Targeting Chondroitin Sulphate Synthase 1 (Chsy1) Promotes Axon Growth Following Neurorrhaphy by Suppressing Versican Accumulation.

Versican is a chondroitin sulfate proteoglycan (CSPG), which deposits in perineurium as a physical barrier and prevents the growth of axons out of the fascial boundary. Several studies have indicated that the chondroitin sulfate (CS) chains on versican have several possible functions beyond the physical barrier, including the ability to stabilize versican core protein in the extracellular matrix. As chondroitin sulfate synthase 1 (Chsy1) is a crucial enzyme for CS elongation, we hypothesized that in vivo knockdown of Chsy1 at peripheral nerve lesion site may decrease CS and versican accumulation, and result in accelerating neurite regeneration. In the present study, end-to-side neurorrhaphy (ESN) in Wistar rats was used as an in vivo model of peripheral nerve injury to evaluate nerve regeneration after surgical intervention. The distribution and expression of versican and Chsy1 in regenerating axons after ESN was studied using confocal microscopy and western blotting. Chsy1 was silenced at the nerve lesion (surgical) site using in vivo siRNA transfection. The results indicated that Chsy1 was successfully silenced in nerve tissue, and its downregulation was associated with functional recovery of compound muscle action potential. Silencing of Chsy1 also decreased the accumulation of versican core protein, suggesting that transient treating of Chsy1-siRNA may be an alternative and an effective strategy to promote injured peripheral nerve regeneration.

Arcade Suture Upper Blepharoplasty Combined With the Forceps Technique.

BACKGROUND: Double-eyelid blepharoplasty is the most popular cosmetic surgery in Taiwan. The creation of a small palpebral fold along with reduction of eyelid fullness makes the eye look slightly larger, thereby leading to an appearance of youthfulness, alertness, and vitality. Herein, we propose a method of combining the techniques of arcade buried suture and forceps, which is designed to create a more physiologically natural double eyelid. MATERIALS AND METHODS: We conducted a retrospective review of 45 patients who underwent double-eyelid surgery between December 2015 and December 2019. The procedures were performed by one senior surgeon using arcade suture upper blepharoplasty combined with the forceps technique. The patients' age ranged from 18 to 38 years (mean, 28 years). Ninety-one percent of the patients were women and were undergoing surgery for cosmetic reasons. RESULTS: Of the 45 patients who underwent arcade suture upper blepharoplasty with the forceps technique, no patients developed stitch abscess or granuloma, obvious asymmetry, disappearance of line, chemosis, and corneal injury. The follow-up period ranged from 3 months to 4 years (mean, 32 months). Patient satisfaction was very high. CONCLUSIONS: The arcade suture upper blepharoplasty combined with the forceps technique is a simple method for establishing a durable double eyelid without serious complication and providing excellent results.

Postoperative Sedation Duration as an Independent Risk Factor for Postoperative Pneumonia in Head and Neck Cancer Patients Undergoing Free Flap Reconstruction.

OBJECTIVE: Patients who had reconstruction for head and neck cancer usually have long duration of postoperative sedation and intensive care. This is due to the complex nature of large-area soft tissue defect surgeries and upper respiratory tract infections associated with them. Postoperative pulmonary complications are common in these patients. In this study, we analyzed the risk factors and the relationship between postoperative complications and the duration of sedation to improve the patients' recovery process after free flap reconstruction for head and neck surgery. MATERIALS AND METHODS: This was a retrospective study that included 188 patients who had head and neck surgery with free flap reconstruction in 2011 (traditional recovery group) and 2018 (early recovery group). Postoperative recovery events were compared between the 2 groups. Complications such as pneumonia, wound infection, vascular thrombosis, and bleeding were also analyzed. RESULTS: The results showed that the early recovery group had a shorter duration of sedation (P < 0.001), shorter duration of intensive care unit stay (P = 0.05), more rapid ventilator weaning (P < 0.001), and fewer pneumonia events (8.8% vs 39.1%) than the traditional recovery group. Wound- and vessel-related complications were not affected by the duration of sedation. CONCLUSIONS: Our study demonstrated that shortening the duration of postoperative sedation can effectively decrease the length of intensive care unit stay and reduce postoperative incidence of pneumonia without increasing wound- and vessel-related complications.

