Hak Chang

The Efficacy and Safety of Platelet-Rich Plasma and Adipose-Derived Stem Cells: An Update

During the past decade, many studies using platelet-rich plasma (PRP) or adipose-derived stem cells (ASCs) have been conducted in various medical fields, from cardiovascular research to applications for corneal diseases. Nonetheless, there are several limitations of practical applications of PRP and ASCs. Most reports of PRP are anecdotal and few include controls to determine the specific role of PRP. There is little consensus regarding PRP production and characterization. Some have reported the development of an antibody to bovine thrombin, which was the initiator of platelet activation. In the case of ASCs, good manufacturing practices are needed for the production of clinical-grade human stem cells, and in vitro expansion of ASCs requires approval of the Korea Food and Drug Administration, such that considerable expense and time are required. Additionally, some have reported that ASCs could have a potential risk of transformation to malignant cells. Therefore, the authors tried to investigate the latest research on the efficacy and safety of PRP and ASCs and report on the current state and regulation of these stem cell-based therapies.

The Effectiveness of Mapping Biopsy in Patients with Extramammary Paget's Disease

Background Extramammary Pagets disease (EMPD) is an intraepithelial carcinoma usually occurring on the skin or mucosa of the perineum. Clinically, it resembles eczema or dermatitis, and misdiagnosis and treatment delays are common. The treatment of choice for EMPD is a wide excision with adequate margins. Wide excision with intraoperative frozen biopsy and Mohs micrographic surgery are common methods; however, these are associated with a high recurrence rate and long operation time, respectively. Methods Between January 2010 and June 2013, 21 patients diagnosed with EMPD underwent mapping biopsy. Biopsy specimens were collected from at least 10 areas, 2 cm from the tumor margin. When the specimens were positive for malignancy, additional mapping biopsy was performed around the biopsy site of the positive result, and continued until no cancer cells were found. Based on the results, excision margins and reconstruction plans were established preoperatively. Results The patients (18 male, 3 female) had a mean age of 66.5 years (range, 50-82 years). Almost all cases involved in the perineal area, except one case of axillary involvement. Permanent biopsy revealed one case (4.8%) of positive cancer cells on the resection margin, in which additional mapping biopsy and re-operation was performed. At the latest follow-up (mean, 27.4 months; range, 12-53 months), recurrence had not occurred. Conclusions Preoperative mapping biopsy enables accurate resection margins and a preoperative reconstructing plan. Additionally, it reduces the operation time and risk of recurrence. Accordingly, it represents an effective alternative to Mohs micrographic surgery and wide excision with intraoperative frozen biopsy.

Effectiveness of autologous serum as an alternative to fetal bovine serum in adipose-derived stem cell engineering

In cell culture, medium supplemented with fetal bovine serum is commonly used, and it is widely known that fetal bovine serum supplies an adequate environment for culture and differentiation of stem cells. Nevertheless, the use of xenogeneic serum can cause several problems. We compared the effects of four different concentrations of autologous serum (1, 2, 5, and 10xa0%) on expansion and adipogenic differentiation of adipose-derived stem cells using 10xa0% fetal bovine serum as a control. The stem cells were grafted on nude mice and the in vivo differentiation capacity was evaluated. The isolation of adipose-derived stem cells was successful irrespective of the culture medium. The proliferation potential was statistically significant at passage 2, as follows: 10xa0% autologous serum >10xa0% fetal bovine serumxa0=xa05xa0% autologous serum >2xa0% autologous serumxa0=xa01xa0% autologous serum. The differentiation capacity appeared statistically significant at passage 4, as follows: 10xa0% fetal bovine serum >10xa0% autologous serumxa0=xa05xa0% autologous serum >2xa0% autologous serumxa0=xa01xa0% autologous serum. Ten percent autologous serum and 10xa0% fetal bovine serum had greater differentiation capacity than 1 and 2xa0% autologous serum in vivo, and no significant difference was observed between the groups at ≥5xa0% concentration at 14xa0weeks. In conclusion, 10xa0% autologous serum was at least as effective as 10xa0% fetal bovine serum with respect to the number of adipose-derived stem cells at the end of both isolation and expansion, whereas 1 and 2xa0% autologous serum was inferior.

