DNA methylation analysis of multiple imprinted DMRs in Sotos syndrome reveals IGF2-DMR0 as a DNA methylation-dependent, P0 promoter-specific enhancer.

Haploinsufficiency of NSD1, which dimethylates histone H3 lysine 36 (H3K36), causes Sotos syndrome (SoS), an overgrowth syndrome. DNMT3A and DNMT3B recognizes H3K36 trimethylation (H3K36me3) through PWWP domain to exert de novo DNA methyltransferase activity and establish imprinted differentially methylated regions (DMRs). Since decrease of H3K36me3 and genome-wide DNA hypomethylation in SoS were observed, hypomethylation of imprinted DMRs in SoS was suggested. We explored DNA methylation status of 28 imprinted DMRs in 31 SoS patients with NSD1 defect and found that hypomethylation of IGF2-DMR0 and IG-DMR in a substantial proportion of SoS patients. Luciferase assay revealed that IGF2-DMR0 enhanced transcription from the IGF2 P0 promoter but not the P3 and P4 promoters. Chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) revealed active enhancer histone modifications at IGF2-DMR0, with high enrichment of H3K4me1 and H3 lysine 27 acetylation (H3K27ac). CRISPR-Cas9 epigenome editing revealed that specifically induced hypomethylation at IGF2-DMR0 increased transcription from the P0 promoter but not the P3 and P4 promoters. NSD1 knockdown suggested that NSD1 targeted IGF2-DMR0; however, IGF2-DMR0 DNA methylation and IGF2 expression were unaltered. This study could elucidate the function of IGF2-DMR0 as a DNA methylation dependent, P0 promoter-specific enhancer. NSD1 may play a role in the establishment or maintenance of IGF2-DMR0 methylation during the postimplantation period.

Multiple Peripheral Osteomas Related to Frontal Exposure by Bicoronal Incision.

Osteoma of the skull is a benign slow-growing osteogenic lesion typically composed of well-differentiated mature bone tissue. It is characterized by the proliferation of compact or cancellous bone and is found almost exclusively in the head and neck region. Central, peripheral, and extraskeletal are the major variants of craniofacial osteomas. Trauma, inflammation, developmental disorders, and genetic defects are considered their etiologic factors. Paranasal sinuses, especially frontal and ethmoidal sinuses, are the favorite locations of peripheral craniofacial osteomas.Peripheral osteomas are usually benign, innocuous lesions, but their size, prominence, and visibility on the face necessitate a surgical intervention.The authors describe a rare patient in whom multiple osteomsas were located in the frontal area likely related to an exposure of the site by bicoronal incision made 10 years earlier.

Revisiting Microsurgical Distal Bypass for Critical Limb Ischemia.

Background The purpose of this study was to investigate the efficacy of introducing microsurgical techniques to distal bypass surgery for critical limb ischemia. Methods Datasets of 83 consecutive microsurgical distal bypasses in a multicenter (SKY) study were compared with the results of the PREVENT III (PIII) study regarding the following: (1) patients' characteristics, (2) clinical severity according to the PIII risk score, (3) conduits and procedures for revascularization, (4) proximal and distal anastomosis sites, and (5) primary patency and amputation-free survival (AFS) rates at 1 year. Results The high-risk group in the SKY study was larger compared with that in the PIII study (37 vs. 9%, respectively; p < 0.0001). Although all patients underwent revascularization in the perimalleolar region (100 vs. 65.1%, respectively; p < 0.0001), the primary patency rate at 1 year was 71.8%, compared with 59.9% in the PIII study (p = 0.0227). The AFS rate at 1 year was not significantly different between the SKY and PIII studies (80.6 vs. 75.1%, respectively; p = 0.189); however, there was a significant difference between the high-risk subsets of each group: 74.1% in the SKY study and 45% in the PIII study (p < 0.0001). Conclusions Our data demonstrated that microsurgical distal bypass is an effective and durable procedure, especially for high-risk patients. We believe that microsurgical techniques should be considered for distal bypass to optimize the treatment of ischemic limbs with severe peripheral artery disease.

