Reduction en masse of Inguinal Hernia in a 2-Month-Old Male Infant.

Reduction en masse is the reduction of the hernial sac into the preperitoneal space, with a loop of bowel remaining trapped at the neck of the hernial sac. This complication is rare, usually associated with inguinal hernias, and is characterized by the absence of a noticeable bulge in the groin. The patient was a 2-month-old male infant and presented with a nonreducible bulge in his left groin, and incarceration of the left inguinal hernia was diagnosed. Manual reduction was performed, and the hernia bulge became less noticeable. He was admitted, and laparoscopic percutaneous extraperitoneal closure was scheduled for the next day. The laparoscopy revealed remarkably dilated intestines, serous ascites, and an ischemic intestine in the left groin. A laparotomy was performed and revealed reduction en masse of the left inguinal hernia with a strangulated ileum at its neck. We made an incision at the neck, followed by the resection of 20-cm long strangulated ileum. The patient's condition was unstable on the day of operation, but the postoperative period was uneventful, and the left inguinal hernia was repaired, 11 months after the operation. Reduction en masse in pediatrics is significantly rare but when it occurs, the diagnosis can be delayed and occasionally the patient will be life-threatening. To avoid reduction en masse, it is crucial to perform the reduction gently and confirm the absence of a hernia sac in the preperitoneal space containing a loop of bowel by ultrasound scanning. Moreover, contrary to common practice, overnight observation and close monitoring will avoid missing a late presentation, leading to timely interventions.

Augmented Reality-Assisted Transcanal Endoscopic Ear Surgery for Middle Ear Cholesteatoma.

Background: The indications for transcanal endoscopic ear surgery (TEES) for middle ear cholesteatoma have expanded for cases involving mastoid extension. However, TEES is not indicated for all cases with mastoid extension. In addition, predicting the extent of external auditory canal (EAC) removal needed for cholesteatoma resection is not always easy. The purpose of this study was to use augmented reality (AR) to project the lesion onto an intraoperative endoscopic image to predict EAC removal requirements and select an appropriate surgical approach. Methods: In this study, patients showing mastoid extension were operated on using a navigation system with an AR function (Stryker). Results: The results showed that some cases with lesions slightly extending into the antrum required extensive resection of the EAC, while cases with lesions extending throughout the antrum required smaller resection of the EAC, indicating TEES. Conclusions: By predicting the extent of the needed EAC removal, it is possible to determine whether TEES (a retrograde approach) or canal wall-up mastoidectomy, which preserves as much of the EAC as possible, should be performed. We believe that our findings will contribute to the success of middle ear surgeries and the implementation of robotic surgery in the future.

Recent advances in Otology: Current landscape and future direction.

Hearing is an essential sensation, and its deterioration leads to a significant decrease in the quality of life. Thus, great efforts have been made by otologists to preserve and recover hearing. Our knowledge regarding the field of otology has progressed with advances in technology, and otologists have sought to develop novel approaches in the field of otologic surgery to achieve higher hearing recovery or preservation rates. This requires knowledge regarding the anatomy of the temporal bone and the physiology of hearing. Basic research in the field of otology has progressed with advances in molecular biology and genetics. This review summarizes the current views and recent advances in the field of otology and otologic surgery, especially from the viewpoint of young Japanese clinician-scientists, and presents the perspectives and future directions for several topics in the field of otology. This review will aid next-generation researchers in understanding the recent advances and future challenges in the field of otology.

Adeno-Associated Virus-Encapsulated Alginate Microspheres Loaded in Collagen Gel Carriers for Localized Gene Transfer.

This work reports localized in vivo gene transfer by biodegradation of the adeno-associated virus-encapsulating alginate microspheres (AAV-AMs) loaded in collagen gel carriers. AAV-AMs are centrifugally synthesized by ejecting a mixed pre-gel solution of alginate and AAV to CaCl2 solution to form an ionically cross-linked hydrogel microsphere immediately. The AAV-AMs are able to preserve the AAV without diffusing out even after spreading them on the cells, and the AAV is released and transfected by the degradation of the alginate microsphere. In addition, AAV-AMs can be stored by cryopreservation until use. By implanting this highly convenient AAV-encapsulated hydrogel, AAV-AMs can be loaded into collagen gel carriers to fix the position of the implanted AAV-AMs and achieve localized gene transfer in vivo. In vivo experiments show that the AAV-AMs loaded in collagen gel carriers are demonstrated to release the encapsulated AAV for gene transfer in the buttocks muscles of mice. While conventional injections caused gene transfer to the entire surrounding tissue, the biodegradation of AAV-AMs shows that gene transfer is achieved locally to the muscles. This means that the proposed AAV-loaded system is shown to be a superior method for selective gene transfer.

