Background: Submandibular gland carcinoma is rare, but compared with parotid gland tumors, submandibular gland tumors show a high rate of malignancy. In this report, a series of 76 cases is analyzed, all treated at the Cancer Institute Hospital, Tokyo, Japan during a 32-year period.
Methods: All cases of submandibular gland carcinoma treated at our institute between 1979 and 2012 were analyzed through a medical chart review. Radical surgical resections were performed as initial treatment in 58 cases. In these cases, prognostic factors, including histological type, clinical stage, T-stage, N-status, and whether malignant diagnosis was completed before surgery, were analyzed. In cases involving unresectable submandibular gland carcinoma, palliative chemotherapy was administered. At our institute, the present regimen of palliative chemotherapy for salivary gland carcinoma is paclitaxel (200 mg/m² on day 1) plus carboplatin (AUC=6 on day 1) every three weeks. Seven patients received this combination chemotherapy in the current study, and their results were analyzed.
Results: Five- and 10-year overall survival rates were 51.0% and 48.0%, respectively. Both N-status and clinical stage were shown to be significant predictors for survival, the former being more significant. Combination chemotherapy with paclitaxel and carboplatin was shown to be effective for unresectable submandibular gland carcinoma.
Conclusions: N-status is the primary predictor of survival outcomes, and paclitaxel plus carboplatin is an effective chemotherapy regimen for palliative cases. More effective adjuvant chemotherapies are urgently needed to improve prognosis for submandibular gland carcinoma.

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Particle therapy, such as proton therapy and carbon ion therapy, is capable of delivering high-dose radiation to tumors while minimizing the dose delivered to organs at risk because it emits the maximum level of energy just before stopping in the deep portion of the body. Carbon ion therapy, which efficiently induces DNA double-strand breaks due to its high ionizing density, is expected to be effective even for photon-resistant tumors. In the head and neck region, carbon ion therapy has been mainly used for photon-resistant tumors, such as malignant melanomas and adenoid cystic carcinomas, and favorable results have been achieved. At the Hyogo Ion Beam Medical Center, where both proton therapy and carbon ion therapy are available, retrospective analyses of clinical outcomes have shown that there are no significant differences between the two therapies in either efficacy or toxicity. Owing to its sharper penumbra, carbon ion therapy often demonstrates better dose distribution compared with proton therapy especially in the head and neck region, which is densely packed with high-risk organs. Prospective randomized controlled trials are warranted to elucidate whether there is any difference in clinical outcomes between proton therapy and carbon ion therapy; however, performing a prospective study is practically difficult because the main targets of particle therapy are rare tumors.

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We have treated 7,014 cases with the CyberKnife (CK) system over 13 years. Of them, 1,317 cases were head and neck cancer patients. Lately, reirradiation by using the shrinking field technique for recurrent cancer is topical. 80% of our patients were reirradiation cases. The median overall survival rate was 13.5 months. Reirradiation is feasible, but 20% of these patients showed CTCAE Gr III adverse events. Careful selection of indications is essential.

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Various kinds of reconstructive procedures for maxillary and mandibular bony defects have been reported. In oncologic surgery, it could be difficult to reconstruct the maxillo-mandible because bony defects are usually long, both bony and soft tissue defects often remain and avascular problems at the recipient site due to multiple surgeries included neck dissection or irradiation. Moreover, it is well known that denture fabrication is difficult because of loss of the alveolar ridge in edentulous patients. Based on these reasons, a dental implant was introduced for denture stability in the reconstructed bone. Forty-one implants, in 8 patients, in reconstructed bones by the revascularized fibular osteoseptcutaneous flap since October 1992 have been retrospectively discussed. As for the results of these surgeries, only 3 implants placed in the same patient have failed and the success rate is 92.4%. These 3 implants were installed again 6 months later. Concerning the timing of dental implant placement, 3 patients had implants placed at the same time as reconstruction of the maxillo-mandible and the other 5 were secondarily placed from 6 to 12 months after reconstruction. As for the superstructures fabricated, one was a screw on denture system and the others were removable denture systems connected with several kinds of attachments. Treatment using dental implants for reconstructed maxilla-mandibles following oral cancer ablation has been covered by Japanese public health insurance since 2012.

