Comparative study of arterial and venous grafting for pedicle lengthening in head and neck microvascular reconstruction.

BACKGROUND: In the field of head and neck microvascular reconstruction, no previous study has compared arterial and venous grafting as methods of anterolateral thigh (ALT) pedicle lengthening. Therefore, we conducted this comparative study to compare the outcomes between the two pedicle lengthening techniques. METHODS: We performed comparative effectiveness research by conducting a retrospective chart review from January 2012 to December 2021 to identify patients who underwent head and neck reconstruction with non-descending branch ALT perforator flaps using either the in situ pedicle lengthening (ISPL) technique or the vein graft (VG) technique. A total of 26 patients were analyzed, including 14 who underwent ISPL, and 12 who underwent VG. The collected data, including patient demographics, surgical indications, history of prior free flap, prior neck dissection, radiation therapy, chemotherapy, graft length, and flap outcomes, were analyzed. The flap outcomes were categorized as total flap loss, partial flap loss, flap compromise that required operating room visits, or minor issues, including infection or dehiscence. The flap characteristics and postoperative outcomes were compared between the two groups. RESULTS: The VG group had two flap losses, whereas the ISPL group had none. Although the failure rate was higher in the VG group than that in the ISPL group, the difference was not statistically significant (0% vs. 16.7%, p = 0.203). Additionally, there were no significant differences in flap take-back (14.3% vs. 16.7%, p = 1) and minor complications between the two groups (35.7% vs. 33.3%, p = 1). CONCLUSIONS: If pedicle lengthening with vessel graft is inevitable in head and neck reconstruction, arterial graft may provide a reliable outcome and may be considered an effective alternative when compared to vein grafts.

Clinical predictors of early surgical intervention in patients with venomous snakebites.

BACKGROUND: Venomous snakebites induce tissue destruction and secondary infection; however, the optimal timing of surgical intervention for these complications remains unknown. This study assessed the clinical predictors of early surgical intervention in patients with snakebites. METHODS: This retrospective study included 63 patients (45 men and 18 women) with venomous snakebites. In addition to the snake species, the demographics, affected body parts, clinical characteristics, and ultrasound findings of the patients in the surgical (32 patients) and nonsurgical (31 patients) groups were analyzed and compared. RESULTS: A higher incidence of acute compartment syndrome, local ecchymosis, skin necrosis, bullae, blisters, and fever was found in the surgical group than in the nonsurgical group, and ultrasound findings of the absence of Doppler flow were more frequently noted in the surgical group than in the nonsurgical group. After adjustment using a multivariate logistic regression model, only advanced age, Naja atra bite, local ecchymosis, and bulla or blister formation remained significant factors for surgical intervention. Furthermore, comparison of the outcomes of patients who received early (≤ 24 h) and late (> 24 h) surgical intervention revealed that the duration of continuous negative pressure wound therapy (6 vs. 15 days; P = 0.006), duration of hospital stay (13 vs. 26 days; P = 0.002), and duration of outpatient follow-up (15 vs. 36 days; P < 0.001) were significantly lower in patients who received early surgical intervention. The final reconstructive surgery was simple among the patients who received surgical intervention within 24 h of being bitten (P = 0.028). CONCLUSION: In patients with snakebites, advanced age, high-risk clinical manifestations (e.g., local ecchymosis and bulla or blister formation), and Naja atra envenomation are predictors of surgical intervention within 24 h.