Olfactory Stimulation Successfully Modulates the Neurochemical, Biochemical and Behavioral Phenotypes of the Visceral Pain.

Visceral pain (VP) is the organ-derived nociception in which increased inflammatory reaction and exaggerated activation of the central nucleus of the amygdala (CeA) may contribute to this deficiency. Considering the amygdala also serves as the integration center for olfaction, the present study aimed to determine whether olfactory stimulation (OS) would effectively depress over-activation and inflammatory reaction in CeA, and successfully relieve VP-induced abnormalities. Adult rats subjected to intraperitoneal injection of acetic acid inhaled lavender essential oil for 2 or 4 h. The potential benefits of OS were determined by measuring the pro-inflammatory cytokine level, intracellular potassium and the upstream small-conductance calcium-activated potassium (SK) channel expression, together with detecting the stress transmitters that participated in the modulation of CeA activity. Results indicated that in VP rats, strong potassium intensity, reduced SK channel protein level, and increased corticotropin-releasing factor, c-fos, and substance P immuno-reactivities were detected in CeA. Enhanced CeA activation corresponded well with increased inflammatory reaction and decreased locomotion, respectively. However, in rats subjected to VP and received OS, all above parameters were significantly returned to normal levels with higher change detected in treating OS of 4h. As OS successfully depresses inflammation and CeA over-activation, application of OS may serve as an alternative and effective strategy to efficiently relieve VP-induced deficiency.

Syndecan-3 contributes to the regulation of the microenvironment at the node of Ranvier following end-to­side neurorrhaphy: sodium image analysis.

Syndecan-3 (SDC3) and Syndecan-4 (SDC4) are distributed throughout the nervous system (NS) and are favourable factors in motor neuron development. They are also essential for regulation of neurite outgrowth in the CNS. However, their roles in the reconstruction of the nodes of Ranvier after peripheral nerve injury (PNI) are still unclear. Present study used an in vivo model of end-to-side neurorrhaphy (ESN) for 1-3 months. The recovery of neuromuscular function was evaluated by grooming test. Expression and co-localization of SDC3, SDC4, and Nav1.6 channel (Nav1.6) at regenerating axons were detected by proximity ligation assay and confocal microscopy after ESN. Time-of-flight secondary ion mass spectrometry was used for imaging ions distribution on tissue. Our data showed that the re-clustering of sodium and Nav1.6 at nodal regions of the regenerating nerve corresponded to the distribution of SDC3 after ESN. Furthermore, the re-establishment of sodium and Nav1.6 correlated with the recovery of muscle power 3 months after ESN. This study suggested syndecans may involve in stabilizing Nav1.6 and further modulate the distribution of sodium at nodal regions after remyelination. The efficiency of sodium re-clustering was improved by the assistance of anionic syndecan, resulting in a better functional repair of PNI.

Treatment effects of the combination of ceftriaxone and valproic acid on neuronal and behavioural functions in a rat model of epilepsy.

NEW FINDINGS: What is the central question of this study? Imbalance of activities between GABAergic and glutamatergic systems is involved in epilepsy. It is not known whether simultaneously increasing GABAergic and decreasing glutamatergic activity using valproic acid and ceftriaxone, respectively, leads to better seizure control. What is the central question of this study? Ceftriaxone suppressed seizure and cognitive deficits and restored neuronal density and the number of newborn cells in the hippocampus in a rat model of epilepsy. Combined treatment with ceftriaxone and valproic acid showed additive effects in seizure suppression. ABSTRACT: The pathophysiology of epilepsy is typically considered as an imbalance between inhibitory GABA and excitatory glutamate neurotransmission. Valproic acid (Val), a GABA agonist, is one of the first-line antiepileptic drugs in the treatment of epilepsy, but it exhibits adverse effects. Ceftriaxone (CEF) elevates expression of glutamate transporter-1, enhances the reuptake of synaptic glutamate, increases the number of newborn cells and exhibits neuroprotective effects in animal studies. In this study, we evaluated effects of the combination of CEF and Val on behavioural and neuronal measures in a rat epilepsy model. Male Wistar rats were injected i.p. with pentylenetetrazol (35 mg/kg, every other day for 13 days) to induce the epilepsy model. Ceftriaxone (10 or 50 mg/kg), Val (50 or 100 mg/kg) or the combination of CEF and Val were injected daily after the fourth pentylenetetrazol injection for seven consecutive days. Epileptic rats exhibited seizure and impairments in motor and cognitive functions. Treatment with CEF and Val reduced the seizure and enhanced motor and cognitive functions in a dose-dependent manner. The combination of CEF (10 mg/kg) and Val (50 mg/kg) improved behaviours considerably. Histologically, compared with control animals, epileptic rats exhibited lower neuronal density and a reduction in hippocampal newborn cells but higher apoptosis in the basolateral amygdala, all of which were restored by the treatment with CEF, Val or the combination of CEF and Val. The study findings demonstrated that the combination of low doses of CEF and Val has beneficial effects on seizure suppression, neuroprotection and improvement in motor and cognitive functions in epilepsy.

