The dawn of robotic surgery in otolaryngology-head and neck surgery.

Transoral robotic surgery (TORS) utilizing the da Vinci robotic system has opened a new era for minimally-invasive surgery (MIS) in Otolaryngology-Head and Neck Surgery. Awareness of the historical steps in developing robotic surgery (RS) and understanding its current application within our field can help open our imaginations to future of the surgical robotics. We compiled a historical perspective on the evolution of surgical robotics, the road to the da Vinci surgical system, and conducted a review of TORS regarding clinical applications and limitations, prospective clinical trials and current status in Japan. We also provided commentary on the future of surgical robotics within our field. Surgical robotics grew out of the pursuit of telerobotics and the advances in robotics for non-medical applications. Today in our field, cancers and diseases of oropharynx and supraglottis are the most common indications for RS. It has proved capable of preserving the laryngopharyngeal function without compromising oncologic outcomes, and reducing the intensity of adjuvant therapy. TORS has become a standard modality for MIS, and will continue to evolve in the future. As robotic surgical systems evolve with improved capabilities in visual augmentation, spatial navigation, miniaturization, force-feedback and cost-effectiveness, we will see further advances in the current indications, and an expansion of indications. By promoting borderless international collaborations that put 'patients first', the bright future of surgical robotics will synergistically expand to the limits of our imaginations.

One hundred supracricoid laryngectomies with cricohyoidoepiglottopexy: do we achieve better local control?

OBJECTIVE: Supracricoid laryngectomy with cricohyoidoepiglottopexy has been known to be able to cope with tumor excisions with minimal margins. Extended resection may result in a limited margin and may impair the prognosis. We conducted a clinicopathologic analysis of local recurrence in supracricoid laryngectomy with cricohyoidoepiglottopexy patients. METHODS: Between 1997 and 2013, 100 patients with glottic cancers underwent supracricoid laryngectomy with cricohyoidoepiglottopexy. The clinicopathologic findings were evaluated. We also analyzed: (i) cancer-specific and overall survival rates, (ii) the correlation between locoregional recurrence and overall survival, (iii) T staging and larynx preservation rates and (iv) previous radiation history and larynx preservation rates. RESULTS: Local recurrence was recognized in eight of the 100 patients (8%); all were initially staged as T3 or T4. Recurrence was identified in the submucosal regions of the ipsilateral arytenoid and/or infraglottis. Six patients were salvaged by completion total laryngectomy except two. Cancer-specific survival at 5 years was 93%; overall survival at 5 years was 89%. There was no significant difference between overall survival and locoregional recurrence. There was a significant difference between larynx preservation in T1-2 and T3-4 patients. There was no significant difference between larynx preservation and the previous radiation therapy status. CONCLUSIONS: Our experience convinced us of the clinical potential of supracricoid laryngectomy with cricohyoidoepiglottopexy as one of the effective options for functional larynx preservation. Supracricoid laryngectomy with cricohyoidoepiglottopexy is the most suitable for unfavorable T2 and T3a cases and is applicable for appropriately selected radiation-failed patients. Thorough pre-operative evaluation, proper surgical techniques and careful follow-up are prerequisites for the success of supracricoid laryngectomy with cricohyoidoepiglottopexy.

Clinical outcomes of 849 laryngeal cancers treated in the past 40 years: are we succeeding?

