Predictive factors for false negatives following sentinel lymph node biopsy in early oral cavity cancer.

Prophylactic elective neck dissection (ND) with navigation surgery using radioisotope-based sentinel lymph node biopsy (SLNB) is non-inferior to elective ND in terms of survival but has an advantage in postoperative functional disability. We conducted a subgroup analysis to identify predictive factors for false-negative (FN)-SLNB in patients with early oral cavity cancer. This study is a supplementary analysis using the dataset of a previously reported randomized clinical trial on SLN navigation surgery for oral cancers. This study investigated the association of clinical and SLN-related factors with false-negative cases in the SLNB group. From 2011 to 2016, 275 patients were enrolled and randomly assigned to the ND and SLNB study groups, with 134 patients assigned to the SLNB group. In the SLNB group, seven cases with negative SLNs and neck recurrences were judged as FN-SLNBs according to the general definition. The number of detected SLNs with and without adjusting for the propensity score was significantly associated with FNs in the logistic analysis. FN-SLNB was associated with the number of identified SLNs, suggesting the need for careful postoperative monitoring for neck recurrence in patients with one or two identified SLNs after acquiring sufficient experience in the identification technique.

Latent changes in the pharyngeal stage of swallowing in non-aspirating older adults.

PURPOSE: The characteristic changes in the swallowing mechanism with aging are collectively termed presbyphagia. Although several studies have investigated presbyphagia in older adults, few have assessed oldest-old adults. We aimed to characterize the latent changes of swallowing function in oldest-old adults and to consider risk ages for presbyphagia. METHODS: We analyzed the records of 85 individuals (44 males and 41 females, aged 25-101 years) who underwent videofluoroscopic swallowing studies. The included participants had penetration and aspiration scores of ≤ 2 and no history of aspiration, pneumonia, or diseases that affect swallowing. They were divided into four age groups: 25-64 years (non-older), 65-74 years (young-old), 75-84 years (middle-old), and ≥ 85 years (oldest-old). We analyzed and compared the pharyngeal delay time (PDT), duration of tongue base and posterior pharyngeal wall contact, duration and dimension of upper esophageal sphincter opening (UES-O), and maximal hyoid bone displacement between the age groups. RESULTS: Among the older groups, the oldest-old showed significantly longer PDT than younger-old adults, and the UES-O tended to be wider in the former. However, no other remarkable differences were found between the oldest-old and other old groups. Statistical comparisons between the < 75 and ≥ 75-year age groups revealed significant age-related changes in the PDT and duration and dimension of UES-O. CONCLUSION: On videofluoroscopic evaluation, physiological changes with aging affected few parameters of swallowing in our cohort. These findings indicate that in non-aspirating oldest-old adults, any deterioration may be adjusted for by compensatory changes to maintain swallowing function.

Neck Dissections Based on Sentinel Lymph Node Navigation Versus Elective Neck Dissections in Early Oral Cancers: A Randomized, Multicenter, and Noninferiority Trial.

PURPOSE: This study aimed to compare patients with early oral cavity squamous cell carcinoma (OCSCC) (tumor category [T] 1-2, node-negative, and no distant metastasis) treated with traditional elective neck dissection (ND) with those managed by sentinel lymph node biopsy (SLNB) using survival and neck function and complications as end points. METHODS: Sixteen institutions in Japan participated in the study (trial registration number: UMIN000006510). Patients of age ≥ 18 years with histologically confirmed, previously untreated OCSCC (Union for International Cancer Control TNM Classification of Malignant Tumors 7th edition T1-2, node-negative no distant metastasis), with ≥ 4 mm (T1) depth of invasion, were randomly assigned to undergo standard selective ND (ND group; n = 137) or SLNB-navigated ND (SLNB group; n = 134). The primary end point was the 3-year overall survival rate, with a 12% noninferiority margin; secondary end points included postoperative neck functionality and complications and 3-year disease-free survival. Sentinel lymph nodes underwent intraoperative multislice frozen section analyses for the diagnosis. Patients with positive sentinel lymph nodes underwent either one-stage or second-look ND. RESULTS: Pathologic metastasis-positive nodes were observed in 24.8% (34 of 137) and 33.6% (46 of 134) of patients in the ND and SLNB groups, respectively (P = .190). The 3-year overall survival in the SLNB group (87.9%; lower limit of one-sided 95% CI, 82.4) was noninferior to that in the ND group (86.6%; lower limit 95% CI, 80.9; P for noninferiority < .001). The 3-year disease-free survival rate was 78.7% (lower limit 95% CI, 72.1) and 81.3% (75.0) in the SLNB and ND groups, respectively (P for noninferiority < .001). The scores of neck functionality in the SLNB group were significantly better than those in the ND group. CONCLUSION: SLNB-navigated ND may replace elective ND without a survival disadvantage and reduce postoperative neck disability in patients with early-stage OCSCC.