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The infratemporal fossa (ITF) is well known to be a difficult region to access surgically. Especially in salvage resection of recurrent malignant tumors in the ITF, modifications of classic surgical approaches are often needed. We report 2 cases of recurrent malignant tumors located around the Eustachian tube, which were resected successfully via a trans-temporal bone approach. In both of the cases, the tumor was of low grade malignant potential and recurred after a skull base resection for an ITF lesion. The recurrent lesion was resected in an en-bloc fashion with negative margins using a trans-temporal bone approach, which is a modification of subtotal temporal bone resection. In the procedure, dissection of the scar tissue surrounding the internal carotid artery was the most difficult step. Free rectus abdominis myocutaneous flap was effective to fill the dead space after resection. The advantages of this approach are that it is a modification of the established technique of subtotal temporal bone resection, thus reproducible, and that en-bloc resection of the tumor around the Eustachian tube is possible. The disadvantage is that the facial and the vestibular nerves are sacrificed in most cases. As a posterolateral approach to the ITF, this method is useful for resecting recurrent ITF tumors involving the Eustachian tube.

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[Purpose] To assess the current status in Japan of the treatment for squamous cell carcinoma of the T4 maxillary sinus (MS-SCC) and its use to plan clinical trials in the future.
[Patients] The data for 128 patients with previously untreated MS-SCC were obtained from 28 institutions from 2006 to 2007. Of the 128 patients, 118 patients with curative intent were included in an analysis of the treatment and its results.
[Results] Of the 118 patients, 73 patients had T4a disease, and 45 with T4b. Thirty-nine patients (33.1%) were treated with total maxillectomy, 25 (21.2%) with partial maxillectomy, 22 patients (18.6%) with RADPLAT, 19 patients (16.1%) with IV-CRT, and 13 patients (11.0%) with others. The 5-year overall survival rate and local control rate for 118 patients were 49.8% and 48.9%, respectively. The 5-year overall survival rates for patients with T4aN0M0 and T4bN0M0 were 67.5% and 29.8%, respectively.
[Conclusion] This study was retrospective, but we could understand the tendency of treatment choice and treatment results. It will be useful information to plan clinical trials in the future.

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In the present study, we examined the augmentation effect of S-1 by Cetuximab on oral squamous cell carcinoma (OSCC) and the mechanism of the enhancing effect. Treatment of OSCC cells (HSC2, HSC3, HSC4) with Cetuximab (1μg/ml) and 5-FU (1μg/ml) resulted in a significant suppression of cell growth. Moreover, it was found by Hoechst 33258 staining that DNA fragmentation markedly occurred in cells treated with Cetuximab and 5-FU. Furthermore, reduction of p-EGFR, p-Akt and thymidylate synthase (TS) was detected in cells treated with Cetuximab and 5-FU by Western blotting. Tumor-bearing nude mice were treated with Cetuximab (20mg/kg/day, twice/week, 3weeks) and/or S-1 (6.9mg/kg/day, 7times/week, 3weeks). The combined treatment resulted in a significant suppression of tumor growth. Moreover, immunohistochemical staining revealed that expression of p-Akt and TS was down-regulated in tumors treated with Cetuximab and S-1. Furthermore, TUNEL staining showed that expressions of TUNEL positive cells were up-regulated in tumors treated with Cetuximab and S-1. Overall, these results indicate that Cetuximab may enhance the effect of S-1 on OSCC through the down-regulation of TS expressions.

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To evaluate indications for concurrent chemoradiotherapy for mesopharyngeal squamous cell carcinoma, we retrospectively analyzed 32 patients in terms of treatment achievement rate, adverse events, locoregional free survival rate, laryngeal preservation rate and state of oral uptake after the therapy. The patients were divided into two groups: group A consisted of 13 patients who were considered curable (under c-stage III and T2N2a, T2N2b, T3N2a and T3N2b), and group B consisted of 19 patients who were considered far advanced or unresectable. Locoregional free survival rates were 76.9% (at 3 years) and 76.9% (at 5 years) in group A and 49.4% (at 3 years) and 20.5% (at 5 years) in group B. The rates in group B were significantly lower than in group A. The treatment achievement rate, adverse events, laryngeal preservation rate and state of oral uptake were all good in group A, but were all worse in group B. When deciding on the indications for concurrent chemoradiotherapy, it is important to evaluate comprehensively whether concurrent chemoradiotherapy can be achieved completely, prognosis, long-term QOL after the therapy, expected adverse events and the risk of aspiration.

