- Email: [email protected]
Endoscopic laryngo-pharyngeal surgery for elderly patients
G Model
ANL-2496; No. of Pages 6 Auris Nasus Larynx xxx (2018) xxx–xxx Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Endoscopic laryngo-pharyngeal surgery for elderly patients Yo Kishimoto a, Hiroyuki Harada a, Makiko Funakoshi b, Shin-ichi Miyamoto c, Atsushi Suehiro a, Morimasa Kitamura a, Manabu Muto b, Ichiro Tateya a,*, Koichi Omori a a
Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Japan c Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 4 July 2018 Accepted 13 August 2018 Available online xxx
Objective: Due to the rising number of elderly patients and advances in endoscopic devices, early laryngeal and pharyngeal cancers are increasingly found in elderly patients. In these cases, minimally invasive endoscopic larygo-pharyngeal surgery (ELPS) may be indicated. However, the safety and efficacy of ELPS in elderly populations has not been established. The purpose of this study was to investigate the safety, outcomes and feasibility of ELPS in very elderly patients. Methods: Between February 2010 and April 2016, 29 pharyngeal cancerous or pre-cancerous lesions in 19 patients aged 75 years or older were treated with ELPS. Twenty-six resections were performed in total, and the patients’ clinical courses were reviewed. Results: Sixteen patients had multiple comorbidities and moderate to severe comorbidities were observed in 17 patients. The average surgical time and hospitalization period was 54.3 min and 18.8 days, respectively. On average, oral intake began 4.4 days after the procedure, and all patients eventually received nourishment by mouth; no percutaneous endoscopic gastrostomy dependency was observed. Complications included post-operative bleeding and aspiration pneumonia in two cases each, and all complications were safely managed. The 3-year overall survival rate was 90.2% and the 3-year disease-specific survival rate was 100%. Conclusion: ELPS was safely performed in elderly patients, suggesting that it is a feasible treatment option for pharyngeal lesions in very elderly patients. © 2018 Elsevier B.V. All rights reserved.
Keywords: ELPS Pharyngeal cancer Elderly Trans-oral surgery
1. Introduction Over the past decade, several clinical trials have investigated treatment options for head and neck cancers (HNC). Consequently, the treatment algorithm for HNC has become more complex and aggressive. The cornerstones of HNC
* Corresponding author at: Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail address: [email protected] (I. Tateya).
treatment include surgery and radiotherapy, often given in combination with one another and additionally intensified with chemotherapy [1]. These multidisciplinary therapeutic modalities have improved local regional control and overall survival in HNC. However, the treatment of elderly patients remains controversial, in part because elderly patients often have multiple comorbidities, and suffer more treatment-induced adverse effects and non-cancer related death compared to younger patients [2]. Previously, pharyngeal lesions, such as hypopharyngeal cancer, tended to present at an advanced stage and had a poor
https://doi.org/10.1016/j.anl.2018.08.008 0385-8146/© 2018 Elsevier B.V. All rights reserved.
Please cite this article in press as: Kishimoto Y, et al. Endoscopic laryngo-pharyngeal surgery for elderly patients. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.08.008
G Model
ANL-2496; No. of Pages 6 Y. Kishimoto et al. / Auris Nasus Larynx xxx (2018) xxx–xxx
2
prognosis [3]. However, recent innovations in optical technology, such as ME (magnifying endoscopy) and NBI (Narrow Band Imaging), have enabled the detection of very early stage laryngeal and pharyngeal cancers [4,5]. Because of these advances in endoscopic diagnostics and the establishment of transoral surgical procedures, a paradigm shift has occurred in the treatment strategy for laryngo-pharyngeal cancer [6]. Because of advances in clinical practice and the rising elderly population worldwide, early laryngeal or pharyngeal cancers are increasingly found in elderly patients. In these cases, minimally invasive treatment options are preferred and endoscopic laryngo-pharyngeal surgery (ELPS) is sometimes indicated. ELPS is less invasive than conventional open procedures or (chemo) radiotherapy, but its safety and efficacy in the elderly has not been established. The purpose of this study was to investigate the safety, acceptability and outcomes of ELPS in very elderly patients.
Medical Instruments Company, Ltd.) and a curved electrosurgical needle knife (Olympus Medical Systems, KD-600). The subepithelial tissues were preserved as much as possible. 2.3. Assessment of acceptability Patient clinical information such as comorbidities, hospitalization period, operative time, fasting period, complications and oncological outcomes was retrospectively reviewed. Comorbidity was scored using the Adult Comorbidity Evaluation 27 (ACE-27) index, which classifies comorbidity into grade (none = 0, mild = 1, moderate = 2 and severe = 3) and type (12 different organ systems). Local recurrence was defined as tumor detected at the site of the ELPS scar even though the initial specimen had revealed a negative margin. Postoperative bleeding was defined as the need for endoscopic hemostasis after surgery. 2.4. Statistical analysis
2. Materials and Methods JMP (SAS institute Inc., NC) was used for all statistical analysis. Cause-specific and overall survival rates were estimated using the Kaplan–Meier method.
