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.

COVID19 detection in appendix of acute appendicitis in a child: a case report and review of literature.

BACKGROUND: Gastrointestinal symptoms are one of the most common presentations of Coronavirus disease-19 (COVID-19), even in children. Higher rates of complicated appendicitis have been demonstrated in the era of the COVID-19 outbreak, and it has been recently suggested that acute appendicitis may occur as a complication of COVID-19. However, the relationship between appendicitis and COVID-19 remains unclear. CASE PRESENTATION: A 7-year-old male presented to the pediatric emergency department with 2 days' history of lower abdominal discomfort and tenderness. On examination, his abdomen was distended with diffuse mild tenderness at the lower abdomen, which was aggravated by movement. He was also tested and was found to be positive for SARS-CoV-2. Computed tomography showed perforated appendicitis with a fecalith. The patient was admitted and laparoscopic appendectomy was successfully performed. Postoperatively, a minor intra-abdominal abscess was present, which successfully treated with antibiotics. Histopathology showed a markedly inflamed appendix with mucosal ulceration and transmural neutrophilic inflammation, which was consistent with phlegmonous appendicitis. Reverse transcription quantitative polymerase chain reaction using a surgically extracted appendix specimen revealed the presence of SARS-CoV-2 virus, which indicated a pathophysiological relationship between appendicitis and COVID-19. CONCLUSION: The present case will provide further understanding of pediatric patients with concomitant COVID-19 and acute appendicitis.

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.

The utility of core-needle tumor biopsy for pediatric patients.

BACKGROUND: Core-needle biopsy (CNB) is used less frequently for the diagnosis of tumors in pediatric patients. In this report, the utility and safety of CNB for pediatric patients are described. METHODS: The medical records of patients who underwent CNB at the Department of Pediatric Surgery, Kyushu University Hospital from April 2020 to November 2021 were retrospectively reviewed. A 14 G or 16 G BARDMISSION Disposable Needle Instrument was used. For the diagnosis of neuroblastoma, a 14 G needle was selected; for the diagnosis of other tumors a 16 G needle was selected. RESULTS: During the above period 17 CNBs were performed in 17 patients, and the median patient age was 8 years (range, 15 days-19 years). The pathological diagnoses of the tumors were as follows: neuroblastoma, n = 6; lymphoma, n = 3; hepatoblastoma, n = 2; and others, n = 6. The quantity and quality of all tumor samples obtained by CNB was sufficient to make a diagnosis. The postoperative course after CNB was uneventful in most cases, with the exception of one case of hepatoblastoma (pseudoaneurysm). CONCLUSIONS: Core-needle biopsy is useful for pediatric patients. Sufficient tumor specimens were able to be obtained in all cases, irrespective of the type of tumor, and an accurate diagnosis could be made.

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.

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.

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.

Clinicopathological Significance and Antitumor Effect of MPHOSPH1 in Testicular Germ Cell Tumor.

MPHOSPH1, which is one of the kinesin superfamily proteins, has been reported to play an essential role in the carcinogenesis and progression of several kinds of cancers. MPHOSPH1 has also been suggested to be involved in STAT3 phosphorylation in hepatocellular carcinoma. However, the biological behavior of MPHOSPH1 in testicular germ cell tumors (TGCTs) is unclear at present. The purposes of this study were to investigate the correlation between the expression of MPHOSPH1 and clinicopathological factors and to examine the efficacy of MPHOSPH1 target therapy in TGCTs. We investigated 75 formalin-fixed paraffin-embedded TGCT samples, containing a total of 86 germ cell tumor components, by immunohistochemistry and 12 frozen samples by Western blotting. Moreover, we carried out in vitro studies to clarify the antitumor effect of MPHOSPH1 knockdown in embryonal carcinoma cell lines, NEC8 and NEC14, using small interference RNA (siRNA). A significantly high expression of MPHOSPH1 was recognized in embryonal carcinoma and yolk sac tumor components compared to the seminoma component (p<0.001, respectively). Clinically, non-seminoma cases are known to have worse prognosis than pure-seminoma cases. Interestingly, high MPHOSPH1 expression was associated with distant metastasis (p=0.001), and thus with advanced-stage disease in this study. High expression of MPHOSPH1 interacted with high expression of phosphorylated STAT3 (p=0.01). The in vitro experiments demonstrated that MPHOSPH1 interruption by siRNA resulted in a significant reduction of cell migration, invasion, proliferation and colony formation in both embryonal carcinoma cell lines (p<0.001, respectively). In conclusion, MPHOSPH1 may be a potential treatment option for TGCTs, and its expression may be a novel biomarker of poor prognosis.