Anatomic basis of interfascicular nerve splitting of innervated partial latissimus dorsi muscle flap

PURPOSEnTo study the anatomic basis for the interfascicular nerve-splitting technique applied to the innervated latissimus dorsi muscle flap to preserve the remnant muscle function. Cadaveric dissection was performed to study the distribution of the thoracodorsal nerve and artery, and simulation of the surgical technique was also executed.nnnMETHODSnA total of 42 latissimus dorsi muscles from 21 preserved cadavers were dissected, and the distribution of the nerves and arteries were studied. The thoracodorsal neurovascular bundles were identified entering the muscle, and the distance from the upper margin and lateral margin of the muscle, and the distance from the angle of scapula were measured. The distance from the brachial plexus to the branching of the thoracodorsal nerve were measured and the distance between the branching of the nerve and artery were also measured. Interfascicular splitting of the thoracodorsal nerve was performed under operating microscope and the validity of the technique was confirmed by histology.nnnRESULTSnThe thoracodorsal neurovascular bundle entered the muscle at a distance of 39.1 ± 8.8 mm from the upper margin, and 23.8 ± 10.3 mm from the lateral margin. In addition, from the angle of scapula, the distance was 47.8 ± 17.8 mm in the transverse axis, and 48.9 ± 13.5 mm in the sagittal axis. The distance from the brachial plexus to the first branching of the thoracodorsal nerve was 78.5 ± 11.0 mm, and distance to the second branching was 96.3 ± 12.9 mm. The thoracodorsal nerve always branched before the artery, and the distance from the first branching of the nerve to the first branching of the artery was 20.4 ± 8.9 mm. Interfascicular dissection of the nerve was performed under operating microscope, by opening the epineurium and splitting the fascicles with utter care not to injure the perineurium. This procedure was very similar to splitting a wire cable. Histological analysis of the dissected nerve confirmed that the interfascicular dissection was performed without injuring the fascicules and the perineurium was intact.nnnCONCLUSIONnWe simulated and confirmed that the preservation of the remnant muscle function was possible by using the nerve-splitting technique in the innervated latissimus dorsi muscle flap. It is easy and simple to separate the nerve branch entering the muscle flap from the nerve branch entering the remnant muscle without injury, which results in increasing the nerve length while preserving the muscle function of the donor site. Further, the distribution of the thoracodorsal neurovascular bundle was studied in 42 muscles, which can be used as a reference point during surgery. With this novel technique, preservation of the remnant muscle function is possible when using innervated muscle flaps, which can be applied in areas such as reconstruction of facial paralysis and reconstruction of the chest wall in Poland syndrome.

Penoscrotal Extramammary Paget's Disease with Multiple Lymph Node Metastasis.

