MRI radiomics may predict early tumor recurrence in patients with sinonasal squamous cell carcinoma.

OBJECTIVES: Sinonasal squamous cell carcinoma (SCC) follows a poor prognosis with high tendency for local recurrence. We aimed to evaluate whether MRI radiomics can predict early local failure in sinonasal SCC. METHODS: Sixty-eight consecutive patients with node-negative sinonasal SCC (January 2005-December 2020) were enrolled, allocated to the training (n = 47) and test sets (n = 21). Early local failure, which occurred within 12 months of completion of initial treatment, was the primary endpoint. For clinical features (age, location, treatment modality, and clinical T stage), binary logistic regression analysis was performed. For 186 extracted radiomic features, different feature selections and classifiers were combined to create two prediction models: (1) a pure radiomics model; and (2) a combined model with clinical features and radiomics. The areas under the receiver operating characteristic curves (AUCs) were calculated and compared using DeLong's method. RESULTS: Early local failure occurred in 38.3% (18/47) and 23.8% (5/21) in the training and test sets, respectively. We identified several radiomic features which were strongly associated with early local failure. In the test set, both the best-performing radiomics model and the combined model (clinical + radiomic features) yielded higher AUCs compared to the clinical model (AUC, 0.838 vs. 0.438, p = 0.020; 0.850 vs. 0.438, p = 0.016, respectively). The performances of the best-performing radiomics model and the combined model did not differ significantly (AUC, 0.838 vs. 0.850, p = 0.904). CONCLUSION: MRI radiomics integrated with a machine learning classifier may predict early local failure in patients with sinonasal SCC. CLINICAL RELEVANCE STATEMENT: MRI radiomics intergrated with machine learning classifiers may predict early local failure in sinonasal squamous cell carcinomas more accurately than the clinical model. KEY POINTS: • A subset of radiomic features which showed significant association with early local failure in patients with sinonasal squamous cell carcinomas was identified. • MRI radiomics integrated with machine learning classifiers can predict early local failure with high accuracy, which was validated in the test set (area under the curve = 0.838). • The combined clinical and radiomics model yielded superior performance for early local failure prediction compared to that of the radiomics (area under the curve 0.850 vs. 0.838 in the test set), without a statistically significant difference.

Correction: Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Molecular subtypes of oropharyngeal cancer show distinct immune microenvironment related with immune checkpoint blockade response.

BACKGROUND: Oropharyngeal cancer (OPC) exhibits diverse immunological properties; however, their implications for immunotherapy are unknown. METHODS: We analysed 37 surgically resected and nine recurrent or metastatic anti-programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1)-treated OPC tumours. OPCs were classified into immune-rich (IR), mesenchymal (MS) and xenobiotic (XB) subtypes based on RNA-sequencing data. RESULTS: All IR type tumours were human papillomavirus (HPV) positive, most XB types were HPV negative, and MS types showed mixed HPV status. The IR type showed an enriched T cell exhaustion signature with PD-1+ CD8+ T cells and type I macrophages infiltrating the tumour nest on multiplex immunohistochemistry. The MS type showed an exclusion of CD8+ T cells from the tumour nest and high MS and tumour growth factor-ß signatures. The XB type showed scant CD8+ T cell infiltration and focal CD73 expression. The IR type was associated with a favourable response signature during anti-PD-1/PD-L1 therapy and showed a high APOBEC mutation signature, whereas the MS and XB types showed resistance signature upregulation. Among anti-PD-1/PD-L1-treated OPC patients, the IR type showed a favourable clinical response (3/4 patients), whereas the XB type showed early progression (3/3 patients). CONCLUSION: Our analysis classified OPCs into three subtypes with distinct immune microenvironments that are potentially related to the response to anti-PD-1/PD-L1 therapy.

Mouse-human co-clinical trials demonstrate superior anti-tumour effects of buparlisib (BKM120) and cetuximab combination in squamous cell carcinoma of head and neck.

