Preoperative Computed Tomography Angiography for Evaluation of Feasibility of Free Flaps in Difficult Reconstruction of Head and Neck.

BACKGROUND: Free tissue transfer has been advocated for anatomic and functional reconstruction of soft tissue defects after surgical removal of an extensive recurrent tumor and/or arising from previous irradiation in the head and neck. We report a case series of difficult reconstruction in the head and neck in which preoperative computed tomography (CT) angiography was utilized to evaluate the feasibility of free flap reconstruction. The preoperative radiological evaluation was performed to determine the availability of reliable vessels for anastomosis in free flap reconstruction. If none was found, regional pedicle flap or palliative treatment was applied instead. The use of CT angiography allows the clinical surgeon to perform precise surgical planning with greater confidence. This may improve surgical results, thereby potentially reducing perioperative morbidity. METHODS: Twenty CT angiograms were obtained from 20 patients. All patients were men with a mean age of 57.2 years (range, 42-72 years) and were scheduled to undergo difficult reconstruction in the head and neck. All patients (20/20 [100%]) suffered from oral squamous cell carcinoma. They had all received extensive operations and radiation therapy. Eighteen patients (18/20 [90%]) had completed a course of perioperative irradiation. The CT angiography reports were used to perform detailed preoperative surgical planning accordingly. The findings of CT angiography were classified into 3 groups: group I: normal CT angiography (patent recipient arteries) (Fig. 3); group II: abnormal CT angiography (recipient vessels were present but stenosis or atherosclerotic lesions were noted) (Fig. 4); group III: abnormal CT angiography with no patent recipient arteries in bilateral sides of the neck (Fig. 5); CT angiography results were correlated to the operative findings. RESULTS: The patients were classified into 3 groups based on the angiographic findings. Six patients (6/20 [30%]) were assigned to group I, 8 patients (8/20 [40%]) to group II, and 6 patients (6/20 [30%]) to group III. In groups I and III, all patients (12/12 [100%]) underwent the treatment according to the original preoperative detailed planning. No flap failure was noted in these 2 groups. In group II, 4 patients' recipient vessels (4/8 [50%]) possessed adequate blood flow intraoperatively; hence, microvascular free flaps were transplanted. Venous congestion in 1 case (1/4 [25%]) was noted. The remaining patients in this group (4/8 [50%]) underwent reconstruction with pedicle flaps rather than free flaps because of the lack of suitable target vessels intraoperatively. All flaps (4/4 [100%]) survived. Among the patients who were treated surgically, intraoperative findings were in accordance with those predicted by CT angiography. The total abnormality rate of CT angiography was 70%. Vascular abnormalities detected as a result of preoperative CT angiography led to changes in the operative plan in 50% (10/20) of the patients. CONCLUSIONS: The use of CT angiography should be considered for difficult microsurgical reconstructions in the head and neck. When an abnormality in vascular anatomy is detected by CT angiography, the surgeon is advised to consider altering the operative plan accordingly. This allows precise operation, thereby maximizing the possibility of an optimal outcome. Changing the operative plan based on results of CT angiography may also help to avoid the difficult situation in which the surgeon finds that there are no suitable recipient vessels for free flap reconstruction during the operation. In addition, CT angiography enables surgeons to conduct the preoperative surgical planning with greater confidence, thereby potentially enhancing the success rate of difficult reconstructions in the head and neck, which in turn would tend to improve the perioperative course for the patient and consequently to improve results by decreasing vascular complication rates.

Endovascular intervention in Taiwanese patients with critical limb ischemia: patient outcomes in 333 consecutive limb procedures with a 3-year follow-up.