Survival analysis of extramammary Paget's disease (EMPD) in a tertiary hospital in Taiwan.

BACKGROUND: This study aimed to investigate the survival analysis of extramammary Paget's disease (EMPD) in a Taiwanese population and to provide data for comparison with other studies in various locations and racial populations. METHODS: We retrospectively analyzed the medical records of 63 patients with EMPD who were surgically treated from 2002 to 2019 at a single institution. The primary endpoint was the 5-year overall survival rate of EMPD, and the secondary endpoint was recurrence-free 5-year survival. Independent variables included patients' demographic data, concurrent malignancy (i.e., non-EMPD-related cancers), tumor size, distant metastasis, and surgery and/or radiation. RESULTS: Of all the 63 patients, 8 cases were excluded. A total of 43 patients (78.18%) were male, and 12 were female, with a mean age of 72.67 years (range 44-89 years). The most common affected anatomic site was the penoscrotal region (22 patients, 40.00%), followed by the perianal and perineal regions (17 patients, 30.91%). Among the 55 patients, 41 patients (74.55%) were diagnosed with at least one underlying disease, whereas the most common underlying disease was cardiovascular disease (30 patients, 54.55%). The overall survival rate was 80.00% at 36 months and 65.45% at the end of follow-up. EMPD with deep dermal invasion was a significant poor prognostic factor of overall survival in cause-specific hazard model (sub-hazard ratio (HR) 5.167, p = 0.0015, 95% confidence interval (CI) 1.876-14.230). Patients with regional metastasis or distant metastasis had poorer prognosis of 5-year survival (sub-HR 4.513, p = 0.0028, CI 1.683-12.103). The limitations of this study include its retrospective nature and sample size. CONCLUSIONS: In our series, EMPD with metastasis and deep dermal invasion was the significant harmful factors in both overall 5-year survival and 5-year recurrence-free survival. The surgical excision is not associated with a low risk of local recurrence or overall survival, and long-term follow-up is still needed.

Using Various Skin Graft Techniques in Major Burn Reconstruction: A Lesson Learned From a Taiwanese Cornstarch Explosion.

PURPOSE: Four hundred and ninety-nine patients had burn injuries in an explosion in Taiwan on June 27, 2015, 24 were admitted to the intensive care units of Taipei Veterans General Hospital. This study details our experience with surgical management of these patients, focusing primarily on various skin graft techniques. MATERIALS AND METHODS: This single-center retrospective study included patients who underwent at least one of the previously mentioned skin graft techniques because of extensive skin defects. The demography, burn diagram, treatment modalities, postoperative outcome, and costs were all analyzed, and a comparison with traditional mesh skin grafts was performed. The literature was also reviewed. RESULTS: Fourteen patients underwent the Meek skin graft technique. Only 3 received ReCell and 1 cultured epithelial autograft (CEA) at separate time point. Overall, the autologous skin grafts, including Meek/ReCell/CEA were completed within 6 months. The average skin graft success rate was approximately 72.9%, 79.2%, and 38% in Meek, ReCell, and CEA, respectively. The infection rate was approximately 35.7%, 25%, and 100% in Meek, ReCell, and CEA, respectively. The average surgical cost and total medical cost were significantly higher in patients who underwent Meek/ReCell/CEA treatments. CONCLUSIONS: In our experience, Meek and ReCell treatments had acceptable success rates, but CEA treatment not. ReCell and CEA treatments are useful in the event of extremely limited donor sites, and they are fragile, easily infected, and technically challenging. These techniques also require longer hospitalization and tend to be more expensive, all factors that should be considered when assessing treatment options.