2.1. Patients Between February 2010 and April 2016, 29 pharyngeal cancerous or pre-cancerous lesions in 22 patients aged 75 years and older were treated by ELPS at Kyoto University Hospital (Table 1). All specimens were histologically evaluated according to the World Health Organization classification, and staged according to the Union for International Cancer Control tumor-nodemetastasis (UICC/TNM) classification (8th edition). Written informed consent was obtained in all cases, and the study was approved by the institutional review board of the Graduate School of Medicine, Kyoto University. 2.2. Surgical procedures All procedures were performed as previously reported [7]. Briefly, under general anesthesia, a curved rigid laryngoscope (Nagashima Medical Instruments Company, Ltd., Tokyo, Japan) was inserted to provide a working space, then a ME-NBI (GIF TYPE H260Z or Q240Z; Olympus Medical Systems, Tokyo, Japan) was inserted transorally to visualize the surgical field. The extent and exact margin of each lesion was identified by NBI and iodine staining. A mixed solution of epinephrine (0.02 mg/mL) and saline was injected into the subepithelial layer beneath the lesion to raise it up for resection. Lesions were resected using transorally inserted curved forceps (Nagashima Table 1 Patient characteristics. Patient characteristics Number of cases Number of lesions Age Gender History of esophageal cancer History of head and neck cancer
22 29 78.4 (75–85) years Male 21, female 1 15 14
3. Results 3.1. Patient and lesion characteristics Patient and lesion characteristics are shown in Table 1. Patients were predominantly male (95.5%), and patient age ranged from 75 to 85 years (average 78.3 years). Sixteen patients had multiple comorbidities and moderate to severe comorbidities were observed in 17 patients. The most common comorbidity was prior malignancy; over 90% of Table 2 Comorbidity characteristics. Type of comorbidities Type
Number of patients
Prior malignancy Cardiovascular Respiratory Neurological Endocrine Gastrointestinal Substance abuse
20 11 8 7 6 1 1
90.9% 50.0% 36.4% 31.8% 27.3% 4.5% 4.5%
Number of comorbidities Number of comorbidities
Number of patients
1 2 3 4
6 4 8 4
Adult Comorbidity Evaluation 27 (ACE-27) index ACE-27
Number of patients
1 2 3
5 13 4
Please cite this article in press as: Kishimoto Y, et al. Endoscopic laryngo-pharyngeal surgery for elderly patients. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.08.008
G Model
ANL-2496; No. of Pages 6 Y. Kishimoto et al. / Auris Nasus Larynx xxx (2018) xxx–xxx
3
patients had a history of malignancy. Cardiovascular, respiratory and neurological comorbidities were observed in 50, 36.4 and 31.8% of patients, respectively (Table 2). Of the 22 patients with prior malignancies, 15 had prior or simultaneous esophageal cancer, and 14 had prior or simultaneous head and neck cancer. Three patients had a history of previous irradiation to head and neck cancer in other site or other subsite. The number of oropharyngeal and hypopharyngeal lesions was 12 and 17, respectively. Only one recurrent lesion was included. Histologic diagnoses included squamous cell carcinoma (SCC) in 19 lesions, carcinoma in situ in five lesions, high-grade dysplasia in three lesions and low to moderate grade dysplasia in two lesions. A small lesion of moderate grade dysplasia was resected simultaneously with a lesion of SCC at the other subsite. A lesion of low grade dysplasia was resected because preoperative biopsy specimen was suspicious for high grade dysplasia. Eventually, five lesions were diagnosed as Tis, 12 lesions as T1, five lesions as T2 and two lesions as T3 (Table 3). The size of the resected specimens varied from 10 to 60 mm (average 33.5 mm).
3.3. Nutrient intake
3.2. Operation and hospitalization data
3.4. Post-operative complications
A total of 26 resections were performed for 29 lesions, and resection was safely completed in all cases. Multiple lesions were identified in four patients. In one case, four lesions were
Clinical information is summarized in Table 4. Post-operative bleeding, temporal emphysema and aspiration pneumonia were observed in two, three and two cases, respectively, and these complications were safely managed. No complication was observed in the patients with a history of irradiation for previous head and neck cancer. No prophylactic tracheostomy was needed and no vocal fold impairment was observed after the procedure.
Table 3 Lesion characteristics. Site of the lesions Origin
Number of lesions
Subsite
Oropharynx
12
Anterior wall Posterior wall Superior wall Lateral wall
2 8 1 1
Piriform sinus Post cricoid Posterior wall
11 2 4
Hypopharynx
17
Number of lesion(s) resected at the same operation Number of lesion(s)
Number of operation(s)
1 2 3 4
18 2 1 1
treated with a single resection, and in three cases multiple resections were required. Simultaneous neck dissection for metastatic lymph nodes was performed in one case and endoscopic submucosal dissection for an esophageal lesion was performed in one case. The average ELPS surgical time and the average hospitalization period after ELPS was 54.3 (6–133) min and 13.6 (3–34) days, respectively (the median was 55.0 min and 12.0 days).
Oral intake was started more than one week after ELPS in seven cases, because of aspiration (two cases), laryngeal penetration (one case), laryngeal penetration and laryngeal edema (one case) and emphysema (three cases). In the remaining 15 cases, oral intake started after 1.9 (1–3) days. In total, the average and median oral fasting period after the procedure were 4.4 and 2 (1–15) days, respectively. All patients eventually received nourishment by mouth and no percutaneous endoscopic gastrostomy (PEG) dependency was observed.
3.5. Oncological outcomes The post-operative follow-up period varied from 346 to 2544 days (average, 1245.6 days). Local recurrence was occurred in one case, and the lesion was treated with ELPS again. Post-operative cervical lymph node metastasis developed in two cases, and both were successfully controlled by neck dissection. Two patients died of other diseases, namely gastric cancer and esophageal cancer (Table 4). The 3-year overall survival rate was 90.2% and the 3-year disease specific survival rate was 100% (Fig. 1). 4. Discussion
Diagnosis of lesions Diagnosis
Number of lesion(s)
Squamous cell carcinoma Carcinoma in situ High grade dysplasia Low to moderate grade dysplasia
19 5 3 2
T stage of the lesions T stage
Number of lesion(s)
is 1 2 3
5 12 5 2
Advanced age is a major risk factor for cancer [8]. This is applicable to head and neck cancers, as more than 50% of head and neck cancers occur in patients over 60 years of age, and 28% in patients over 70 [9]. These numbers are expected to increase as the size of the elderly population increases. However, the treatment strategy for head and neck cancer in elderly patients remains a point of controversy, and a clinical practice guideline has not yet been established. In treating head and neck cancer in the elderly, some agerelated factors such as life expectancy, comorbidities, performance status, impaired functional status and cognitive decline should be considered before determining a management
Please cite this article in press as: Kishimoto Y, et al. Endoscopic laryngo-pharyngeal surgery for elderly patients. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.08.008
Age (y. o.)GenderLesions SiteSubsiteHistologySize of resected specimen (mm)T stageOther lesions New H New O New H New H New H New H New O New O New O New H New H New O New H New O New H New H RecurrentO New H New H New O New O New H
PW LW PC PS PS PS PW AW PW PS PS PW PS AW PC PW PW PS PS SW PW PW
SCC HGD SCC SCC SCC LGD SCC SCC CIS CIS SCC SCC SCC SCC CIS SCC SCC CIS SCC SCC CIS SCC
37 15 34 28 31 13 20 60 23 57 48 45 47 50 30 35 30 35 44 22 45 35 35.6
2 2 1 1 1 2 is is 3 1 3 1 is 1 1 is 2 1 is 1
Vertical marginHorizontal marginPost-operative complicationsRecurrenceCause of death
Negative Negative Negative MGD Negative Negative Negative 2 lesions of HGDNegative Positive Negative Negative Negative 3 lesions of SCC Negative Negative Negative Negative Negative Negative Negative SCC Negative Negative Negative Negative
Negative Negative Positive Negative Negative Negative Negative Positive Negative Negative Positive Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Positive
SE
Neck
POB
Neck
SE, POB
Gastric cancer Local
AP
SE
Esophageal cancer
AP
H: hypopharynx, O: oropharynx, PW: posterior wall, LW: lateral wall, PC: post cricoid, PS: pyriform sinus, AW: anterior wall, SW: superior wall, SCC: squamous cell carcinoma, HGD: high grade dysplasia, MGD: moderate grade dysplasia, LGD: low grade dysplasia, CIS: carcinoma in situ, SE: subcutaneous emphysema, POB: post-operative bleeding, AP: aspiration pneumonia.
