Successful Treatment of Transverse Testicular Ectopia by Laparoscopically Assisted Orchiopexy.

Transverse testicular ectopia (TTE) is a rare congenital malformation where both testes descend through the same inguinal canal and are located in the same hemiscrotum. It is usually treated with transseptal orchiopexy. In this article, we report the case of a 1-year-old boy diagnosed with TTE who was successfully treated with laparoscopically assisted orchiopexy by going through the anatomical conventional route. A four-month-old boy was referred to our department with bilateral empty scrotum. On the physical examination, the left testis was palpable in the left groin region and the right testis was impalpable. A follow up ultrasonography was performed after 4 months, and an oval-shaped testis-like structure was detected in left internal inguinal ring near the left testis. Right side TTE was suspected in the initial diagnosis. Laparoscopic surgery was performed at age one. The left testis was observed in the inguinal canal, and the right testis was ectopically located in the left opening inguinal canal above the left testis. Two spermatic cord and testes were separated respectively, and the right testis was pulled into abdominal space laparoscopically and brought down to the right hemiscrotum via the right inguinoscrotal canal. Bilateral orchiopexy was performed via the normal anatomical route. The postoperative course was uneventful, and testes were in the scrotum bilaterally one year after orchiopexy.

Encouraging Young Pediatric Surgeons and Evaluation of the Effectiveness of a Pediatric Endosurgery Workshop by Self-Assessment and an Objective Skill Validation System.

Background: Japanese pediatric endosurgery experts conducted a workshop for young pediatric surgeons in Russia in collaboration with Russian expert pediatric surgeons. This study was aimed to develop a contributive workshop program and evaluate its impact on young pediatric surgeons. Methods: A 2-day pediatric endosurgery workshop was held in Moscow in February 2020. After conducting a needs assessment survey, Japanese and Russian faculties developed the workshop contents, including pre- and postworkshop skills assessments, lectures, and hands-on training. Skills assessments were performed using the objective skill validation system, the "A-Lap Mini," mimicking intestinal anastomosis. The trainees self-evaluated their knowledge and skills using a five-point scale. Results: Fifteen novice trainee participated and 14 (93.3%) completed the workshop program. The completion rate for the suturing task before and after the workshop was 40.0% (6/15) and 85.7% (12/14), respectively. The following five skill evaluation criteria, which were objectively evaluated: performance time changed from 751.6 ± 247.1 seconds to 780.0 ± 313.3 seconds (P > .05), number of full-thickness sutures improved from 1.0 ± 1.41 to 2.64 ± 0.84 (P = .003), area of wound-opening changed from 0.42 ± 0.83 mm2 to 0.53 ± 1.13 mm2 (P > .05), suture tension improved from 55.48% ± 19.51% to 61.95% ± 23.91% (P > .05), and maximum air leakage pressure improved from 3.76 ± 2.11 kPa to 8.42 ± 7.68 kPa (P > .05). Regarding the self-assessed questionnaire administered before and after the workshop, the confidence in endosurgery skills significantly improved as follows: forceps manipulation ability improved from 2.7 to 3.7 (P < .05), and suturing performance improved from 2.5 to 3.6 (P < .05). The usefulness of the workshop for clinical surgery was scored at 4.3. Conclusions: Quantitative skill evaluation with an automatic feedback function was useful for endosurgery training. Delivering feedback concerning the assessment results to the trainee helps them to determine the specific training requirements needed for clinical endosurgery.

Laparoscopic Approach to Presacral Recurrence of Sacrococcygeal Teratoma.

A 6-month-old girl was presented to our hospital due to a presacral mass found 5 months after surgery of sacrococcygeal teratoma. The original tumor was a 63 x 50 mm sized round cyst connecting to the coccyx, observed with computed tomography. The initial operation was performed with en bloc removal of the tumor along with the coccyx in the prone position. During a routine follow up, ultrasonography indicated a possible local recurrence, 5 months after the initial operation. The magnetic resonance imaging revealed a polycystic formation with a diameter of 20 x 11 x 17 mm in the presacral space. The laparoscopic operation was conducted with the patient in the lithotomy and Trendelenburg position. The broad ligament of uterus was fixed to the abdominal skin and the rectum was mobilized to identify the tumor, which was resected laparoscopically. A histopathological examination showed the tumor to be a mature cystic teratoma. We observed her without any additional treatment and no recurrence is seen after 6 months.

Photodynamic therapy with 5-aminolevulinic acid: A new diagnostic, therapeutic, and surgical aid for neuroblastoma.