BACKGROUND: Recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) is a common cancer with high recurrence and mortality. Current treatments have low response rates (RRs). METHODS: Fifty-three patients with R/M SCCHN received continuous oral buparlisib. In parallel, patient-derived xenografts (PDXs) were established in mice to evaluate resistance mechanisms and efficacy of buparlisib/cetuximab combination. Baseline and on-treatment tumour genomes and transcriptomes were sequenced. Based on the integrated clinical and PDX data, 11 patients with progression under buparlisib monotherapy were treated with a combination of buparlisib and cetuximab. RESULTS: For buparlisib monotherapy, disease control rate (DCR) was 49%, RR was 3% and median progression-free survival (PFS) and overall survival (OS) were 63 and 143 days, respectively. For combination therapy, DCR was 91%, RR was 18% and median PFS and OS were 111 and 206 days, respectively. Four PDX models were originated from patients enrolled in the current clinical trial. While buparlisib alone did not inhibit tumour growth, combination therapy achieved tumour inhibition in three of seven PDXs. Genes associated with apoptosis and cell-cycle arrest were expressed at higher levels with combination treatment than with buparlisib or cetuximab alone. CONCLUSIONS: The buparlisib/cetuximab combination has significant promise as a treatment strategy for R/M SCCHN. CLINICAL TRIAL REGISTRATION: NCT01527877.

Comparison of Surgical Outcomes of Robotic and Conventional Approaches in Patients with Pre- and Poststyloid Parapharyngeal Space Tumors.

BACKGROUND: Benefits and drawbacks of robotic surgical approaches for parapharyngeal space (PPS) tumors remain undetermined. The purpose of this study is to compare surgical outcomes of PPS tumor patients who underwent robotic surgery with those of patients who received conventional surgical treatment. PATIENTS AND METHODS: We retrospectively analyzed clinicopathologic data from 136 patients who underwent surgical removal of PPS tumors via conventional or robotic approaches. RESULTS: We identified PPS tumors in pre- and poststyloid regions in 87 (64%) and 49 (36%) patients, respectively. There were 48 (35.3%) pleomorphic adenomas, 36 (26.5%) schwannomas, and 24 (17.6%) paragangliomas. Conventional surgical techniques were performed in 83 patients, and robotic surgical approaches were administered to 53 patients. Transcervical-parotid and transcervical approaches were most commonly performed in conventional surgery, while transoral and retroauricular approaches were the preferred surgical methods in robotic surgery for pre- and poststyloid PPS tumors, respectively. Robotic surgery resulted in less estimated blood loss during poststyloid PPS tumor surgery. Postoperative cranial nerve complications were noted in 36 of 83 cases (43.4%) in the conventional surgery group and in 17 of 53 cases (32.1%) in the robotic surgery group. Intraoperative tumor spillage of pleomorphic adenoma showed no significant differences between the two groups (13.6% in conventional vs. 15.4% in robotic surgery). The mean follow-up time was 4.9 ± 3.4 years, and recurrences were observed in two patients during follow-up without a significant difference between the two groups (4.5% in conventional vs. 3.8% in robotic surgery). CONCLUSIONS: Robotic surgery in PPS tumors is feasible through transoral, retroauricular, or combined approaches and provides treatment outcomes comparable to those of conventional open surgery.

Non-invasive postoperative monitoring of pedicled rat skin flap using laser speckle contrast imaging.

PURPOSE: This study used non-invasive laser speckle contrast imaging (LSCI) modality to evaluate the blood flow changes in murine flap model and to investigate the clinical feasibility of the LSCI for postoperative monitoring. METHODS: Ten of 6-8 weeks old Spraque-Dawley rats with superficial inferior epigastric vessel based pedicled skin flaps were used in this experiment. The color changes of skin flap were evaluated by naked eyes and the LSCI modality 6, 24, and 48 h after surgery. RESULTS: In vessel ligated region of skin flap, skin color began to change to a bluish color immediately postoperatively. At 24 h postoperatively, skin necrosis was detectable with the naked eye and total necrosis occurred at 48 h postoperatively. Changes in laser speckle signal were consistent with changes observed with the naked eye, and blood flow index also presented significant differences between the ligated and non-ligated region. CONCLUSION: These correlated laser speckle signal patterns suggest that non-invasive monitoring of perfusion by LSCI is a useful technology that may be used to identify the ischemic skin flap.

Does p16+ Predict a Favorable Prognosis for Oropharyngeal Cancer? Risk Factors for Treatment Failure for Patients Who Underwent Surgery-Based Therapy.