OBJECTIVE: We analyzed the clinical outcomes of 849 laryngeal cancers treated in the past 40 years, which overlapped with the era of the global treatment shift. METHODS: To compare the chronological outcomes, patients were divided into four groups according to their registration year as 1972-82, 1983-92, 1993-2002 and 2003-12; treatment trends, larynx preservation rate and overall survival rate were compared. RESULTS: There were 104, 173, 253 and 319 patients registered in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. Five-year overall survival rates were 74, 76.5, 75.6 and 82.2% in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. The five-year larynx preservation rates were 65.5, 75.7, 75.4 and 80.9% in 1972-82, 1983-92, 1993-2002 and 2003-12, respectively. CONCLUSIONS: The number of patients treated at our institute increased, and the overall survival and larynx preservation rates exhibited favorable improvements over the past four decades. In the analysis of nonsurgical options, S1 combined radiotherapy showed superiority over concurrent chemoradiotherapy and radiotherapy in larynx preservation, and S1 combined radiotherapy, concurrent chemoradiotherapy and Tegafur Uracil combined radiotherapy showed superiority over radiotherapy in overall survival. In nonsurgical approaches, proper case selection is the key to success and may be much more important than pursuing radiotherapy dose escalation. In the analysis of surgical options, laser and supracricoid laryngectomy with cricohyoidoepiglottopexy contributed to larynx preservation in early- and intermediate-stage cancers, respectively. Supracricoid laryngectomy with cricohyoidoepiglottopexy demonstrated overall survival not worse than total laryngectomy, which is the prerequisite treatment basis for larynx preservation options. We must make extra efforts in pursuing an ideal balance between nonsurgical and surgical larynx preservation options.

Incidence and clinical significance of aberrant T-cell marker expression on diffuse large B-cell lymphoma cells.

INTRODUCTION: Aberrant expression of T-cell markers is occasionally observed in B-cell lymphomas. We conducted a retrospective study to establish its incidence and to determine its relationship with clinical features of patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: We reviewed DLBCL patients diagnosed between January 2002 and April 2009. Patients fulfilled the following criteria: (1) age >18 years, (2) HIV negative, (3) B-cell lymphoma confirmed by restricted expression of surface immunoglobulin light chains by flow cytometry (FCM). Aberrant T-cell marker expression (ATCME) was defined as positivity for CD2, CD3, CD4, CD7, and/or CD8 on DLBCL cells by FCM. Phenotyping was also performed by immunohistochemistry (IHC). Patients were grouped according to positive or negative ATCME and their clinical features including survival were compared. RESULTS: Of 150 patients, 11 (7.3%) showed ATCME; CD2 and CD7 were most often expressed. ATCME was less often detected and the signal was weaker using IHC. There were no statistically significant differences in clinical features between the two groups. CONCLUSIONS: FCM may be useful to detect ATCME in a small amount of lymphoma cells. The mechanism responsible for ATCME, and whether it contributes in any way to the pathogenesis of B-cell neoplastic transformation, requires clarification.

A clinical study of transoral pharyngectomies to treat superficial hypopharyngeal cancers.

BACKGROUND: For years, it has been a major interest for surgeons and oncologists to develop a novel technique to detect hypopharyngeal cancers at an early stage and to treat the lesions in a less invasive manner. The advent of the narrow band imaging system combined endoscopy and various endoscopic approaches shed light on the new era of the minimum invasive management of superficial cancers in hypopharyngeal regions. METHODS: Three endoscopic approaches, endoscopic mucosal resection, endoscopic submucosal dissection and endoscopic laryngopharyngeal surgery, were chronologically introduced at our institute. In this study, we focused on the clinical outcomes, advantages and limitations of each procedure. RESULTS: A total of 30 patients (42 procedures) received transoral pharyngectomies between June 2006 and May 2012. Tracheotomy was performed in 9 of 42 (21%) patients. Three patients developed local recurrence and were subsequently controlled by additional transoral pharyngectomies. The 2- and 5-year local control rates were 92.8 and 83.5%. The 2- and 5-year overall survival rates were 82.1%. CONCLUSIONS: Endoscopic mucosal resection, endoscopic submucosal dissection and endoscopic laryngopharyngeal surgery-transoral pharyngectomies are useful procedures for treating superficial hypopharyngeal cancers. Endoscopic mucosal resection manifested the least invasiveness and may be beneficial for resecting small superficial lesions, endoscopic submucosal dissection may be advantageous for patients with difficult laryngopharyngeal exposure and endoscopic laryngopharyngeal surgery has shown the optimal effectiveness and minimal complications and can be applied to most of the hypopharyngeal sub-sites. All three procedures require a high level of technical skill and close collaboration between otolaryngologists and gastroenterologists.

Surveillance after endoscopic mucosal resection or endoscopic submucosal dissection for esophageal squamous cell carcinoma.