Y. Kishimoto et al. / Auris Nasus Larynx xxx (2018) xxx–xxx
F M M M M M M M M M M M M M M M M M M M M M
G Model
No.
1 82 2 76 3 75 4 78 5 76 6 84 7 75 8 79 9 75 10 85 11 76 12 78 13 76 14 76 15 80 16 79 17 80 18 82 19 75 20 77 21 77 22 81 Average 78.3
ANL-2496; No. of Pages 6
4
Please cite this article in press as: Kishimoto Y, et al. Endoscopic laryngo-pharyngeal surgery for elderly patients. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.08.008
Table 4 Clinical information.
G Model
ANL-2496; No. of Pages 6 Y. Kishimoto et al. / Auris Nasus Larynx xxx (2018) xxx–xxx
Fig. 1. Overall survival (A) and disease-specific survival (B) after ELPS for pharyngeal lesions.
strategy [10]. Studies on the safety of surgical treatment of head and neck cancers in the elderly have shown conflicting results. A large retrospective study by Morgan et al. reported increased perioperative mortality and non-lethal complications in patients over 65 years of age [11]. In contrast, several studies have used multivariate analyses to clarify the risk factors for complications after surgery for head and neck cancer, and age was not found to be a contraindication to surgery. However, some comorbidities were shown to be associated with post-operative complications and elderly patients tend to have more comorbidities compared to younger patients [12,13]. Thus it is important to carefully select appropriate treatment modalities for elderly patients based on their comorbidities and functional status. Transoral resection for laryngeal/pharyngeal cancer has recently emerged as a minimally invasive surgical treatment for head and neck cancer. The technique has rapidly spread worldwide. One example of transoral resection is ELPS. Unlike transoral laser microsurgery (TLM) or transoral robotic surgery (TORS), ELPS is a hybrid of head and neck surgery and endoscopic gastrointestinal treatment that developed from endoscopic submucosal dissection (ESD) for gastric and esophageal cancers. ELPS provides safe and precise resection with minimal damage to the surrounding tissues and is performed with the aid of a flexible ME-NBI and specially fabricated curved instruments. It is basically indicated for superficial lesions such as carcinoma in situ or invasive laryngopharyngeal cancer without muscular invasion [6,14]. Because it is less invasive than conventional surgery, ELPS is often used in the elderly.
5
In this study, we clarified the safety and efficacy of ELPS in elderly patients. The National Institute on Aging at the National Institutes of Health classifies the elderly into three categories: young old (65–74 years), older old (75–84 years), and oldest old (>85 years) [10]. Because most clinical studies use the ages of 70 or 75 years as a cut-off to define the elderly [8], we used an age of 75 years or older to define the elderly in this study. As shown in Table 3, the lesions of variable sizes (T stages) at various subsites in the pharynx were included in this study, and ELPS was safely completed in all the cases. We need to be careful in treating near-circumferential lesions or post irradiation cases, however, location and size of the lesions are thought not always be the limits of ELPS in elderlies. Out of 29 lesions, 3 lesions at posterior wall of the pharynx were suspected to invade the muscle layer. These 3 lesions were resected with muscle tissues and one of them is eventually proven to have muscular invasion. Post-operative aspiration pneumonia occurred in the 2 cases with muscle resection. It is difficult to judge the appropriateness of this procedure for the elderly patients with muscular invasion from this study, however at least it can be said that we should be careful in deciding the indication of ELPS for the lesion with muscular invasion especially at the posterior wall of the pharynx. Many patients in this study had a history of head and neck cancer and/or esophageal cancer, which was likely due to common risk factors such as tobacco use and alcohol consumption. A history of previous treatment suggests the presence of irradiated mucosa or scar formation that complicates the procedure and makes post-operative wound healing and swallowing more difficult. However, the average operation time and median operation time per lesion was 54.3 and 25.0 min, respectively, which is comparable to a previous report [7]. Post-operative bleeding and emphysema were observed in two and three cases, respectively. These complications were safely managed and all wounds healed without delay or severe infection. Temporal aspiration and laryngeal penetration were observed in four cases after the procedure, but all patients eventually tolerated oral intake. Post-operative recurrences were observed in 3 cases. Although 4 cases with positive margins at initial surgeries showed no local recurrences, local recurrence occurred in the case with negative margins. This case had multiple lesions at initial surgery, and careful follow-up might be essential in case with multiple lesions. The average hospitalization period after the procedure was 13.6 days. Much shorter hospitalization periods have been reported in previous reports of transoral surgery for head and neck cancer in other countries [15,16]. This difference may be accounted for by the culture and health insurance system in Japan. Given that patients usually stay in the hospital for more than 3 weeks after reconstruction surgery in Japan [17], this period seems acceptable. Many patients in this study had multiple comorbidities. Comorbidities were graded as moderate to severe in 17 patients. The proportion of moderate to severe comorbidities was high compared to a previous report [13]. One reason for this is that many patients had other malignancies within the last five years, particularly in the esophageal or head and neck regions. The high rate of multiple metachronous cancers might be a result of the field cancerization phenomenon [18], and the rate may
Please cite this article in press as: Kishimoto Y, et al. Endoscopic laryngo-pharyngeal surgery for elderly patients. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.08.008
G Model
ANL-2496; No. of Pages 6 Y. Kishimoto et al. / Auris Nasus Larynx xxx (2018) xxx–xxx
6
increase with the development of endoscopic diagnostics. Thus, other metachronous malignancies might develop after ELPS, even in elderly patients, and close surveillance may be required after the procedure. In authors facility, esophagogastroduodenoscopy is usually performed as a post operative surveillance at least once to twice a year. The overall survival of patients with multiple malignancies is generally poor [19,20]. However, in this study we treated malignancies at a very early stage, leading to good oncological outcomes, even in patients with metachronous lesions, that were equivalent to a previous report [7]. Geriatric head and neck cancer patients who are treated similar to younger patients experience similar outcomes [9], hence early detection of lesions with scheduled surveillance will be important, even in elderly patients. Improvements in medical management, anesthesia and devices have allowed ELPS to be performed in the elderly. In this study, we found that ELPS was well tolerated and produced good oncologic outcomes in patients aged 75 years and older. The limitations of this study include the small sample size, poorly defined surgical indications, lack of a control group and the study’s retrospective nature. Because of the small sample size, it was difficult to analyze the risk factors for postoperative complications or recurrences/metastasis in elderly patients. A prospective, comparative study with larger number of patients is warranted to confirm the acceptability and appropriate indications for ELPS in the elderly. 5. Conclusions ELPS for pharyngeal lesions was safely performed in patients aged 75 years and older. This procedure appears to be a well tolerated and efficacious treatment option for pharyngeal lesions in very elderly patients. Financial support Authors have no conflicts of interest or financial ties to disclose. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. References [1] Gugic J, Strojan P. Squamous cell carcinoma of the head and neck in the elderly. Rep Pract Oncol Radiother 2012;18:16–25. http://dx.doi. org/10.1016/j.rpor.2012.07.014. [2] Bonomo P, Desideri I, Loi M, Lo Russo M, Olmetto E, Maragna V, et al. Elderly patients affected by head and neck squamous cell carcinoma unfit for standard curative treatment: is de-intensified, hypofractionated radiotherapy a feasible strategy? Oral Oncol 2017;74:142–7. http://dx.doi.org/10.1016/j.oraloncology.2017.10.004. [3] Chu P-Y, Chang S-Y. Reconstruction of the hypopharynx after surgical treatment of squamous cell carcinoma. J Chin Med Assoc 2009;72:351–5. http://dx.doi.org/10.1016/S1726-4901(09)70386-7.