BACKGROUND: This study aimed to identify prognostic clinicopathologic factors that could predict treatment failure and to analyze clinical data from p16+ oropharyngeal squamous cell carcinoma (OPSCC) patients who underwent surgery. METHODS: Data from p16+ OPSCC patients who underwent surgery at Severance Hospital of Yonsei University were retrospectively reviewed. RESULTS: The average smoking history was 14.6 pack-years (range 0-94 pack-years). Of the 188 patients, 73 (38.8%) underwent transoral robotic surgery (TORS) for surgical treatment of their primary lesions, and the remaining 115 patients (61.2%) underwent conventional surgery. Extracapsular nodal spread was detected in 87 patients (46.3%). At histologic examination, 67 patients (35.6%) showed positive surgical margins, and 121 patients (64.4%) had negative surgical margins. Postoperative adjuvant treatment was performed for 167 patients (88.8%). During the follow-up period, there were 18 recurrences including 2 local recurrences, 10 regional recurrences, and 6 distant metastases. During the study period, 17 deaths occurred. The univariate analysis showed that the American Joint Committee on Cancer (AJCC) 8th-edition staging system, lymphovascular invasion, more than four metastatic lymph nodes, and a smoking history of more than 10 pack-years were significantly associated with treatment failure. In the multivariate analysis, only the AJCC 8th-edition staging system was significantly associated with the patient's survival. CONCLUSION: Surgical treatment methods including TORS for p16+ OPSCC patients showed excellent oncologic results, and many previously known clinicopathologic factors did not show a significant relationship with patient prognosis. Only the newly revised AJCC 8th-edition staging system showed a significant relationship with patient survival, and this should be considered in the setting of p16+ OPSCC treatment guidelines in the future.

The First Human Trial of Transoral Robotic Surgery Using a Single-Port Robotic System in the Treatment of Laryngo-Pharyngeal Cancer.

BACKGROUND: This study aimed to evaluate the feasibility and safety of the DaVinci SP system for performing transoral robotic surgery (TORS) in patients with head and neck cancer. METHODS: From October 2018 to April 2019, the medical records of 41 patients who underwent TORS using the DaVinci SP system were retrospectively reviewed. RESULTS: During TORS, three robotic arms could be used to perform a geometric resection of the lesion in a narrow working space. The mean total operation time was 60 min, and the average time required to set up the robotic system was 10 min or less. All patients successfully underwent TORS. All robotic arms were inserted through a single port, which widened the working space around the patient's head and allowed the operative assistant an easy approach to the patient during the operation. The joggle joint of the robotic arms aided easy manipulation within the confined working space. The joggle joints of the endoscopic arm were controlled through the navigation system, which was very helpful in securing superior visualization of the surgical site, especially in the area of the larynx and the hypopharynx. CONCLUSION: The study confirmed that the DaVinci SP system provided technical advantages above the Si and Xi systems for performing TORS. It was especially helpful in ensuring proper visualization of the surgical field and in performing precise surgery during surgery to the tongue base or the hypopharyngeal lesion.

Prognostic Value of Cervical Nodal Necrosis Observed in Preoperative CT and MRI of Patients With Tongue Squamous Cell Carcinoma and Cervical Node Metastases: A Retrospective Study.

OBJECTIVE. The prognosis of tongue squamous cell carcinoma (SCC) with cervical lymph node metastases is poor, and a subset of patients with aggressive disease experiences treatment failure. The current study evaluated the prognostic value of cervical nodal necrosis (CNN) observed on preoperative imaging studies of patients with tongue SCC and cervical node metastases. MATERIALS AND METHODS. We identified patients with tongue SCC who had undergone preoperative neck CT or MRI (or both) and retrospectively reviewed their demographic and clinical data. Patients with metastatic cervical lymph nodes were divided into two groups according to the presence (CNN group) or absence (non-CNN group) of necrosis, and radiologic extranodal extension (ENE) was assessed for all patients. Follow-up biopsy, imaging, and clinical examinations were used to determine survival and treatment failure. Cox proportional hazard regression analyses were performed to determine clinical, demographic, and pathologic factors for survival. RESULTS. Seventy-two patients with a mean follow-up period of 28.4 months were included. The incidence of CNN was 55.6% (40/72). In univariate analysis, patient age, evidence of CNN on preoperative imaging, radiologic ENE, clinical N classification, and overall stage were significantly associated with survival. The multivariate Cox proportional hazard model showed that patient age and CNN on preoperative imaging were independent negative prognostic factors. CONCLUSION. CNN observed on preoperative imaging studies is an independent predictor of a poor prognosis for patients with tongue SCC, and it may serve as a useful imaging biomarker for tailoring individual treatment regimens.