The role of vein grafts in reconstructive head and neck microsurgery

Abstract Objective: Free tissue transfer is widely used for head and neck reconstruction. In certain circumstances, vein grafting is required to elongate free flap pedicles to connect them to appropriate recipient vessels. Because of controversy regarding the use of interposition vein grafts in free tissue reconstruction, this paper reports vein graft indications, techniques, safety, and outcomes for head and neck microvascular surgery. Methods: Twenty-six patients (23 men and 3 women) who underwent interposition vein grafting concurrent with free tissue transfer were included in this study. The most common reason for head and neck reconstruction with vein graft was tumor recurrence, followed by flap salvage. The interposition vein grafts were applied in two manners as temporary arteriovenous (A-V) loop and conduit to extend the length of the free flap for venous drainage. Results: The most common reconstructions were anterolateral thigh flaps (15 cases), followed by vastus lateralis myocutaneous (3 cases) and radial forearm (2 cases) flaps. The common recipient vessels were superior thyroid artery, superficial temporal artery and external jugular vein. The free flap loss rate was 7.7% with vein grafts and 4.9 without vein grafts (p = 0.380). The free flap complication rate was 50.0% and 16.8% in patients with and without vein grafts, respectively (p < 0.001). Radiation therapy, chemotherapy, prior neck dissection, and prior free flap transfer were more common in the vein graft group (all p < 0.001). The hospital stay was significantly longer for the vein graft group than for the non-vein graft group (29.5 vs. 19.0 days; p = 0.001). Conclusion: Overall free flap survival rates of 92.3% and 95.1% in the vein and non-vein graft groups, respectively - indicating the reliability of the vein grafts in challenging head and neck reconstructions, particularly in salvage cases and patients with multiple reconstructions. Level of evidence: Level 3.

The Contribution of Interleukin-8 Rs4073 Genotypes to Triple Negative Breast Cancer Risk in Taiwan.

BACKGROUND/AIM: Triple negative breast cancer (TNBC) is one of the most challenging breast cancer types. Interleukin-8 (IL-8) is a pro-tumorigenic cytokine, promoting tumor proliferation and migration. This study aimed to examine the contribution of IL-8 rs4073 genotypes to breast cancer risk and provide a summary of related literature. MATERIALS AND METHODS: IL-8 genotypic profiles were determined among 1,232 breast cancer cases and 1,232 controls via polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The IL-8 rs4073 AT and AA genotypes had significantly lower prevalence in the case group compared to control group. Allelic frequency analysis showed that individuals carrying the A allele have relatively decreased risk for breast cancer. The stratification analysis showed that IL-8 rs4073 genotypes were protective markers for those with younger (≤55) age. CONCLUSION: IL-8 rs4073 A allele is a novel predictor for breast cancer, especially TNBC.

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.

The role of vein grafts in reconstructive head and neck microsurgery.

OBJECTIVE: Free tissue transfer is widely used for head and neck reconstruction. In certain circumstances, vein grafting is required to elongate free flap pedicles to connect them to appropriate recipient vessels. Because of controversy regarding the use of interposition vein grafts in free tissue reconstruction, this paper reports vein graft indications, techniques, safety, and outcomes for head and neck microvascular surgery. METHODS: Twenty-six patients (23 men and 3 women) who underwent interposition vein grafting concurrent with free tissue transfer were included in this study. The most common reason for head and neck reconstruction with vein graft was tumor recurrence, followed by flap salvage. The interposition vein grafts were applied in two manners as temporary arteriovenous (A-V) loop and conduit to extend the length of the free flap for venous drainage. RESULTS: The most common reconstructions were anterolateral thigh flaps (15 cases), followed by vastus lateralis myocutaneous (3 cases) and radial forearm (2 cases) flaps. The common recipient vessels were superior thyroid artery, superficial temporal artery and external jugular vein. The free flap loss rate was 7.7% with vein grafts and 4.9 without vein grafts (p = 0.380). The free flap complication rate was 50.0% and 16.8% in patients with and without vein grafts, respectively (p < 0.001). Radiation therapy, chemotherapy, prior neck dissection, and prior free flap transfer were more common in the vein graft group (all p < 0.001). The hospital stay was significantly longer for the vein graft group than for the non-vein graft group (29.5 vs. 19.0 days; p = 0.001). CONCLUSION: Overall free flap survival rates of 92.3% and 95.1% in the vein and non-vein graft groups, respectively - indicating the reliability of the vein grafts in challenging head and neck reconstructions, particularly in salvage cases and patients with multiple reconstructions. LEVEL OF EVIDENCE: Level 3.

Nitric oxide: Is it the culprit for the continued expansion of keloids?