Extramammary Pagets disease (EMPD) is an uncommon intraepithelial adenocarcinoma. EMPD in the penis and scrotum, first described in 1888, is extremely rare [1]. EMPD is a rare skin disease that is limited to the epidermis, but has the potential to invade the dermis and metastasize. If dermal invasion has occurred, the rate of lymph node or distant metastasis will increase [2]. The rate of lymph node metastasis is reported to be 26% in patients with invasive primary lesions [3]. EMPD might be associated with an increased risk of underlying internal malignancy of the lower gastrointestinal or genitourinary tract. We describe a case of penoscrotal extramammary Pagets disease with multiple lymph node metastasis. n nA 69-year-old man was referred to us with a one-year history of a painless erythematous skin rash on the penis and scrotum (Fig. 1). He first visited a local clinic and was treated with topical agents. Despite conventional treatment, the lesion extended to the scrotum and penis. The patient initially underwent a punch biopsy and the pathology report came back as EMPD. On physical examination, there was a 2-cm round, firm mass in the left inguinal area. A computed tomography (CT) scan of the abdomen revealed a 2.1-cm round peripheral rim-enhancing lymph node (LN) in the left inguinal area and a 2.8-cm enlarged ovoid lymph node in the right inguinal area (Fig. 2). Ultrasound-guided biopsy of the localized mass in the left inguinal area confirmed the diagnosis of metastatic carcinoma. n n n nFig. 1 n nPreoperative view: a 69-year-old male patient with penoscrotal extramammary Pagets disease. n n n n n nFig. 2 n nA computed tomography scan of the abdomen revealed bilateral inguinal lymph node metastasis. The white arrow indicates a 2.1-cm round peripheral rim-enhancing lymph node in the left inguinal area. n n n nBefore wide excision of the scrotal and penile lesion, mapping biopsies were performed to determine the exact margins of the lesion. However, during the preoperative period, the mass of the right inguinal area increased from 2.8 to 3.58 cm. Therefore, the patient was admitted to the department of oncology and had an extensive cancer work-up. The tumor markers were within normal range: alpha-fetoprotein 1.5 ng/mL (normal range, 0-20 ng/mL), carcinoembryonic antigen 2.6 ng/mL (normal range, 0-5 ng/mL), and prostate-specific antigen 0.712 ng/mL (normal range, 0-3 ng/mL). Routine colonoscopy and esophagogastroduodenoscopy were performed to check for internal malignancy of the lower gastrointestinal track. However, there was no evidence of an underlying internal malignancy. A whole-body positron emission tomography (PET)/CT scan revealed metastatic lymphadenopathy on both inguinal areas and the left external iliac space. No other abnormal hypermetabolic lesion was found (Fig. 3). n n n nFig. 3 n nA full body positron emission tomography computed tomography scan showed metastatic lymphadenopathy in both inguinal areas and the left external iliac space (white arrows). n n n nAfter the full cancer work-up, the patient underwent wide local excision with both inguinal and left external iliac lymphadenectomy. We performed surgical wide excision of a 16.5 cm×8.5 cm lesion of the scrotum and penis. The skin defect was covered with a scrotal flap and split-thickness skin graft for the penile shaft. n nThe pathologic findings with immunohistochemical staining revealed extramammary Pagets disease (Fig. 4), measuring 7 cm×4.2 cm. Moreover, a 1.5 cm×1 cm dermal invasion lesion of the penis and scrotum was seen (Fig. 5). n n n nFig. 4 n nHistological findings. The black arrow indicates Paget cells with atypical round nuclei with abundant pale granular cytoplasm. The white arrow indicates normal cell lining (H&E, ×100). n n n n n nFig. 5 n nHistological findings. The black arrow indicates a tumor cell nest in the subcutaneous layer (H&E, ×20). n n n nAll of the surgical safety margins were clear. In this report, our data showed that 17 of 20 lymph nodes showed metastasis. The lymph node metastasis was expressed in 75% (3/4) in the right inguinal, 85.7% (6/7) in the left inguinal, 100% (6/6) in the left external iliac, and 66.6% (2/3) in the peri-iliac vessel. n nAn abdomino-pelvic CT scan was performed 1 month postoperatively. Based on the CT scan data, a 1.8 cm×2.5 cm lymphocele was found in the left external iliac and inguinal region. However, there was no evidence of metastasis in the abdomen or pelvis. The patient received 45 Gy/25 Fx postoperative radiotherapy. He was followed up in the outpatient department for 6 months without any evidence of recurrence or other complications. n nEMPD is a rare, slow-growing intraepithelial lesion with well-defined moist erythematous or white plaques. Complete surgical excision is the treatment of choice for EMPD. Mohs micrographic surgery or mapping biopsy is useful for determining the normal skin margin for wide excision. Non-surgical treatments, such as radiation therapy, topical chemotherapy with imiquimod, and photodynamic therapy with topical aminolevulinic acid are effective in inoperable patients. Only radiation therapy can be applied for deep lesions such as lymph node metastasis. Several authors have reported on EMPD patients treated with radiation therapy at total doses of 30 to 54 Gy in 3 to 25 fractions. However, the optimal radiation dose for treatment of a metastatic lymph node is controversial [4]. n nEMPD rarely invades the dermis or spreads to the local inguinal lymph nodes or remote sites; only a few such cases have been reported. Chan et al. [2] reported that dermal invasion was found in 18.8% on histological examination after wide excision. Regional lymph node metastasis was found in 14.5%, and there was a statistically significant relationship between dermal invasion and regional lymph node metastasis. In cases of primary invasive tumor without clinical lymph node metastasis, elective lymph node dissection has been recommended [3]. Our case showed a focal dermal invasion in the primary lesion with bilateral inguinal and left external iliac LN metastasis. The standard treatment for advanced EMPD with distant metastasis is controversial. We performed successful wide excision, obtaining clear margins, and multiple lymphadenectomy. We applied additional radiation therapy because most of the pathologic findings of the lymph nodes were positive. There have been some reports about the clinicopathology and prognosis of metastatic EMPD [5]. However, they have not been well established, so further clinical follow-up is needed.

