targets.

Although hepatoblastoma is the most common pediatric liver cancer, its genetic heterogeneity and therapeutic targets are not well elucidated. Therefore, we conducted a multiomics analysis, including mutatome, DNA methylome, and transcriptome analyses, of 59 hepatoblastoma samples. Based on DNA methylation patterns, hepatoblastoma was classified into three clusters exhibiting remarkable correlation with clinical, histological, and genetic features. Cluster F was largely composed of cases with fetal histology and good outcomes, whereas clusters E1 and E2 corresponded primarily to embryonal/combined histology and poor outcomes. E1 and E2, albeit distinguishable by different patient age distributions, were genetically characterized by hypermethylation of the HNF4A/CEBPA-binding regions, fetal liver-like expression patterns, upregulation of the cell cycle pathway, and overexpression of NQO1 and ODC1. Inhibition of NQO1 and ODC1 in hepatoblastoma cells induced chemosensitization and growth suppression, respectively. Our results provide a comprehensive description of the molecular basis of hepatoblastoma and rational therapeutic strategies for high-risk cases.

Which Is the Better Approach for Late-Presenting Congenital Diaphragmatic Hernia: Laparoscopic or Thoracoscopic? A Single Institution's Experience of more than 10 Years.

Aim: We evaluated a series of late-presenting congenital diaphragmatic hernia (Late-CDH) cases and assessed the reliability and risks of laparoscopic and thoracoscopic approaches for Late-CDH at a single institution. Materials and Methods: From 2005 to 2017, we experienced totally 11 patients with Late-CDH who received endoscopic repairs. We retrospectively surveyed the approach, defect size, operating time, and postoperative outcomes, including recurrence. Results: Eleven patients (Bochdalek, n = 10; Morgagni, n = 1) underwent a total of 14 endoscopic repairs (laparoscopy, n = 10; thoracoscopy, n = 4). The average defect size was ∼3.1 × 1.5 cm. In all 14 endoscopic repairs, patients received intracorporeal interrupted nonabsorbable stitches and extracorporeal knot tying were applied, without the use of an artificial patch. In the laparoscopic repairs, 7 patients received left-handed suturing when closing the diaphragmatic defect, because the reduced viscera lay directly below the posterior rim of the diaphragmatic defect, making it difficult to confirm the rim. In contrast, in the thoracoscopic repairs, the viscera were reduced over the diaphragmatic defect, so the surgeons could easily perform suturing. The average operating time was 172 minutes for laparoscopy and 194 minutes for thoracoscopy. No major intraoperative or postoperative complications occurred in association with either of the approaches. Among the 11 patients, 2 experienced a total of 3 recurrences (all after laparoscopic repairs). Conclusion: Although there were few differences between the laparoscopic and thoracoscopic approaches, because of the technical difficulty of the procedure and the possibility of recurrence with the laparoscopic approach, a thoracoscopic approach may be better for the repair of Late-CDH.

Immunologic Effects of Sirolimus in Patients With Vascular Anomalies.

Emerging data have suggested that sirolimus may be a treatment option for complicated vascular anomalies (VAs). The present study aimed to investigate the immunologic effects of sirolimus treatment for 6 months in patients with VAs. Blood samples obtained from the patients enrolled in 2 multicenter studies to investigate the efficacy of sirolimus for VAs before and after sirolimus treatment for 6 months were used. Data for total white blood cell count, absolute lymphocyte count, serum immunoglobulins (Igs) levels (IgG, IgA, IgM), lymphocyte proliferation assays with mitogens including phytohemagglutinin and concanavalin A, and flow cytometric analysis of lymphocyte subsets were evaluated. A total of 18 patients with VAs receiving sirolimus treatment were included in the study. Comparisons of white blood cell, absolute lymphocyte count, IgG, IgA, IgM, and reaction rates of phytohemagglutinin and concanavalin A revealed no significant differences before and after treatment. No significant differences were observed in the absolute counts of lymphocyte subtypes before and after treatment, except for regulatory T-cell counts, which were significantly decreased after treatment. Severe infections were not observed during sirolimus treatment. The immunologic parameters assessed in the present study were hardly affected by sirolimus treatment for 6 months in patients with VAs.

Factors responsible for stage III disease in patients with Wilms tumor enrolled in the JWiTS-2 study.