Risk of Sensorineural Hearing Loss in Patulous Eustachian Tube.

OBJECTIVE: To investigate whether the long-term presence of a patulous Eustachian tube (PET) is associated with sensorineural hearing loss (SNHL). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Ears (n = 100) were classified into two groups based on duration of PET symptom(s), i.e., Short (≤3 mo; n = 47 ears) and Long (≥48 mo; n = 53 ears). Contralateral ears without PET (n = 28 ears) were classified as the Contralateral group. MAIN OUTCOME MEASURES: We used ISO 7029 to calculate the hearing thresholds of an age- and sex-matched population at a given frequency. Hearing loss was defined as >25% of these calculated values. RESULTS: At 4 kHz, the Long PET group showed a higher prevalence of hearing loss (47%) at 4 kHz than did the Contralateral (21%) and Short PET (19%) groups (p = 0.0280 and 0.0043, respectively). Ears with breathing autophony or a sonotubometric low probe tone level showed a higher prevalence of hearing loss at 4 kHz than those without this symptom or with a high probe tone level (p = 0.0329 or 0.0103, respectively). At low frequencies, ≥89% of the ears in all groups showed mild hearing loss. CONCLUSION: Chronic PET was associated with SNHL at 4 kHz. PET patients showed low-frequency hearing loss regardless of disease duration. Further studies are needed to better understand the pathophysiology of SNHL in patients with PET.

Long term-follow-up multicenter feasibility study of ICG fluorescence-navigated sentinel node biopsy in oral cancer.

In the current study, the utility of sentinel node (SN) identification using indocyanine green (ICG) was investigated for oral cancers in the clinical N0 stage. The current study was a prospective, multicentre, phase II clinical trial that was conducted in Japan. A total of 18 patients were included. Before surgery, the patients underwent lymphoscintigraphy to map the SNs. During surgery, radioactive isotope (RI) mapping was used to detect the SNs, and ICG was subsequently injected. ICG mapping of the SNs was then performed through the skin. The primary tumour was resected, and a neck flap was elevated for neck dissection, followed by SN biopsy (SNB) using RI or ICG mapping. With the RI method, a total of 63 SNs were detected. Among these SNs, 8 (12.7%) were positive for metastasis, including those with isolated tumour cells (ITCs). The median number of SNs per patient identified by SNB was 4. With the ICG method, a total of 67 SNs were detected. Among these SNs, 7 (10.4%) were positive for metastasis, including those with ITCs. The median number of SNs per patient identified by SNB was 4 (range, 1-6). The 5-year overall survival (OS) of all patients was 83.3%, and the 5-year disease-free survival (DFS) of all patients was 76.7%. The neck compression technique is a simple method that can be used to facilitate surgical procedures of ICG fluorescence navigated SNB for head and neck cancer.

In Vitro Study of the Anti-cancer Effect of Alternate-day 5-Fluorouracil in Head and Neck Cancer Cells.

BACKGROUND/AIM: We have previously reported that alternate-day S-1 had comparable effects and milder adverse events than the respective consecutive-day regimen in head and neck cancer (HNC) patients. The aim of this study was to investigate the anticancer effects of both regimens and underlying mechanisms in vitro. MATERIALS AND METHODS: Two head and neck squamous cell carcinoma (HNSCC) cell lines were treated with 5-FU given on an alternate-day or consecutive-day schedule. The relative inhibition (RI) of tumor growth was calculated. Cell cycle distributions and cyclin expression following 5-FU treatment were analyzed. RESULTS: The RI of both regimens was almost identical. The percentage of cells in S phase was significantly increased in the alternate-day group compared to the consecutive-day group (p<0.001). CONCLUSION: The cytotoxic effect of alternate-day was equivalent to that of consecutive-day. S-phase arrest was more prominently observed with the alternate-day regimen, which may help maintain 5-FU sensitivity in head and neck cancer cells.

