Salivary gland neoplasms are relatively uncommon and account for approximately 3% of all tumors in the head and neck region. The most common sites of occurrence are the parotid gland, with nearly 80% of cases. The malignancies, most of which are carcinomas, make up about 20% of parotid gland tumors. Salivary gland carcinomas present a considerable diagnostic challenge for general pathologists owing to their diverse histological features and the presence of a number of types and variants, in addition to overlapping histological patterns similar to those observed in different tumor entities. Furthermore, they are a heterogeneous group of tumors with different biologic behavior. The histological classification is complex, but is closely relevant to the prognostic and therapeutic aspects. Although hematoxylin-eosin staining is still the gold standard method used for the diagnosis, immunohistochemistry can enhance accuracy and be a helpful tool in cases to investigate the subjects that cannot be assessed by histological examination, such as the cell nature and differentiation status, cell proliferation rate, and oncogene protein expression. Recently, tumor-specific recurrent chromosomal translocations, resulting in the formation of fusion genes, have been identified in mucoepidermoid carcinoma (CRTC1[MECT1]-MAML2), adenoid cystic carcinoma (MYB-NFIB), mammary analogue secretory carcinoma (ETV6-NTRK3), and hyalinizing clear cell carcinoma (EWSR1-ATF1). The fusion oncogenes may have diagnostic, prognostic, and future therapeutic implications.

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Proton beams are characterized by their rapid fall-off at the distal end of the Bragg peak and sharp lateral penumbra, depending on energy, depth, and delivery. These physical characteristics give proton beam therapy (PBT) a better dose distribution than X-ray irradiation, and PBT is now deemed a feasible and effective treatment modality that provides curative high-dose irradiation to the tumor volume without increasing normal tissue toxicity.
There are several published data about the outcomes of proton beam therapy for head and neck cancer from our institution. On the other hand, 91 patients who satisfied both criteria, definitive or postoperative PBT (> 50GyE) from January 1999 through December 2008, and more than 1 year follow-up, were traced to check the late toxicity. The median observation period was 57.5 months (range 12.4∼162.7), and the median time to onset of Grade 2 or greater late toxicity except cataract was 39.2 months (range 2.7∼99.8 months). Grade 4 visual loss occurred in 5 patients.
We consider that a relatively short observation period will result in the underestimation of late toxicity.
In the present study, we found many events which would not usually be encountered without long-term follow-up, and an adequate understanding of the toxicity profile of PBT in these patients thus requires long-term follow-up.

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From 2004 to December 2012, 40 cases (43 lesions) of superficial laryngopharyngeal cancer were treated with transoral videolaryngoscopic surgery (TOVS). The 5-year overall survival rate, disease-specific survival rate, and local control rate were 85%, 98%, 97% (100% including salvage treatment), respectively. For initial treatment cases (36 cases), the incidence of lymph node metastasis and endoscopic morphology were evaluated. Lymph node metastasis was not observed in epithelial cancer (n = 5) and was observed in 32% of the cases of subepithelial cancer (n = 31). Subepithelial cancer, which was initially node negative, presented delayed nodal metastasis in 8.7% of the cases. The depth of cancer invasion is associated with lymph node metastasis. Careful management for delayed nodal metastasis is recommended for cancer invading more than 1mm beneath the basement membrane level. The endoscopic type of 0-Is and 0-IIa is associated with deeper tumor infiltration and higher nodal metastasis rate. Among 0-I type lesions, sub-classification into 0-Is (sessile type) and 0-Ip (pedunculated type) is useful for differentiating the risk of lymph node metastasis.

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Neck dissections have recently been classified as either “comprehensive” or “selective”, according to the NCCN Clinical Practice Guidelines in Oncology. In this guideline, selective neck dissection is often recommended for N0 disease, and patients with cervical node metastases who undergo operations with therapeutic intent are generally treated with comprehensive neck dissections. Several authors, however, have advocated some indications of selective neck dissection for pharyngo-laryngeal cancer with clinical nodal metastases.
In order to survey the present policies of neck dissections for pharyngo-laryngeal cancer in Japan, we sent out questionnaires to 139 Board-Certified Facilities for Education of the Japan Society for Head and Neck Surgery. Replies to the questionnaires were obtained from 124 facilities (collection rate: 89.2%). Seventy-eight percent of them advocated selective neck dissection for pharyngo-laryngeal cancer with clinical nodal metastases. It is clear that selective neck dissection is often performed as treatment in certain patients with N1 to N2 diseases in those facilities. It is necessary to standardize the indications for selective neck dissection in pharyngo-laryngeal cancer.