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Concurrent chemoradiation is often chosen for advanced head and neck cancer. Especially, concurrent chemoradiation is effective for oropharyngeal cancer. Single-agent cisplatin (CDDP) is often used in concurrent chemoradiation, and the usual method of radiation is conventional fractionation. A comparative study with conventional fractionated radiotherapy showed that hyperfractionated radiotherapy improves survival rates. We have tried weekly CDDP concurrent chemo-hyperfractionated radiotherapy to decrease the degree of toxic issues. Although the clinical study of weekly CDDP concurrent chemo-hyperfractionated radiotherapy is still ongoing, complete response has been observed in 3 of 5 cases, and G3/G4 toxic issues are myelosuppression, mucositis oral, laryngitis, weight loss, and nutrition disorders.

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Oropharyngeal squamous cell carcinoma (OPSCC) that are associated with human papilloma virus (HPV) infection carry a more favourable prognosis than those that are HPV-negative. For detection of HPV in tumor material, in situ hybridization and PCR-based methods have been used. Recently, p16 is suggested to be an excellent surrogate marker for HPV infection. The simplicity, low cost, and high sensitivity of p16 immunohistochemical analysis (IHC) have prompted consideration of replacing HPV DNA in situ hybridization and PCR-based methods. However, p16 overexpression could suggest pRB pathway disturbances unrelated to HPV. This issue has not yet been fully evaluated in Japan. We performed a retrospective analysis of the association between p16 expression and HPV status of 91 patients with OPSCC at Hokkaido University Hospital, Japan, between 1998 and 2011. Of the 91 patients with OPSCC, 29 were HPV-positive and 31 were p16-positive. The 3-year overall survival rates were 82.2% in the p16-positive subgroup and 65.1% in the p16-negative subgroup; these figures were significantly different. As combined HPV and p16 status, the 3-year overall survival rates were 91.1% (HPV+/p16+ groups, n=24), 60.0% (HPV+/p16- groups, n=5), 65.7% (HPV-/p16- groups, n=55), 60.0% (HPV-/p16+ groups, n=7).
Our results showed that the patients with HPV-/p16+ had poor prognosis as compared with the patients with HPV+/p16+; therefore, p16 IHC alone may not be a perfect surrogate marker for HPV infection.

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The purpose of this study was to assess the usefulness of a sealing technique for the thoracic duct using an ultrasonically activated device during neck dissection.
We evaluated the frequency of postoperative chylous leakage retrospectively, in 43 cases (56 sides) of the FOCUS group which were treated with the sealing technique for the thoracic duct using HARMONIC FOCUS^® (Johnson and Johnson) and 196 cases (232 sides) of the Ligation group which were treated with conventional ligation techniques.
Postoperative chylous leakages occurred in 4 cases (1.7%) in the Ligation group. Three of these cases improved through conservative therapy, but one required re-operation (0.4%). Meanwhile, one patient had postoperative chylous leakage in the FOCUS group (1.8%), and was treated with only conservative therapy. The frequency of chylous leakage was not statistically significantly different between the two groups (Fisher's exact test: p=1.0). The cause of chylous leakage in the FOCUS group is considered to be inadequate tissue tension in the sealing process.
We conclude that the sealing technique using HARMONIC FOCUS^® is useful for safe management of the thoracic duct during neck dissection.

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Background: little has been known about the IJV invasion by untreated papillary thyroid carcinoma (PTC).
Objective: to clarify the clinical features of the IJV invasion by PTC.
Methods: a chart review on the cases of previously untreated PTC which were treated by curative surgery during the period from April 2005 through March 2011 at Kyoto Medical Center.
Results: a total of 175 cases were adopted, among which the IJV was resected partially or circumferentially in 9 sides of 8 cases (“resected group”). In all the affected sides, invasion was non-transmural. A metastatic node in the lateral compartment was the responsible lesion in 8 sides. The responsible node was located in the level IV region in 5 sides. The IJV was resected circumferentially in 7 sides and partially in 2. In the comparison between the resected group and the non-resected group, adjacent organ invasion either by primary or metastatic tumor, intraglandular multicentricity, tall cell variant of histology, and nodal metastasis in the lateral compartment were shown to be statistically more frequent in the resected group (p<0.05).
Conclusion: Most of the IJV invasion by PTC is non-transmural in nature and is caused by a metastatic node in the lateral cervical compartment, especially in the lower part.