[4] Tateya I, Morita S, Muto M, Miyamoto S, Hayashi T, Funakoshi M, et al. Magnifying endoscope with NBI to predict the depth of invasion in laryngo-pharyngeal cancer. Laryngoscope 2015;125:1124–9. http:// dx.doi.org/10.1002/lary.25035. [5] Muto M, Minashi K, Yano T, Saito Y, Oda I, Nonaka S, et al. Early detection of superficial squamous cell carcinoma in the head and neck region and esophagus by narrow band imaging: a multicenter randomized controlled trial. J Clin Oncol 2010;28:1566–72. http://dx.doi.org/ 10.1200/JCO.2009.25.4680. [6] Tateya I, Shiotani A, Satou Y, Tomifuji M, Morita S, Muto M, et al. Transoral surgery for laryngo-pharyngeal cancer – the paradigm shift of the head and cancer treatment. Auris Nasus Larynx 2016;43:21–32. http://dx.doi.org/10.1016/j.anl.2015.06.013. [7] Tateya I, Muto M, Morita S, Miyamoto S, Hayashi T, Funakoshi M, et al. Endoscopic laryngo-pharyngeal surgery for superficial laryngopharyngeal cancer. Surg Endosc 2016;30:323–9. http://dx.doi.org/ 10.1007/s00464-015-4213-y. [8] Szturz P, Vermorken JB. Treatment of elderly patients with squamous cell carcinoma of the head and neck. Front Oncol 2016;6. http://dx.doi. org/10.3389/fonc.2016.00199. [9] Moye VA, Chandramouleeswaran S, Zhao N, Muss HB, Weissler MC, Hayes DN, et al. Elderly patients with squamous cell carcinoma of the head and neck and the benefit of multimodality therapy. Oncologist 2015;20:159–65. http://dx.doi.org/10.1634/theoncologist.2013-0325. [10] Porceddu SV, Haddad RI. Management of elderly patients with locoregionally confined head and neck cancer. Lancet Oncol 2017;18:e274– 83. http://dx.doi.org/10.1016/S1470-2045(17)30229-2. [11] Morgan RF, Hirata RM, Jaques DA, Hoopes JE. Head and neck surgery in the aged. Am J Surg 1982;144:449–51. http://dx.doi.org/10.1016/ 0002-9610(82)90420-2. [12] Goh CS-L, Kok Y-O, Yong CP-C, Tan EW-X, Goh L-G, Chew K-Y, et al. Outcome predictors in elderly head and neck free flap reconstruction: a retrospective study and systematic review of the current evidence. J Plast Reconstr Aesthet Surg 2018;71:719–28. http://dx.doi. org/10.1016/j.bjps.2017.12.011. [13] Peters TTA, van Dijk BAC, Roodenburg JLN, van der Laan BFAM, Halmos GB. Relation between age, comorbidity, and complications in patients undergoing major surgery for head and neck cancer. Ann Surg Oncol 2014;21:963–70. http://dx.doi.org/10.1245/s10434-013-3375-x. [14] Kishimoto Y, Sogami T, Uozumi R, Funakoshi M, Miyamoto S-I, Kitamura M, et al. Complications after endoscopic laryngopharyngeal surgery. Laryngoscope 2018;128:1546–50. http://dx.doi.org/10.1002/ lary.26953. [15] Boudreaux BA, Rosenthal EL, Magnuson JS, Newman JR, Desmond RA, Clemons L, et al. Robot-assisted surgery for upper aerodigestive tract neoplasms. Arch Otolaryngol Head Neck Surg 2009;135:397– 401. http://dx.doi.org/10.1001/archoto.2009.24. [16] Hammoudi K, Pinlong E, Kim S, Bakhos D, Morinie`re S. Transoral robotic surgery versus conventional surgery in treatment for squamous cell carcinoma of the upper aerodigestive tract. Head Neck 2015;37:1304–9. http://dx.doi.org/10.1002/hed.23752. [17] Sarukawa S, Sakuraba M, Kimata Y, Yasumura T, Uchiyama K, Hishinuma S, et al. Standardization of free jejunum transfer after total pharyngolaryngoesophagectomy. Laryngoscope 2006;116:976–81. http://dx.doi.org/10.1097/01.mlg.0000216915.62574.ba. [18] Muto M, Satake H, Yano T, Minashi K, Hayashi R, Fujii S, et al. Longterm outcome of transoral organ-preserving pharyngeal endoscopic resection for superficial pharyngeal cancer. Gastrointest Endosc 2011;74:477–84. http://dx.doi.org/10.1016/j.gie.2011.04.027. [19] Erkal HS, Mendenhall WM, Amdur RJ, Villaret DB, Stringer SP. Synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites. J Clin Oncol 2001;19:1358–62. http://dx.doi. org/10.1200/JCO.2001.19.5.1358. [20] Schwartz LH, Ozsahin M, Zhang GN, Touboul E, De Vataire F, Andolenko P, et al. Synchronous and metachronous head and neck carcinomas. Cancer 1994;74:1933–8.