Acute Limb-Threatening Ischemia Associated With Antiphospholipid Syndrome: A Report of Two Cases.

Acute limb ischemia results from sudden deterioration in the arterial supply to the limb, occasionally leading to limb loss or fatality. Antiphospholipid syndrome (APS) is known to induce acute limb ischemia among the various etiologies responsible for arterial obstruction. APS is a systemic autoimmune disorder characterized by a combination of arterial and/or venous thrombosis and limb loss. It is often accompanied by a mild-to-moderate thrombocytopenia and elevated titers of antiphospholipid antibodies, including the lupus anticoagulant and the anticardiolipin antibodies. In the present report, we present 2 cases of acute limb ischemia due to APS associated with systemic lupus erythematosus. Angiography revealed arterial obstruction distal to the popliteal artery in both patients, and each patient eventually underwent below-the-knee amputation. Surgeons treating acute limb ischemia should remember APS, although this disease might not be common in daily clinical practice.

Humanitarian Cleft Lip/Palate Surgeries in Buddhist Thailand and Neighboring Countries.

OBJECTIVE: This study evaluates surgeries done on patients with cleft lip and/or palate in Thailand and its neighboring countries from 1988 to 2008. This 21-year-long volunteer surgical mission was sponsored by Duang-Kaew Foundation, a volunteer organization. Countries involved, besides Thailand, were Vietnam, Myanmar, Laos, Cambodia, China, Sri Lanka, Bhutan, and India. The same surgical method for primary and secondary repair of lip and/or palate was used throughout: Onizuka method by single surgeon, the second author mainly. DESIGN: We assessed, by way of the patients' medical records including their background, the results of surgeries. The healing rates and complication rates associated with patients for primary and secondary repair of lip and/or palate. PARTICIPANTS: The study consisted of a total of 6832 patients: 3120 with cleft lip (CL); 2190 with cleft palate (CP); and 1522 with cleft lip and palate (CLP). Their primary cases were 675 (CL), 799 (CP), and 301 (CLP). RESULTS: All CP operations were done under general anesthesia. Of the CL surgeries, 10% of adult cases were done under local anesthesia. Of all the patients, 78%, or 5329, had one surgery; and 22%, or 1503, had 2 or more surgeries. Good healing was seen in 73.3%, whereas wound infection was noted in 2.0% and healing by second intention was in 1.2% of all cases. CONCLUSIONS: It is important that the Onizuka method was the only method used in all the countries throughout the mission period. The method has an advantage over other methods in that its design is simple enough so that even a beginning plastic surgeon can easily master, and operative results are constantly good regardless of who did the operation. The Duang-Kaew Foundation's long-term surgical program helped reduce the number of untreated patients to manageable levels for local health care providers in Thailand and neighboring countries for as long as 21 years.

Technical strategies for en bloc resection and immediate reconstruction in hemangioma of the frontal bone.

Hemangioma of the skull is a benign solitary tumor, often found in the frontal or parietal area. A hemangioma lesion typically involves the outer table rather than the inner, but its complete removal at the diploe level is difficult. Full-thickness resection at the calvaria is often needed to ensure a free margin, but it will leave a bony defect that requires reconstruction. Although curettage and covering of the lesion with alloplastic material are a simple treatment option for hemangioma of the skull, it does not always prevent recurrence. Hence, complete resection is needed. As our technical strategies for reconstruction, we organize a split calvarial bone graft if a defect is near the frontal sinus and calcium phosphate cement if it is somewhat far from the sinus.

Update on endoscopic surgery in Japan: Results of the 16th National Survey of endoscopic surgery by the Japan Society for Endoscopic Surgery.