BACKGROUND/PURPOSE: Midterm outcomes of endovascular intervention (EVI) for critical limb ischemia (CLI) have not been previously reported in Taiwan. This study assessed the safety, feasibility, and patient-oriented outcomes for CLI patients after EVI. METHODS: From June 2005 to December 2011, 270 patients underwent EVI for CLI of 333 limbs. Primary patency (PP), assisted primary patency (AP), limb salvage, sustained clinical success (SCS), secondary SCS (SSCS), and survival were assessed using Kaplan-Meier analysis. RESULTS: The procedural success rate was 89%, and the periprocedural mortality and major complication rates within 30 days were 0.6% and 6.9%, respectively. During the mean follow-up time of 27 ± 20 months (1-77), 64 patients died and 25 legs required major amputation. Eighty-one percent of the patients with tissue loss had wound healing at 6 months and 75% of the patients were ambulatory, with or without assisting devices, at 1 year. The overall survival and limb salvage rates at 3 years were 70% and 90%, respectively. The PP and AP at 1 and 3 years were 58% and 37% and 79% and 61%, respectively. The SCS and SSCS were 65% and 46% and 80% and 64% at 1 and 3 years, respectively. CONCLUSION: In Taiwan, EVI was a safe and feasible procedure for CLI patients, with a high procedural success rate and lower complication rate. Sustained limb salvage and clinical success can be afforded with an active surveillance program and prompt intervention during midterm follow-up.

Microcurrent Cloth-Assisted Transdermal Penetration and Follicular Ducts Escape of Curcumin-Loaded Micelles for Enhanced Wound Healing.

Purpose: Larger nanoparticles of bioactive compounds deposit high concentrations in follicular ducts after skin penetration. In this study, we investigated the effects of microcurrent cloth on the skin penetration and translocation of large nanoparticle applied for wound repair applications. Methods: A self-assembly of curcumin-loaded micelles (CMs) was prepared to improve the water solubility and transdermal efficiency of curcumin. Microcurrent cloth (M) was produced by Zn/Ag electrofabric printing to facilitate iontophoretic transdermal delivery. The transdermal performance of CMs combined with M was evaluated by a transdermal system and confocal microscopy. The CMs/iontophoretic combination effects on nitric oxide (NO) production and inflammatory cytokines were evaluated in Raw 264.7 cells. The wound-healing property of the combined treatment was assessed in a surgically created full-thickness circular wound mouse model. Results: Energy-dispersive X-ray spectroscopy confirmed the presence of Zn/Ag on the microcurrent cloth. The average potential of M was measured to be +214.6 mV in PBS. Large particle CMs (CM-L) prepared using surfactant/cosurfactant present a particle size of 142.9 nm with a polydispersity index of 0.319. The solubility of curcumin in CM-L was 2143.67 µg/mL, indicating 250-fold higher than native curcumin (8.68 µg/mL). The combined treatment (CM-L+M) demonstrated a significant ability to inhibit NO production and increase IL-6 and IL-10 secretion. Surprisingly, microcurrent application significantly improved 20.01-fold transdermal performance of curcumin in CM-L with an obvious escape of CM-L from follicular ducts to surrounding observed by confocal microscopy. The CM-L+M group also exhibited a better wound-closure rate (77.94% on day 4) and the regenerated collagen intensity was approximately 2.66-fold higher than the control group, with a closure rate greater than 90% on day 8 in vivo. Conclusion: Microcurrent cloth play as a promising iontophoretic transdermal drug delivery accelerator that enhances skin penetration and assists CMs to escape from follicular ducts for wound repair applications.

Effect of Total Intravenous Anesthesia on Postoperative Pulmonary Complications in Patients Undergoing Microvascular Reconstruction for Head and Neck Cancer: A Randomized Clinical Trial.