BACKGROUND: 5-Aminolevulinic acid (ALA)-based photodynamic therapy (PDT) is widely used in cancer therapy because of the tumor-specific accumulation of photosensitizing protoporphyrin IX (PpIX). We aimed to assess the susceptibility of human neuroblastoma cell lines to ALA-PDT and determine the mechanism of PDT. METHODS: We used four human neuroblastoma cell lines (GOTO, NB9, IMR32, and NB1) and a gastric cancer cell line (MKN45) as a positive control. Cells were treated with increasing concentrations of ALA, and the ALA-induced production of PpIX in tumor cells was quantified using fluorescence spectrophotometry. PDT photocytotoxicity was measured by exposing the cells to a 630-nm irradiation for 10 min, and apoptotic cells stained with phosphatidylserine (PS) and propidium iodide (PI) were detected through flow cytometry. RESULTS: ALA cytotoxicity was not observed in any cell line. The intracellular concentration of PpIX increased in an ALA dose-dependent manner, and intracellular fluorescence of PpIX increased in a time-dependent manner. The viability of NB-1 cells treated with 250 µM 5-ALA rapidly decreased to 5%. Photocytotoxicity was observed in the following order: NB1, IMR32, NB-9, and GOTO. Photocytotoxicity was positively correlated with intracellular PpIX concentrations. PS+/PI- cells increased up to 21% after 12 h, and PS+/PI+ cells accounted for 35% of all cells after 24 h, which suggests that ALA-PDT induced apoptotic cell death. CONCLUSION: This study shows that neuroblastoma cell lines were susceptible to 5-ALA-PDT, resulting in persistent apoptotic cell death. LEVELS OF EVIDENCE: N/A for basic study.

Comprehensive analyses of the cysteine thiol oxidation of PKM2 reveal the effects of multiple oxidation on cellular oxidative stress response.

Redox regulation of proteins via cysteine residue oxidation is involved in the control of various cellular signal pathways. Pyruvate kinase M2 (PKM2), a rate-limiting enzyme in glycolysis, is critical for the metabolic shift from glycolysis to the pentose phosphate pathway under oxidative stress in cancer cell growth. The PKM2 tetramer is required for optimal pyruvate kinase (PK) activity, whereas the inhibition of inter-subunit interaction of PKM2 induced by Cys358 oxidation has reduced PK activity. In the present study, we identified three oxidation-sensitive cysteine residues (Cys358, Cys423 and Cys424) responsible for four oxidation forms via the thiol oxidant diamide and/or hydrogen peroxide (H2O2). Possibly due to obstruction of the dimer-dimer interface, H2O2-induced sulfenylation (-SOH) and diamide-induced modification at Cys424 inhibited tetramer formation and PK activity. Cys423 is responsible for intermolecular disulfide bonds with heterologous proteins via diamide. Additionally, intramolecular polysulphide linkage (-Sn-, n ≧ 3) between Cys358 and an unidentified PKM2 Cys could be induced by diamide. We observed that cells expressing the oxidation-resistant PKM2 (PKM2C358,424A) produced more intracellular reactive oxygen species (ROS) and exhibited greater sensitivity to ROS-generating reagents and ROS-inducible anti-cancer drugs compared with cells expressing wild-type PKM2. These results highlight the possibility that PKM2 inhibition via Cys358 and Cys424 oxidation contributes to eliminating excess ROS and oxidative stress.

Incidentally Detected Microcarcinoma of Thyroid in Surgical Specimens of the Goiter in Pediatric Patient: A Case Report.

A 14 year-old girl with a previous medical history of cholecystic polyps was referred to our department with throat discomfort during swallowing. The cervical ultrasound and magnetic resonance imaging revealed a massive polycystic formation with a diameter of 45 × 24 × 31 mm consistent with a right lobe goiter. However, there were no findings for suspected malignancy. Hemithyroidectomy was performed and the specimen was sent for histopathological assessment. Hematoxylin-eosin staining of the right lower nodule showed variably-sized follicles consistent with adenomatous goiter. The right upper nodule showed a growth of relatively compact sized follicles　with a thick fibrous capsule. A satellite nodule lying outside of the tumor capsule was consistent with minimally invasive follicular thyroid microcarcinoma. We observed her without any additional treatment and no recurrence is seen at present.

Definitive Tumor Resection after Myeloablative High Dose Chemotherapy Is a Feasible and Effective Option in the Multimodal Treatment of High-Risk Neuroblastoma: A Single Institution Experience.