Achaete-scute family bHLH transcription factor 2 activation promotes hepatoblastoma progression.

Achaete-scute family bHLH transcription factor 2 (ASCL2) is highly expressed in hepatoblastoma (HB) tissues, but its role remains unclear. Thus, biological changes in the HB cell line HepG2 in response to induced ASCL2 expression were assessed. ASCL2 expression was induced in HepG2 cells using the Tet-On 3G system, which includes doxycycline. Cell viability, proliferation activity, mobility, and stemness were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, colony-formation, migration, invasion, and sphere-formation assays. Quantitative reverse-transcription polymerase chain reaction was used to assess the expression of markers for proliferation (CCND1 and MYC), epithelial-mesenchymal transition (EMT; SNAI1, TWIST1, and ZEB1), mesenchymal-epithelial transition (CDH1), and stemness (KLF4, POU5F1, and SOX9). Compared with the non-induced HepG2 cells, cells with induced ASCL2 expression showed significant increases in viability, colony number, migration area (%), and sphere number on days 7, 14, 8, and 7, respectively, and invasion area (%) after 90 h. Furthermore, induction of ASCL2 expression significantly upregulated CCND1, MYC, POU5F1, SOX9, and KLF4 expression on days 2, 2, 3, 3, and 5, respectively, and increased the ratios of SNAI1, TWIST1, and ZEB1 to CDH1 on day 5. ASCL2 promoted the formation of malignant phenotypes in HepG2 cells, which may be correlated with the upregulation of the Wnt signaling pathway-, EMT-, and stemness-related genes. ASCL2 activation may therefore be involved in the progression of HB.

Mechanical effect of reconstructed shapes of autologous ossicles on middle ear acoustic transmission.

Conductive hearing loss is caused by a variety of defects, such as chronic otitis media, osteosclerosis, and malformation of the ossicles. In such cases, the defective bones of the middle ear are often surgically reconstructed using artificial ossicles to increase the hearing ability. However, in some cases, the surgical procedure does not result in increased hearing, especially in a difficult case, for example, when only the footplate of the stapes remains and all of the other bones are destroyed. Herein, the appropriate shapes of the reconstructed autologous ossicles, which are suitable for various types of middle-ear defects, can be determined by adopting an updating calculation based on a method that combines numerical prediction of the vibroacoustic transmission and optimization. In this study, the vibroacoustic transmission characteristics were calculated for bone models of the human middle ear by using the finite element method (FEM), after which Bayesian optimization (BO) was applied. The effect of the shape of artificial autologous ossicles on the acoustic transmission characteristics of the middle ear was investigated with the combined FEM and BO method. The results suggested that the volume of the artificial autologous ossicles especially has a great influence on the numerically obtained hearing levels.

Controlled release of adeno-associated virus from alginate hydrogel microbeads with enhanced sensitivity to ultrasound.

Adeno-associated virus (AAV)-based gene therapy holds promise as a fundamental treatment for genetic disorders. For clinical applications, it is necessary to control AAV release timing to avoid an immune response to AAV. Here we propose an ultrasound (US)-triggered on-demand AAV release system using alginate hydrogel microbeads (AHMs) with a release enhancer. By using a centrifuge-based microdroplet shooting device, the AHMs encapsulating AAV with tungsten microparticles (W-MPs) are fabricated. Since W-MPs work as release enhancers, the AHMs have high sensitivity to the US with localized variation in acoustic impedance for improving the release of AAV. Furthermore, AHMs were coated with poly-l-lysine (PLL) to adjust the release of AAV. By applying US to the AAV encapsulating AHMs with W-MPs, the AAV was released on demand, and gene transfection to cells by AAV was confirmed without loss of AAV activity. This proposed US-triggered AAV release system expands methodological possibilities in gene therapy.

Hearing Outcome and Predictors after Implanting Bone Conduction or Middle Ear Implants in Ears with Refractory Otitis Media.