Please cite this article in press as: Kishimoto Y, et al. Endoscopic laryngo-pharyngeal surgery for elderly patients. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.08.008
ANL-2496; No. of Pages 6 Auris Nasus Larynx xxx (2018) xxx–xxx Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Endoscopic laryngo-pharyngeal surgery for elderly patients Yo Kishimoto a, Hiroyuki Harada a, Makiko Funakoshi b, Shin-ichi Miyamoto c, Atsushi Suehiro a, Morimasa Kitamura a, Manabu Muto b, Ichiro Tateya a,*, Koichi Omori a a
Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Japan Department of Therapeutic Oncology, Graduate School of Medicine, Kyoto University, Japan c Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan b
A R T I C L E I N F O
A B S T R A C T
Article history: Received 4 July 2018 Accepted 13 August 2018 Available online xxx
Objective: Due to the rising number of elderly patients and advances in endoscopic devices, early laryngeal and pharyngeal cancers are increasingly found in elderly patients. In these cases, minimally invasive endoscopic larygo-pharyngeal surgery (ELPS) may be indicated. However, the safety and efficacy of ELPS in elderly populations has not been established. The purpose of this study was to investigate the safety, outcomes and feasibility of ELPS in very elderly patients. Methods: Between February 2010 and April 2016, 29 pharyngeal cancerous or pre-cancerous lesions in 19 patients aged 75 years or older were treated with ELPS. Twenty-six resections were performed in total, and the patients’ clinical courses were reviewed. Results: Sixteen patients had multiple comorbidities and moderate to severe comorbidities were observed in 17 patients. The average surgical time and hospitalization period was 54.3 min and 18.8 days, respectively. On average, oral intake began 4.4 days after the procedure, and all patients eventually received nourishment by mouth; no percutaneous endoscopic gastrostomy dependency was observed. Complications included post-operative bleeding and aspiration pneumonia in two cases each, and all complications were safely managed. The 3-year overall survival rate was 90.2% and the 3-year disease-specific survival rate was 100%. Conclusion: ELPS was safely performed in elderly patients, suggesting that it is a feasible treatment option for pharyngeal lesions in very elderly patients. © 2018 Elsevier B.V. All rights reserved.
Keywords: ELPS Pharyngeal cancer Elderly Trans-oral surgery
1. Introduction Over the past decade, several clinical trials have investigated treatment options for head and neck cancers (HNC). Consequently, the treatment algorithm for HNC has become more complex and aggressive. The cornerstones of HNC
* Corresponding author at: Department of Otolaryngology Head and Neck Surgery, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail address: [email protected] (I. Tateya).
treatment include surgery and radiotherapy, often given in combination with one another and additionally intensified with chemotherapy [1]. These multidisciplinary therapeutic modalities have improved local regional control and overall survival in HNC. However, the treatment of elderly patients remains controversial, in part because elderly patients often have multiple comorbidities, and suffer more treatment-induced adverse effects and non-cancer related death compared to younger patients [2]. Previously, pharyngeal lesions, such as hypopharyngeal cancer, tended to present at an advanced stage and had a poor
https://doi.org/10.1016/j.anl.2018.08.008 0385-8146/© 2018 Elsevier B.V. All rights reserved.
Please cite this article in press as: Kishimoto Y, et al. Endoscopic laryngo-pharyngeal surgery for elderly patients. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.08.008
G Model
ANL-2496; No. of Pages 6 Y. Kishimoto et al. / Auris Nasus Larynx xxx (2018) xxx–xxx
2
prognosis [3]. However, recent innovations in optical technology, such as ME (magnifying endoscopy) and NBI (Narrow Band Imaging), have enabled the detection of very early stage laryngeal and pharyngeal cancers [4,5]. Because of these advances in endoscopic diagnostics and the establishment of transoral surgical procedures, a paradigm shift has occurred in the treatment strategy for laryngo-pharyngeal cancer [6]. Because of advances in clinical practice and the rising elderly population worldwide, early laryngeal or pharyngeal cancers are increasingly found in elderly patients. In these cases, minimally invasive treatment options are preferred and endoscopic laryngo-pharyngeal surgery (ELPS) is sometimes indicated. ELPS is less invasive than conventional open procedures or (chemo) radiotherapy, but its safety and efficacy in the elderly has not been established. The purpose of this study was to investigate the safety, acceptability and outcomes of ELPS in very elderly patients.
Medical Instruments Company, Ltd.) and a curved electrosurgical needle knife (Olympus Medical Systems, KD-600). The subepithelial tissues were preserved as much as possible. 2.3. Assessment of acceptability Patient clinical information such as comorbidities, hospitalization period, operative time, fasting period, complications and oncological outcomes was retrospectively reviewed. Comorbidity was scored using the Adult Comorbidity Evaluation 27 (ACE-27) index, which classifies comorbidity into grade (none = 0, mild = 1, moderate = 2 and severe = 3) and type (12 different organ systems). Local recurrence was defined as tumor detected at the site of the ELPS scar even though the initial specimen had revealed a negative margin. Postoperative bleeding was defined as the need for endoscopic hemostasis after surgery. 2.4. Statistical analysis
2. Materials and Methods JMP (SAS institute Inc., NC) was used for all statistical analysis. Cause-specific and overall survival rates were estimated using the Kaplan–Meier method.