BACKGROUND/PURPOSE: The delayed local treatment approach (DL) in high-risk neuroblastoma (HR-NB) refers to the process in which tumor resection is performed after the completion of all the courses of chemotherapy, including myeloablative high-dose chemotherapy (HDC). Alternatively, in the conventional local treatment approach (CL), tumor resection is performed during induction chemotherapy. In this study, we compared the surgical outcomes in HR-NB patients treated by CL and DL. METHOD: Forty-seven patients with abdominal HR-NB underwent primary tumor resection from 2002 to 2018. The timing of surgery was generally determined by following the trials and guidelines available at the time. The outcomes and surgical complications between the two strategies were compared. RESULT: Operation time, blood loss, and postoperative WBC counts were lower in the DL group (n = 25) when compared to the CL group (n = 22), statistical significance notwithstanding. Major vascular structures were less frequently encased in the DL group tumors, while immediate surgical complications were significantly more frequent in the CL group (P < 0.05). Furthermore, the 3-year EFSs were 50.0% and 53.9% in the DL and CL groups, respectively. CONCLUSION: DL appears to be a feasible and effective treatment option for HR-NB. Nonetheless, further verifications using larger cohorts are warranted. LEVEL OF EVIDENCE: Treatment study, Level III.

Laparoscopic Partial Closure for Congenital Portosystemic Shunt-Indications, Postoperative Management, and Subsequent Complete Closure.

Extrahepatic congenital portosystemic shunts (CPSSs) can be occluded by surgical or endovascular approaches. However, when the estimated portal vein (PV) pressure after the closure is high enough to induce symptoms associated with portal hypertension, partial closure is recommended to avoid life-threatening events. In this study, we attempted laparoscopic partial closure of a CPSS in two patients. Along with intraoperative real-time measuring of the PV pressure and angiography, laparoscopic partial closure was performed to achieve a PV pressure of ≤25 mmHg. Subsequently, the intrahepatic portal system grew in both patients. The partially ligated CPSS closed spontaneously in the first patient. In the second patient, laparoscopic complete closure was performed for the residual CPSS 6 months after the first operation. To our knowledge, this is the first report of laparoscopic partial closure for CPSS. Minimally invasive laparoscopic partial ligation of CPSS is technically feasible and useful when the estimated PV pressure is too high to tolerate one-step complete closure.

Predictors of early lobectomy after birth in prenatally diagnosed congenital pulmonary airway malformation.

PURPOSE: The purpose of this study was to clarify the relationship between congenital pulmonary airway malformation volume ratio (CVR) of bronchial atresia (BA), CVR of congenital cystic adenomatoid malformations (CCAM), and time of surgery after birth. METHOD: We retrospectively analyzed data of 36 BA and CCAM cases, prenatally diagnosed as CPAM from 2009 through 2014. RESULTS: Within 2 h after birth, 12 neonatal patients underwent emergent (EMG) lobectomy. Five cases of lobectomy were performed urgently (UG) from 12 to 48 h after birth. Four cases of lobectomy were required within 30 days after birth (early = EAG). We performed lobectomy in 15 other patients at 11 months after birth (late = LG). Of the EMG cases, 11 were macrotype CCAM (maximal CVR >2.0), and 4 of 5 UG cases were microtype CCAM (CVR >2.0). Of the EAG cases, 3 of 4 were macrotype CCAM with CVR of <1.5. Of 15 LG, 13 were BA and showed a CVR of 0.13-3.0 (median, 0.78). The CVR of the cases operated on within 48 h after birth was significantly larger than that of the cases operated on after 2 weeks (p = 0.001). CONCLUSION: EMG or UG lobectomy was usually required after birth in CCAM, indicating maximal CVR >2.0. By contrast, elective surgery was performed in most BA cases. LEVEL OF EVIDENCE: IV.

An investigation on clinical differences between congenital pulmonary airway malformation and bronchial atresia.