Transoral Robotic Surgery With Transoral Retropharyngeal Lymph Node Dissection in Patients With Tonsillar Cancer: Anatomical Points, Surgical Techniques, and Clinical Usefulness.

OBJECTIVE: The purpose of this study was to evaluate the clinical usefulness of TORS and transoral robotic retropharyngeal lymph node (RPLN) dissection in tonsillar cancer patients with suspicious RPLN metastasis. METHODS: From April 2008 to March 2014, 71 patients with tonsillar cancer underwent transoral robotic surgery and standard neck dissection at the Yonsei Head and Neck Cancer Center. RESULTS: Three patients underwent transoral robotic ropharyngectomy with transoral robotic RPLN dissection because of suspicious RPLN metastasis. The mean age of the patients was 42 years (range, 31-50 years). There were no cases of wound infection or serious complications related to wound healing. Mild nasal regurgitation was observed during an oral diet immediately after surgery, but all patients spontaneously resolved without surgical treatment. There was no significant bleeding due to great vessel injury during surgery or swallowing difficulty due to cranial nerve IX injury. CONCLUSION: Although the oncologic stability and usefulness of this technique should be confirmed based on large-scale research, RPLN can be easily accessed and resected through our approach with less morbidity compared to the conventional surgical approach. In addition, because RPLN metastasis can be performed pathologically based on obtained specimens, it will be helpful to explore whether to perform adjuvant radiation.

Clinicopathological factors influencing the outcomes of surgical treatment in patients with T4a hypopharyngeal cancer.

BACKGROUND: The purpose of this study was to determine prognostic factors influencing outcomes of surgical treatment in patients with T4a hypopharyngeal cancer. METHODS: The present study enrolled 93 patients diagnosed with T4a hypopharyngeal cancer who underwent primary surgery between January 2005 and December 2015 at six medical centers in Korea. Primary tumor sites included pyriform sinus in 71 patients, posterior pharyngeal wall in 14 patients, and postcricoid region in 8 patients. Seventy-two patients received postoperative radio(chemo)therapy. RESULTS: Five-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 38% and 45%, respectively. In univariate analysis, 5-year DFS was found to have significant and positive correlations with margin involvement (p < 0.001) and extracapsular spread (p = 0.025). Multivariate analysis confirmed that margin involvement (hazard ratio (HR): 2.81; 95% confidence interval (CI): 1.49-5.30; p = 0.001) and extracapsular spread (HR: 2.08; 95% CI: 1.08-3.99; p = 0.028) were significant factors associated with 5-year DFS. In univariate analysis, cervical lymph node metastasis (p = 0.048), lymphovascular invasion (p = 0.041), extracapsular spread (p = 0.015), and esophageal invasion (p = 0.033) were significant factors associated with 5-year DSS. In multivariate analysis, extracapsular spread (HR: 2.98; 95% CI: 1.39-6.42; p = 0.005) and esophageal invasion (HR: 2.87; 95% CI: 1.38-5.98; p = 0.005) remained significant factors associated with 5-year DSS. CONCLUSION: Margin involvement and extracapsular spread are factors influencing recurrence while extracapsular spread and esophageal invasion are factors affecting survival in patients with T4a hypopharyngeal cancer treated by primary surgery.

c-Met-mediated reactivation of PI3K/AKT signaling contributes to insensitivity of BRAF(V600E) mutant thyroid cancer to BRAF inhibition.

BRAF (V600E) mutation is the most commonly detected genetic alteration in thyroid cancer. Unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response in thyroid cancer is reported to be low. The purpose of this study is to investigate the resistance mechanism responsible for this low treatment response to BRAF inhibitor in order to maximize the effect of targeted therapy. We examined the expression of feedback regulation mechanisms and alterations in the upper signal transduction pathway in thyroid cancer cell lines harboring BRAF mutation. Also, we investigated the effect of dual inhibition from combinatorial therapy. Two thyroid cancer cell lines, 8505C (anaplastic thyroid cancer) and BCPAP (papillary thyroid cancer) were selected and treated with PLX4032 and its drug sensitivity were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on orthotopic xenograft mouse models. Unlike BCPAP cells, 8505C cells presented drug resistance to PLX4032 treatment and this was mainly due to increased expression of c-Met. Effective inhibitions of c-Met, p-AKT, and p-ERK were achieved after dual treatment with BRAF inhibitor (PLX4032) and c-Met inhibitor (PHA665752). Similar results were confirmed by in vivo study with orthotopic xenograft mouse model. c-Met-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF (V600E) mutant anaplastic thyroid cancer cells to PLX4032. Dual inhibition of BRAF and c-Met leads to sustained treatment response. © 2015 Wiley Periodicals, Inc.