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As the use of concurrent chemoradiotherapy (CCRT) is becoming more widespread, with numerous facilities performing it to maintain function and form, the number of cases requiring salvage surgery is also increasing. We investigated the postoperative prognosis of patients who experienced complications during salvage surgery after CCRT. Subjects were 27 patients who underwent salvage surgery following CCRT at our department during the 7-year period between January 2005 and December 2011. We selected all cases of salvage surgery, comprising neck dissections, total laryngectomies, partial laryngectomies, esophageal resections, and reconstructive surgeries, for analysis. The results were favorable, with a complication rate during salvage surgery after CCRT of 14.8% and a survival rate of 77.8%. Although it is difficult to compare these complications and outcome findings with available reports on salvage surgery without CCRT, it is believed complications can arise in approximately half of the cases. Thus, surgeons should be cognizant of the potential for serious complications, which are sometimes unexpected. Different from our findings, the prognosis following salvage surgery is generally not thought to be favorable and therefore care should be taken to detect recurrence and provide treatment early in salvage surgery cases.

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The objective of this study was to examine the post-operative complications of surgical procedures in oral or pharyngeal carcinoma by analyzing and comparing between patients who underwent salvage surgery after chemoradiation and radiation. A retrospective review was performed of 18 patients who underwent salvage surgery and reconstruction after concurrent chemoradiotherapy (CCRT group), and another 41 patients who underwent salvage surgery and reconstruction after radiation therapy (RT group). No perioperative deaths or life threatening systemic complications occurred, and all flaps survived completely in both groups. Surgical site infection (SSI) occurred in five patients (12.2%) in the RT group and seven patients (38%) in the CCRT group. SSI other than donor site infection occurred in four patients (9%) in the RT group and four patients (22%) in the CCRT group. The rate of SSI excluding donor site infection did not differ significantly between patients who underwent salvage surgery after CCRT and RT. The rate of donor site infection was higher in the CCRT group than in the RT group (p = 0.04). This study showed that salvage surgery after CCRT or RT can be performed safely, without significant morbidity or mortality. However, patients who received CCRT are at risk for major complications caused by minor troubles, and thus reconstruction after salvage surgery should be performed with sufficient care.

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The presence of distant metastasis after initial treatment of head and neck squamous cell carcinoma is not considered common, and the ideal treatment for such cases remains controversial. In this study, we reviewed the data for 68 head and neck squamous cell carcinoma patients with distant metastasis without loco-regional recurrence who underwent radical therapy between September 2002 and December 2009. The time until recurrence of distant metastasis ranged from one to 46.2 months (mean: 11.1 months). The lungs were the most common site of distant metastasis (60 cases, 88.2%), followed by the liver (15 cases, 22.0%), mediastinal LN (12 cases, 17.6%) and bone (nine cases, 13.2%). Among these patients, 10 underwent surgical treatment, 37 underwent chemotherapy or radiotherapy, and 21 received palliative treatment. The overall 3-year survival rates in the surgical treatment group, the chemotherapy or radiotherapy group and the palliative treatment group were 65.6%, 5.4% and 0%, respectively. The resection of distant metastasis offers significant survival benefits for patients with head and neck squamous cell carcinoma, in comparison to the current common strategy of chemotherapy, radiotherapy and palliative treatment.

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Recently, second free-flap reconstruction procedures after an initial flap failure or tumor recurrence have been reported. This study evaluated the reliability of reusing recipient vessels for a second free-flap reconstruction of the head and neck. From July 1992 through July 2011, 1834 patients underwent free-flap reconstruction of the head and neck at our center. Of these patients, 99 underwent a total of 104 second or third free-flap reconstruction procedures; in 28 of these patients (age range, 39 to 78 years; mean age, 62.1 years), an artery or vein or both were reused as recipient vessels. The reasons for the second or third procedures were as follows: failure of the initial flap in 13 patients (46.4%); recurrent disease or second primary lesion requiring a second ablation in 12 patients (42.9%); and late complications, such as mandibular fracture and deformity, in 3 patients (20.7%). Reused vessels were an artery only in 11 patients (39.3%), a vein only in 10 patients (35.7%), and both an artery and a vein in 7 patients (25.0%). The vessels most frequently reused were the superior thyroid artery and the internal jugular vein and its direct branches. The overall rate of flap success in these patients was 96.4% (27 of 28 patients); total flap necrosis occurred in 1 patient. Recipient vessels previously used for anastomosis can occasionally be reused, but care should be taken in patients who have received radiotherapy unless the vessel quality is obvious.