The objectives of surveillance after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma are: (i) early detection and treatment of recurrence; and (ii) early detection and treatment of metachronous esophageal squamous cell carcinoma and second primary cancers. Protocols for follow up after EMR or ESD for esophageal squamous cell carcinoma should be based on the risks of lymph node metastasis and distant metastasis as assessed on the basis of tumor staging at initial treatment. Early detection of recurrence or metachronous carcinomas often allows curative or less invasive treatment. Particular attention should be paid to the development of metachronous esophageal squamous cell carcinomas and second primary cancers (in particular, head and neck cancer and gastric cancer because of their high incidence).

Pediatric internal auditory canal cavernous hemangioma with rapid progression of sensorineural hearing loss: illustrative case.

BACKGROUND: Cavernous hemangioma of the internal auditory canal is extremely rare and is characterized by symptoms such as vertigo, sensorineural hearing loss, and facial nerve dysfunction. OBSERVATIONS: A health examination on an 11-year-old female in the fifth grade revealed hearing loss in the left ear. She also had dizziness that had persisted for approximately 1 year. Pure-tone audiometry revealed sensorineural hearing loss in her left ear. Rightward horizontal and rotatory nystagmus was detected. Facial paralysis was not present. Magnetic resonance imaging showed a lesion that was suspected to be hemangioma. The authors selected a left suboccipital retrosigmoid approach. The tumor showed a berry-tufted appearance throughout the cerebellopontine angle. The seventh cranial nerve penetrated the tumor and partly circulated outside the tumor with marked adhesion. The authors partially resected the tumor to avoid damaging the facial nerve. A histological examination identified cavernous hemangioma. LESSONS: The fundamental treatment for cavernous hemangioma of the internal auditory canal is complete surgical removal; however, any surgical intervention may result in hearing loss and facial paralysis. The extent of surgery needs to be decided intraoperatively based on the balance between preoperative symptoms and postoperative complications.

Novel color fluorescence imaging for sentinel lymph node detection in oral and oropharyngeal cancer.

AIM: Fluorescence imaging (FI) using indocyanine green (ICG) is a noteworthy alternative technique for sentinel lymph node (SLN) detection without radiation exposure in oral cavity and oropharynx cancer. However, conventional FI is monochrome, so the visibility is limited. This study assessed whether color FI using the HyperEye Medical System (HEMS) is feasible as an alternative for SLN detection. METHODS: Patients with previously untreated cT1-2N0 oral or oropharyngeal cancer who were to undergo primary tumor resection and elective neck dissection (END) in our hospital were enrolled from November 2012 to March 2016. The patients underwent SLN detection for biopsy via the HEMS following the injection of ICG solution around the primary lesion before neck dissection. The visibility and the diagnostic accuracy of the imaging were evaluated. RESULTS: SLNs were visualized in all eight cases; however, transcutaneous fluorescence detection was not observed in all cases. Utilizing color mode imaging simplified harvest by clearly discriminating SLNs from surrounding structures, while the monochrome mode proved to be more sensitive for detection. Two cases showed occult metastases on both sentinel and regional nodes. The identification and false negative rates were 100% and 0%, respectively. There were no complications incurred due to this method. CONCLUSION: Our results suggest that color FI with the HEMS allows for the accurate and safe harvest of SLNs with a preparatory skin incision. Although there is room for improvement of sensitivity, this easy-to-handle procedure might provide the potential to expand the role of the ICG method for SLN detection in head and neck cancer.

Narrow-field supracricoid partial laryngectomy: Procedure development and initial clinical experiences.