Trends in breast reconstruction: Implications for the National Health Insurance Service

Background Breast reconstruction has become more common as mastectomy has become more frequent. In Korea, the National Health Insurance Service (NHIS) began covering breast reconstruction in April 2015. This study aimed to investigate trends in mastectomy and breast reconstruction over the past 10 years and to evaluate the impact of NHIS coverage on breast reconstruction. Methods Nationwide data regarding mastectomy and breast reconstruction were collected from the Korean Breast Cancer Society registry database. Multiple variables were analyzed in the records of patients who underwent breast reconstruction from January 2005 to March 2017 at a single institution. Results At Seoul National University Hospital, the total number of reconstruction cases increased 13-fold from 2005 to 2016. The proportion of immediate breast reconstruction (IBR) cases out of all cases of total mastectomy increased from 4% in 2005 to 52.0% in 2016. The proportion of delayed breast reconstruction (DBR) cases out of all cases of breast reconstruction and the overall number of DBR cases increased from 8.8% (20 cases) in 2012 to 18.3% (76 cases) in 2016. After NHIS coverage was initiated, the proportions of IBR and DBR showed statistically significant increases (P<0.05). Among the IBR cases, the percentage of prosthesis-based reconstructions increased significantly (P<0.05), but this trend was not found with DBR. Total mastectomy became significantly more common after the expansion of NHIS coverage (P<0.05). Conclusions Over the last decade, there has been an increase in mastectomy and breast reconstruction, and the pace of increase accelerated after the expansion of NHIS coverage. It is expected that breast reconstruction will be a routine option for patients with breast cancer under the NHIS.

Distraction histogenesis of an anastomosed artery.

This study examined the possibility of an adaptive reaction of anastomosed arteries under tension during a distraction lengthening procedure in the tibiae of rabbits. After an osteotomy at the mid tibia, the posterior tibial arteries were transected and anastomosed. Using a pair of small external fixators, the tibiae were distracted at a rate of 0.5mm/day (groups I-IV rabbits). Three weeks after 25% lengthening, the patency and histology of the arteries were examined. Angiography revealed that all of the anastomosed arteries were patent, and intimal hyperplasia was a constant finding. The mean thickness of the intima of the lengthened segment in group I was 60.4 microm, which is 5.0, 3.4 and 2.1 times higher that of the controls in groups IV (un-manipulated arteries, 12.2 microm), III (unlengthened but anastomosed arteries, 17.8 microm) and II (lengthened but untouched arteries, 28.7 microm), respectively. These results show that an anastomosed artery can maintain its patency at a certain level and speed of distraction lengthening. Therefore, it is possible that distraction lengthening and vascular anastomoses can be performed simultaneously provided there is careful monitoring of the circulation.