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This is a retrospective case series study to develop a simple, standard, and more objective tool for speech intelligibility evaluation in Japanese patients following tongue reconstruction after a glossectomy for oral cancer.
Speech samples consisting of a single-sentence utterance plus counting 1 through 10, 5 consonant-vowel pairs (for /t/, /s/, /k/, /g/, /r/, and /p/ groups), and diadochokinesis were recorded by 10 native-Japanese speakers who underwent tongue reconstruction surgery. Five medical personnel rated their speech intelligibility using a visual analogue scale (VAS) for the sentence plus counting sample, and assigned a score of 0–3 for the consonant-vowel pairs and a score of 0 or more for diadochokinesis.
The VAS scores of all 5 raters were positively correlated with each other. The total correlation coefficient between the mean VAS score and total intelligibility score was highest for the consonant-vowel pairs of /t/, /k/, and /r/, indicating speech samples using these pairs best correlated with everyday speech.
On the basis of these findings, the test items for the newly developed evaluation tool, named the TKR Speech Test, were finalized as the /t/, /k/, and /r/ consonant-vowel pairs, each scored 0–3. The TKR Speech Test shows promise as a simple yet accurate tool for speech intelligibility evaluation in Japanese patients following tongue reconstruction surgery.

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The incidence of surgical site infection (SSI) is high in surgery for head and neck cancer requiring reconstruction with microvascular free flap. SSI is a serious postoperative complication: previous reports have revealed that it can lead to a longer period of admission and increased medical expenses. However, there have been no reports on the association between SSI and prognosis. The purpose of this study was to determine the association between SSI and prognosis in oral cancer patients. We investigated 52 oral cancer patients who underwent cancer resection and reconstruction with microvascular free flap at the Shikoku Cancer Center from February 2000 to July 2010. We compared the disease-specific 5-year survival rate in two groups, 16 cases who had surgical site infection (SSI group) and 36 cases without infection (non-SSI group). The survival rate showed a statistically significant difference between the two groups (P=0.039); the rate of recurrence in the SSI group was higher than in the non-SSI group. The most frequent site of recurrence in the SSI group was the cervical cutaneus, and surgical site infection was significantly associated with metastasis at the cervical cutaneus (p<0.0001). The results of this study confirm that patients with surgical site infection have a higher risk of recurrence and metastasis. Furthermore, our data suggest that the prevention of surgical site infection has contributed to the improvement of prognosis in oral cancer patients undergoing surgical treatment and reconstruction.

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We used Glucerna^®-EX (low glucide, low GI·GL (glycemic index·glycemic load) for perioperative care after head and neck reconstruction and examined the utility of glycemic control.
The rear watched 79 cases (the Glucerna^®-EX group included 34 cases and the other enteral feeding group included 45 cases) whose histories from August 1, 2008 to December 31, 2011 did not have diabetes, and the subject parsed a mark.
Regarding the mean highest blood glucose level, blood glucose standard deviation, and blood glucose band, the Glucerna^®-EX group showed significantly low levels.
There was no hypoglycemia, more G2 diarrhea and little insulin consumption, so it was considered that glycemic control can be safely and easily carried out in the perioperative period.

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The NCCN guideline and the MASCC/ESMO guideline define high-dose cisplatin (CDDP≧50mg/m²) as highly emetologenic chemotherapy, and recommend the use of an aprepitant. According to the guidelines, we performed radiation plus concurrent weekly cisplatin (CDDP: 40mg/m²) (weekly CDDP+RT) without prophylactic aprepitant in outpatient chemotherapy. We evaluated incidence of nausea and vomiting in the weekly CDDP+RT regimen retrospectively. The subjects included 42 head and neck cancer patients who received a weekly CDDP+RT chemotherapy regimen between September 2009 and December 2011. We investigated the rate of completion of the chemotherapy without aprepitant and worst nausea grade through the course of the chemotherapy regimen. The median age of the patients was 60 years old (range: 20–74) and the male/female ratio was 30/12. In the first cycle of chemotherapy, four patients already received 80%-reduced CDDP due to renal dysfunction. The rate of completion without aprepitant was 90% (38/42). The worst grades of nausea were Gr.1/2/3: 14(33%)/7(16%)/1(2%). Therefore, the weekly CDDP+RT regimen does not need prophylactic APR from the first cycle of the chemotherapy, and we should use antiemetics when the patients' nausea and vomiting cannot be controlled.

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