Keloids are characterized by excessive proliferation of fibroblasts and invasion of surrounding healthy skin. High levels of Nitric Oxide (NO) are thought to be the crucial factor within the micro-environment in promoting keloid formation. However, the effects and mechanisms of NO on the proliferation of Keloid Fibroblasts (KDFs) remain unclear. In this study, we investigated the effect of NO on KDFs proliferation by Sodium Nitroprusside (SNP), an NO donor. Our results show that SNP significantly enhanced KDFs proliferation. Moreover, with prolonged treatment with SNP after cell confluence, the growth of KDFs escape contact inhibition and experience significant pile up growth. Furthermore, PTIO, an NO scavenger, attenuated SNP-enhanced cell proliferation effectively. The mechanism involved in SNP-induced KDFs proliferation was soluble Guanylyl Cyclase (sGC) and cGMP independent. ODQ, a specific sGC inhibitor, failed to suppress SNP-enhanced KDFs proliferation. 8-Bromo-c GMP, a cell-permeable cGMP analogue, could not stimulate KDFs proliferation. Erk and Akt provide important signaling for cell growth. U0126 and LY294002, inhibitors of Erk and Akt respectively, block SNP-enhanced KDFs proliferation effectively. As expected, a Western blot showed that SNP up-regulated the phosphorylation levels of Erk and Akt. Moreover, it decreased the expression of p27, a cell cycle inhibitor. Our results reveal that SNP induced KDFs proliferation and loss contact inhibition led to pile up growth via activation of the Erk and Akt pathways, as well as a decreased expression of p27. Thus, we speculate that the pathological feature of continuous expansion in keloids is caused by NO-induced KDFs sustained growth.

Transposition of Duplicated Thumb for Reconstruction of Asymmetric Radial Polydactyly.

BACKGROUND: In this study, we present the long-term functional and aesthetic outcomes in patients with complicated asymmetric radial polydactyly treated with this surgical technique involving the transposition of a duplicated thumb. METHODS: We evaluated 6 thumbs in 6 patients who underwent radial polydactyly reconstruction using the transposition of duplicated thumb procedure between 2001 and 2017. The procedure was used when one of the thumbs was not obviously dominant over the other, with one having a better proximal portion and the other having a better distal portion. The average age at the time of surgery was 35 months, and at the final follow-up, average age was 86.5 months. Objective outcome values were obtained, and the Japanese Society for Surgery of the Hand evaluation form was adopted to assess functional and cosmetic outcomes. RESULTS: Neither soft tissue loss nor nonunion of the osteotomy was noted. No patients reported pain or difficulties in their activities. Mean flexion-extension arc for the metacarpophalangeal joint was 72.9° (range, 8.8° extension to 64.1° flexion), and that for the interphalangeal joint was 44.0° (range, 5.7° extension to 38.3° flexion). Mean key pinch, tip pinch, and grip strength of unaffected thumb were 75.1%, 68.7%, and 81.9%, respectively. Total scores using the Japanese Society for Surgery of the Hand scoring system averaged 18.2 points, and the results were excellent in 1 case and good in 5. CONCLUSIONS: Transposition of duplicated thumb can provide durable functional and cosmetic results for Rotterdam types IV and VI with asymmetric radial polydactyly in which neither thumb has adequate distal and proximal components.

Functional Outcomes and Complications of Robot-Assisted Free Flap Oropharyngeal Reconstruction.

BACKGROUND: Robotic surgical systems provide a clear, magnified 3-dimensional visualization as well as precise, stable instrumental movement, thereby minimizing technical difficulties that may be encountered in the surgical treatment of oropharyngeal tumors. This study assessed the outcomes of robotic-assisted free flap oropharyngeal reconstruction compared with those of conventional free flap reconstruction. MATERIALS AND METHODS: A retrospective review of 47 patients who underwent reconstructive operations using a free radial forearm fasciocutaneous flap for oropharyngeal defects was conducted over a 20-month period (May 2013-December 2014). Complications were evaluated for a robot-assisted reconstruction group and a conventional reconstruction group; postoperative complication rates and revision rates were further evaluated. The Functional Intraoral Glasgow Scale (FIGS) was adopted for functional outcome assessment. RESULTS: This study recruited 47 people who underwent reconstructive operations using a free radial forearm fasciocutaneous flap for oropharyngeal defects (14 robot-assisted and 33 conventional reconstructions). The mean postoperative FIGS score was 10.29 ± 2.02 in the robot-assisted group (P = 0.010) and 8.42 ± 2.29 in the conventional group at 1 month postoperatively. The mean postoperative FIGS score was 12.57 ± 1.91 in the robot-assisted group (P = 0.005) and 9.91 ± 3.09 in the conventional group at 3 months postoperatively. Complication rates between the robot-assisted and conventional groups were similar for flap failure (P = 0.531), partial necrosis, wound infection, hematoma or seroma formation (P = 0.893), wound dehiscence, and fistula formation (P = 0.515). The number of flap revision operations requiring additional surgery (P = 0.627) was comparable between the cohorts. CONCLUSIONS: There is no significant difference in complications or revision rates between the robot-assisted and conventional oropharyngeal reconstructions. The functional postoperative outcomes of robot-assisted reconstructions are superior to those of conventional reconstructions. Robotic surgical systems provide a safe option with optimal postoperative oral function for the free flap reconstruction of oropharyngeal defects without lip or mandible splitting.