This article reports the results of the 16th National Survey conducted by the Japan Society for Endoscopic Surgery (JSES) for 2020 and 2021. Laparoscopic cholecystectomy was first introduced to Japan in 1990 and has rapidly become popular because of its minimally invasive nature. Since then, the number of objective organs and indications for laparoscopic surgery have gradually expanded. In 2021, 290 787 patients underwent endoscopic surgery in all surgical domains. Of these, 124 614, 110 757, 23 156, 21 771, 6543, 2614, 535, 465, 247, and 58 underwent abdominal, obstetric and gynecologic, thoracic, urological, pediatric, orthopedic, bariatric, mammary and thyroid gland, cardiovascular, and plastic surgery, respectively. Owing to the impact of the coronavirus disease 2019 (COVID-19) infection spread, the incidence of many surgeries decreased in 2020, and levels are only now gradually recovering. However, despite the impact of COVID-19, robot-assisted surgeries were increasingly applied. The rate of complications did not change significantly, indicating that the procedure was performed safely, even with the spread of COVID-19.

The effect of different positions on lower limbs skin perfusion pressure.

We have encountered situations of patients with critical limb ischemia accompanied by pain at rest and necrosis, who hang their legs down from the bed during sleep. This lower limb position is known to be a natural position, which reduces pain in the lower extremity induced by ischemia. However, the effect of this position on blood flow of the lower extremity is poorly understood. We studied whether measurements of skin perfusion pressure (SPP) changes by leg position and the difference between healthy adults and patients with critical limb ischemia. The subjects of this study were 10 healthy adults and 11 patients with critical limb ischemia. Patients with critical limb ischemia, including both dorsum of foot and plantar of foot, having SPP of lower limbs of less than 40 mmHg (supine position) were the object of this study. SPP was measured on four positions (supine position, lower limbs elevation position, sitting position, and reclining bed elevation of 20(°) position). In sitting position, both the number of healthy adults and critical patients show significant increases in SPP compared with the other three positions. These results suggest that sitting position is effective to keep good blood stream of lower limbs not only in healthy adults but also in patients with critical limb ischemia. However, an appropriate leg position should not have lower limbs hang downwards for long periods time because edema is caused by the fall in venous return in lower limbs, and the wound healing is prolonged. Our clinical research could be more useful in the future, particularly in developing countries, for surgeons managing wounds in leg and foot and preserving ischemic limbs.

Current Status of Endoscopic Surgery in Japan: The 15th National Survey of Endoscopic Surgery by the Japan Society for Endoscopic Surgery.

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, operative procedures have been standardized, and the safety and efficacy of endoscopic surgery have been evaluated. In accordance with the social acceptance of endoscopic surgery as a less invasive type of surgery, the number of endoscopic procedures performed has increased in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has played an important role in the development of endoscopic surgery in Japan. Notably, a technical skills certification system for surgeons was established by the JSES to train instructors on how to teach safe endoscopic surgery. Furthermore, the JSES has conducted a national survey every 2 years. In 2019, 291,792 patients underwent endoscopic surgery in all surgical domains, such as abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The 15th National Survey of Endoscopic Surgery conducted by the JSES demonstrated the status of laparoscopic surgery in Japan in 2018-2019.

A Minimally Invasive Full Endoscopic Approach to Tibial Nerve Neurolysis in Diabetic Foot Neuropathy: An Alternative to Open Procedures.