Surgical consensus guidelines on sentinel node biopsy (SNB) in patients with oral cancer.

BACKGROUND: The eighth international symposium for sentinel node biopsy (SNB) in head and neck cancer was held in 2018. This consensus conference aimed to deliver current multidisciplinary guidelines. This document focuses on the surgical aspects of SNB for oral cancer. METHOD: Invited expert faculty selected topics requiring guidelines. Topics were reviewed and evidence evaluated where available. Data were presented at the consensus meeting, with live debate from panels comprising expert, nonexpert, and patient representatives followed by voting to assess the level of support for proposed recommendations. Evidence review, debate, and voting results were all considered in constructing these guidelines. RESULTS/CONCLUSION: A range of topics were considered, from patient selection to surgical technique and follow-up schedule. Consensus was not achieved in all areas, highlighting potential issues that would benefit from prospective studies. Nevertheless these guidelines represent an up-to-date pragmatic recommendation based on current evidence and expert opinion.

Adjuvant chemotherapy with S-1 after curative chemoradiotherapy in patients with locoregionally advanced squamous cell carcinoma of the head and neck: Reanalysis of the ACTS-HNC study.

BACKGROUND: Chemoradiotherapy (CRT) has improved organ preservation or overall survival (OS) of locoregionally advanced head and neck squamous cell cancer (LAHNSCC), but in clinical trials of conventional CRT, increasing CRT intensity has not been shown to improve OS. In the Adjuvant ChemoTherapy with S-1 after curative treatment in patients with Head and Neck Cancer (ACTS-HNC) phase III study, OS of curative locoregional treatments improved more with adjuvant chemotherapy with S-1 (tegafur gimeracil oteracil potassium) than with tegafur/uracil (UFT). ACTS HNC study showed the significant efficacy of S-1 after curative radiotherapy in sub-analysis. We explored the efficacy of S-1 after curative CRT in a subset of patients from the ACTS-HNC study. METHODS: Patients with stage III, IVA, or IVB LAHNSCC were enrolled in this study to evaluate the efficacy of S-1 compared with UFT as adjuvant chemotherapy after curative CRT in the ACTS-HNC study. Patients received S-1 at 80-120 mg/day in two divided doses for 2 weeks, followed by a 1-week rest, or UFT 300 or 400 mg/day in two or three divided doses daily, for 1 year. The endpoints were OS, disease-free survival, locoregional relapse-free survival, distant metastasis-free survival (DMFS), and post-locoregional relapse survival. RESULTS: One hundred eighty patients (S-1, n = 87; UFT, n = 93) were included in this study. Clinical characteristics of the S-1 and UFT arms were similar. S-1 after CRT significantly improved OS (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.22-0.93) and DMFS (HR, 0.50; 95% CI, 0.26-0.97) compared with UFT. CONCLUSION: As adjuvant chemotherapy, S-1 demonstrated better efficacy for OS and DMFS than UFT in patients with LAHNSCC after curative CRT and may be considered a treatment option following curative CRT. For this study was not preplanned in the ACTS-HNC study, the results is hypothesis generating but not definitive.

Submucosal Inferior Turbinoplasty Using a New Continuous Suction Irrigation Method.

INTRODUCTION: Numerous surgical techniques for inferior turbinate hypertrophy (ITH) have been reported, each with advantages and disadvantages. Submucosal turbinoplasty with removal of the bony component of the inferior turbinate (IT) is an excellent procedure to expand the nasal cavity. However, this procedure requires a large incision to remove the inferior turbinate bone (ITB) and is associated with hemorrhage, crust formation, and adhesion. A smaller incision would avoid such complications. We developed a continuous suction irrigation method that maintains a clear view of the limited surgical field of the IT. Only a single small incision is needed to insert the rigid endoscope. The surgeon can flush blood with continuous water flow and perform IT surgery without difficulty. We performed this method in 39 cases from January 2016 to January 2017. This video article demonstrates our new submucosal inferior turbinoplasty technique. METHODS: Submucosal turbinoplasty using a continuous suction irrigation method was performed under general anesthesia. An irrigation-suction straw sheath system was used to create an underwater surgical field. RESULTS: The ITB was removed safely with no severe complications. An expanded common nasal cavity was confirmed postoperatively on computed tomographic images. CONCLUSION: We resected the ITB safely using a continuous suction irrigation method without difficulty or complications. We believe that this method may become one of the best surgical options for ITH.