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The prognostic factors for a postoperative case vary in effect. Microscopic positive margins and extra capsular spread are high-risk factors. For a case with two or more recurrent risk factors (except a high-risk factor), postoperative radiotherapy is recommended. With postoperative radiotherapy, the survival rate improves approximately 10% or more. When a high-risk factor is found, we need high doses through postoperative radiotherapy. Also, a period of less than eight weeks is desirable for starting postoperative radiotherapy after surgery. There should not be an interval in the radiotherapy. From the results of the recent clinical trial, the standard treatment for a postoperative high-risk case is chemoradiotherapy. The extra effect of the combination anticancer drug is considered to be approximately 10%.
If chemoradiotherapy is used after surgery, it places a large burden on the patient. Therefore, we must properly choose the subjects for postoperative chemoradiotherapy. It will be carried out after the merits have been clearly understood. Since we provide postoperative treatment, we should aim at completing the process and must be careful with drug withdrawal and reduction.

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This paper introduces the mandibular reconstruction using a custom-made titanium mesh (Ti-mesh) tray and autogenous particulate cancellous bone and marrow (PCBM), with a representative case report. The Ti-mesh tray is accurately adapted to the mandibular defect and its configuration is suitable for reproducing the final dental occlusion in each patient by utilizing computer-aided design/computer-aided manufacture (CAD/CAM) and dental laboratory technology. Eleven patients with mandibular defects (9 segmental defects and 2 marginal defects) underwent the present mandibular reconstruction. All reconstructive surgeries were successful and postoperative facial contour was acceptable for most patients. Although fracture of the Ti-mesh tray was recognized within 3 months after surgery in 2 patients with mandibular defect including the mentum area, we carried out successful additional reconstructive surgeries using a reinforced Ti-mesh tray and PCBM in these 2 patients. Although the present mandibular reconstruction requires several improvements, it seems to be clinically more predictive than the conventional mandibular reconstruction.

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In this study, we suggest a new classification for skull base defects that is in accordance with the following flap selection and reconstructive procedures. We define the new classification as outlined below.
For the anterior skull base, the cribriform plate is defined as the center of the defect, and for the middle skull base, the infratemporal fossa is defined as the center of the defect. The defects are classified as localized in the defect's center (Ia, IIa) or extended horizontally (Ib, IIb) or vertically (Ic, IIc) from the defect's center. The accompanying defects of the orbital contents and skin are indicated by “+O” and “+S,” respectively. Ia , IIa, Ic and IIc are reconstructed with locoregional flaps, and Ib, IIb, “O”, “S” and patients with combined defects are reconstructed with free flaps.
Between July 2000 and January 2012, 127 skull base reconstructions were performed in our institute. The patients were 73 males and 54 females, ranging in age from 2 to 79 years (median 43 years). Of the cases, 76 were malignant and 51 were benign tumors. All defects were re-sorted according to the new classification without omission. The correlation rate ranged from 92 to 100% between the flaps indicated by the new classification and the flaps that had actually been used. The rate of postoperative complications tended to be higher with Ic defects.
As a result, the concept of our new classification will not only adequately classify skull base defects but also has the possibility of deciphering the appropriate flap to apply and the reconstructive procedure to perform. Moreover, this new classification will provide information about the trend of postoperative complications, which will improve reconstructive procedures of skull base.

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The benefits of neoadjuvant chemotherapy (NAC) for patients with locally advanced head and neck cancer include a reduction in distant metastasis and the preservation of organ function; however, NAC has failed to demonstrate any significant improvement of survival in several randomized control trials. The efficacy of NAC is controversial, and no report supports NAC with a high level of evidence. We retrospectively analyzed 73 patients who underwent radical surgery for tongue cancer, and examined the effect of NAC on surgical margin.
NAC, regional lymph node metastasis, depth of invasion, local recurrence, perineural invasion, and the status of the surgical margin were identified as factors influencing survival. Moreover, NAC increased the local recurrence rate over that in patients without NAC. The deep surgical margin was resected closely in many NAC-treated cases, suggesting that NAC may lead to local recurrence and a poor outcome. We identified the ABCG2 (cancer stem cell marker) positive cells at the tumor / host interface in NAC-treated recurrent cases, and suggested that the local recurrence in NAC-treated cases may be associated with cancer stem cells.