Cross-Talk of Toll-Like Receptor 5 and Mu-Opioid Receptor Attenuates Chronic Constriction Injury-Induced Mechanical Hyperalgesia through a Protein Kinase C Alpha-Dependent Signaling.

Recently, Toll-like receptors (TLRs), a family of pattern recognition receptors, are reported as potential modulators for neuropathic pain; however, the desired mechanism is still unexplained. Here, we operated on the sciatic nerve to establish a pre-clinical rodent model of chronic constriction injury (CCI) in Sprague-Dawley rats, which were assigned into CCI and Decompression groups randomly. In Decompression group, the rats were performed with nerve decompression at post-operative week 4. Mechanical hyperalgesia and mechanical allodynia were obviously attenuated after a month. Toll-like receptor 5 (TLR5)-immunoreactive (ir) expression increased in dorsal horn, particularly in the inner part of lamina II. Additionally, substance P (SP) and isolectin B4 (IB4)-ir expressions, rather than calcitonin-gene-related peptide (CGRP)-ir expression, increased in their distinct laminae. Double immunofluorescence proved that increased TLR5-ir expression was co-expressed mainly with IB4-ir expression. Through an intrathecal administration with FLA-ST Ultrapure (a TLR5 agonist, purified flagellin from Salmonella Typhimurium, only the CCI-induced mechanical hyperalgesia was attenuated dose-dependently. Moreover, we confirmed that mu-opioid receptor (MOR) and phospho-protein kinase Cα (pPKCα)-ir expressions but not phospho-protein kinase A RII (pPKA RII)-ir expression, increased in lamina II, where they mostly co-expressed with IB4-ir expression. Go 6976, a potent protein kinase C inhibitor, effectively reversed the FLA-ST Ultrapure- or DAMGO-mediated attenuated trend towards mechanical hyperalgesia by an intrathecal administration in CCI rats. In summary, our current findings suggest that nerve decompression improves CCI-induced mechanical hyperalgesia that might be through the cross-talk of TLR5 and MOR in a PKCα-dependent manner, which opens a novel opportunity for the development of analgesic therapeutics in neuropathic pain.

Salivary Gland Tumors: A Clinicopathologic Analysis From Taipei Veterans General Hospital.

BACKGROUND: The aim of this study was to investigate the epidemiological and clinical characteristics of salivary gland tumors (SGTs) in a Taiwanese population and to provide data for comparison with other studies in various locations and racial populations. METHODS: We retrospectively analyzed the medical records of 559 patients with tumors of the salivary glands who were surgically treated from 2002 to 2017 at a single institution. RESULTS: There were 430 benign and 129 malignant tumors with a mean age of 53.5 years (range, 1-91 years). The mean age of patients with benign SGTs was 52.6 years, and the mean age of patients with malignant SGTs was 55.8 years. Most findings were similar to those reported in literature, with some variations. The salivary tumors slightly predominated in males. There were no differences in age and incidence of benign or malignant major SGTs between males and females. The frequency was 76.9% for benign tumors (430 patients) and 23.1% for malignant tumors (129 patients). The majority of the tumors occurred in the parotid gland (351 cases), followed by the submandibular gland (152 cases), the minor salivary glands (46 cases), and, lastly, the sublingual gland (10 cases). Minor SGTs occurred most frequently on the palate, with pleomorphic adenoma, the most frequent benign tumor type, and adenoid cystic carcinoma and mucoepidermoid carcinoma, the commonest malignant tumor types. Tumors of the sublingual gland were rare, but 80% were malignant. CONCLUSIONS: In our series, SGTs were uncommon neoplasms that typically arose in the parotid gland. Benign tumors were far more common than malignant tumors. Pleomorphic adenoma was the most common benign tumors. Adenoid cystic carcinoma and mucoepidermoid carcinoma constituted the most common malignancies. Almost 60% of the tumors arising from minor salivary glands were malignant; thus, special care must be taken when these glands are affected.