Application of Dynamic Contrast-Enhanced MRI Parameters for Differentiating Squamous Cell Carcinoma and Malignant Lymphoma of the Oropharynx.

OBJECTIVE: The purpose of this study was to investigate the usefulness of histogram analysis of dynamic contrast-enhanced MRI (DCE-MRI) parameters for the differentiation of squamous cell carcinoma (SCC) and malignant lymphoma of the oropharynx. MATERIALS AND METHODS: Pretreatment DCE-MRI was performed in 21 patients with pathologically confirmed oropharyngeal SCC and six patients with malignant lymphoma. DCE-MRI parameter maps including the volume transfer constant (K(trans)), flux rate constant (kep), and extravascular extracellular volume fraction (ve) based on the Tofts model were obtained. Enhancing tumors were manually segmented on each slice of the parameter maps, and the data were collected to obtain a histogram for the entire tumor volume. The Wilcoxon rank sum test was used to compare the histogram parameters of each DCE-MRI-derived variable of oropharyngeal SCC and lymphoma. RESULTS: Histogram analysis of K(trans) and ve maps revealed that the median and mode of K(trans) were significantly higher in SCC than in lymphoma (p = 0.039 and 0.032, respectively), and the mode, skewness, and kurtosis of ve were significantly different in SCC than in lymphoma (p = 0.046, 0.039, and 0.032, respectively). On ROC analysis, the kurtosis of ve had the best discriminative value for distinguishing between oropharyngeal SCC and lymphoma (AUC, 0.865; cutoff value, 2.60; sensitivity, 83.3%; specificity, 90.5%). CONCLUSION: Our preliminary evidence using histogram analysis of DCE-MRI parameters based on the whole tumor volume suggests that it might be useful for differentiating SCC from malignant lymphoma of the oropharynx.

Endoscopic retroauricular thyroidectomy: preliminary results.

BACKGROUND: We sought to seek the potential role of endoscopic thyroidectomy with the retroauricular (RA) approach prior to future comparative study with the robotic RA thyroidectomy. Therefore, this study aims to verify the surgical feasibility of endoscopic RA thyroidectomy. METHODS: Eighteen patients who underwent endoscopic RA thyroidectomy for clinically suspicious papillary thyroid carcinoma or benign lesions from January to December 2013 were retrospectively reviewed and analyzed. RESULTS: All endoscopic operations via RA or modified facelift approach were successfully performed, without any significant intraoperative complications or conversion to open surgery. Based on patient-reported outcome questionnaires, all patients were satisfied with their postoperative surgical scars. CONCLUSION: Endoscopic RA thyroidectomy is technically feasible and safe with satisfactory cosmetic results for patients where indicated.

Robot-Assisted Neck Dissection Through a Modified Facelift Incision.

OBJECTIVES: The aim of this study is to describe the feasibility as well as oncologic outcomes of robot-assisted neck dissection (RAND) through a modified facelift incision in an American population. STUDY DESIGN: Retrospective case series. SETTING: University tertiary care hospital. METHODS: All patients who underwent RAND between November 2012 and December 2014 were included. Medical records were reviewed for demographics, medical histories, staging, operative information, postoperative hospital course and complications, and oncologic outcomes. RESULTS: There were 11 RANDs identified among 10 patients. Five patients had known nodal metastasis at the time of surgery. Two patients had been previously irradiated. The average time of surgery was 284.4 ± 72.3 minutes, including other associated procedures. The average lymph node yield was 28.5 ± 9.3 nodes. There were no major complications. Average follow-up was 19.4 months. There was 1 supraclavicular recurrence in a previously irradiated patient. All patients are currently alive and without evidence of disease. CONCLUSIONS: Robot-assisted neck dissection is a safe and feasible procedure that can be performed by surgeons with familiarity with neck dissection and robot-assisted surgery and who have been trained in RAND. Appropriate oncologic outcomes can be obtained in a patient wishing to avoid a noticeable scar.