2.1. Patients Between February 2010 and April 2016, 29 pharyngeal cancerous or pre-cancerous lesions in 22 patients aged 75 years and older were treated by ELPS at Kyoto University Hospital (Table 1). All specimens were histologically evaluated according to the World Health Organization classification, and staged according to the Union for International Cancer Control tumor-nodemetastasis (UICC/TNM) classification (8th edition). Written informed consent was obtained in all cases, and the study was approved by the institutional review board of the Graduate School of Medicine, Kyoto University. 2.2. Surgical procedures All procedures were performed as previously reported [7]. Briefly, under general anesthesia, a curved rigid laryngoscope (Nagashima Medical Instruments Company, Ltd., Tokyo, Japan) was inserted to provide a working space, then a ME-NBI (GIF TYPE H260Z or Q240Z; Olympus Medical Systems, Tokyo, Japan) was inserted transorally to visualize the surgical field. The extent and exact margin of each lesion was identified by NBI and iodine staining. A mixed solution of epinephrine (0.02 mg/mL) and saline was injected into the subepithelial layer beneath the lesion to raise it up for resection. Lesions were resected using transorally inserted curved forceps (Nagashima Table 1 Patient characteristics. Patient characteristics Number of cases Number of lesions Age Gender History of esophageal cancer History of head and neck cancer
22 29 78.4 (75–85) years Male 21, female 1 15 14
3. Results 3.1. Patient and lesion characteristics Patient and lesion characteristics are shown in Table 1. Patients were predominantly male (95.5%), and patient age ranged from 75 to 85 years (average 78.3 years). Sixteen patients had multiple comorbidities and moderate to severe comorbidities were observed in 17 patients. The most common comorbidity was prior malignancy; over 90% of Table 2 Comorbidity characteristics. Type of comorbidities Type
Number of patients
Prior malignancy Cardiovascular Respiratory Neurological Endocrine Gastrointestinal Substance abuse
20 11 8 7 6 1 1
90.9% 50.0% 36.4% 31.8% 27.3% 4.5% 4.5%
Number of comorbidities Number of comorbidities
Number of patients
1 2 3 4
6 4 8 4
Adult Comorbidity Evaluation 27 (ACE-27) index ACE-27
Number of patients
1 2 3
5 13 4
Please cite this article in press as: Kishimoto Y, et al. Endoscopic laryngo-pharyngeal surgery for elderly patients. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.08.008
G Model
ANL-2496; No. of Pages 6 Y. Kishimoto et al. / Auris Nasus Larynx xxx (2018) xxx–xxx
3
patients had a history of malignancy. Cardiovascular, respiratory and neurological comorbidities were observed in 50, 36.4 and 31.8% of patients, respectively (Table 2). Of the 22 patients with prior malignancies, 15 had prior or simultaneous esophageal cancer, and 14 had prior or simultaneous head and neck cancer. Three patients had a history of previous irradiation to head and neck cancer in other site or other subsite. The number of oropharyngeal and hypopharyngeal lesions was 12 and 17, respectively. Only one recurrent lesion was included. Histologic diagnoses included squamous cell carcinoma (SCC) in 19 lesions, carcinoma in situ in five lesions, high-grade dysplasia in three lesions and low to moderate grade dysplasia in two lesions. A small lesion of moderate grade dysplasia was resected simultaneously with a lesion of SCC at the other subsite. A lesion of low grade dysplasia was resected because preoperative biopsy specimen was suspicious for high grade dysplasia. Eventually, five lesions were diagnosed as Tis, 12 lesions as T1, five lesions as T2 and two lesions as T3 (Table 3). The size of the resected specimens varied from 10 to 60 mm (average 33.5 mm).
3.3. Nutrient intake
3.2. Operation and hospitalization data
3.4. Post-operative complications
A total of 26 resections were performed for 29 lesions, and resection was safely completed in all cases. Multiple lesions were identified in four patients. In one case, four lesions were
Clinical information is summarized in Table 4. Post-operative bleeding, temporal emphysema and aspiration pneumonia were observed in two, three and two cases, respectively, and these complications were safely managed. No complication was observed in the patients with a history of irradiation for previous head and neck cancer. No prophylactic tracheostomy was needed and no vocal fold impairment was observed after the procedure.
Table 3 Lesion characteristics. Site of the lesions Origin
Number of lesions
Subsite
Oropharynx
12
Anterior wall Posterior wall Superior wall Lateral wall
2 8 1 1
Piriform sinus Post cricoid Posterior wall
11 2 4
Hypopharynx
17
Number of lesion(s) resected at the same operation Number of lesion(s)
Number of operation(s)
1 2 3 4
18 2 1 1
treated with a single resection, and in three cases multiple resections were required. Simultaneous neck dissection for metastatic lymph nodes was performed in one case and endoscopic submucosal dissection for an esophageal lesion was performed in one case. The average ELPS surgical time and the average hospitalization period after ELPS was 54.3 (6–133) min and 13.6 (3–34) days, respectively (the median was 55.0 min and 12.0 days).
Oral intake was started more than one week after ELPS in seven cases, because of aspiration (two cases), laryngeal penetration (one case), laryngeal penetration and laryngeal edema (one case) and emphysema (three cases). In the remaining 15 cases, oral intake started after 1.9 (1–3) days. In total, the average and median oral fasting period after the procedure were 4.4 and 2 (1–15) days, respectively. All patients eventually received nourishment by mouth and no percutaneous endoscopic gastrostomy (PEG) dependency was observed.
3.5. Oncological outcomes The post-operative follow-up period varied from 346 to 2544 days (average, 1245.6 days). Local recurrence was occurred in one case, and the lesion was treated with ELPS again. Post-operative cervical lymph node metastasis developed in two cases, and both were successfully controlled by neck dissection. Two patients died of other diseases, namely gastric cancer and esophageal cancer (Table 4). The 3-year overall survival rate was 90.2% and the 3-year disease specific survival rate was 100% (Fig. 1). 4. Discussion
Diagnosis of lesions Diagnosis
Number of lesion(s)
Squamous cell carcinoma Carcinoma in situ High grade dysplasia Low to moderate grade dysplasia
19 5 3 2
T stage of the lesions T stage
Number of lesion(s)
is 1 2 3
5 12 5 2
Advanced age is a major risk factor for cancer [8]. This is applicable to head and neck cancers, as more than 50% of head and neck cancers occur in patients over 60 years of age, and 28% in patients over 70 [9]. These numbers are expected to increase as the size of the elderly population increases. However, the treatment strategy for head and neck cancer in elderly patients remains a point of controversy, and a clinical practice guideline has not yet been established. In treating head and neck cancer in the elderly, some agerelated factors such as life expectancy, comorbidities, performance status, impaired functional status and cognitive decline should be considered before determining a management
Please cite this article in press as: Kishimoto Y, et al. Endoscopic laryngo-pharyngeal surgery for elderly patients. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.08.008
Age (y. o.)GenderLesions SiteSubsiteHistologySize of resected specimen (mm)T stageOther lesions New H New O New H New H New H New H New O New O New O New H New H New O New H New O New H New H RecurrentO New H New H New O New O New H
PW LW PC PS PS PS PW AW PW PS PS PW PS AW PC PW PW PS PS SW PW PW
SCC HGD SCC SCC SCC LGD SCC SCC CIS CIS SCC SCC SCC SCC CIS SCC SCC CIS SCC SCC CIS SCC
37 15 34 28 31 13 20 60 23 57 48 45 47 50 30 35 30 35 44 22 45 35 35.6
2 2 1 1 1 2 is is 3 1 3 1 is 1 1 is 2 1 is 1
Vertical marginHorizontal marginPost-operative complicationsRecurrenceCause of death
Negative Negative Negative MGD Negative Negative Negative 2 lesions of HGDNegative Positive Negative Negative Negative 3 lesions of SCC Negative Negative Negative Negative Negative Negative Negative SCC Negative Negative Negative Negative
Negative Negative Positive Negative Negative Negative Negative Positive Negative Negative Positive Negative Negative Negative Negative Negative Negative Negative Negative Negative Negative Positive
SE
Neck
POB
Neck
SE, POB
Gastric cancer Local
AP
SE
Esophageal cancer
AP
H: hypopharynx, O: oropharynx, PW: posterior wall, LW: lateral wall, PC: post cricoid, PS: pyriform sinus, AW: anterior wall, SW: superior wall, SCC: squamous cell carcinoma, HGD: high grade dysplasia, MGD: moderate grade dysplasia, LGD: low grade dysplasia, CIS: carcinoma in situ, SE: subcutaneous emphysema, POB: post-operative bleeding, AP: aspiration pneumonia.