Primary Merkel Cell Carcinoma: The Clinical Experience of Taipei Veterans General Hospital Revisited.

BACKGROUND: Merkel cell carcinoma (MCC) is rare among Asians. To evaluate the presence and characteristics of MCC in Taiwan, we described the characteristics, treatment, and prognostic findings of MCC in our institution. METHODS: We revisited and carried out a retrospective chart review of 16 consecutive patients with MCC treated from 1995 to 2018. Patient demographic data, tumor size, location, previous treatment, and follow-up data about presence of locoregional recurrence and metastasis were evaluated. RESULTS: There were 14 male and 2 female patients (mean age = 75.1 years; range = 26-91 years). Clinical follow-up revealed local recurrences in 5 patients 1 to 4 months after surgical excision. Lymph node metastasis was observed in 3 patients. We reviewed previously published articles and analyzed the clinical findings, pathologic examinations, and treatments. CONCLUSIONS: Surgical wide excision of the primary tumor remains the mainstay of treatment for patients with local/regional MCC. Additional management strategies, such as lymphadenectomy, radiotherapy, chemotherapy, and targeted therapy, depend on the presence or absence of clinically detectable lymph node disease. The prognosis for MCC is variable. Our findings highlight the importance of maintaining a high clinical suspicion for this malignancy in the appropriate clinical context to avoid delays in diagnosis and management.

Madelung Disease: Analysis of Clinicopathological Experience in Taipei Veterans General Hospital.

BACKGROUND: The main feature of Madelung disease (MD), a rare condition, is the growth of adipose tissue without a capsule. Usually, this disease is known for its prominent features with fat deposition around the neck, shoulder, back, or chest wall. Clinically, the patient is likely to exhibit alcohol, neuropathy, and metabolic disorders; however, no clear cause has been confirmed. AIMS: The aim of this study was to analyze the morphological, pathophysiological, and various treatment methods of MD. We have presented and discussed 16 cases of treatment of this disease at our hospital and reviewed the literature on this subject. METHODS: We carried out a retrospective chart review of 16 consecutive patients with MD treated from 1989 through 2017. Patient demographic data, tumor size and location, and follow-up data were evaluated. Patients usually seek treatment because of the disfigured appearance, restricted range of the motion of the head and neck, inconvenience in daily activity such as eating or speaking, and worry about the mass effect. All patients underwent surgical resection and/or combined liposuction. RESULTS: Among the patients, 14 were men, aged 38 to 80 years, with a history of disease ranging from 6 months to 7 years. The mean duration from symptoms to diagnosis of MD was 4.4 years. The mean duration of follow-up was 82.8 months (range, 5-192 months). Three patients died of coronary artery disease at follow-up of 27, 78, and 141 months. The functional results were satisfactory in all patients. Severe complications were not observed. CONCLUSIONS: According to our experience, surgical resection is the main method of improving the appearance, ensuring eradication of the tumor, and reducing the possibility of recurrence. In addition, we have a case in which atypical changes were confirmed by histological examination in fractional surgery. A long follow-up period is recommended considering the high propensity and mean time to recurrence. Although malignant transformation of MD is rare occurrence, it occurred in 1 of the 16 patients.

Determinants of Free Fasciocutaneous Flap Outcomes in Partial Hypopharyngeal Defects.

BACKGROUND: Most of the patients with hypopharyngeal cancer are still diagnosed with advanced stage, and total or partial pharyngectomy with free flap reconstruction is the mainstay of treatment. The aim of this study was to find out the possible risk factors related to surgical complications after free fasciocutaneous flap reconstruction for partial pharyngeal defect and its sequelae in the follow-up. PATIENTS AND METHODS: We retrospectively reviewed the charts of patients with advanced hypopharyngeal cancer who received free fasciocutaneous flaps for partial pharyngeal defects reconstruction. From 2005 to 2015, 79 free fasciocutaneous flaps (59 free fasciocutaneous flaps and 20 anterolateral thigh flaps) were performed in our department. The risk factors for free flap outcome and complications were evaluated with multivariant linear regression model. RESULTS: The mean age of patients was 60.8 years with male predominance. The mean follow-up duration was 39.6 months. Most of the cases (97.5%) were in stage III or IV. Patients with comorbidities showed significant correlation to flap failure (95% confidence interval [CI] = 0.038 to 0.264, P = 0.10). Anastomosis style (end-to-side vs end-to-end) was the only operation-related factors significantly related to flap failure rate (18.8% vs 3.2%, 95% CI = 0.031 to 0.32, P = 0.18). Flap size was significantly associated with fistula formation (95% CI = -0.005 to 0.000, P = 0.38). CONCLUSIONS: In our experience, patients with comorbidities and end-to-side anastomosis illustrate significantly higher flap failure rate in free fasciocutaneous flap reconstruction of partial hypopharyngeal defect. Reconstruction with smaller flap size had higher possibility of fistula formation.