A Study Comparing Free-Flap Reconstruction via the Retroauricular Approach and the Traditional Transcervical Approach for Head and Neck Cancer: A Matched Case-Control Study.

BACKGROUND: Free-flap reconstruction via a retroauricular approach (RRA) after robot-assisted neck dissection (RAND) could have cosmetic benefits. This study aimed to compare the surgical outcomes of free-flap reconstruction via a RRA and via a transcervical approach in head and neck cancer. METHODS: For this matched case-control study, 50 patients with head and neck cancer requiring free-flap reconstruction were divided into two groups: those reconstructed via a RRA group and those reconstructed via a transcervical approach (RTA group). The total operation time for free-flap reconstruction, the flap survival rate, the length of the hospital stay, the complications, and the scar satisfaction scores were compared between the two groups. RESULTS: The RRA group comprised 25 patients, and the RTA group had 25 patients. The mean operation time for reconstruction was 288 ± 77 min in the RRA group and 250 ± 98 min in the RTA group (p = 0.132). Flap failure occurred for two patients in the RRA group (8 %) and for one patient in the RTA group (4 %) (p = 1.000). The mean hospital stay was 21 ± 18 days in the RRA group and 23 ± 14 days in the RTA group (p = 0.669). The complications were comparable between the two groups. However, the overall scar satisfaction was significantly higher in the RRA group (p = 0.000). CONCLUSIONS: For patients with head and neck cancer, RRA has better cosmetic outcomes than RTA. The RRA approach could be used for select patients who undergo RAND and prefer to avoid a visible anterior neck scar.

A Study on the Efficiency Improvement of Dye-Sensitized Solar Cell (DSSC) by Repeated Dye Coating.

Dye-sensitized solar cell (DSSC) is being extensively investigated as the next generation energy source. Despite of the attractive features like simple fabrication process and its economic efficiency, there are some problems such as low efficiency, long fabrication time and low long-term stability. Conventionally, the dye adsorption on TiO2 photo-electrode film needs long time in the solvent with low concentration of dye to get the high efficiency. In this work, the dye coating process was considerably shortened, albeit plenty of dye was used comparing with the conventional way. Our needs were met for the best result in our working environment and the relevant conditions to our work were obtained, which were the coating temperature of 70 °C, the dye concentration of 10 mM and the coating time of 3 min. And this coating process was successively repeated several times to maximize the dye adsorption and to improve the cell efficiency. Therefore, the efficiency increased by 13% in the proper condition.

Robotic excision of a huge parathyroid adenoma via a retroauricular approach.

Primary hyperparathyroidism results from the overproduction of parathyroid hormone by 1 or more autonomously hyperfunctioning parathyroid glands and often causes hypercalcemia. Once this condition has been diagnosed, the treatment of choice is surgical removal. There have been many attempts to remove the hyperfunctioning gland with minimally invasive surgical techniques, with cure rates comparable with those of conventional techniques. On the basis of our initial surgical experiences of robotic thyroidectomy and other head and neck surgeries via a retroauricular (RA) approach, we have recently successfully performed robotic excision of a huge parathyroid tumor via an RA approach on a 44-year-old woman who had been diagnosed with a parathyroid adenoma. It is the first to describe in detail the successful completion of a robotic parathyroidectomy via an RA approach.

Robotic total thyroidectomy with modified radical neck dissection via unilateral retroauricular approach.