BACKGROUND: Dellon et al. have reported that chronic nerve compression of the tibial nerve inside the tarsal tunnel, caused by diabetes mellitus, can be relieved following open decompression surgery. However, the large skin incision resulting from Dellon's procedure may cause wound healing problems. The authors report the possibility of a minimally invasive full endoscopic procedure. METHODS: Operations were performed under local anesthesia without a pneumatic tourniquet. An anesthetic agent was applied at the proximal part of the flexor retinaculum of the foot, and a hypodermic needle was advanced into the tarsal tunnel. Tarsal tunnel pressure and blood circulation of the tibial nerve using indocyanine green assessment were measured preoperatively. One 1-cm portal skin incision was made at the anesthetized area and the Universal Subcutaneous Endoscope system was inserted into the tarsal tunnel. The flexor retinaculum, tibial nerve, blood vessels, and abductor hallucis muscle fascia were identified under endoscopic observation. After decompression of the tarsal tunnel, the authors measured tarsal tunnel pressure and blood circulation of the tibial nerve for analysis of the effectiveness of the endoscopic decompression during the procedure. RESULTS: Fourteen operations were compiled and analyzed. Postoperative clinical status was improved based on the preoperative modified Toronto Clinical Neuropathy Score. The mean tarsal tunnel pressure dropped to 4.5 mmHg during surgery from the initial preoperative 49.4 mmHg in resting position. Endoscopic indocyanine green assessment showed more than 30 percent improvement of the vascularity surrounding the tibial nerve. CONCLUSION: The authors' minimally invasive full endoscopic procedure is a viable alternative approach for tarsal tunnel syndrome patients with diabetic foot neuropathy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Less Invasive Management of Tissue Deficits for Deep Sternal Wound Infections.

BACKGROUND: The frequency of sternomyelitis after cardiovascular surgery has been reported to be 0.4% -5%. METHODS: The treatment method used for 47 patients (29 male and 18 female) who developed sternomyelitis after sternotomy with tissue defects in the chest was examined retrospectively. RESULTS: Of the original conditions, the most frequent was coronary artery disease undergoing bypass grafting (22 cases, 46.8%), followed by acute aortic dissection (10 cases, 21.3%). The number of times debridement was performed was: once, 35 cases; twice, 11 cases; 7 times, 1 case; and unknown, 2 cases. The most frequent time of occurrence of sternomyelitis was within 2 weeks after surgery (12 patients, 25.5%). A residual internal thoracic artery remained on both sides in 28 cases (59.6%), and only on the right side in 17 cases (36.2%); there was no remaining one in 2 cases (4.2%). The reconstruction method was a pectoralis major musculocutaneous flap in 31 cases (66.0%), internal mammary artery perforator flap in 7 cases (14.9%), rectus abdominis musculocutaneous flap in 4 cases (8.5%), omentum transplant in 3 cases (6.4%), superior epigastric artery perforator flap in 2 cases (4.3%), external abdominal oblique muscle flap in 1 case (2.1%), and latissimus dorsi musculocutaneous flap in 1 case (2.1%). The internal mammary artery perforator flap and the superior epigastric artery perforator flap have been effective treatment. CONCLUSIONS: In 47 patients, our method of treatment for tissue defects of the chest wall after sternal osteomyelitis was examined, and an algorithm using less invasive management was proposed.

Current status of endoscopic surgery in Japan: The 14th National Survey of Endoscopic Surgery by the Japan Society for Endoscopic Surgery.

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, operative procedures have been standardized, and the safety and efficacy of endoscopic surgery have been evaluated. In accordance with the social acceptance of endoscopic surgery as a less invasive type of surgery, the number of endoscopic procedures performed has increased in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has played an important role in the development of endoscopic surgery in Japan. Notably, a technical skills certification system for surgeons was established by the JSES to train instructors on how to teach safe endoscopic surgery. Furthermore, the JSES has conducted a national survey every two years to evaluate the status of endoscopic surgery over time. In 2017, 248 743 patients underwent endoscopic surgery in all surgical domains, such as abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The 14th National Survey of Endoscopic Surgery conducted by the JSES demonstrated the status of laparoscopic surgery in Japan in 2016-2017.

Giant microcystic adnexal carcinoma of the scalp.

Microcystic adnexal carcinoma (MAC) is an uncommon, locally aggressive tumor. It typically involves the upper lip of middle-aged adults, and in rare instances the scalp. We report a Japanese woman with a giant MAC on the scalp. Physical examination revealed a 110 mm x 120 mm induration on her parietal region. Microscopically, the tumor showed both pilar and sweat gland differentiation. Resection included the cranium; for reconstruction we used a titan mesh allograft and covered it with a free latissimus dorsi muscle flap and a mesh skin graft. Ours is the first case of a MAC measuring more than 100 cm2 arising on the scalp of an individual in the third decade of life.