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Concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion demonstrates good local control and overall survival rates due to the advantage of simultaneous infusion of anticancer agent with the synergistic effects of chemotherapy and radiotherapy. This study was conducted to evaluate the therapeutic results of 17 patients with locally advanced squamous cell carcinoma of the upper gingiva (T3, T4) treated with definitive concurrent chemoradiotherapy using retrograde superselective intra-arterial infusion.
Treatment consisted of superselective intra-arterial infusions (docetaxel, total 60mg/m²; cisplatin, total 150mg/m²) and daily concurrent radiotherapy (total 60 Gy) for 6 weeks. Patients underwent biopsy of the primary lesion and radiological examinations 4 weeks after the completion of all treatments. Complete response (CR) of the primary site was achieved in 14 (82.4%) patients. Among them, 1 patient showed local recurrence and 1 patient showed cervical and pulmonary metastases. Four patients died, 1 of pulmonary metastases, 1 of cervical metastases, and 2 of uncontrolled local lesion during follow-up. Two-year cumulative local control and overall survival rates by the Kaplan-Meier method were 76.5% and 81.4%, respectively.

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Purpose: To assess the current status of the treatment for oropharyngeal cancer (OPC) in Japan to assist the planning of clinical trials in the future.
Patients: The data for 523 patients with previously untreated OPC were obtained from 12 institutions from April 2005 to March 2007. Of the 523 patients, 471 patients with squamous cell carcinoma and with curative intent were included in an analysis of the treatment and its results.
Results: Of the 471 patients with OPC treated with curative intent, 186 patients (39.5%) were treated with surgery, 118 (25.1%) with RT alone and 167 (355%) with CRT. Surgery was indicated for 60.4% of the patients with stage I, 47.8% in stage II, 29.4% in stage III, and 36.44% in stage VI. CRT was indicated for 8.3% in stage II, but the percentage increased with higher stage. The percentage of RT was around 30% among stage I-III, but in stage VI, 21.3% of the patients were indicated for RT. The median follow-up period was 4 years and 5 months. The 2-year and 5-year overall survival rates for the 471 patients were 85% and 69.9%, respectively. The 5-year overall survival rates for patients treated initially with surgery, RT and CRT were 73%, 69.1% and 65.6%, respectively. The 5-year overall survival rates for patients with stage I, II, III, VIA, and VIB were 78.9%, 87.3%, 69.7%, 66.6%, and 47.7%, respectively. Conclusions: Although this study was retrospective, we could understand the tendency of treatment choice according to various factors and treatment results. The information will be useful for planning clinical trials in the future.

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One hundred ninety-two cases with hypopharyngeal carcinoma who underwent pharyngo-laryngo-esophagectomy at Kurume University Hospital between 1989 and 2011 were clinically analyzed. The 192 cases consisted of 173 males and 19 females with ages ranging from 39 to 84 years old (median: 63). The five-year overall survival rate and disease-specific survival rate were 45% and 60%, respectively. Ninety-five patients were alive, thirty-one patients died because of distant metastasis, and thirty patients died because of other diseases, twenty-one patients died because of lymph node metastasis, 9 patients died because of primary cancer and 6 patients died because of postoperative complications. In cases with operative complications, 29 patients showed anastomotic stricture, 5 patients showed anastomotic fistula, 4 patients showed total necrosis of the transplanted jejunum, 4 patients showed infection around the tracheostoma. This review indicates that the treatment result of hypopharyngeal carcinoma has dramatically improved because of well-organized team practice.

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We report the treatment outcomes of 195 patients with hypopharyngeal carcinoma treated at our institute during the nine-year period between 2001 and 2009. The five-year overall survival rate and cause-specific survival rate of all patients except for M1 cases were 47.7% and 56.8%. The five-year cause-specific survival rates of patients with Stage I, II, III, VIa and VIb were 80.2%, 86.9%, 66.8%, 45.5 and 0.0%, respectively.
We consider that TPLE and CCRT are standard treatments. We select CCRT for patients of CR or PR after induction chemotherapy. The five-year cause-specific survival rate of the ICT good response (CCRT) group, good response (TPLE) group, poor response (CCRT) group, and poor response (TPLE) group were 68.7%, 65.6%, 53.6%, and 32.9%, respectively. Patients of the good response (CCRT) group had a good prognosis, but patients of the poor response (TPLE) group had a poor prognosis.