Molecular mechanisms of gallic acid-induced growth inhibition, apoptosis, and necrosis in hypertrophic scar fibroblasts.

AIMS: To explore the effect and molecular mechanism of gallic acid (GA) on the cytostatic and cytotoxicity of hypertrophic scar fibroblasts (HSFs). MATERIALS AND METHODS: HSFs were treated with a serial dose of GA for indicated time. The cytostatic and cytotoxicity of GA were evaluated by microscopy, trypan blue exclusion assay and LDH releasing. The mechanisms of GA-induced cytostatic were examined by cell cycle distribution assay and the expression of cell cycle-relative protein. GA-elicited apoptosis were verified by TUNEL assay, mitochondria membrane potential, caspase activity and the expression of apoptosis-relative protein. GA-induced necrosis was confirmed by lysosome rupture using acridine orange stain. Various blockers, including intracellular calcium chelator; BAPTA-AM, IP3R blocker; 2-APB, calpain inhibitor, ALLM and ALLN were used to address the signaling cascade in GA-induced HSF necrosis. KEY FINDINGS: GA-induced growth inhibition, apoptosis, and necrosis in HSFs depend on increasing dose. HSFs treated with GA at non-cytotoxic concentrations (50 to 75µM) significant increased both the S- and G2/M-phase HSFs population, and this event was accompanied with down-regulation of cyclin A, cyclin B, CDK1 and CDK2. Incubation of HSFs with 100-150µM of GA induced apoptosis through Bcl2/Bax-mitochondrial-dependent pathway. While the concentrations up to 200µM of GA that elicited necrosis via a calcium/calpain I/lysosome rupture signaling axis. Interestingly, GA at 200µM did not harm to keratinocyte. SIGNIFICANCE: These results revealed that GA might have the potential to be developed as a treatment for patients with hypertrophic scar.

Gallic acid attenuates TGF-ß1-stimulated collagen gel contraction via suppression of RhoA/Rho-kinase pathway in hypertrophic scar fibroblasts.

AIMS: To examine the effect and molecular mechanism of gallic acid (GA) on transforming growth factor-ß1 (TGF-ß1)-stimulated hypertrophic scar fibroblast (HSF) contraction. MATERIALS AND METHODS: A fibroblast-populated collagen lattice (FPCL) was developed to examine the effect of GA on TGF-ß1-enhanced HSF contraction. The changes in crucial factors related to cell contraction including α-smooth muscle actin (α-SMA), F-actin, and the phosphorylation level of myosin light chain (MLC) were evaluated using western blot and immunostaining. The activation and expression of RhoA/ROCK after the TGF-ß1 challenge and GA insult were evaluated using RhoA-G-LISA and RhoA-ELISA kit while the phosphorylation level of MYPT1 and the expression of ROCK1 and ROCK2 were examined by western blot, respectively. KEY FINDINGS: GA significantly suppressed TGF-ß1-stimulated HSF contraction in a dose- and time-dependent manner. Moreover, the TGF-ß1-enhanced α-SMA expression, F-actin formation, and MLC phosphorylation were obviously attenuated by GA. TGF-ß1 significantly stimulated RhoA activation but did not alter the expression of RhoA in the HSFs. However, both the activation and expression of RhoA decreased obviously with GA pretreatment followed by TGF-ß1 stimulation. Furthermore, GA inhibited ROCK activity but did not affect its expression after TGF-ß1 stimulation. SIGNIFICANCE: These results suggest that GA exhibited the potential to prevent HSF contraction after TGF-ß1 stimulation by down regulating the RhoA/ROCK signal cascade, followed by the inhibition of the expression of α-SMA, F-actin formation, and phosphorylation of MLC.