Mano-videoendoscopic assessment in the evaluation of the pharyngeal contraction and upper esophageal sphincter function in dysphagic patients.

OBJECTIVE: Mano-videoendoscopy (MVE) is a manometry technique with endoscopic confirmation of the pressure catheter. This study aimed to investigate the possibility of replacing a videofluorographic swallowing study (VFSS) with MVE for the precise evaluation of the pharyngeal contraction and the upper esophageal sphincter (UES) function. METHODS: The data from 69 patients with dysphagia were retrospectively reviewed. All of the patients underwent both MVE and a VFSS for the evaluation of dysphagia. Manometry was performed with a transnasally inserted catheter (2.6-mm outer diameter and 4 pressure sensors) under endoscopic observation. The sensors were kept at the tongue base, upper pyriform sinus, apex of the pyriform sinus, and UES. We evaluated the pharyngeal contraction and UES function fluorographically and statistically compared the manometric parameters. RESULTS: The fluorographic pharyngeal contraction was diagnosed as good in 28 patients and poor in 41 patients. The UES opening was diagnosed as good in 44 patients and poor in 25 patients. The highest pressure values at the tongue base (sensor 1), upper pyriform sinus (sensor 2), and apex of the pyriform sinus (sensor 3) were significantly larger in the good contraction group than in the poor contraction group. A stepwise logistic regression test revealed that the peak pressure of sensor 2 (upper pyriform sinus) was a robust predictor of fluorographic pharyngeal contraction, and the cut-off level for good fluorographic pharyngeal contraction was >81.5mmHg (specificity, 0.929; sensitivity, 0.870; area under the curve, 0.923). The nadir pressure, pressure drop, and pressure rise in the UES were significantly correlated with the fluorographic UES opening. A stepwise logistic regression test revealed that the pressure drop-the gap between the resting pressure and the nadir of the UES pressure-was a robust predictor of fluorographic UES opening, and the cut-off level to anticipate good fluorographic opening was ≥33.5mmHg (specificity, 0.853; sensitivity, 0.759). CONCLUSION: MVE can supplement the information obtained regarding the pharyngeal contraction and UES function, and overcomes the drawbacks of a videoendoscopic swallowing study (VESS).

Inhibition of epithelial-mesenchymal transition by cetuximab via the EGFR-GEP100-Arf6-AMAP1 pathway in head and neck cancer.

BACKGROUND: Despite improved survival by the addition of a monoclonal antibody against epidermal growth factor receptor (EGFR), cetuximab, to chemotherapy or radiotherapy for squamous cell carcinoma of the head and neck (SCCHN), cetuximab by itself is not a potent antiproliferative agent against SCCHN. We aimed to elucidate working mechanism of cetuximab in SCCHN. METHODS: The effect of cetuximab on the proliferation, migration, invasion, epithelial-mesenchymal transition, and signaling events downstream of the EGFR were investigated in 4 SCCHN cell lines. The in vivo efficacy of cetuximab was evaluated in a xenotransplant model. RESULTS: Cetuximab inhibited migration, invasion, epithelial-mesenchymal transition, and lymph node metastasis by suppressing EGFR-GEP100-Arf6-AMAP1 pathway, but it did not inhibit cancer cell proliferation. CONCLUSION: The improved survival by the addition of cetuximab is likely to be attributable to the antiepithelial-mesenchymal transition action of cetuximab via inhibiting EGFR-GEP100-Arf6-AMAP1 pathway. © 2016 Wiley Periodicals, Inc. Head Neck 39: 476-485, 2017.

[Emergency Care System in Otolaryngology].