BACKGROUND/PURPOSE: Differences in clinical features between congenital pulmonary airway malformation (CPAM) and bronchial atresia (BA) have not yet been clearly described. METHODS: We retrospectively reviewed 112 patients with a pathological diagnosis of CPAM or BA. The clinical parameters were statistically analyzed between these diseases. RESULTS: Seventy-one patients received prenatal diagnosis and 41 received postnatal diagnosis. The percentage of prenatal diagnosis was significantly higher in CPAM patients (84% vs 50%, p < 0.001). Among patients with prenatal diagnosis, the backgrounds were not different between the two diseases except for the number of Caesarean sections (81% vs 9%, p < 0.0001). The numbers of patients that underwent fetal interventions and emergent neonatal surgery were higher in CPAM (51% vs 15%, p < 0.01 and 76% vs 12%, p < 0.0001), although there was no statistical difference in survival rate (86% vs 97%, p = 0.2). In patients receiving postnatal diagnosis, pneumonia was the primary symptom in most BA patients, whereas respiratory distress was the major symptom in patients with CPAM. Age at presentation of the primary symptom was significantly older in BA patients (4.2 years vs 1.2 years, p < 0.005). CONCLUSION: CPAM and BA have distinct clinical features in terms of therapeutic and natural history. Careful imaging evaluation and pathological analysis can lead to an accurate diagnosis of BA. TYPE OF STUDY: Prognostic study. LEVEL OF EVIDENCE: Level II. This study is categorized as a "Prognostic Study" with LEVEL III of Evidence.

Congenital hyperinsulinism treated by surgical resection of the hyperplastic lesion which had been preoperatively diagnosed by 18F-DOPA PET examination in Japan: a nationwide survey.

PURPOSE: Congenital hyperinsulinism is a rare disease, and the newly developed 18 fluoro-L-dihydroxyphenylalanine-positron emission tomography (18F-DOPA PET) examination can detect hyperplastic lesions. Our purpose was to report the results of a nationwide survey on surgical treatment of congenital hyperinsulinism in Japan. METHODS: A questionnaire was sent to the 159 accredited and affiliated training institutes certified as pediatric surgical institutes by the Japanese Association of Pediatric Surgeons, asking if they had encountered patients who underwent surgical treatment for congenital hyperinsulinism after 18F-DOPA PET examination from 2000 to 2017. Six institutes answered that they had treated such cases, and the total number of cases was 14. RESULTS: 18F-DOPA PET examination detected the focal lesion in 12 of the 14 cases. 18F-DOPA PET examination could accurately determine the site of the hyperplastic lesion in the pancreas in 11 (91.7%) of the 12 cases. All cases underwent surgical resection of the hyperplastic lesion at under 2 years of age. CONCLUSION: Surgical resection of a focal hyperplastic lesion in the pancreas was a safe and effective treatment if the hyperplastic lesion was a focal lesion. However, it is necessary to check the exact distribution of the lesion by intraoperative pathologic examination of frozen sections.

Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease, 2017.

BACKGROUND: Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as "allied disorders of Hirschsprung's disease" and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. METHODS: These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis-microcolon-intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo-obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese- and English-language articles in PubMed and Ichu-Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. RESULTS: We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full-thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. CONCLUSIONS: Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies.

Blood biochemistry and hematological changes in rats after administration of a mixture of three anesthetic agents.

Currently, given the concerns regarding animal welfare, it is required that anesthesia or analgesia be used during surgery in experimental animals. Therefore, it is important to understand how anesthesia affects the health conditions of experimental animals. In this study, rat blood biochemistry and hematological changes were examined following administration of a mixture of three anesthetic agents-medetomidine, midazolam and butorphanol (MMB). One of three MMB dose combinations was subcutaneously administered to rats. After 1 hr, rats were treated with atipamezole, to reverse the anesthetic effects. Blood biochemistry and hematological parameters were assessed at 1, 4 and 24 hr post-MMB treatment. We also recorded body weight and food intake at 0, 2, 4, 6 and 24 hr post-MMB administration. Following MMB administration, transient increases were observed in glucose (GLUC) levels, hematocrit (HCT) values and hemoglobin (HGB) levels, whereas transient decreases were observed in total protein (TP) content and white blood cell (WBC) counts. Most of these parameters returned to control values 24 hr following MMB administration. Additionally, body weight and food intake decreased in MMB-treated rats. In conclusion, intermediate and high doses of MMB changed some blood biochemistry and hematological parameters, body weight and food intake. In contrast, low-dose MMB did not cause these effects. Therefore, depending on the experimental design, MMB may influence the results of studies that use laboratory animals. Consequently, anesthetic agents used in laboratory animals should be chosen based on detailed knowledge of their pharmacological effects.

Resolution of liver disease in transient abnormal myelopoiesis with fish oil emulsion.