Transverse twist flap for lip reconstruction in patient with lentigo maligna of the labial mucosa.

The transverse twist flap technique is used for secondary reconstruction of asymmetric volume-deficits of the cleft lip. We present a patient with lentigo maligna of the labial mucosa who underwent reconstruction using this technique. The result was excellent and there was no postoperative complications. The transverse twist flap is a useful and effective option for the reconstruction of lip defects after excision of lentigo maligna.

In Situ Splitting of a Rib Bone Graft for Reconstruction of Orbital Floor and Medial Wall.

In situ splitting of rib bone graft was conducted in 22 patients for the repair of orbital fracture with no other complicating fractures. A bone graft was harvested from the sixth or seventh rib in the right side. The repair of the orbital floor and medial wall was successful in all the cases. Ten patients had bone grafting to the orbital floor, eight had it done onto medial wall, and 4 onto both floor and wall after reduction. The mean length of in situ rib bone graft was 40.9 mm (range, 20-70 mm), the mean width of these was 14.9 mm (range, 8-20 mm). The bone grafting was done by one leaf for 15 cases and two leafs for 7 cases in size of defects. The technique of in situ splitting of a rib bone graft for the repair of the orbital floor and medial wall is a simple and safe procedure, easily taking out the in situ splitting of a rib, and less pain in donor site. It has proved to be an optimal choice in craniofacial reconstruction, especially the defects of orbital floor and medial wall.

Switch Flap for Upper Eyelid Reconstruction-How Soon Should the Flap Be Divided?

BACKGROUND: The results of a cohort of patients treated at one institution for upper eyelid reconstruction with the switch flap method after a defect due to excision of malignant tumor were reviewed. METHODS: A retrospective data file review of all patients who had undergone total upper eyelid reconstruction with the switch flap method was conducted at the Saga University Hospital between April 2000 and October 2014. The follow-up lasted for varying periods during which the preoperative and postoperative photographs were compared as well. RESULTS: A total of 10 patients with upper eyelid tumors, that is, 7 sebaceous carcinoma, 2 squamous cell carcinoma, and 1 basal cell carcinoma, underwent reconstructive surgery. With the switch flap technique, the defects resulting from tumor excision were completely covered in all cases. The mean of defect widths after tumor excision (A) was 18.8 mm (range, 15-25 mm), the mean of widths of switch flaps (B) was 13.3 mm (range, 8-22 mm), and the mean of B/A ratios was 0.69 (range, 0.5-0.88). When the switch flap was divided at 7 to 14 days, there was no flap loss, trichiasis, or corneal ulcer. CONCLUSION: Our protocol managed to make flaps with a B/A ratio of 0.5-0.7, and the flaps were divided at 7 to 14 days after surgery, the timing of which was much earlier than in the conventional method, lessening the possibility of complications.

Retroseptal Transconjunctival Approach for Blowout Fracture of the Orbital Floor: An Ideal Choice in East-Asian Patients.

OBJECTIVE: To ask experts in the field to evaluate a surgeon's experience with a retroseptal transconjunctival approach for the repair of the orbital floor damaged by blowout fracture that the surgeon encountered in 12 East-Asian patients. METHODS: Patients were identified from a database, and a retrospective case note review was conducted. A total of 12 conjunctival procedures were conducted for the repair of blowout fracture with no other complicating fractures. All operative procedures were done by transconjunctival approach alone without lateral canthotomy or any other additional approach. RESULTS: The repair of the orbital floor was successful in all the cases. Three patients had bone grafting to the orbital floor after reduction. The mean of overall surgical time was 48.8 minutes (range, 22-85 minutes) for orbit exposure by transconjunctival approach plus reduction and bone grafting when applicable. There were 6 urgent surgeries associated with missing or entrapment of the inferior rectus muscle, and its repair took an average of 32.0 minutes (range, 22-41 minutes). Postoperative diplopia recovered at an average of 12.4 weeks (range, 0-60 weeks); in urgent cases, it took an average of 5.3 weeks (range, 0-14 weeks) before recovery. CONCLUSIONS: A retroseptal transconjunctival approach in repairing the orbital floor is a simple, easily manageable, and effective procedure, leaving no conspicuous facial scars. It has proved to be an optimal choice in blowout fracture cases, especially when there was urgency to decompress the ischemic inferior rectus muscle in as short a surgery time as possible.