OBJECTIVES: To evaluate the feasibility of narrow-field supracricoid partial laryngectomy with cricohyoidoepiglottopexy (NF-SCPL-CHEP). METHODS: Between 2019 and 2020, five patients with glottic cancers underwent NF-SCPL-CHEP. The mean durations of surgical drains, tracheostomy canula, and nasogastric tube use were evaluated. Length of stay following NF-SCPL-CHEP was compared with that of our open SCPL historical controls. A case summary is provided for the first patients, with detailed information about postoperative management and function. RESULTS: All five patients achieved uneventful postoperative recoveries without major complications. The average time for surgical drains, tracheostomy canula, and nasogastric tube use were 2, 15, and 46 days, respectively. The mean overall hospitalization period was 36 days for NF-SCPL-CHEP patients. The mean period of hospitalization based on our early experiences between 1997 and 2005 with classical open SCPL was 72 days. All patients were fully functional and local recurrences or distant metastases were not encountered during a mean observation period of 39 months. CONCLUSIONS: NF-SCPL-CHEP with 6 cm cervical access appeared technically feasible and oncologically sound in this initial clinical experience. An extra 2 cm incision, which enabled lateral neck dissection, was not felt to detract from the overall minimally invasive basis of NF-SCPL-CHEP. The clinical results were encouraging with limited complications and predictable postoperative recovery. The length of stay for patients undergoing NF-SCPL was half that of open SCPL historical controls. Less damages to local circulation may associate with the positive influences. Further study with a large patient sample across multiple institutions are needed to carefully evaluate long-term functional and oncological outcomes.

Impact of lymph node ratio and number of lymph node metastases on survival and recurrence in laryngeal squamous cell carcinoma.

INTRODUCTION: The aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma. MATERIALS AND METHODS: We conducted a retrospective multicenter international study involving 24 Otorhinolaryngology-Head and Neck Surgery divisions. Disease-specific survival (DSS) and disease-free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut-off values. RESULTS: 2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5-year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging. CONCLUSION: Our data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma.

Association of CD20 levels with clinicopathological parameters and its prognostic significance for patients with DLBCL.

Diffuse large B-cell lymphomas (DLBCL) express CD20. CD20 expression is described as negative, weak, or normal as determined by flow cytometry (FCM) and is an important target for the treatment of DLBCL. However, the impact of CD20 levels at onset of the disease on patient prognosis has not been fully elucidated. We analyzed 174 DLBCL cases newly diagnosed between January 1998 and April 2010. The relationship of the association between CD20 levels and patients' backgrounds and prognoses was analyzed using the Kaplan-Meier method and Cox proportional hazard regression. Of the 174 patients, three cases (1.7%) were defined as CD20 negative based on immunohistochemistry (IHC). Although the other 171 cases were positive by IHC, eight cases (4.7%) were defined as negative and 33 cases (19.3%) were defined as weak when analyzed by FCM. Of the 105 patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy, those who were CD20 negative (FCM) showed significantly inferior overall (hazard ratios (HR): 6.79, 95% CI: 1.32-34.96, p = 0.04) and progression-free survival (HR: 7.3, 95% CI: 1.49-35.8, p = 0.04) compared to patients who were CD20 normal. Our findings indicate that the CD20 level (FCM) at onset is an independent predictor of the prognosis of patients with DLBCL.

Functional organ preservation for laryngeal cancer: past, present and future.

OBJECTIVE: Management of laryngeal cancer has focused on improving survival while preserving function. Over the past 20 years, the trends have shifted from surgery to chemoradiotherapy and presently we are facing various challenges. It is imperative to re-examine what has happened and what can be done. METHODS: Review of the literature along with our experience in the management of functional organ preservation for laryngeal cancer. RESULTS: There was an increasing use of chemoradiotherapy with a decreasing use of surgery. Inappropriate patient selection along with inability to properly apply salvage surgeries have been presumed to be responsible for survival deterioration in laryngeal cancer. Reports concerning late adverse events after chemoradiotherapy are also increasing. Reconfirmation of the multidisciplinary team approach is imperative. Transoral laser microsurgery can be used for early laryngeal cancer and, in some experienced institutes, for advanced-stage cancers. Supracricoid laryngectomy demonstrated satisfactory oncologic and functional outcomes, based on our experience. CONCLUSIONS: Treatment selection for larynx preservation should not merely be decided by guidelines but considering each patient's individual condition. Head and neck surgeons are encouraged to take reasonable risks in performing salvage larynx preservation surgery when it is the only option to save a functioning larynx.