Bone conduction implants (BCIs) and middle ear implants (MEIs) are promising options for individuals with persistent chronic inflammation of the middle or outer ear. However, the structure of the middle ear is often altered in patients who undergo mastoidectomy or posterior wall removal for refractory otitis media, leaving uncertainty regarding the efficacy of hearing devices. Only a few studies have examined auditory outcomes based on the etiology of hearing impairment. We investigated hearing outcomes, including speech audiometry, in patients who underwent implantation after surgery for refractory otitis media. Our findings indicated that patients who received BCIs or MEIs achieved favorable hearing outcomes. Furthermore, a correlation was observed between the preoperative bone-conduction threshold at 1 kHz in the better ear and the sound-field threshold at 1 kHz with BCIs, whereas no correlation was observed between the preoperative bone-conduction threshold and the sound-field threshold with MEIs. This study highlights the positive impact of BCIs and MEIs in patients who undergo implantation after surgery for refractory otitis media. Additionally, our study identified parameters that predict postoperative efficacy.

Time Analysis of Recidivism in Acquired Cholesteatoma Using the Kaplan-Meier Method.

OBJECTIVE: To analyze the time trends of recidivism of acquired cholesteatoma using the Kaplan-Meier method. STUDY DESIGN: We conducted a retrospective, observational study of 256 patients having their first cholesteatoma surgery. The cumulative recidivism-free rate was calculated using Kaplan-Meier survival analysis related to the follow-up period, pathophysiology, the extent of the disease, and recidivism pathologies. RESULTS: Pars flacida cholesteatoma with tympanic cavity progression had a high likelihood of recurrence disease. Pars tensa cholesteatoma led to more recurrence of the disease than the residual disease. In both pars flacida and pars tensa cholesteatoma, the incidence of disease recurrence increased even 3 years after surgery. On the contrary, the incidence of residual disease peaked within 3 years after surgery, and thereafter, the incidence of residual disease tended to be small. In particular, pars flacida cholesteatoma extending into the mastoid cavity or tympanic cavity tended to recur up to 5 years postoperatively. CONCLUSIONS: We calculated the cumulative recidivism-free rates of 256 patients with cholesteatoma using Kaplan-Meier survival analysis. These results can lead to better estimates of the length of the follow-up period. LEVEL OF EVIDENCE: Level IV evidence from case-control studies.

Radiological and audiological predictors of stapes destruction in adherent pars tensa.

PURPOSE: Progressive adherent pars tensa occasionally induces ossicular erosion. Specifically, stapes discontinuity adversely affects postoperative hearing. However, this irretrievable sequela is challenging to prove preoperatively, partly because perimatrix inflammation on the pars tensa can obscure the visibility of the ossicles or the partial volume effect of computed tomography (CT) imaging can hamper detailed ossicular visualization. Therefore, there is no consensus regarding the ideal timing for switching from a wait-and-see approach to a surgical one. Herein, we aimed to explore the potential predictors of stapes superstructure destruction in adherent pars tensa. METHODS: This retrospective cohort study enrolled consecutive patients who underwent primary tympanoplasty for adherent pars tensa categorized as grade IV on Sadé's grading scale between April 2016 and September 2021. The impact of features on otoscopy and CT and air-bone gap (ABG) on stapes superstructure destruction was assessed using uni- and multivariable logistic regression analyses. RESULTS: Sixty-four ears were included. Multivariate analysis revealed the presence of debris on the adherent pars tensa (odds ratio [OR] [95% confidence interval {CI}]): 4.799 [1.063-21.668], p = 0.0415), presence of soft-tissue density occupying the oval window (OR [95% CI]: 13.876 [3.084-62.437], p = 0.0006), and a ≥ 20-dB preoperative ABG at 3 kHz (OR [95% CI]: 7.595 [1.596-36.132], p = 0.0108) as independent predictors for stapes superstructure destruction. CONCLUSION: High preoperative awareness of the possibility of destruction of the stapes superstructure would enable the surgeon to make a timely decision to provide surgical intervention before progression to severe stapes destruction, thereby maintaining long-term satisfactory hearing.

Radiological and audiological prediction for hearing outcome in cholesteatoma recidivism surgery.