Otolaryngologists play a very important role in the field of emergency care in otolaryngology because their field requires a particular expertise in dealing with a variety of diseases. However, the emergency medical service system at night or during holidays has not yet been completely organized. Clarification of the present problems is essential to improve our emergency medical service system. Thus, we investigated the present state of otolaryngological emergency care in Tokyo and in Kyorin University Hospital. In Tokyo, outpatient clinics and hospitals see the emergency patients in the otolaryngology field by rotation during holidays. More than 13,000 patients were referred to the outpatient clinics, and more than 2, 000 patients were referred to the hospitals per year using this emergency care system. There are some problem with this system. One is that patients have to rush to a hospital in consecutive holidays and the other is that only a few clinics and hospitals see patients at night. Otolaryngologists have to regard these problem as an otolaryngologist-wide issue. For both public administration or academic societies a site for discussion needs to be provided.

Sentinel Node Biopsy for the Head and Neck Using Contrast-Enhanced Ultrasonography Combined with Indocyanine Green Fluorescence in Animal Models: A Feasibility Study.

BACKGROUND: Sentinel node navigation surgery is gaining popularity in oral cancer. We assessed application of sentinel lymph node navigation surgery to pharyngeal and laryngeal cancers by evaluating the combination of contrast-enhanced ultrasonography and indocyanine green fluorescence in animal models. METHODS: This was a prospective, nonrandomized, experimental study in rabbit and swine animal models. A mixture of indocyanine green and Sonazoid was used as the tracer. The tracer mixture was injected into the tongue, larynx, or pharynx. The sentinel lymph nodes were identified transcutaneously by infra-red camera and contrast-enhanced ultrasonography. Detection time and extraction time of the sentinel lymph nodes were measured. The safety of the tracer mixture in terms of mucosal reaction was evaluated macroscopically and microscopically. RESULTS: Sentinel lymph nodes were detected transcutaneously by contrast-enhanced ultrasonography alone. The number of sentinel lymph nodes detected was one or two. Despite observation of contrast enhancement of Sonazoid for at least 90 minutes, the number of sentinel lymph nodes detected did not change. The average extraction time of sentinel lymph nodes was 4.8 minutes. Indocyanine green fluorescence offered visual information during lymph node biopsy. The safety of the tracer was confirmed by absence of laryngeal edema both macro and microscopically. CONCLUSIONS: The combination method of indocyanine green fluorescence and contrast-enhanced ultrasonography for detecting sentinel lymph nodes during surgery for head and neck cancer seems promising, especially for pharyngeal and laryngeal cancer. Further clinical studies to confirm this are warranted.

An Inflammatory Pseudotumor Arising from Pterygopalatine Fossa with Invasion to the Maxillary Sinus and Orbital Cavity.

We report a patient who had an inflammatory pseudotumor (IPT) that invaded to the maxillary sinus and orbital cavity, with the left pterygopalatine fossa as the principal site; this is a very rare case. The patient was an 83-year-old woman who suddenly became aware of impairment in the eyesight and visual field of the left eye. CT images showed a neoplastic lesion that invaded to the maxillary sinus and orbital cavity, with the left pterygopalatine fossa as the principal site, and also showed contrast effects. To obtain a definitive diagnosis from histopathological analysis, the lesion was biopsied, and she was diagnosed as the inflammatory pseudotumor with the immunohistochemical study and multiplex polymerase chain reaction-based clonality assays. The patient had a lymphoid-predominant lesion that responded to radiotherapy but corticosteroids were not effective. It is important to scrutinize the pathology to avoid unnecessary and mutilating surgery.

Intra-Adenoid Cyst: A Case Report with an Immunohistochemical Study and Review of Literature.

A woman in her 50s was referred to our department with the chief complaint of nasal congestion and pharyngeal discomfort. The patient had been diagnosed with sleep apnea at the Department of Internal Medicine, and had undergone nasal continuous positive airway pressure (nCPAP) therapy, but her response to the treatment was poor. A cystic lesion occupying the nasopharynx, which was detected by nasopharyngeal fiberscopy, computed tomography, and magnetic resonance imaging, was thought to be the cause of the nasal congestion, pharyngeal discomfort, and obstructive sleep apnea syndrome (OSAS). Consequently, the patient underwent extirpation of the lesion under general anesthesia for the purpose of obtaining a definitive diagnosis as well as for treatment of the nasopharyngeal tumor. The diagnosis of intra-adenoid cyst was eventually made based on the pathological findings, which revealed lymphoid tissue accompanied by expansion of the crypt, as well as inflammatory cell infiltration with follicular hyperplasia. After the operation, the patient reported subjective improvement of her symptoms, and began to respond to the nCPAP therapy for her sleep apnea syndrome. Nasopharyngeal cysts, in particular adult intra-adenoid cyst, are relatively rare. The outcomes of the current case indicated that the presence of a nasopharyngeal cystic disease was hampering the nCPAP treatment of refractory OSAS.