Importance: Free flap surgery is a lengthy procedure with massive tissue destruction and reconstruction, which makes postoperative pulmonary complications (PPCs) a noticeable issue among patients with head and neck cancer. Propofol-based total intravenous anesthesia (TIVA) has better survival outcomes than inhalational anesthesia (INH) in several types of cancer surgery. A previous retrospective study found that patients in the TIVA group had a lower PPC rate, which may be correlated with a lower intraoperative fluid requirement. We hypothesize that the protective effect remains among patients undergoing free flap surgery for head and neck cancer in a prospective and goal-directed fluid therapy setting. Objective: To assess the effect of TIVA vs INH on PPCs in patients undergoing microvascular reconstruction for head and neck cancer. Design, Setting, and Participants: This prospective, 2-arm, randomized clinical trial was conducted at a tertiary hospital in Taiwan; a total of 78 patients 18 years and older with American Society of Anesthesiologists physical status classification 1 to 3 who were scheduled for elective free flap surgery under general anesthesia were included. The trial started in October 2017, completed in October 2019, and finished analysis in January 2022. Interventions: Patients were enrolled and randomized to the TIVA or INH group. All patients received goal-directed fluid therapy and hemodynamic management if they had a mean arterial pressure (MAP) below 75 mm Hg or a reduction of 10% from baseline MAP. Main Outcomes and Measures: The primary outcome was a composite of PPCs. The secondary outcomes were the differences in intraoperative hemodynamic values (mean arterial pressure, MAP; cardiac index, CI; systemic vascular resistance index, SVRI; and stroke volume variation, SVV). Results: A total of 70 patients (65 men [93%]; 5 women [7%]) completed the trial; median (IQR) age was 52.0 (48-59) years in the TIVA group and 57.0 (46-64) years in the INH group. The demographic characteristics were similar between the 2 groups, except that patients in the TIVA group had a slightly lower body mass index. Patients in the TIVA group had a lower risk of developing PPCs (unadjusted odds ratio, 0.25; 95% CI, 0.08-0.80). The TIVA group had significantly higher MAP, lower CI, and higher SVRI than the INH group after the third hour of monitoring. The TIVA group showed a relatively stable hourly MAP, CI, SVRI, and SVV across time points, while the INH group showed a more varying pattern. The generalized estimating equation showed no clinical differences in the trend of hemodynamic parameters across time between groups. Conclusions and Relevance: In this randomized clinical trial, using propofol-based TIVA reduced the incidence of PPCs in free flap surgery. This finding may be related to more stable hemodynamic manifestations and a lower total balance of fluid throughout the surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03263078.

Chloroquine alleviates the heat-induced to injure via autophagy and apoptosis mechanisms in skin cell and mouse models.

Burns can cause cell death and irreversible tissue damage. We examined the pathway of human dermis fibroblasts cell death caused by skin burns and the roles of chloroquine in human skin keratinocytes HaCaT wound healing. Western blot assays were performed to assess expression of proteins associated with autophagy, apoptosis, and endoplasmic reticulum stress in skin cells following burns. Changes in apoptosis-related proteins were assessed using flow cytometry, and wound cell migration was examined using wound healing assays. The burn animal model was used to test whether chloroquine would promote wound healing. In human burned fibroblasts, expression of LC3B-II and Cleave-caspase-7 was increased, whereas expression of Beclin-1, p62, and Grp78 was decreased. Severe burn induced ER stress and ERK phosphorylation, but PD98059 or necrostatin-1 treatment cells did not affect expression of autophagy LC3B-II protein and can induce apoptosis. Even though added with TGF-ß and FGF did not repair autophagy caused by burns. Suggesting that autophagy and apoptosis were involved in heat-injured mechanism. Recombinant Wnt3a protein can help restore expression of ß-catenin which reduced following burns in keratinocytes. Wnt3a protein can promote migration of keratinocytes after burns. Interesting, chloroquine increased expression of LC3B-II protein and restored cell migration activity after 24 h of burns. Consistently, surgical dressing containing chloroquine promoted wound healing in a burn animal mode. Autophagy and Wnt/ß-catenin is two signalling pathways that participate in cell repair and wound healing in human fibroblasts, keratinocytes. Surgical dressing containing chloroquine can recover wound healing in burned rats.

Invasive Candidiasis in Hospitalized Patients with Major Burns.

BACKGROUND: Invasive candidiasis (IC) is a major cause of morbidities and mortality in patients hospitalized with major burns. This study investigated the incidence of IC in this specific population and analyzed the possible risk factors. MATERIALS AND METHODS: We retrospectively analyzed data from the National Health Insurance Research Database (NHIRD) of Taiwan. We identified 3582 patients hospitalized with major burns on over 20% of their total body surface area (TBSA) during 2000-2013; we further analyzed possible risk factors. RESULT: IC was diagnosed in 452 hospitalized patients (12.6%) with major burns. In the multivariate analysis, patients older than 50 years (adjusted odds ratio (OR) = 1.96, 95% confidence interval (CI) 1.36-2.82), those of female sex (adjusted OR = 1.33, 95% CI 1.03-1.72), those with burns on the head (adjusted OR = 1.33, 95% CI 1.02-1.73), and those with burns over a greater TBSA had higher risks of IC. CONCLUSION: Treating IC is crucial in healthcare for major burns. Our study suggests that several risk factors are associated with IC in patients hospitalized with major burns, providing reliable reference value for clinical decisions.