PURPOSE: In cholesteatoma recidivism, achieving satisfactory hearing outcome after revision surgery remains challenging. The presence of concomitant recidivism pathology or related anatomical abnormalities can impact revision reconstruction of the sound transmission system. The current study aimed to identify prognostic factors affecting hearing outcomes after surgery for cholesteatoma recidivism. METHODS: This retrospective cohort study included consecutive patients whose ears required initial surgery for recidivism between January 2016 and December 2021. Patients followed up for < 6 months and those not indicated for ossiculoplasty were excluded. The impact of preoperative otoscopic findings, computed tomography (CT) features, and hearing levels on the prediction of satisfactory hearing (postoperative air-bone gap [ABG] ≤ 20 dB) was evaluated using univariate and multivariate logistic regression analyses. RESULTS: Overall, 102 patients were included, with a mean follow-up of 24.8 months. Multivariate logistic regression analysis revealed the following independent predictive factors for satisfactory hearing: presence of aeration in the tympanic cavity (odds ratio [OR] [95% confidence interval {CI}]: 13.287 [1.113-158.604], p = 0.0409), absence of soft-tissue density occupying the oval window (OR [95% CI]: 13.445 [3.178-56.887], p = 0.0040), and ≤ 22.5 dB preoperative ABG in four-frequency average (OR [95% CI]: 9.339 [2.026-43.050], p = 0.0042). CONCLUSIONS: For cholesteatoma recidivism, reliable preoperative prediction based on CT and ABG would facilitate decision-making regarding the probability of efficient revision ossiculoplasty or appropriate preoperative counseling, including early hearing rehabilitation using hearing aids or implementation of simultaneous implantable hearing equipment during surgery for recidivism.

Single-cell next-generation sequencing of circulating tumor cells in patients with neuroblastoma.

Circulating tumor cells (CTCs) derived from any tumor tissue could contribute to metastasis and resistance to cancer treatments. In this study, we performed single-cell next-generation sequencing of CTCs and evaluated their usefulness for characterizing tumor biology and the mechanisms of metastasis in neuroblastomas (NB). We aimed to isolate CTCs from 10 patients with NB at diagnosis before any treatments and four patients at relapse. GD2+ CD90+ CD45- CD235a- DAPI- cells were isolated as neuroblastoma CTCs using fluorescence-activated cell sorting. In five patients with advanced stages (M stage), DNA and RNA sequencing of CTCs at single-cell level were performed. NB CTCs were isolated from eight of the 10 patients at diagnosis and three of the four patients at relapse. More CTCs could be isolated from patients with advanced stages. In one patient, ALK mutation (p.F1174L), was identified in both tumor tissue and a CTC. In patients with MYCN amplification, this gene was amplified in 12 of 13 CTCs. Using single-cell RNA sequencing, angiogenesis-related and cell cycle-related genes together with CCND1 and TUBA1A genes were found to be upregulated in CTCs. In one patient, CTCs were divided into two subgroups showing different gene expression profiles. In one subgroup, cell cycle-related and proliferation-related genes were differentially upregulated compared with the other group. In conclusion, next-generation sequencing of CTCs at single-cell level might help to characterize the tumor biology and the mechanisms of metastasis in NB.

Imaging analysis of dural exposure in cholesteatomas with a skull base defect.

PURPOSE: Dural exposure during cholesteatoma surgery can pose a risk of cerebrospinal fluid leakage or residual disease. Therefore, delicate handling of the area surrounding the bone defect in the cranial fossa is required. However, in small-sized defects, preoperative prediction of dural exposure can be challenging. This study aimed to evaluate the diagnostic value of computed tomography (CT) for preoperative prediction of cholesteatoma-related dural exposure in bone discontinuities in the skull base. METHODS: We evaluated serial high-resolution CT images showing bone density discontinuities in the middle cranial fossa (MCF) requiring mastoidectomy for cholesteatoma. The CT and intraoperative findings were analyzed retrospectively. We evaluated the length between the superior margins of the bone density discontinuities using coronal CT planes. Receiver operating characteristic (ROC) curves were constructed to determine the optimal cut-off values. RESULTS: We extracted data from 107 bone density discontinuities, among which 54 (50.5%) showed dural exposure intraoperatively. Discontinuities with dural exposure (n = 54) had significantly greater lengths than did those without (n = 53) (p < 0.001, Wilcoxon rank-sum test). The area under the curve was 0.9780 according to the ROC analysis, and the optimal cut-off value was determined to be 2.99 mm (sensitivity 92.59%; specificity 94.34%). CONCLUSION: A bone density discontinuity length of > 2.99 mm in the MCF on coronal CT plane is a reliable diagnostic marker for cholesteatoma-related dural exposure. Thus, preoperative high-resolution CT analysis can inform optimal surgical preparation and planning before manipulating the area surrounding the osteolytic lesion in the MCF.