BACKGROUND/OBJECTIVES: Treatment is more intensive for stage III Wilms tumor (WT) than for stages I and II non-metastatic WTs. Various factors including tumor spillage, unresectability, and lymph node metastasis are responsible for stage III disease. The present study aimed to not identify clinical factors associated with the features of stage III WT to establish new treatment strategies. DESIGN/METHODS: Of 166 patients with non-metastatic WT enrolled in the Japan Wilms Tumor Study (JWiTS)-2, 51 patients had stage III disease. The treatment protocol for JWiTS-2 was essentially the same as that in the National Wilms Tumor study (NWTS)-5. Local hospitals were surveyed to collect details of clinical findings related to stage III disease, and data regarding 45 (88%) patients were obtained. RESULTS: Nine patients with massive tumors underwent preoperative chemotherapy. Biopsy was performed in 6. Reduction in the tumor size was achieved in 8 of the 9 cases. Nephrectomy was finally performed in all of them. Thirty-six patients underwent primary nephrectomy. The reason for the stage III disease was lymph node metastasis (n = 9, 25%), tumor spillage (n = 20, 56%), and tumor extension/incomplete resection (n = 17, 47%). Some patients had more than one of these factors. Most patients were treated with the DD-4A regimen, and 43 (95.6%) of the 45 patients received abdominal radiation therapy. Tumors recurred in three patients (local, 1; metastasis, 2), and two patients died. Overall and relapse-free survival rates were 95.2% and 90.8%, respectively. CONCLUSION: The prognosis of stage III WT was good. In the next stage, the doses of chemotherapy and radiotherapy should be reduced to avoid late effects. The high rate of tumor spillage after primary resection suggests that preoperative chemotherapy should be started instead of aggressive tumor resection in the large tumor cases with surgical risks.

Continuous Skill Training Using the Disease-Specific Endoscopic Surgical Simulator to Promote Young Pediatric Surgeons: Learning Curve for Trainees.

Purpose: This study aimed to evaluate the learning effects of continuous training with a disease-specific endoscopic surgical simulator for young pediatric surgeons. Materials and Methods: Participants trained with a laparoscopic fundoplication simulator for 1 hour every 10 days. At the start of each training session, we assessed the participant's surgical technique using the surgical skill evaluation system, which evaluates the following items: (1) task time, (2) right-left balance of suturing, (3) suture spacing between the three ligatures, (4) total path length traveled by forceps, (5) velocity of the forceps tips, (6) length of the wrap, (7) number of ligature failures, and (8) comparison of improvements according to assessment point. We examined the learning effects of this continuous training program. Results: Task time, right-left balance of suturing, and sum of the distance traveled by each forceps showed significant progressive improvements (P < .05). Suture spacing and average velocity of forceps tips did not change significantly with training (P = .5781, P = .0781, respectively). However, the ratio of traveled distance between left and right forceps significantly improved (P < .05). There was a significant trend for the wrap length to approach the target value (P < .05). According to the linear mixed-effects model, the number of training sessions required for learning was not uniform and varied depending on the skill. Conclusion: This simulator training program can help pediatric surgeons to acquire surgical skills easily, economically, and safely. In the future, we need to evaluate how surgical skills acquired during this continuous training are reflected in clinical operations.

Japanese clinical practice guidelines for sacrococcygeal teratoma, 2017.

BACKGROUND: Sacrococcygeal teratoma (SCT) is the most common extragonadal germ cell tumor in neonates and infants. Although most cases of infantile SCT are benign tumors by nature, some develop into extremely large lesions, leading to massive bleeding, high-output heart failure, disseminated intravascular coagulation, and even fatal outcomes during the neonatal period. In addition, some patients may present with tumor recurrence, malignant transformation, long-term sequelae (including bladder and bowel dysfunction) and lower leg palsy during the long-term follow up. SCT, however, is very rare, and there are few opportunities to encounter this disease, therefore general physicians without expert credentials currently lack information relevant to clinical practice. For this reason, the research project committee has compiled guidelines concerning SCT. METHODS: The purpose of these guidelines was to share information concerning the treatment and follow up of infantile SCT. The guidelines were developed using the methodologies in the Medical Information Network Distribution System. A comprehensive search of the English- and Japanese-language articles in PubMed and Ichu-Shi Web identified only case reports or case series, and the recommendations were developed through a process of informal consensus. RESULTS: The clinical questions addressed the risk factors, the efficacy of cesarean section, the initial devascularization of tumor feeding vessels, interventional radiology, recommended clinical studies for follow up and possible long-term complications. CONCLUSIONS: These are the first guidelines for SCT to be established in Japan, and they may have huge clinical value and significance in terms of developing therapeutic strategies and follow up, potentially contributing to the improvement of the prognosis and quality of life of SCT patients.