Neonates with Down syndrome are at risk of developing transient abnormal myelopoiesis (TAM), which is characterized by transient clonal myeloproliferation of the blast cells. TAM can resolve spontaneously, but some patients die at an early age due to organ failure. Liver fibrosis in TAM is a life-threatening condition, but treatment options have not yet been established. Here, we report on the case of an infant with TAM complicated by liver disease, whose hyperbilirubinemia was successfully ameliorated with omega-3 fatty acid (ω3FA) lipid emulsion. Timely ω3FA lipid emulsion may be a feasible treatment for liver disease in TAM before serious liver damage develops.

Redox-dependent Regulation of Gluconeogenesis by a Novel Mechanism Mediated by a Peroxidatic Cysteine of Peroxiredoxin.

Peroxiredoxin is an abundant peroxidase, but its non-peroxidase function is also important. In this study, we discovered that Tsa1, a major peroxiredoxin of budding yeast cells, is required for the efficient flux of gluconeogenesis. We found that the suppression of pyruvate kinase (Pyk1) via the interaction with Tsa1 contributes in part to gluconeogenic enhancement. The physical interactions between Pyk1 and Tsa1 were augmented during the shift from glycolysis to gluconeogenesis. Intriguingly, a peroxidatic cysteine in the catalytic center of Tsa1 played an important role in the physical Tsa1-Pyk1 interactions. These interactions are enhanced by exogenous H2O2 and by endogenous reactive oxygen species, which is increased during gluconeogenesis. Only the peroxidatic cysteine, but no other catalytic cysteine of Tsa1, is required for efficient growth during the metabolic shift to obtain maximum yeast growth (biomass). This Tsa1 function is separable from the peroxidase function as an antioxidant. This is the first report to demonstrate that peroxiredoxin has a novel nonperoxidase function as a redox-dependent target modulator and that pyruvate kinase is modulated via an alternative mechanism.

Morphology-based investigation of metachronous inguinal hernia after negative laparoscopic evaluation - is it acquired indirect inguinal hernia?

PURPOSE: Patients who developed apparent metachronous contralateral inguinal hernia (MCIH) after negative laparoscopic diagnosis have been reported. We performed this study to investigate the morphological characteristics and etiology of this phenomenon. PATIENTS AND METHODS: A consecutive series of 1,747 patients (858 boys and 889 girls) with symptomatic unilateral inguinal hernia were studied. During laparoscopic percutaneous completely extraperitoneal closure, morphological appearances at the asymptomatic groin were inspected for contralateral patent processus vaginalis (CPPV) with definitive criteria. If positive CPPV was identified, it was closed by the same technique used for the affected side. The patients were reviewed for occurrence of metachronous contralateral hernia. RESULTS: A total of 755 patients (43.2%) had positive CPPV. Of the 992 patients whose CPPVs were evaluated as true negative, eight (seven boys, one girl) developed MCIH (time taken, three months to five years six months). During second-look operations, morphological appearances of the CPPV that was originally considered as true negative CPPV was found to be wide open. CONCLUSIONS: Despite a true negative evaluation by laparoscopy, there was a 0.8% chance of developing a MCIH. This phenomenon was male-oriented and may be acquired indirect inguinal hernia without preceding of CPPV.

Perinatal features of congenital cystic lung diseases: results of a nationwide multicentric study in Japan.

PURPOSE: The current study aimed to assess the perinatal risk and clinical features of congenital cystic lung diseases (CCLD). MATERIALS AND METHODS: Of the 874 CCLD patients identified in a nationwide survey, 428 patients born between 1992 and 2012 and treated at 10 high-volume centers, were retrospectively reviewed. RESULTS: Fetal hydrops was visualized using MRI in 9.2 % of the patients. Prenatal interventions were described for 221 of the 428 patients, including the maternal administration of steroid and pleuro-amniotic shunting. Postnatally, a right-to-left shunt flow through a persistent ductus arteriosus was observed in 7.8 % of the patients. The fetal lung lesion volume ratio (LVR) was significantly higher among these symptomatic patients (2.04 ± 1.71 vs. 0.98 ± 0.50, P < 0.00071), and decreased to a greater degree in non-CCAM patients compared with CCAM patients during the late gestational period (from 1.37 ± 1.28 to 1.14 ± 0.84 in CCAM and from 1.08 ± 0.47 to 0.46 ± 0.64 in non-CCAM). CONCLUSIONS: An estimated 8-9 % of prenatally diagnosed patients carry the highest risk of perinatal respiratory distress. Fetal LVR remaining at a high level during the late gestational period seems to predict a high risk.