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Hemodialysis patients often have various underlying diseases that hinder radical treatment for cancer. We herein report a hemodialysis patient with advanced hypopharyngeal carcinoma who was successfully treated by concurrent chemoradiotherapy (CCRT).
A 75-year-old man was presented with a one-month history of bilateral cervical swelling and pharyngeal pain. He had been receiving hemodialysis for 10 years, and had a number of underlying diseases including diabetes mellitus, hypertension, angina pectoris, and depression. From the findings of endoscopic, imaging and histopathological examinations, he was diagnosed as a hypopharyngeal carcinoma (pyriform sinus, T2N2cM0). Upon the patient's request for laryngeal preservation, we performed bilateral neck dissection followed by CCRT with cisplatin. Cisplatin was intravenously administered at a dose of 10 mg/body on the days of hemodialysis (3 times/week). Hemodialysis was started 30 minutes after the completion of cisplatin infusion. Total and free cisplatin concentrations in the blood were measured just before and after hemodialysis on each day. CCRT was completed without severe adverse events except grade 3 anemia and thrombopenia, and complete remission of the disease was achieved. The total cisplatin concentration remained within a safety limit (< 1.0 μg/ml) throughout the course.
We emphasize that CCRT with cisplatin can be conducted safely and successfully even in hemodialysis patients by monitoring cisplatin concentration.

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Dermatomyositis is known as one of the skin diseases that is sometimes associated with malignant tumors. In Japan, there are many reports of cancers such as gastric cancer, colon cancer, but the merger case of hypopharyngeal cancer is extremely rare. The patient was a 69-year-old male. In January 2011, the patient was aware of a sensation of pharyngeal abnormality. He was admitted to our hospital in late December of the same year. The diagnosis of hypopharyngeal cancer was made. Weakness of the proximal arm muscles was observed and a diagnosis of dermatomyositis was made. When a malignant tumor is complicated, priority is given to the treatment of tumors. In the present case, postoperatively, muscle weakness was exacerbated and tapering of steroid therapy started. However, the effect was minimum and the ADL dropped. High dose gamma globulin therapy started. It is necessary to plan the treatment for hypopharyngeal cancer associated with dermatomyositis with careful consideration of ADL.

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In the present study we reappraised the utilities of squamous cell carcinoma antigen (SCCAg) for the initial diagnosis, the efficacies of treatments and the prediction of recurrence, regarding 346 cases of the primarily-untreated head and neck squamous cell carcinoma (HNSCC) and 136 cases assigned as the negative control.
First, we statistically re-determined the cut-off value of serum SCCAg 2.0ng/ml.
At the initial diagnosis the mean level in the group with more than 2.0ng/ml SCCAg of HNSCC was significantly statistically different from that in the group with less than 2.0ng/ml. Furthermore, the 3-year cause-specific survival rates between the two groups also had significant statistical difference.
The levels were found to increase gradually with staging, and the sensitivity for Stage III + VI was significantly higher than that for Stage I + II. Regarding the histopathological differentiation of HNSCC, cases diagnosed as the well type were measured with higher mean levels. As to the 6 primary lesions of HNSCC, the mean levels in nasopharynx, mesopharynx, and maxillary sinus cancers were more than 2.0ng/ml, and the sensitivities in hypopharynx, mesopharynx, and maxillary sinus cancers were all counted higher than 50%. But in larynx cancer both data were shown as the lowest among the 6 lesions.
In the 83 recurrent cases, all of which were measured with serum SCCAg at the three therapeutic points of the first visit, the end of the initial treatments, and the recurrence, had significant statistical differences among the mean serum levels of the antigen. Especially at the point of the recurrence the serum levels and the sensitivities rose significantly higher than those at the end of the initial treatments. Therefore, strong suspicion of the recurrence should be mandatory for the rise of serum SCCAg with more than 2.0ng/ml in the prognosis after the initial treatments.

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Concurrent chemotherapy may cause various adverse events and complications, which can greatly influence oral health care or the preoperative detection of complications, whole-body control during treatment, and the subsequent completion rate or response to treatment.
We clinically examined the therapeutic effects as well as the disease-specific survival rate, completion rate, adverse events, complications, recurrence rate, and poor performance status in 100 patients who received S-1 plus nedaplatin with concurrent radiotherapy (SN therapy) as primary treatment for head and neck squamous cell cancer in our department between January 2005 and August 2011.
The results were as follows: the 3-year disease-specific survival rate was 93.0%, complete response rate was 88.0%, partial response rate was 12.0%, rate of effect was 100%, and completion rate was 85.0%. As for adverse events, grade 3 or greater hematologic toxicity and no hematologic toxicity were observed in 66.0% and 45.0% of the patients, respectively. Major complications after treatment initiation were observed in 9.0% of the patients; the most common complication was delirium in 5.0% of the patients. The recurrence rate was 13.0%, and 4.0% of the patients had poor performance status. Therefore, SN therapy was considered effective for head and neck squamous cell cancer.