BACKGROUND: Traditionally, total thyroidectomy was performed through an open transcervical incision; in cases where there was evident nodal metastasis, the conventional surgical approach was to extend the incision into a large single transverse incision to complete the required neck dissection. However, recent innovation in the surgical technique of thyroidectomy has offered the opportunity to reduce the patient's burden from these prominent surgical scars in the neck. Minimally invasive surgical techniques have been developed and applied by many institutions worldwide, and more recently, various techniques of remote access surgery have been suggested and actively applied.1-6 Since the advent of robotic surgical systems, some have adopted the concept of remote access surgery into developing various robotic thyroidectomy techniques. The more former and widely acknowledged robotic thyroidectomy technique uses a transaxillary (TA) approach, which has been developed by Chung et al. in Korea.7,8 This particular technique has some limitations in the sense that accessing the lymph nodes of the central compartment is troublesome. Terris et al. realized some shortcomings of robotic TA thyroidectomy, especially in their patients in the United States, and developed and reported the feasibility of robotic facelift thyroidectomy.9-13 In cases of thyroid carcinomas with lateral neck node metastases, most abandoned the concept of minimally invasive or remote access surgery and safely adopted conventional open surgical methods to remove the tumor burden. However, Chung et al. have attempted to perform concomitant modified radical neck dissection (MRND) after robotic thyroidectomy through the same TA port.14 This type of robot-assisted neck dissection (RAND) had some inherent limitations, due to fact that lymph nodes of the upper neck were difficult to remove. Over the past few years, we have developed a RAND via modified facelift (MFL) or retroauricular (RA) approach and reported the feasibility and safety of this technique.15, 16 Since then, we have actively applied such RAND techniques in various head and neck cancers. In our country, almost all cases of robotic total thyroidectomy utilize the TA approach. According to the reports made by Terris et al., robotic facelift thyroidectomy technique has been solely applied for ipsilateral hemithyroidectomy. For total thyroidectomy, Terris et al. performed the robotic surgery with bilateral RA incisions. Here, we intend to introduce our novel surgical method after successfully attempting simultaneous robotic total thyroidectomy and RAND via a single RA approach without an axillary incision. To our knowledge, this is the first to report in the medical literature. METHODS: We present four cases of our surgical experience since the beginning of 2013. All patients received robotic total thyroidectomy with MRND via single RA port without axillary incision after approval from the institutional review board at Severance Hospital, Yonsei University College of Medicine. The inclusion criteria for this operation were as follows: (1) patients with malignant carcinomas of the thyroid gland with evident cervical lymph node metastasis on preoperative imaging studies which are indicated for surgery; (2) patients with no previous history of treatment for thyroid carcinoma. The exclusion criteria were as follows: (1) patients with recurred thyroid tumors; (2) patients with thyroid carcinomas that showed gross invasion to local structures or extensive extrathyroidal capsular spread; (3) patients with clinically evident neck nodal metastasis with extracapsular spread; (4) patients with past history of neck surgery of any kind. In order to assess the extent of disease, neck ultrasonography with fine needle aspiration, neck CT or MRI and PET-CT were performed as preoperative evaluation. All patients were given full information of the possible treatment options for their thyroid cancer comprising of open transcervical approach and robotic surgery via RA approach, including the advantages and disadvantages of each treatment choice and provided written, informed consents before the surgery. General clinical information of the patients is outlined in Table 1. The skin incision for the operation was designed just like the approach for robotic facelift thyroidectomy by Terris et al. and RAND, which has been first reported by our institution.11 (,) 16 The operation was performed by the following sequence. Initially, the skin-subplatysmal flap was elevated after making the skin incision to create sufficient working space. During this process, the elevated skin flap was retracted and maintained by retractors held by the assistant. After application of the self-retaining retractor (Sangdosa Inc., Seoul), neck dissection of the upper neck levels was performed under gross vision. Next, RAND through the RA incision was conducted followed by ipsilateral thyroidectomy with central compartment neck dissection (CCND) via the same approach. Finally, contralateral thyroidectomy with CCND was performed via the single RA port. During these steps, the operator is aided by the bedside assistant with long-suction tips to manipulate and direct the dissected specimen to maintain optimal surgical view or to suck out the fume created by the thermocoagulation from the Harmonic shears. The da Vinci robotic surgical system (Intuitive Surgical, Sunnyvale, CA) was introduced via the RA port with a facedown 30° dual-channel endoscopic arm placed in the center, and two instrument arms equipped at either side with 5-mm Maryland forceps and Harmonic curved shears. During the step of robotic contralateral thyroidectomy, a ProGrasp forceps was utilized at times, instead of 5-mm Maryland forceps. The rest of the surgery was completed with the robotic system (see Video for demonstration of operation for patient 2). Table 1 Clinical characteristics of the patients Patient Sex/age (yr) BMI Side(a) Approach Pathology(b) Tumor size(c) (cm) CCND(d) MRND(d) Drain removal day Drainage amount (ml) Hospital stay (days) 1 F/38 23.8 L RA PC 0.7 2/5 8/23 8 788 11 2 F/18 18.3 L RA PC 0.8 2/8 7/35 6 398 9 3 F/44 23.1 L RA PC 0.9 5/12 5/27 6 607 9 4 F/26 32.9 L RA PC 1.4 3/14 9/48 7 476 15 BMI body mass index, RA retroauricular approach, PC papillary carcinoma, CCND central compartment neck dissection, MRND modified radical neck dissection (a)Side refers to the site of main lesion (b)Pathology refers to the primary tumor within the thyroid gland (c)Tumor size refers to the diameter of the largest tumor in the thyroid gland (d)For each type of lymph node dissection, the number of positive nodes/total number of retrieved nodes is stated RESULTS: For all of the patients, robotic total thyroidectomy with MRND (levels II, III, IV, V) via unilateral RA approach was successfully completed without any significant intraoperative complications or conversion to open or other approach methods. The total operation time was defined as the time from initial skin incision to removal of the final specimen, which was an average 306.1 ± 11.1 min (Table 2). This included the time for skin flap elevation and neck dissection under gross vision (87 ± 2.8 min), setting up the robotic system for RAND (6.8 ± 2.4 min), console time using the robotic system for RAND (59.3 ± 2.2 min), flap elevation for thyroidectomy (11.3 ± 2.5 min), robotic arms docking for ipsilateral thyroidectomy (6.3 ± 2.5 min), console time for ipsilateral thyroidectomy (61.3 ± 2.1 min), robotic arms docking for contralateral thyroidectomy (6.3 ± 2.5 min), and console time for contralateral thyroidectomy (61.8 ± 2.1 min). The working space created from RA incision was sufficient, and manipulations of the robotic instruments through this approach were technically feasible and safe without any mutual collisions throughout the entire operation. It also allowed for an excellent magnified surgical view enabling visualization of important local anatomical structures. There was no postoperative vocal cord palsy due to recurrent laryngeal nerve injury. However, two patients developed transient hypoparathyroidism, which resolved in the end without the need for calcium or vitamin D supplementation after certain period of medical management (Table 3). Also, there was no incidence of postoperative hemorrhage or hematoma formation, although a single patient developed a postoperative seroma on postoperative day 9, which was managed conservatively without the need for further surgical intervention. On average, the wound catheter was removed 6.8 ± 1 days after surgery and the patient was discharged from the hospital at an average 11 ± 2.8 days from admission (Table 1). Final surgical pathology confirmed the diagnosis of papillary carcinoma for every patient. The total number of cervical nodes retrieved from CCND and MRND was 9.8 ± 4 and 33.1 ± 11 respectively, and the number of positive metastatic nodes was 3 ± 1.4 and 7.3 ± 1.7 respectively (Table 1). In three patients (patients 2, 3, and 4), the presence of one parathyroid gland was each verified in the pathology specimen. All four patients have received high-dose (150 mCi) radioiodine ablation (RAI) therapy after the operation and are being followed up (average 11.3 months, range 9-13 months) on a regular basis with no evidence of recurrence (post-RAI, most recent, nonsuppressed thyroglobulin range 0.1-0.4 ng/ml, antithyroglobulin antibody range 13.7-147.5 IU/ml). (ABSTRACT TRUNCATED)