Rearrangement of potassium ions and Kv1.1/Kv1.2 potassium channels in regenerating axons following end-to-end neurorrhaphy: ionic images from TOF-SIMS.

The voltage-gated potassium channels Kv1.1 and Kv1.2 that cluster at juxtaparanodal (JXP) regions are essential in the regulation of nerve excitability and play a critical role in axonal conduction. When demyelination occurs, Kv1.1/Kv1.2 activity increases, suppressing the membrane potential nearly to the equilibrium potential of K+, which results in an axonal conduction blockade. The recovery of K+-dependent communication signals and proper clustering of Kv1.1/Kv1.2 channels at JXP regions may directly reflect nerve regeneration following peripheral nerve injury. However, little is known about potassium channel expression and its relationship with the dynamic potassium ion distribution at the node of Ranvier during the regenerative process of peripheral nerve injury (PNI). In the present study, end-to-end neurorrhaphy (EEN) was performed using an in vivo model of PNI. The distribution of K+ at regenerating axons following EEN was detected by time-of-flight secondary-ion mass spectrometry. The specific localization and expression of Kv1.1/Kv1.2 channels were examined by confocal microscopy and western blotting. Our data showed that the re-establishment of K+ distribution and intensity was correlated with the functional recovery of compound muscle action potential morphology in EEN rats. Furthermore, the re-clustering of Kv1.1/1.2 channels 1 and 3 months after EEN at the nodal region of the regenerating nerve corresponded to changes in the K+ distribution. This study provided direct evidence of K+ distribution in regenerating axons for the first time. We proposed that the Kv1.1/Kv1.2 channels re-clustered at the JXP regions of regenerating axons are essential for modulating the proper patterns of K+ distribution in axons for maintaining membrane potential stability after EEN.

Melatonin successfully rescues hippocampal bioenergetics and improves cognitive function following drug intoxication by promoting Nrf2-ARE signaling activity.

Prolonged exposure to gamma-hydroxybutyric acid (GHB) would cause drug intoxication in which impaired cognitive function results from enhanced hippocampal oxidative stress may serve as a major symptom in this deficiency. Considering melatonin possesses significant anti-oxidative efficacy, this study aimed to determine whether melatonin would successfully promote the nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) signaling, depress oxidative stress, and rescue hippocampal bioenergetics and cognitive function following drug intoxication injury. Adolescent rats subjected to 10 days of GHB were received melatonin at doses of either 10 or 100 mg/kg. Time-of-flight secondary ion mass spectrometry, biochemical assay, quantitative histochemistry, [14 C]-2-deoxyglucose analysis, together with Morris water maze were employed to detect the molecular signaling, oxidative status, bioenergetic level, as well as the cognitive performances, respectively. Results indicated that in GHB-intoxicated rats, enhanced oxidative stress, increased cholesterol level, and decreased anti-oxidative enzymes activities were detected in hippocampal regions. Intense oxidative stress paralleled well with reduced bioenergetics and poor performance in behavioral testing. However, in rats treated with melatonin following GHB intoxication, all above parameters and cognitive function were gradually returned to nearly normal levels. Melatonin also remarkably promoted the translocation of Nrf2 from cytoplasm to nucleus in a dose-dependent manner, thereby increased the Nrf2-ARE signaling-related downstream anti-oxidative enzymes activities. As melatonin effectively rescues hippocampal bioenergetics through depressing the oxidative stress by promoting Nrf2-ARE molecular machinery, this study thus highlights for the first time that clinical use of melatonin may serve as a therapeutic strategy to improve the cognitive function in unsuspecting victims suffered from GHB intoxication injury.