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During the past 23 years, from June 1989 to December 2012, our treatment paradigm for head and neck squamous cell carcinoma (HNSCC) had involved comprehensive use of chemotherapy and radiation therapy followed by surgery.
Between 1989 and 2005, chemotherapy using fluorouracil and carboplatin had been administered via intravenous drip infusion as induction chemotherapy (ICT), and more recently between 2006 and 2012 as concurrent chemoradiotherapy (CCRT).
In the present study, we examined the superiority of definitive CCRT (dCCRT) over the ICT followed by definitive radiotherapy (ICT-dRT) as to the impact on the treatment of HNSCC with the stage-categories of T2-T4a, retrospectively analyzing survival rates and laryngeal preservation rates at the 3-year point between the two groups. The number of patients assigned for this study was 76, all of whom were previously untreated, and of whom 51 suffered from laryngeal carcinoma and 25 from hypopharyngeal carcinoma: 21 with Stage II, 25 with Stage III, 23 with Stage IVA, 7 with Stage IVC.
The three-year overall survival rate and cause-specific survival rate were 54.5%, 73.5% in the ICT-dRT group and 69.2%, 80.5% in the dCCRT group, respectively, both of which statistically had no difference. But the dCCRT was found to contribute to obtaining a higher rate of laryngeal preservation than that of the ICT-dRT in T2 and T3 but not in T4a.
In conclusion, dCCRT showed more significant efficacy for organ preservation on T2 and T3 HNSCC than ICT-dRT.

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We performed salvage surgery for five patients who had undergone combined radiation and cetuximab therapy from November 2009 through July 2012 at the National Cancer Center Hospital East. Two patients underwent total laryngectomy, and three patients underwent total pharyngo-laryngo-esophagectomy. A pharyngocutaneous fistula developed in one of these patients, and tracheal cartilage necrosis developed in another patient. Both complications healed with conservative treatment. We performed salvage surgery safely by considering the necessity and method of operation.

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Over an eleven-year period from 2001 to 2011, 471 neck dissections were performed for 352 patients. Of the 471, 18 (3.8%) patients developed chylous fistulas, 3 in the right neck and 15 in the left neck. The most common primary site was the thyroid (n = 8), followed by the larynx (n = 4), the hypopharynx (n = 3), the nasopharynx (n = 1), the tongue (n = 1), and the facial skin (n = 1). The mean maximum drain volume per day was 412ml (81∼1400ml). The days to the onset were a mean of 2.2 days (1-7 days). The duration of leakage ranged from 5 to 82 days (mean 20.5 days). All 18 patients were initially managed conservatively; this was successful for 14 patients. Minocycline local injection therapy was performed on 2 patients. Surgical exploration was required on 2 patients. Three patients had local infection as complications.

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The patient was a 74-year-old man. A total laryngectomy was performed due to recurrence of laryngeal cancer after chemoradiotherapy (CRT). Postoperatively, a pharyngocutaneous fistula developed and patch-graft reconstruction using a pectoral major musculocutaneous flap was planned. However, due to expansion of the necrotic area, we needed to perform tubular reconstruction. Nevertheless, infection and pus discharge were observed and a second surgery was performed. Resection and reconstruction at the neck were considered impossible because advanced necrosis was seen at the cervical esophageal stump, and the operative procedure was changed to esophageal resection, gastric pull-up and free jejunum transfer. Although leakage was found at the jejunum-gastric anastomosis site by fluoroscopy on the 14^th postoperative day, it disappeared through conservative therapy. In addition, oral ingestion was begun on the 28^th postoperative day. At 6 months after the surgery, the patient was able to regularly intake food and no constriction of the tracheostoma was seen. In this case, unexpected expansion of the necrotic area was a significant problem. As for the causes, diminished blood flow to the esophagus due to total thyroidectomy and bilateral paratracheal lymph node dissection, and infection in the surrounding area, along with remarkable tissue damage with CRT were considered possible. In salvage surgery, attention will be necessary in evaluating necrotic range and selection of appropriate reconstructive procedure.

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