The Utility of Muscle-Sparing Axillar Skin Crease Incision with Thoracoscopic Surgery in Children.

BACKGROUND: Thoracoscopic surgery for pediatric benign tumors is a common procedure. However, a large incision is needed to remove large tumors from the thoracic cavity. And, for intrapulmonary sequestration in lower lobe, it sometimes needs a large incision to ligate the aberrant vessels. A muscle-sparing axillar skin crease incision (MSASCI) has been introduced for thoracic open surgery, resulting in excellent aesthetic outcomes compared with a standard incision. We herein report the utility of this MSASCI technique in thoracoscopic surgery to remove large tumors from the thoracic cavity and to ligate the aberrant vessels in intrapulmonary sequestration in lower lobe. MATERIALS AND METHODS: From 2014 April to 2016 March, we performed the MSASCI technique in thoracoscopic surgeries for 5 children. RESULT: Five cases were diagnosed as mediastinal masses (mature teratoma for 1 case, ganglioneuroblastoma for 2 cases, and extrapulmonary sequestration and intrapulmonary sequestration for 1 case each). The age at surgery was 32.0 ± 25.0 months (range 5-58 months). The size of the mediastinal mass was 9 × 5 × 5 cm, 4 × 3 × 3 cm, 5 × 5 × 2.5 cm, and 3 × 2.5 × 2 cm. For 4 other cases, except for the intrapulmonary sequestration case, the mass was resected under thoracoscopic surgery using only three or four 5-mm trocars and the mass was removed from the thoracic cavity using the MSASCI technique. For the intrapulmonary sequestration case, the aberrant vessels were resected under thoracoscopic surgery using only two 5-mm and one 12-mm trocars and the left lower lobectomy was performed using the MSASCI technique. All lesions were resected completely. No cases had surgical complications, none showed recurrence, and all cases demonstrated good cosmetic outcomes. CONCLUSIONS: Performing thoracoscopic surgery using a MSASCI technique is associated with good cosmetic outcome.

Immunostaining for Hu C/D and CD56 is useful for a definitive histopathological diagnosis of congenital and acquired isolated hypoganglionosis.

Isolated hypoganglionosis (IHG) has been proposed as a distinct entity with two subtypes: congenital IHG (CIHG) and acquired IHG (AIHG). However, due to the rarity of the disease and the lack of defining histological criteria, the concept of IHG is not widely accepted. We studied paraffin-embedded intestinal specimens from 79 patients diagnosed with Hirschsprung's disease (HD) (n = 49), CIHG (n = 25), and AIHG (n = 5) collected between January 1996 and December 2015. Histopathological diagnosis of HD, CIHG, and AIHG was confirmed by hematoxylin and eosin staining and immunohistochemical staining using Hu C/D and CD56. We evaluated (immuno)histopathological findings, counted the number of ganglion cells, and measured the size of Auerbach's plexus. Hu C/D labeled neuronal cell bodies, whereas CD56 was detected in all neuronal components. In HD, all ganglion cells in Auerbach's plexus in the normoganglionic segment (NGS) were immunoreactive for Hu C/D, whereas in the aganglionic segment (AGS), these were replaced by CD56-positive extrinsic nerve fibers and bundles. The number of ganglion cells in AIHG and CIHG was significantly lower than in the NGS of HD (p < 0.05). Auerbach's plexus was significantly smaller in CIHG (p < 0.05) but in AIHG equivalent to the NGS in HD. In summary, immunostaining for Hu C/D and CD56 is useful for definitive histopathological diagnosis of IHG.

Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes.