Y. Kishimoto et al. / Auris Nasus Larynx xxx (2018) xxx–xxx
F M M M M M M M M M M M M M M M M M M M M M
G Model
No.
1 82 2 76 3 75 4 78 5 76 6 84 7 75 8 79 9 75 10 85 11 76 12 78 13 76 14 76 15 80 16 79 17 80 18 82 19 75 20 77 21 77 22 81 Average 78.3
ANL-2496; No. of Pages 6
4
Please cite this article in press as: Kishimoto Y, et al. Endoscopic laryngo-pharyngeal surgery for elderly patients. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.08.008
Table 4 Clinical information.
G Model
ANL-2496; No. of Pages 6 Y. Kishimoto et al. / Auris Nasus Larynx xxx (2018) xxx–xxx
Fig. 1. Overall survival (A) and disease-specific survival (B) after ELPS for pharyngeal lesions.
strategy [10]. Studies on the safety of surgical treatment of head and neck cancers in the elderly have shown conflicting results. A large retrospective study by Morgan et al. reported increased perioperative mortality and non-lethal complications in patients over 65 years of age [11]. In contrast, several studies have used multivariate analyses to clarify the risk factors for complications after surgery for head and neck cancer, and age was not found to be a contraindication to surgery. However, some comorbidities were shown to be associated with post-operative complications and elderly patients tend to have more comorbidities compared to younger patients [12,13]. Thus it is important to carefully select appropriate treatment modalities for elderly patients based on their comorbidities and functional status. Transoral resection for laryngeal/pharyngeal cancer has recently emerged as a minimally invasive surgical treatment for head and neck cancer. The technique has rapidly spread worldwide. One example of transoral resection is ELPS. Unlike transoral laser microsurgery (TLM) or transoral robotic surgery (TORS), ELPS is a hybrid of head and neck surgery and endoscopic gastrointestinal treatment that developed from endoscopic submucosal dissection (ESD) for gastric and esophageal cancers. ELPS provides safe and precise resection with minimal damage to the surrounding tissues and is performed with the aid of a flexible ME-NBI and specially fabricated curved instruments. It is basically indicated for superficial lesions such as carcinoma in situ or invasive laryngopharyngeal cancer without muscular invasion [6,14]. Because it is less invasive than conventional surgery, ELPS is often used in the elderly.
5
In this study, we clarified the safety and efficacy of ELPS in elderly patients. The National Institute on Aging at the National Institutes of Health classifies the elderly into three categories: young old (65–74 years), older old (75–84 years), and oldest old (>85 years) [10]. Because most clinical studies use the ages of 70 or 75 years as a cut-off to define the elderly [8], we used an age of 75 years or older to define the elderly in this study. As shown in Table 3, the lesions of variable sizes (T stages) at various subsites in the pharynx were included in this study, and ELPS was safely completed in all the cases. We need to be careful in treating near-circumferential lesions or post irradiation cases, however, location and size of the lesions are thought not always be the limits of ELPS in elderlies. Out of 29 lesions, 3 lesions at posterior wall of the pharynx were suspected to invade the muscle layer. These 3 lesions were resected with muscle tissues and one of them is eventually proven to have muscular invasion. Post-operative aspiration pneumonia occurred in the 2 cases with muscle resection. It is difficult to judge the appropriateness of this procedure for the elderly patients with muscular invasion from this study, however at least it can be said that we should be careful in deciding the indication of ELPS for the lesion with muscular invasion especially at the posterior wall of the pharynx. Many patients in this study had a history of head and neck cancer and/or esophageal cancer, which was likely due to common risk factors such as tobacco use and alcohol consumption. A history of previous treatment suggests the presence of irradiated mucosa or scar formation that complicates the procedure and makes post-operative wound healing and swallowing more difficult. However, the average operation time and median operation time per lesion was 54.3 and 25.0 min, respectively, which is comparable to a previous report [7]. Post-operative bleeding and emphysema were observed in two and three cases, respectively. These complications were safely managed and all wounds healed without delay or severe infection. Temporal aspiration and laryngeal penetration were observed in four cases after the procedure, but all patients eventually tolerated oral intake. Post-operative recurrences were observed in 3 cases. Although 4 cases with positive margins at initial surgeries showed no local recurrences, local recurrence occurred in the case with negative margins. This case had multiple lesions at initial surgery, and careful follow-up might be essential in case with multiple lesions. The average hospitalization period after the procedure was 13.6 days. Much shorter hospitalization periods have been reported in previous reports of transoral surgery for head and neck cancer in other countries [15,16]. This difference may be accounted for by the culture and health insurance system in Japan. Given that patients usually stay in the hospital for more than 3 weeks after reconstruction surgery in Japan [17], this period seems acceptable. Many patients in this study had multiple comorbidities. Comorbidities were graded as moderate to severe in 17 patients. The proportion of moderate to severe comorbidities was high compared to a previous report [13]. One reason for this is that many patients had other malignancies within the last five years, particularly in the esophageal or head and neck regions. The high rate of multiple metachronous cancers might be a result of the field cancerization phenomenon [18], and the rate may
Please cite this article in press as: Kishimoto Y, et al. Endoscopic laryngo-pharyngeal surgery for elderly patients. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.08.008
G Model
ANL-2496; No. of Pages 6 Y. Kishimoto et al. / Auris Nasus Larynx xxx (2018) xxx–xxx
6
increase with the development of endoscopic diagnostics. Thus, other metachronous malignancies might develop after ELPS, even in elderly patients, and close surveillance may be required after the procedure. In authors facility, esophagogastroduodenoscopy is usually performed as a post operative surveillance at least once to twice a year. The overall survival of patients with multiple malignancies is generally poor [19,20]. However, in this study we treated malignancies at a very early stage, leading to good oncological outcomes, even in patients with metachronous lesions, that were equivalent to a previous report [7]. Geriatric head and neck cancer patients who are treated similar to younger patients experience similar outcomes [9], hence early detection of lesions with scheduled surveillance will be important, even in elderly patients. Improvements in medical management, anesthesia and devices have allowed ELPS to be performed in the elderly. In this study, we found that ELPS was well tolerated and produced good oncologic outcomes in patients aged 75 years and older. The limitations of this study include the small sample size, poorly defined surgical indications, lack of a control group and the study’s retrospective nature. Because of the small sample size, it was difficult to analyze the risk factors for postoperative complications or recurrences/metastasis in elderly patients. A prospective, comparative study with larger number of patients is warranted to confirm the acceptability and appropriate indications for ELPS in the elderly. 5. Conclusions ELPS for pharyngeal lesions was safely performed in patients aged 75 years and older. This procedure appears to be a well tolerated and efficacious treatment option for pharyngeal lesions in very elderly patients. Financial support Authors have no conflicts of interest or financial ties to disclose. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. References [1] Gugic J, Strojan P. Squamous cell carcinoma of the head and neck in the elderly. Rep Pract Oncol Radiother 2012;18:16–25. http://dx.doi. org/10.1016/j.rpor.2012.07.014. [2] Bonomo P, Desideri I, Loi M, Lo Russo M, Olmetto E, Maragna V, et al. Elderly patients affected by head and neck squamous cell carcinoma unfit for standard curative treatment: is de-intensified, hypofractionated radiotherapy a feasible strategy? Oral Oncol 2017;74:142–7. http://dx.doi.org/10.1016/j.oraloncology.2017.10.004. [3] Chu P-Y, Chang S-Y. Reconstruction of the hypopharynx after surgical treatment of squamous cell carcinoma. J Chin Med Assoc 2009;72:351–5. http://dx.doi.org/10.1016/S1726-4901(09)70386-7.