Free flap reconstruction after robot-assisted neck dissection via a modified face-lift or retroauricular approach.

BACKGROUND: We performed robot-assisted neck dissection (RAND) via a modified face-lift (MFLA) or retroauricular approach for neck management and carried out free flap reconstruction via these approaches in patients with head and neck cancer. We assessed the feasibility of free flap reconstruction in patients who had undergone transoral resection of a primary lesion and RAND via these approaches. METHODS: In this prospective study, seven patients with head and neck squamous cell carcinoma were enrolled between August 2011 and May 2012. Approval was obtained from the institutional review board of Yonsei University. A radial forearm free flap was used for reconstruction because of its thin structure and pliability. Microvascular anastomosis was performed via an MFLA or retroauricular approach using a microscope and microvascular instrument set. RESULTS: Pathology reports showed a negative margin in all patients. On the basis of pathologic information for the primary lesion and neck specimens, 5 patients underwent surgery alone and two received adjuvant radiotherapy. At the last outpatient department visit, all patients were alive without locoregional recurrence. All patients were extremely satisfied with the invisible postoperative scar. On average, patients tolerated an oral diet after 1-2 weeks. The status of the free flap was viable and functioning in all patients. CONCLUSIONS: Although long-term follow-up of oncologic safety is required to establish these approaches as valid treatment methods, our study has demonstrated the feasibility of free flap reconstruction and RAND via an MFLA or retroauricular approach.