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.

Robot-assisted free flap reconstruction of oropharyngeal cancer--a preliminary report.

BACKGROUND: The robotic surgical system provides a clear, magnified, 3-dimensional (3D) view as well as a precise and stable instrumental movement, which minimizes many technical difficulties that may be encountered in the surgical treatment of oropharyngeal tumors. A preliminary result of transoral robot-assisted free flap reconstruction of oropharyngeal cancer is presented herein. MATERIALS AND METHODS: Between May and December 2013, the Da Vinci Surgical System (Da Vinci Si, Intuitive Surgical, Sunnyvale, CA) was used in 5 (4 men and 1 woman) cases of oropharyngeal reconstruction. Robot-assisted reconstruction was performed for inset of the flap and for performing a venous anastomosis of the free radial forearm fasciocutaneous flap. RESULTS: All of the reconstructive surgeries were successful without flap failure or take-backs. There were no wound infections or fistulas. CONCLUSION: The application of a robotic surgical system seems to be a safe option in the free flap reconstruction of oropharyngeal defects without lip or mandible splitting.

Gallic acid selectively induces the necrosis of activated hepatic stellate cells via a calcium-dependent calpain I activation pathway.

AIMS: The activation of hepatic stellate cells (HSCs) in response to liver injury is critical to the development of liver fibrosis, thus, the blockage of the activation of HSCs is considered as a rational approach for anti-fibrotic treatment. In this report, we investigated the effects and the underlying mechanisms of gallic acid (GA) in interfering with the activation of HSCs. MAIN METHODS: The primary cultured rat HSCs were treated with various doses of GA for different time intervals. The morphology, viability, caspase activity, calcium ion flux, calpain I activity, reactive oxygen species generation and lysosomal functions were then investigated. KEY FINDINGS: GA selectively killed HSCs in both dose- and time-dependent manners, while remained no harm to hepatocytes. Besides, caspases were not involved in GA-induced cell death of HSCs. Further results showed that GA toxicity was associated with a rapid burst of reactive oxygen species (ROS) and a subsequent increase of intracellular Ca(2+) and calpain activity. Addition of calpain I but not calpain II inhibitor rescued HSCs from GA-induced death. In parallel, pretreatment with antioxidants or an intracellular Ca(2+) chelator eradicated GA responses, implying that GA-mediated cytotoxicity was dependent on its pro-oxidative properties and its effect on Ca(2+) flux. Furthermore, application of ROS scavengers also reversed Ca(2+) release and the disruption of lysosomal membranes in GA-treated HSCs. SIGNIFICANCE: These results provide evidence for the first time that GA causes selective HSC death through a Ca(2+)/calpain I-mediated necrosis cascade, suggesting that GA may represent a potential therapeutic agent to combat liver fibrosis.

Management of extremity neurilemmomas: clinical series and literature review.

BACKGROUND: Delicate enucleation of neurilemmoma preserves most of nerve fascicles and causes minimal nerve function impairment. Accurate preoperative diagnosis of neurilemmoma is based on clinical findings and image studies. MATERIALS AND METHODS: Between November 2003 and February 2013, operations for the treatment of neurilemmoma were performed on 14 patients (12 men and 2 women) at our institution. The image studies in this series were collected. The tumor mass was approached by splitting the epineurium. In a few cases, enucleation of the neurilemmoma caused some fascicles loss, but reconstruction with sural nerve grafts preserved nerve function. RESULTS: Before surgery, 7 patients received computed tomographic scan, 4 patients underwent magnetic resonance imaging, and 3 patients received sonography. Six patients presented with motor or sensory deficits immediately after tumor enucleation. Three patients recovered completely from the neurological defects with or without nerve reconstruction. CONCLUSIONS: Our results indicate that neurilemmoma can be removed by delicate enucleation with an acceptable risk of injury to the nerve trunk.