[4] Tateya I, Morita S, Muto M, Miyamoto S, Hayashi T, Funakoshi M, et al. Magnifying endoscope with NBI to predict the depth of invasion in laryngo-pharyngeal cancer. Laryngoscope 2015;125:1124–9. http:// dx.doi.org/10.1002/lary.25035. [5] Muto M, Minashi K, Yano T, Saito Y, Oda I, Nonaka S, et al. Early detection of superficial squamous cell carcinoma in the head and neck region and esophagus by narrow band imaging: a multicenter randomized controlled trial. J Clin Oncol 2010;28:1566–72. http://dx.doi.org/ 10.1200/JCO.2009.25.4680. [6] Tateya I, Shiotani A, Satou Y, Tomifuji M, Morita S, Muto M, et al. Transoral surgery for laryngo-pharyngeal cancer – the paradigm shift of the head and cancer treatment. Auris Nasus Larynx 2016;43:21–32. http://dx.doi.org/10.1016/j.anl.2015.06.013. [7] Tateya I, Muto M, Morita S, Miyamoto S, Hayashi T, Funakoshi M, et al. Endoscopic laryngo-pharyngeal surgery for superficial laryngopharyngeal cancer. Surg Endosc 2016;30:323–9. http://dx.doi.org/ 10.1007/s00464-015-4213-y. [8] Szturz P, Vermorken JB. Treatment of elderly patients with squamous cell carcinoma of the head and neck. Front Oncol 2016;6. http://dx.doi. org/10.3389/fonc.2016.00199. [9] Moye VA, Chandramouleeswaran S, Zhao N, Muss HB, Weissler MC, Hayes DN, et al. Elderly patients with squamous cell carcinoma of the head and neck and the benefit of multimodality therapy. Oncologist 2015;20:159–65. http://dx.doi.org/10.1634/theoncologist.2013-0325. [10] Porceddu SV, Haddad RI. Management of elderly patients with locoregionally confined head and neck cancer. Lancet Oncol 2017;18:e274– 83. http://dx.doi.org/10.1016/S1470-2045(17)30229-2. [11] Morgan RF, Hirata RM, Jaques DA, Hoopes JE. Head and neck surgery in the aged. Am J Surg 1982;144:449–51. http://dx.doi.org/10.1016/ 0002-9610(82)90420-2. [12] Goh CS-L, Kok Y-O, Yong CP-C, Tan EW-X, Goh L-G, Chew K-Y, et al. Outcome predictors in elderly head and neck free flap reconstruction: a retrospective study and systematic review of the current evidence. J Plast Reconstr Aesthet Surg 2018;71:719–28. http://dx.doi. org/10.1016/j.bjps.2017.12.011. [13] Peters TTA, van Dijk BAC, Roodenburg JLN, van der Laan BFAM, Halmos GB. Relation between age, comorbidity, and complications in patients undergoing major surgery for head and neck cancer. Ann Surg Oncol 2014;21:963–70. http://dx.doi.org/10.1245/s10434-013-3375-x. [14] Kishimoto Y, Sogami T, Uozumi R, Funakoshi M, Miyamoto S-I, Kitamura M, et al. Complications after endoscopic laryngopharyngeal surgery. Laryngoscope 2018;128:1546–50. http://dx.doi.org/10.1002/ lary.26953. [15] Boudreaux BA, Rosenthal EL, Magnuson JS, Newman JR, Desmond RA, Clemons L, et al. Robot-assisted surgery for upper aerodigestive tract neoplasms. Arch Otolaryngol Head Neck Surg 2009;135:397– 401. http://dx.doi.org/10.1001/archoto.2009.24. [16] Hammoudi K, Pinlong E, Kim S, Bakhos D, Morinie`re S. Transoral robotic surgery versus conventional surgery in treatment for squamous cell carcinoma of the upper aerodigestive tract. Head Neck 2015;37:1304–9. http://dx.doi.org/10.1002/hed.23752. [17] Sarukawa S, Sakuraba M, Kimata Y, Yasumura T, Uchiyama K, Hishinuma S, et al. Standardization of free jejunum transfer after total pharyngolaryngoesophagectomy. Laryngoscope 2006;116:976–81. http://dx.doi.org/10.1097/01.mlg.0000216915.62574.ba. [18] Muto M, Satake H, Yano T, Minashi K, Hayashi R, Fujii S, et al. Longterm outcome of transoral organ-preserving pharyngeal endoscopic resection for superficial pharyngeal cancer. Gastrointest Endosc 2011;74:477–84. http://dx.doi.org/10.1016/j.gie.2011.04.027. [19] Erkal HS, Mendenhall WM, Amdur RJ, Villaret DB, Stringer SP. Synchronous and metachronous squamous cell carcinomas of the head and neck mucosal sites. J Clin Oncol 2001;19:1358–62. http://dx.doi. org/10.1200/JCO.2001.19.5.1358. [20] Schwartz LH, Ozsahin M, Zhang GN, Touboul E, De Vataire F, Andolenko P, et al. Synchronous and metachronous head and neck carcinomas. Cancer 1994;74:1933–8.
Please cite this article in press as: Kishimoto Y, et al. Endoscopic laryngo-pharyngeal surgery for elderly patients. Auris Nasus Larynx (2018), https://doi.org/10.1016/j.anl.2018.08.008