Cutaneous Leiomyosarcoma: The Clinical Experience of Taipei Veterans General Hospital Revisited.

BACKGROUND: Cutaneous leiomyosarcoma (CLM) is a rare soft tissue tumor of smooth muscle derivation. We report the clinical treatment, long-term outcomes, and prognostic findings of CLM in our institution. MATERIALS AND METHODS: We revisited and carried out a retrospective chart review of 16 consecutive patients with CLM treated from 1991 through 2015. Patient demographic data, tumor size, location, previous treatment, follow-up data, and the presence or absence of recurrence were evaluated. RESULTS: There were 6 males and 10 females (mean age, 48.6 years; range, 20-78 years). Clinical follow-up revealed local recurrences in 4 patients 1.3 to 72 months after surgical excision. No distant metastases were observed. We reviewed previously published articles and analyzed the clinical findings, pathologic examinations, and treatments. CONCLUSIONS: Surgical tumor excision with a wide lateral and deep margin is the most appropriate method. Other therapeutic methods such as radio- or chemotherapy provide no significant benefits. We recommend long-term follow-up of patients because recurrence is possible although not common.

Investigation of Prognostic Features in Primary Cutaneous and Soft Tissue Angiosarcoma After Surgical Resection: A Retrospective Study.

Primary cutaneous and soft tissue angiosarcoma is a rare but highly aggressive malignancy. To date, surgical resection is the mainstay of treatment, but poor prognosis is expected. To investigate whether there are factors associated with poor prognosis after surgical resection and to develop a treatment guideline for current therapy, we retrospectively collected data on 28 patients who underwent surgery as initial treatment and reviewed patient demographics, tumor characteristics, disease courses, and prognoses from September 1996 to May 2013. Of these 28 patients, 17 (60.7%) were men and the mean age at first diagnosis was 66.57 ± 18.57 years. Anatomically, 17 (60.7%) tumors were in the scalp and 11 (39.3%) were in other sites of the body. Of the 28 patients, 23 (82.1%) had achieved negative surgical margins, 24 (85.7%) received adjuvant radiation therapy, and 17 (60.7%) received adjuvant chemotherapy. Twenty-one patients (75%) died during a mean follow-up time of 35.86 ± 28.91 months, and all deaths were caused by angiosarcoma. The 5-year overall survival rate was 17.86%. Sixteen (57.1%) patients had locoregional tumor recurrence, and 20 (71.4%) had distant metastases, with a median of 9.17 (range, 1.9-98.07) months to recurrence or metastasis. Possible predictors of poor prognosis (P < 0.05) in terms of disease-free survival after surgical resection were male sex, cardiovascular disease, smoking, and scalp angiosarcomas, those in terms of overall survival were older than 70 years, male sex, cardiovascular disease, smoking, scalp angiosarcomas, distant metastases, and not receiving adjuvant chemotherapy. In conclusion, although multimodal treatments are used, the overall prognosis after surgical resection is still poor, especially for patients with the above predictive factors. An early diagnosis and complete resection of the primary tumor with or without adjuvant radiotherapy and chemotherapy are suggested for a potential better outcome. For those who have a diffuse lesion pattern with the involvement of vital structures, recurrence, or metastasis, palliative resection could be an alternative treatment choice.

Redistribution of Cav2.1 channels and calcium ions in nerve terminals following end-to-side neurorrhaphy: ionic imaging analysis by TOF-SIMS.