Evaluation of lymphedema in upper extremities by MR lymphangiography: Comparison with lymphoscintigraphy

PURPOSEnTo validate usefulness of magnetic resonance (MR) lymphangiography for evaluation of peripheral lymphedema in upper extremities by comparison with lymphoscintigraphy.nnnMATERIALS AND METHODSnThis prospective study had institutional review board approval and written informed consent was obtained from all patients. Initially, protocol of MR lymphangiography for upper extremity was established in seven healthy volunteers with 3.0T fat-saturated three-dimensional gradient-echo MR after gadobutrol injection. Then six patients with unilateral lymphedema of the upper extremities were examined with MR lymphangiography and lymphoscintigraphy, and the results were correlated with each other. Four categories were defined to scale the quality of drainage. Results of both techniques were separately evaluated by two radiologists and a nuclear physician. We evaluated sensitivity, specificity and correlation of both techniques.nnnRESULTSnMR lymphangiography showed sensitivities of 100% for all four categories, while lymphoscintigraphy yielded a sensitivity of 83.3% for delineation of lymph vessels and 100% for the other three categories. Specificity of MR lymphangiography was 85.7% for delay of drainage and 100% for other three categories, while lymphoscintigraphy showed specificity of 66.7% for pattern of lymphatic drainage and 100% for other three categories. Delay and pattern of drainage was same in 83.3% and non-visualization of axillary LNs was indistinguishably noted in all patients on both techniques. Anatomic level of enhanced lymph vessel was identical in 66.7% of the patients.nnnCONCLUSIONnMR lymphangiography showed better performance for depiction of lymph vessels. MR lymphangiography and lymphoscintigraphy yielded same results in all or most patients for evaluation of axillary lymph nodes enhancement and lymphatic drainage in upper extremity.

The Role of Periostin in Capsule Formation on Silicone Implants

Although silicone implants are widely used in breast and other reconstructive surgeries, the limited biocompatibility of these materials leads to severe complications, including capsular contracture. Here, we aimed to clarify the relationship between periostin and the process of capsule formation after in vivo implantation. Seven-week-old wild-type (WT) C57BL/6 mice and periostin-deficient mice were used. Round silicone implants were inserted into a subcutaneous pocket on the dorsum of the mice. After 8 weeks, the fibrous capsule around the implant was harvested and histologically examined to estimate capsular thickness and the number of inflammatory cells. Additionally, immunohistochemical analysis (periostin, α-SMA, and collagen type I) and western blotting (CTGF, TGF-β, VEGF, and MPO) were performed for a more detailed analysis of capsule formation. The capsules in periostin-knockout mice (PN-KO) were significantly thinner than those in WT mice. PN-KO mice showed significantly lower numbers of inflammatory cells than WT mice. Fibrous tissue formation markers (α-SMA, periostin, collagen type I, and CTGF) were significantly reduced in PN-KO mice. We also confirmed that inflammatory reaction and angiogenesis indicators (TGF-β, MPO, and VEGF) had lower expression in PN-KO mice. Inhibition of periostin could be important for suppressing capsule formation on silicone implants after in vivo implantation.

Rhabdomyolysis After Cosmetic Laser-Assisted Liposuction

A 34-year-old-female patient visited our emergency room for symptoms of disturbance of urination and shortness of breath. She was diagnosed with rhabdomyolysis with acute kidney injury after laser-assisted liposuction and required hemodialysis. Although laser-assisted liposuction is a well-used procedure, it can cause local complications, such as burns and skin irregularities, as well as systemic complications, such as infection, fever, and emboli. However, laser-assisted, liposuction-induced rhabdomyolysis has not been reported. Repetitive exercises, trauma, and crush injury are the major causes of rhabdomyolysis. In this study, a unique case of rhabdomyolysis that developed after laser-assisted liposuction is reported.Level of Evidence VThis journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.