Clinical significance of positive Delphian node in supracricoid laryngectomy with cricohyoidoepiglottopexy.

OBJECTIVE: A positive Delphian node is known to predict a poor prognosis in laryngeal cancer. To elucidate the clinical significance of positive Delphian node metastasis in supracricoid laryngectomized patients, we conducted a thorough clinical review. METHODS: We reviewed clinical data from 65 patients who underwent supracricoid laryngectomy with cricohyoidoepiglottopexy; in these patients, the Delphian node was examined by frozen section as a routine process. Incidence, positivity rates and clinical impact of the positive Delphian node were analyzed. RESULTS: The presence of the Delphian node was detected in 27 of 65 (41.5%) patients; among these 27 patients, 3 (3/65 = 4.6%) were positive for metastasis. Case 1 (pT3N2b) died of lung metastases 32 months after supracricoid laryngectomy with cricohyoidoepiglottopexy. Case 2 (pT4N2c) underwent conversion to total laryngectomy during supracricoid laryngectomy with cricohyoidoepiglottopexy because of unexpected submucosal lymphatic infiltration; this patient is currently alive with disease 23 months after surgery. Case 3 (T3N1) is currently alive without disease 48 months after surgery. CONCLUSIONS: The positive Delphian node is exclusively encountered in advanced laryngeal cancers and suggests an ominous outcome. Sufficient dissection of the paratracheal and lateral neck nodes is recommended. Delphian node evaluation is advised for all supracricoid laryngectomy surgeries.

Delayed wound infection after supracricoid partial laryngectomy following failure of high dose radiation.

Past radiation therapy is known as a major risk factor promoting post-supracricoid partial laryngectomy (SCPL) complications. Risk of post-SCPL complications may further increase following failure of high dose radiation; in these patients, wound infection may become evident more than 1 month after an uneventful post-surgical course. By defining this complication as "Delayed Wound Infection" and reviewing the clinical features, we intended to elucidate the mechanism, risk factors, and management of this post-SCPL complication. Between 1997 and 2009, 60 patients received SCPL. The incidence of post-SCPL wound infection was analyzed in reflect to radiation status, radiation dose, and medical histories. Of 60 patients, delayed wound infection was identified in 4 (7%); radiation doses were 65, 68, 70, and 76.8 Gy (avg. 70 Gy). Blood data including white blood cell and C-reactive protein showed slight elevation before the delayed infection became evident. Patients with high dose radiation (≥ 65 Gy) accompanied by histories of diabetes and renal insufficiency are considered a high risk group. Delayed re-epithelialization of the inner surface of the cricohyoido gap was presumed to be the main pathogenesis. Early initiation of antibiotics and hyperbaric oxygen therapy are effective for rapid recovery. "Delayed Wound Infection" was treatable and patients undergoing surgery after failure of high dose radiation should be managed with extra precaution, but should not be excluded from the indications for SCPL.

Phase I/II trial of concurrent use of S-1 and radiation therapy for T2 glottic cancer.

OBJECTIVE: A Phase I/II study of S-1 combined radiation therapy was conducted in patients with Stage II (T2N0) glottic cancer. The purpose of the Phase I study was to identify the maximum tolerated dose, the recommended dose and the dose limiting toxicity. The objectives in the phase II study were to estimate the local control and the overall survival, and the incidence of adverse events. METHODS: In Phase I, S-1 was administered orally in a split-course fashion as two doses of 40 mg/m(2), for a total daily dose of 80 mg/m(2). The course involved a 2-week rest after a 2-week administration (Level 1) and a 1-week rest after a 3-week administration (Level 2). Radiation therapy was administered in 2-Gy daily (total 60-Gy) standard fractionation. RESULTS: Seven patients were enrolled in the Phase I, and 19 in the Phase II study. Mucositis was the most common toxicity encountered. All 26 patients completed radiation therapy without delay. The overall response rate was 100% (26/26) with all patients showing a complete response. One patient developed a local recurrence 28 months after the treatment. The 3-year local control and overall survival rates were 94.7 and 85.4%, respectively (limited to 22 patients from Level 2). CONCLUSIONS: The use of S-1 at 80 mg/m(2) per day in a split-course with 1-week rest during the course of radiation therapy was safe and effective for Stage II glottic cancer. The treatment strategy employing orally available S-1 proved to be beneficial over the conventional injection of antitumor agents for maintaining the patients' quality of life.