Validity of sentinel lymph node biopsy by ICG fluorescence for early head and neck cancer.

AIM: This study was designed to assess the validity of sentinel lymph node (SLN) biopsy using either the combination of indocyanine green (ICG) fluorescence and radioisotope (RI) or ICG-alone in SLN mapping for early head and neck cancer patients. PATIENTS AND METHODS: Nineteen patients received SLN biopsy with the following method. Thirteen patients received SLN biopsy with only RI, 2 patients with only ICG and 4 patients with the combination of ICG and RI. Detection time for each method of SLN biopsy was measured to evaluate the validity of SLN with the combination of ICG and RI. RESULTS: A total of 41 SLNs were identified by RI or ICG. All SLNs identified by ICG could be localized intraoperatively. The number of SLNs identified by the combination of ICG and RI was greater than that of SLNs identified by RI-alone. One of the patients who underwent SLN biopsy by RI-alone was diagnosed with a metastatic lymph node one year later, then underwent neck dissection. Mean detection time for SLN biopsy with ICG or with the combination of ICG and RI tended to be shorter than that of RI-alone. CONCLUSION: SLN biopsy with the combination of ICG and RI enabled us to identify SLNs more easily and rapidly than by using RI alone.

An endoscopic endonasal approach for early-stage olfactory neuroblastoma: an evaluation of 2 cases with minireview of literature.

We describe the clinical findings in two patients with pathologically diagnosed olfactory neuroblastoma (ONB) of the sinonasal area and the surgical methods used for its treatment. Using an endoscopic endonasal approach (EEA) without dura resection, along with radiotherapy, we successfully treated ONB at the Kadish stage A. One of our patients, however, experienced tumor recurrence 24 years after open surgery with radiotherapy that was conducted at another hospital. This patient was no longer eligible for radiotherapy, and the tumor was therefore resected with dura resection using an EEA combined with duraplasty. The dura resection with duraplasty using fascia lata and a pedicled nasal septal flap was minimally invasive. As with surgery without duraplasty, a postoperative computed tomography (CT) examination revealed that EEA with duraplasty led to quick improvement of the postoperative inflammatory response as well as pneumocranium. Here, we investigated whether to modify the method of surgery depending upon the primary site of early-stage ONB. We suggest that, in early-stage ONB, an endoscopic endonasal approach is an effective and less invasive method. It is also advisable to perform dura mater resection of the lesion site despite the absence of obvious intracranial invasions in image findings.

Association between odontogenic infections and unilateral sinus opacification.

OBJECTIVES: Consideration of the causes of unilateral paranasal sinusitis, which frequently occurs in routine medical care and is often associated with odontogenic infection. STUDY DESIGN: Retrospective data analysis. METHODS: A review of the charts of all 190 patients treated for unilateral paranasal sinusitis at our department between 2005 and 2012 was carried out. All patients were diagnosed based on clinical signs, symptoms, and imaging findings, including computed tomography (CT), orthopantomography (OP), and other modalities. Patients were classified in three groups: patients with odontogenic infection involvement (Group A); patients without odontogenic infection involvement (Group B); and patients with inconclusive odontogenic infection involvement (Group C). RESULTS: The most common cause of unilateral paranasal sinusitis was odontogenic infection, as seen in 138 cases (72.6%), followed by chronic inflammation in 43 cases (22.6%). Among patients diagnosed with odontogenic infection, one patient was also diagnosed with coexistent polyps and mycosis. Based on CT, OP, EPT, and oral examination, final distribution was 138 patients (72.6%) in Group A, 32 (16.8%) in Group B, and 20 (10.5%) in Group C. CONCLUSIONS: Odontogenic infection involvement was implicated in approximately 70% cases of unilateral paranasal sinusitis. Odontogenic maxillary sinusitis can be difficult to diagnose, and consideration of imaging performed under various conditions is recommended. In order to determine the most appropriate treatment for unilateral paranasal sinusitis, whether such treatment will be surgery, dental treatment, conservative therapy, or other treatments, collaboration between concerned doctors is essential.