Aesthetic Total Reconstruction of Lower Eyelid Using Scapha Cartilage Graft on a Vascularized Propeller Flap.

BACKGROUND: The aim of this study was to review the results of a cohort of patients based on our experience with a new technique for total lower eyelid reconstruction after a large defect caused by malignant tumor and trauma. A scapha cartilage graft with small skin on a vascularized propeller flap was used for 16 cases requiring lower eyelid reconstruction. METHODS: Patients were identified from a database, and a retrospective case note review was conducted. The scapha cartilage graft was sutured to the margin of the defect of the palpebral conjunctiva and tarsus. The propeller flap, rotated by a perforator-based lateral orbital flap or a subcutaneous-based nasolabial flap, was vascularized on the scapha cartilage graft as anterior lining of the lower eyelid. The follow-up, including results of slit-lamp examination, lasted for varying periods, but often it was for 12 months. RESULTS: The scapha cartilage graft with small skin on a vascularized propeller flap was viable in all cases. Slit-lamp examination detected no irritation or injury of the conjunctiva and cornea, and visual acuity was maintained in all cases. A deformity in the donor helix by this technique was also improved by getting a smaller skin harvested from the scapha. CONCLUSION: Use of the scapha cartilage graft with small skin on a vascularized propeller flap allows for a good fit to the orbit, short operative time under local anesthesia, good graft viability, and a good esthetic result with minimal donor site morbidity.

Transconjunctival Approach for Zygomatic Fracture: A Single Surgeon's Experience of More Than 20 Years.

BACKGROUND: To let experts evaluate a single surgeon's experience with a combined transconjunctival and intraoral upper vestibular approach in the repair of zygomatic fractures encountered in 46 East Asian patients whom he treated over the past 20 years. METHODS: Patients were identified from a database, and a retrospective case note review was conducted. A total of 67 conjunctival and secondary incisions were made on 46 patients for repair of zygomatic fractures. All operative procedures were performed using a combination of transconjunctival and intraoral upper vestibular approaches to repair zygomatic fractures. RESULTS: The infraorbital rim and/or lateral buttress and/or lateral orbit was stabilized with titanium miniplates in 28 patients and absorbable miniplates in 11 patients. Seven patients required only reduction technique with no need of plates. Four cases needed additional canthotomy besides a conjunctival approach. No ectropion or entropion developed in any of the patients. Complications included eyelid laceration during surgery (n = 1), herniation of the conjunctiva (n = 1), temporary pyogenic granuloma of the conjunctiva after surgery (n = 1), and temporary entropion in a secondary incision (n = 1). CONCLUSIONS: A combined transconjunctival and intraoral upper vestibular approach in repairing zygomatic fractures is simple, easy, and effective, leaving no conspicuous facial scars. It is vitally important, however, that the surgeon masters the technique of transconjunctival approach well before he has good results in East Asian patients.

Intramuscular benign lipoma of the temporalis muscle.

An intramuscular lipoma within the musculature of the head and neck is unusual. Most of them are infiltrating lipomas, and we know of no description of a well-circumscribed lipoma of the temporalis muscle. We present a 64-year-old woman who had a non-pulsatile, soft, mobile mass in the right temporal fossa. The lesion 11 x 8 x 3 cm in size was diagnosed using magnetic resonance imaging, it was resected, and she has recovered well with a good cosmetic result.