Efficacy and safety of sirolimus treatment for intractable lymphatic anomalies: A study protocol for an open-label, single-arm, multicenter, prospective study (SILA).

INTRODUCTION: Lymphatic anomalies (LAs) refer to a group of diseases involving systemic dysplasia of lymphatic vessels. These lesions are classified as cystic lymphatic malformation (macrocystic, microcystic or mixed), generalized lymphatic anomaly, and Gorham-Stout disease. LAs occur mainly in childhood, and present with various symptoms including chronic airway problems, recurrent infection, and organ disorders. Individuals with LAs often experience progressively worsening symptoms with a deteriorating quality of life. Although limited treatment options are available, their efficacy has not been validated in prospective clinical trials, and are usually based on case reports. Thus, there are no validated standards of care for these patients because of the lack of prospective clinical trials. METHODS: This open-label, single-arm, multicenter, prospective study will assess the efficacy and safety of a mammalian target of the rapamycin inhibitor sirolimus in the treatment of intractable LAs. Participants will receive oral sirolimus once a day for 52 weeks. The dose is adjusted so that the nadir concentration remains within 5-15 ng/ml. The primary endpoint is the response rate of radiological volumetric change of the target lesion confirmed by central review at 52 weeks after treatment. The secondary endpoints are the response rates at 12 and 24 weeks, respiratory function, pleural effusion, ascites, blood coagulation parameters, bleeding, pain, quality of life, activities of daily living, adverse events, side effects, laboratory examinations, vital signs, and pharmacokinetic data. RESULTS: This is among the first multicenter studies to evaluate sirolimus treatment for intractable LAs, and few studies to date have focused on the standard assessment of the efficacy for LAs treatment. Our protocol uses novel, uncomplicated methods for radiological assessment, with reference to the results of our previous retrospective survey and historical control data from the literature. CONCLUSIONS: We propose a multicenter study to investigate the efficacy and safety of sirolimus for intractable LAs (SILA study; trial registration UMIN000028905). Our results will provide pivotal data to support the approval of sirolimus for the treatment of intractable LAs.

Navigation surgery using indocyanine green fluorescent imaging for hepatoblastoma patients.

BACKGROUND: Technology for detecting liver tumors and identifying the bile ducts using indocyanine green (ICG) has recently been developed. However, the usefulness and limitations of ICG navigation surgery for hepatoblastoma (HB) have not been fully clarified. We herein report our experiences with surgical navigation using ICG for in HB patients. METHODS: In 5 HB patients, 10 ICG navigation surgeries were performed using a 10-mm infrared fluorescence imaging scope after the injection of 0.5 mg/kg ICG intravenously. The surgical and clinical features were collected retrospectively. RESULTS: Navigation surgery using ICG was performed for primary liver tumors in 4 cases, and the timing of ICG injection was 90.5 ± 33.7 h before the operation. All tumors exhibited intense fluorescence from the liver surface. ICG navigation for the primary liver tumor was useful for detecting the residual tumor at the stump and invasion to the diaphragm during surgery. Six lung surgeries using ICG navigation were performed. The timing of ICG injection was 21.8 ± 3.4 h before the operation. The size of the metastatic tumor was 7.4 ± 4.1 mm (1.2-15 mm). Of 11 metastatic tumors detected by computed tomography (CT), 10-including the smallest tumor (1.2 mm)-were able to be detected by ICG from the lung surface. The depth of the 10 ICG-positive tumors from the lung surface was 0.9 ± 1.9 mm (0-6 mm), and the depth of the single ICG-negative tumor was 12 mm. One lesion not detected by CT showed ICG false positivity. CONCLUSION: Navigation surgery using ICG for patients with HB was useful for identifying tumors and confirming complete resection. However, in ICG navigation surgery, we must be aware of the limitations with regard to the tumor size and the depth from the surface.

The Influence of Sarcopenia on High-Risk Neuroblastoma.