Determination of the umbilicus position in Japanese children.

BACKGROUND: Although there have been many reports concerning the normal position of the umbilicus, the measurements were performed from the surface of the body in all cases. We examined computed tomography (CT) images to determine the accurate position of the umbilicus in children. METHODS: We retrospectively examined the CT data of 120 Japanese children (60 boys, 60 girls). The angle between both iliac crests to the umbilicus (IU angle), the angle between both anterior superior iliac spines and the umbilicus (AU angle), and the ratio of the length from the xiphoid process to the umbilicus and length from the umbilicus to the pubic symphysis were measured. RESULTS: The mean AU angle was 33.7° ± 5.1°, showing the least data variations. A significant difference was noted in the AU angle between boys and girls (32.7° ± 4.6° and 34.6° ± 5.4° respectively; p = 0.04). When we defined the position of the umbilicus as an AU angle of 33° in boys and 35° in girls, 115 children (95.8%) fell within ±10°. CONCLUSIONS: The AU angle is the preferable predictor of the umbilicus position in children.

A new surgical technique for short bowel syndrome.

OBJECTIVE: Short bowel syndrome (SBS) is a severe intestinal disease that causes malabsorption. Long-term parental nutrition therapy induces infection and liver failure. For the surgical management of intestinal rehabilitation, the intestinal loop lengthening method and serial transverse enteroplasty (STEP) method have been reported, although their effects have proven limited. We herein report a new surgical technique, Saeki-Spiral-Shark (3S) method for SBS using biomimetics of shark intestine. METHODS: In the 3S method, a spiral valve is formed inside the intestine by external sutures. Using a 25 cm length intestinal organ model, we performed both the 3S method and STEP procedure. We then compared the length and fluid passage times of the subsequently formed intestine. RESULTS: After the 3S method was performed, the length of the intestinal model changed to 22 cm, and after the STEP procedure, that was elongated to 30 cm. Although the water passage times did not change markedly, the semi-digestive nutritional supplement passage time slowed down in the model with the 3S method. There was slight leakage in the STEP procedure model. CONCLUSIONS: The 3S method is a unique method of treating SBS based on biomimetics. This procedure does not require an incision of the intestine, which thereby enabling clean and less-invasive surgery. We plan to conduct animal experiments in the future.

Preoperative prediction by artificial intelligence for mastoid extension in pars flaccida cholesteatoma using temporal bone high-resolution computed tomography: A retrospective study.

Cholesteatoma is a progressive middle ear disease that can only be treated surgically but with a high recurrence rate. Depending on the extent of the disease, a surgical approach, such as microsurgery with a retroarticular incision or transcanal endoscopic surgery, is performed. However, the current examination cannot sufficiently predict the progression before surgery, and changes in approach may be made during the surgery. Large amounts of data are typically required to train deep neural network models; however, the prevalence of cholesteatomas is low (1-in-25, 000). Developing analysis methods that improve the accuracy with such a small number of samples is an important issue for medical artificial intelligence (AI) research. This paper presents an AI-based system to automatically detect mastoid extensions using CT. This retrospective study included 164 patients (80 with mastoid extension and 84 without mastoid extension) who underwent surgery. This study adopted a relatively lightweight neural network model called MobileNetV2 to learn and predict the CT images of 164 patients. The training was performed with eight divided groups for cross-validation and was performed 24 times with each of the eight groups to verify accuracy fluctuations caused by randomly augmented learning. An evaluation was performed by each of the 24 single-trained models, and 24 sets of ensemble predictions with 23 models for 100% original size images and 400% zoomed images. Fifteen otolaryngologists diagnosed the images and compared the results. The average accuracy of predicting 400% zoomed images using ensemble prediction model was 81.14% (sensitivity = 84.95%, specificity = 77.33%). The average accuracy of the otolaryngologists was 73.41% (sensitivity, 83.17%; specificity, 64.13%), which was not affected by their clinical experiences. Noteworthily, despite the small number of cases, we were able to create a highly accurate AI. These findings represent an important first step in the automatic diagnosis of the cholesteatoma extension.