Endoscopic Transoral Hybrid Supracricoid Partial Laryngectomy with Cricohyoidoepiglottopexy.

OBJECTIVES: The hybrid supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCPL-CHEP, that is, open partial horizontal laryngectomies OPHL Type IIa) has been described using a flexible next generation robotic surgical platform for manipulation. We sought to evaluate the feasibility of performing this procedure using endoscopic transoral (EndoT) surgical techniques without robotics. METHODS: Preclinical cadaveric study using two human cadavers. Hybrid SCPL-CHEP was performed with a flexible endoscope for visualization and hand-held instruments for manipulation (SILS Hook monopolar and Dissect, HAVAS LaryngoFIT malleable straight jaw instruments, and Stratafix 4-0 spiral knotless barbed suture). RESULTS: EndoT hybrid SCPL-CHEP was successfully performed. The hand-manipulated rigid instruments allowed for transoral incisions and mucosal suturing. We provide the procedural steps of EndoT hybrid techniques. CONCLUSIONS: EndoT hybrid SCPL-CHEP was technically feasible in the preclinical cadaveric laboratory setting and appeared comparable to the hybrid SCPL-CHEP via transoral robotic surgery (TORS). Selected handheld instruments and flexible endoscopy appear to facilitate minimally invasive surgery of the larynx. This novel procedure and technique warrant further clinical study for consideration of feasibility, applicability, and patient benefit.

Clinicopathological analyses of fifty supracricoid laryngectomized specimens: evidence base supporting minimal margins.

OBJECTIVES: Supracricoid laryngectomy (SCL) is a reliable laryngeal preservation surgery. However, close surgical margins are often inevitable. Based on clinicopathological analyses of supracricoid laryngectomized specimens, we evaluated the evidence base supporting minimal margins. METHODS: The distance between tumor edge and resected margin was measured macro- and microscopically at the anterior, posterior, superior and inferior edges, using 50 surgical specimens. The margins were correlated with pathological T staging and the prognoses. RESULTS: The anterior and posterior margins were the shortest, and the superior margin was the longest. The inferior margin was the only edge at which a positive margin was encountered. Cancer extending 10 mm below the glottal free edge significantly decreased the inferior margin. CONCLUSIONS: The surgical potential of SCL with cricohyoidoepiglottopexy was confirmed to be able to cope with tumor extensions showing margins of a few millimeters at the anterior, posterior and superior ends. Accurate assessment and management at the inferior margin is the key to stable local control.

[Clinical review of supracricoid laryngectomy with CHEP and CHP: 50 patients treated in 11 years].

An analysis of clinical data on 50 patients undergoing supracricoid laryngectomy (SCL) between 1997 and 2008 i.e., cricohyoidoepiglottopexy (CHEP) in 47 and cricohyoidopexy (CHP) in 3 cases showed that the number of SCL cases operated on within a year surpassed that of Total Laryngectomy after 2003. Selection criteria included performance status 0-1 and blood gas PO2>80 torr, especially in those patients over 70-years-old. Postoperative wound infection occurred in 16 patients (32%), with four requiring additional surgical intervention (two ruptured pexis and two chondritis induced by C3-C4 osteophytes). A history of radiotherapy and systemic complications, i.e., diabetes and renal failure, added to the risk of wound infection. Introducing a clinical pathway shortened hospitalization. Vocal function was achieved in 96% and swallowing function in 89% of patients. Five-year crude survival in CHEP was 69% and in TL 51%. Laryngeal preservation was 70%, increasing to 89% after the introduction of SCL. SCL-CHEP is thus indicated for unfavorable T2 (ASCO 2006), well-selected T3, T4, and rT1-4 (radiation failures). Effort should emphasize a good balance in prognosis and function in organ preservation for laryngeal cancer.