CIC-DUX4 and BCOR-CCNB3 fusion-gene-associated small round cell sarcomas account for a proportion of pediatric small round cell sarcomas, but their pathological features have not been sufficiently clarified. We reviewed a large number of soft tissue tumors registered at our institution, retrieved the cases of unclassified tumors with a small round cell component, and subjected them to histopathological, immunohistochemical, and gene profile analysis. We reviewed 164 cases of unclassified tumors with a small round cell component and analyzed them by RT-PCR and FISH. Tumors positive for a specific fusion-gene were also subjected to histopathological and immunohistochemical examinations. We identified 16 cases of BCOR-CCNB3/CIC-associated (CIC-DUX4 or CIC gene rearrangement-positive) sarcomas. These included seven BCOR-CCNB3 sarcomas and nine CIC-associated sarcomas. Heterogeneous elements included a myxoid spindle cell component in three BCOR-CCNB3 sarcomas and an epithelioid cell component in two CIC-associated sarcomas (one CIC-DUX4-positive and one CIC-DUX4-negative sarcomas). Mitotic activity was low in both heterogeneous components. By immunohistochemistry, in seven BCOR-CCNB3 sarcomas expression of EMA was positive in two cases, of p63 in three, of CD56 in six, of TLE1 in seven, of NKX2.2 in two, of CCNB3 in seven, and of BCOR in six cases (one case could not be tested for BCOR). In nine cases of CIC-associated sarcoma, CD56 was expressed in five, alpha-smooth muscle actin in one, ERG in three, and CD99, WT1 and TLE1 each in eight cases. Both sarcoma types showed not only a small round cell component, but also a myxoid/epithelioid component with low mitotic activity.

Severe acquired subglottic stenosis in children: analysis of clinical features and surgical outcomes based on the range of stenosis.

PURPOSE: The present study analyzed the clinical features and surgical outcomes of laryngotracheal reconstruction (LTR) in pediatric patients with severe acquired subglottic stenosis (SGS) based on the range of stenosis. The aim was to clarify the indications for LTR in severe acquired SGS. METHODS: The medical records of 33 pediatric patients with severe acquired SGS (Myer-Cotton grade III or IV) at our institution between January 1994 and December 2013 were retrospectively reviewed. RESULTS: Nine patients had stenosis localized at the subglottis (localized SGS), and twenty-four patients had stenosis extending to the glottis or supraglottis from the subglottis (extended SGS). 66.7 % (6/9) of localized SGS patients were intubated after infancy, and 95.8 % (22/23) of extended SGS patients were intubated in the neonatal period. The duration of intubation was significantly shorter with localized than with extended SGS. Sixteen patients underwent LTR. The operation-specific decannulation rate was 80.0 % (4/5) in the localized SGS group and 14.3 % (1/7) in the extended SGS group. CONCLUSION: The range of stenosis was affected by the period and duration of endotracheal intubation. Surgical outcomes of LTR tended to differ between localized SGS and extended SGS. LTR can be effective for localized SGS.

Single-incision laparoscopic surgery for gallstone ileus: An alternative surgical procedure.

INTRODUCTION: Gallstone ileus (GI) results from the passage of a stone through a cholecystoenteric fistula, subsequently causing a bowel obstruction. The ideal treatment procedure for GI remains controversial. PRESENTATION OF CASE: A 63-year-old female was admitted to our hospital following persistent nausea and vomiting for 7 days. Computed tomography revealed a partially calcified 4-cm circular object in the jejunum, and the proximal intestine was dilated, with concomitant pneumobilia. Based on the preoperative diagnosis of GI, enterotomy with stone extraction by single-incision laparoscopic surgery (SILS) was performed. The patient's postoperative course was uneventful, and the cholecystoduodenal fistula closed spontaneously 4 months after the surgery. DISCUSSION: Recent studies have reported that enterotomy with stone extraction alone is associated with better outcomes than with more invasive techniques. This case also suggests that enterotomy with stone extraction alone and careful postoperative follow-up is feasible for the management of GI. Although the use of laparoscopy in the management of GI has been described previously, laparoscopic surgery has not been widely performed, and SILS is not generally performed. When only this less demanding procedure is required, laparoscopic surgery, including SILS, can be a viable option. CONCLUSION: SILS can be an alternative surgical procedure for the management of GI.