Inhibition of proliferation and migration of melanoma cells by ketoconazole and Ganoderma immunomodulatory proteins.

Ketoconazole, an antifungal agent, has been used to inhibit hormone synthesis in types of prostate and breast cancer. Immunomodulatory proteins of Ganoderma microsporum (GMI) inhibit the tumor necrosis factor-α- and epidermal growth factor-induced metastatic ability of lung cancer cells. Cutaneous malignant melanoma is a highly invasive and metastatic skin cancer. However, to the best of our knowledge, there is limited understanding regarding the effects of ketoconazole and GMI on melanoma. The current study aimed to investigate the inhibitory effects of GMI combined with ketoconazole on melanoma survival and metastasis. The effects of GMI combined with ketoconazole on the viability, migration and protein expression of melanoma cells were determined by MTT assay, Boyden chamber assay and western blot analysis, respectively. The expression of monocyte chemoattractant protein-1 (MCP-1) was investigated by enzyme-linked immunoabsorbent assay. The present results indicate that ketoconazole enhances the GMI-induced decrease in proliferation and migration of A375.S2 melanoma cells in a concentration-dependent manner. Ketoconazole was identified to reduce the level of GMI-induced phosphorylated-adenosine monophosphate-activated protein kinase (p-AMPK)-α and autophagy; however, ketoconazole did not affect p-AMPK-ß levels in A375.S2 cells. In addition, ketoconazole and dorsomorphin dihydrochloride, an AMPK inhibitor, were revealed to reduce MCP-1 secretion in A375.S2 cells. In summary, the present study revealed that ketoconazole enhances GMI-inhibited proliferation and migration of A375.S2 melanoma cancer cells, and inhibits the secretion of MCP-1.

Ganoderma immunomodulatory protein and chidamide down-regulate integrin-related signaling pathway result in migration inhibition and apoptosis induction.

BACKGROUND: In terms of melanoma, recent advances have been made in target therapies and immune checkpoint inhibitors, but durable remission is rare. Ganoderma immunomodulatory proteins (GMI) induce a cytotoxic effect in cancer cells via autophagy. However, the role of GMI in melanoma is not clear. PURPOSE: The aims of this study are to investigate the inhibiting effects of GMI combined with chidamide on survival and metastases of melanoma cells via integrin-related signaling pathway and to propose strategies for combining GMI and chidamide using animal model. METHODS: Cell viability was measured by cell CCK-8. The activities of apoptosis- and migration-related proteins were detected on Western blot. Flow cytometry was used to analyze cell cycle distribution and sub-G1 fraction in treated melanoma cells. To evaluate the activity of combination GMI and chidamide treatment, an in vivo anti-tumor metastasis study was performed. RESULTS: GMI combined with chidamide additively induced apoptosis. GMI inhibited the expressions of Integrin α5, αV, ß1, and ß3. The level of p-FAK was inhibited by GMI. Combination treatment of GMI and chidamide decreased survivin and increased cleaved caspase-7 and LC3 II/I. Integrin-αV overexpression activated p-FAK pathways in A375.S2 cells. GMI significantly inhibited cell growth and migration of A375.S2 cells on wound healing assay. In vivo, GMI combined with chidamide suppressed distal tumor metastasis. CONCLUSION: GMI inhibits the migration and growth of melanoma cells via integrin-related signaling pathway. GMI and chidamide induces apoptosis. In vivo, GMI and chidamide additively reduce distant metastases. GMI and chidamide are potential immunotherapeutic adjuvant for metastatic melanoma.

Advances and Applications of Ion Torrent Personal Genome Machine in Cutaneous Squamous Cell Carcinoma Reveal Novel Gene Mutations.