The P/Q-type voltage-dependent calcium channel (Cav2.1) in the presynaptic membranes of motor nerve terminals plays an important role in regulating Ca2+ transport, resulting in transmitter release within the nervous system. The recovery of Ca2+-dependent signal transduction on motor end plates (MEPs) and innervated muscle may directly reflect nerve regeneration following peripheral nerve injury. Although the functional significance of calcium channels and the levels of Ca2+ signalling in nerve regeneration are well documented, little is known about calcium channel expression and its relation with the dynamic Ca2+ ion distribution at regenerating MEPs. In the present study, end-to-side neurorrhaphy (ESN) was performed as an in vivo model of peripheral nerve injury. The distribution of Ca2+ at regenerating MEPs following ESN was first detected by time-of-flight secondary ion mass spectrometry, and the specific localization and expression of Cav2.1 channels were examined by confocal microscopy and western blotting. Compared with other fundamental ions, such as Na+ and K+, dramatic changes in the Ca2+ distribution were detected along with the progression of MEP regeneration. The re-establishment of Ca2+ distribution and intensity were correlated with the functional recovery of muscle in ESN rats. Furthermore, the re-clustering of Cav2.1 channels after ESN at the nerve terminals corresponded with changes in the Ca2+ distribution. These results indicated that renewal of the Cav2.1 distribution within the presynaptic nerve terminals may be necessary for initiating a proper Ca2+ influx and shortening the latency of muscle contraction during nerve regeneration.

Experience With the Use of Free Fasciocutaneous Flap in Through-and-Through Cheek-Buccal Defect Reconstruction: Surgical Outcome and Quality of Life Analysis.

BACKGROUND: Through-and-through cheek-buccal soft tissue defects usually require fasciocutaneous flaps for reconstruction. However, no ideal flap has been established for reconstruction. METHODS: A retrospective chart review of head and neck reconstruction performed at Taipei Veterans General Hospital between 2003 and 2012 was conducted. Surgical outcomes and quality-of-life assessments between different fasciocutaneous flaps were collected and compared. RESULTS: Eighty-five patients received a free anterolateral thigh flap, and 25 patients received a free forearm flap. The flap success rates were 96.4% for the free anterolateral thigh flap and 96% for the free forearm flap. Appearance, swallowing, and speech were less satisfactory in long-term follow-up; and recurrent tumor, flap size (>100 cm²), oral commissure involvement, and long hospital stay (>40 days) were associated with unsatisfactory quality of life. CONCLUSIONS: Free fasciocutaneous flap can result in acceptable success rates, but patient satisfaction with appearing, swallowing, and speech function was relatively low after reconstruction. Tumor status (primary or recurrent), flap size, oral commissure involvement, and length of hospital stay are the main factors that affect quality of life.

Atypical Lipomatous Tumors of the Extremities and Trunk Wall-The First Case Series of Chinese Population With 45 Cases.

BACKGROUND: Atypical lipomatous tumor (ALT) is a low-grade, slow-growing, locally aggressive malignant mesenchymal neoplasm. ALT of the extremities and trunk wall is associated with a relatively favorable outcome. However, these tumors can still recur locally and secondary dedifferentiation after recurrence has been reported. There is currently no consensus about the optimal surgical treatment of ALT. Therefore, we aimed to clarify the clinical behavior, appropriate treatment, and outcomes of ALT of the extremities and trunk wall. METHODS: We retrospectively reviewed the files of 45 patients treated between 2000 and 2014 with the diagnosis of atypical lipomatous tumors of the extremities and trunk wall at our institution. The median follow-up period was 84.5 months (range, 24-183 months). The patient demographics, clinical presentation, surgical methods, margin status, and administration of radiation therapy were recorded. Patients were evaluated for their local recurrence, dedifferentiation, and postoperative complications. RESULTS: Wide resection was performed on 11 patients, and marginal resection was performed on 34 patients. Seven patients underwent adjuvant radiotherapy. The overall recurrence rate was 17.8% (8/45), and dedifferentiation rates was 0% (0/8). The mean time to local recurrence was 5.25 years (range, 2.6-10.6 years). No ALT-related deaths occurred during the follow-up period. There were no differences in recurrence-free survival for the different surgical methods (P = 0.337) and radiotherapy (P = 0.228), whereas the R0 resection had better recurrence-free survival (P = 0.031). The postoperative complication rates were higher in wide resection group than in marginal resection group. (45.5% vs 14.7%, P = 0.048). CONCLUSIONS: Atypical lipomatous tumors of the extremities and trunk wall are associated with a favorable overall survival and do not metastasis. Although they have a tendency to recur, the risk of secondary dedifferentiation is small. Wide resection had similar recurrence rates to marginal resection, but it might lead to more complications. Therefore, marginal resection is considered appropriate for the treatment of ALTs.