PURPOSE: Sarcopenia is a syndrome that is defined by the loss of skeletal muscle mass, quality, and strength. In adult patients with malignancies, the presence of sarcopenia is known to be correlated with a poor prognosis; however, there have been no reports on the influence of sarcopenia on malignant tumors in pediatric patients. In the present study, we investigated whether or not sarcopenia affects the prognosis of high-risk neuroblastoma. MATERIALS AND METHODS: Thirteen patients with high-risk neuroblastoma who were treated according to the standard protocol at our hospital from 2007 to 2016 were divided into a progression-free survival group (n = 8) and a relapse/death group (n = 5). The rate of change in sarcopenia was calculated by comparing the psoas muscle area (PMA) of the L3-level lumbar spine on computed tomography before and after treatment with the standard protocol. The rate of change in the PMA, Kaup index, and serum albumin level were compared. Furthermore, we determined the cutoff rate of change in the PMA and compared the overall and progression-free survival. RESULTS: The rates of change in the PMA were 1.24 and 0.84 in the progression-free survival and relapse/death groups, respectively (P = 0.0472). There were no significant differences in the rates of change in the Kaup index or the serum albumin level of the two groups. The patients whose rate of change in the PMA was >1.00 showed a prolonged overall (P = 0.0078) and progression-free survival (P = 0.006). CONCLUSIONS: A decrease in the skeletal muscle mass was suggested to be a significant prognostic factor for high-risk neuroblastoma.

HuC/D expression in small round cell tumors and neuroendocrine tumors: a useful tool for distinguishing neuroblastoma from childhood small round cell tumors.

The RNA-binding protein HuC/D displays a neuron-specific expression and is involved in neuronal differentiation and the maintenance of the nervous system. Here we investigated the diagnostic value of HuC/D in neuroblastomas. We evaluated 85 neuroblastic tumors: 81 neuroblastomas; 3 ganglioneuroblastomas, intermixed; 1 ganglioneuroma, maturing; and 101 other tumors consisting of 34 Ewing sarcomas, 14 nephroblastomas, 11 rhabdomyosarcomas, 15 pulmonary small cell carcinomas, 18 pancreatic neuroendocrine tumors, and 9 pheochromocytomas. Immunohistochemistry for HuC/D, PHOX2B, and tyrosine hydroxylase was performed. The immunoreactivity for HuC/D was semiquantified using the total score (TS; range, 0-8). HuC/D positivity was defined as a TS ≥6. The TS of the neuroblastic tumors (mean TS, 7.94) was significantly higher than those of the other small round cell tumors and neuroendocrine tumors (P < .001) except for the pheochromocytomas (mean TS, 6.89; P = .074). HuC/D was positive in all 85 neuroblastic tumors, 1 (2.9%) Ewing sarcoma, 1 (6.7%) pulmonary small cell carcinoma, and 8 (89%) pheochromocytomas. PHOX2B was positive in all of the neuroblastic tumors and pheochromocytomas. Tyrosine hydroxylase was positive in 80 (94%) neuroblastic tumors, 1 (9.1%) rhabdomyosarcoma, and all of the pheochromocytomas. Therefore, HuC/D serves as a highly sensitive diagnostic marker to distinguish neuroblastomas from other small round cell tumors. The combination of HuC/D and PHOX2B staining may be valuable for the diagnosis of neuroblastic tumors, especially in the assessment of small sections. HuC/D expression in tumors may be related to catecholamine production or a neural crest-derived cell origin.

[Survey of Anticancer Drug Exposure to Attendant Families in Pediatric Medical Centers].

The occupational exposure to hazardous drugs(HD)has already been investigated; however, the actual exposure of the attendant family members of patients with childhood cancer has remained unknown. Here, we analyzed cyclophosphamide (CPM)exposure in attendant family members and the environment after the administration of CPM to patients with pediatric cancer. CPM of 320(8.39-1,510)ng from infant-families and 0(0-58.4)ng from adolescent-families were detected(p= 0.01). The exposure of infant-families was significantly greater than those of adolescent-families. In addition, CPM were detected in the hot water after bathing the infant, underwear, and sheets. We elucidated that the exposures take place through body fluid and excretions of the children. In the field of childhood cancer, HD exposure measures should be taken according to the age of the child to minimize health damage to medical personnel, family members, and other children who share the room. Nurses are recommended to educate the patients and their family members about preventing exposure to HD in pediatric medical centers.