The Ion Torrent Personal Genome Machine (Ion PGM) is a semiconductor-based sequencing technology that is high quality, scalable, and economic. Its applications include genomic sequencing, drug resistance testing, microbial characterization, and targeted sequencing in cancer studies. However, little is known about the application of Ion PGM in cutaneous squamous cell carcinoma (cSCC). We therefore investigated the utility and validity of Ion PGM in cSCC and also gained a better understanding of the underlying molecular biology of cSCC. We detected novel gene mutations (KDR, FGFR2, and EGFR) in two cSCC patients. Moreover, we validated these mutations by pyrosequencing and Sanger sequencing. Our results indicated that the mutation screen using Ion PGM is consistent with traditional sequencing methods. Notably, these identified mutations were present at significantly higher rates in high-risk cSCC. Our results demonstrate a method to detect targetable genes in high-risk cSCC, and suggest that Ion PGM may enable therapeutic decision-making and future potential targets for personalized therapies in cSCC.

Differences between Total Intravenous Anesthesia and Inhalation Anesthesia in Free Flap Surgery of Head and Neck Cancer.

BACKGROUND: Many studies have evaluated risk factors associated with complications after free flap surgery, but these studies did not evaluate the impact of anesthesia management. The goal of the current study was to evaluate the differences between patients who received inhalation and total intravenous anesthesia (TIVA) in free flap surgery. METHODS: One hundred and fifty-six patients who underwent free flap surgery for head and neck cancer were retrospectively divided into the TIVA (96 patients) and the inhalation group (87 patients). Perioperative hemodynamic data and postoperative medical complications were determined by documented medical records. RESULTS: Ninety-six patients in the TIVA group were compared with 87 patients who received inhalation anesthesia. There were no differences in gender, age, classification of physical status based on American Society for Anesthesiologists (ASA) score, and cormobidities between the two groups. Patients in the TIVA group required less perioperative crystalloid (4172.46 ± 1534.95 vs. 5183.91 ± 1416.40 ml, p < 0.0001) and colloid (572.46 ± 335.14 vs. 994.25 ± 434.65 ml, p < 0.0001) to maintain hemodynamic stability. Although the mean anesthesia duration was shorter in the TIVA group (11.02 ± 2.84 vs. 11.70± 1.96 hours, p = 0.017), the blood loss was similar between groups (p = 0.71). There was no difference in surgical complication rate, but patients in the TIVA group developed fewer pulmonary complications (18 vs. 47, p = 0.0008). After multivariate regression, patients in the TIVA group had a significantly reduced risk of pulmonary complication compared with the inhalation group (Odds ratio 0.41, 95% CI 0.18-0.92). CONCLUSIONS: Total intravenous anesthesia was associated with significantly fewer pulmonary complications in patients who received free flap reconstruction.

Xeroderma pigmentosum complementation group C protein (XPC) expression in basal cell carcinoma.

BACKGROUND: The Xeroderma pigmentosum complementation group C protein (XPC) is a general sensor of damaged DNA. Individuals carrying a mutation in XPC genes exhibit marked photosensitivity and increased occurrence of skin cancers. Little is known about the distribution of XPC protein in basal cell carcinoma (BCC). AIM: To determine whether the XPC protein is associated with basal cell carcinoma. MATERIALS AND METHODS: In the present study, we investigated the protein expression of XPC by immunohistochemistry in 86 cases of BCC and paired-adjacent normal epidermis. RESULTS: The intensity of nuclear XPC expression was significantly higher in BCC compared to adjacent normal epidermis (p<0.001). Attenuated XPC expression was associated with high-risk BCC (p=0.045) but was not significantly associated with age, gender and body area. CONCLUSION: Our results indicate that XPC is associated with BCC and further studies are warranted to determine if the XPC-BCC interaction is specific to just one cancer cell type and to investigate potential mechanisms.

Immediate toe transfer following index finger amputation for extensive giant cell tumor of the tendon sheath with intraosseous invasion.

Giant cell tumor of the tendon sheath (GCTTS) is the second most common benign tumor of the hand. Although bony indentation from external compression by the GCTTS is frequently seen on x-ray film, the intraosseous invasion is relatively rare and is a sign for high recurrence. We present a woman with extensive GCTTS located in the left index finger at the level of distal interphalangeal joint. X-ray films revealed multiple osteolytic cystic cavities in the shaft of the middle phalanx. Amputation of the index finger at the base of the middle phalanx was performed because of extensive bony involvement and concern about possible recurrence from inadequate excision. Her left second toe was transferred to replace the amputated index finger in the same session. Follow-up examination at 15 months postoperative revealed good function and appearance of the reconstructed index.