MicroRNAs (miRNAs) are abundant classes of small non-coding RNAs of about 19-21 nucleotides in length, which regulate gene expression primarily at the posttranscriptional level. Growing evidence suggests that miRNAs are aberrantly expressed in many human cancers, and that they play significant roles in carcinogenesis and cancer progression. Recently, we identified a subset of down-regulated miRNAs (miR-145, miR-133a and miR-133b) in various cancer signatures. In this study, we elucidate the tumor suppressive functions of miR-145, miR-133a and miR-133b and identify their target genes in head and neck squamous cell carcinoma (HNSCC). These findings may provide new insight into the potential mechanisms of HNSCC carcinogenesis.
Three cases, in which intra-arterial cisplatinum chemotherapy of the ethmoid and/or orbital portion of advanced maxillary antrum cancer (T4a or T4b) combined with concurrent radiotherapy (RADPLAT) was conducted, are presented to discuss the feasibility of this radical treatment. Those tumors seemed uncontrollable with intra-arterial chemotherapy only through the external carotid artery and radiotherapy because there was no tumor staining on the external carotid artery angio-CT. Those tumors, on the other hand, showed intense tumor staining when internal carotid artery (ophthalmic artery) angio-CT was performed. The treatment was initiated upon obtaining the patient's informed consent in addition to the informed consent obtained at chemotherapy through the external carotid artery. The amount of CDDP administered via the ophthalmic artery ranged from 50-100mg per infusion and from 200-275mg in total (given over three to four courses). All patients showed CR and two survived without disease. As a significant complication, all patients went blind on the affected side in about two weeks. No other significant complications including those related to infusion techniques were encountered. Intra-arterial chemotherapy via the ophthalmic artery may be a final treatment of choice in advanced maxillary antrum cancers with ethmoid and/or orbital extension to better control the tumor while avoiding facial disfigurement.
The clinical findings of 43 cases with maxillary sinus squamous cell carcinoma treated between 1994 and 2007 were analyzed retrospectively. The patients ranged from 39-81 years of age (median of 63 years) and consisted of 34 men and nine women. In terms of the clinical T factor for these patients according to the AJCC classification (1997), there were three cases with T2, 12 cases with T3, 12, and 28 cases with T4. Three patients were diagnosed with lymph node metastases. The median follow-up time was 52 months (range of 6-162 months). From 1994 to 2004, accelerated hyperfractionated radiotherapy combined with low-dose carboplatin (CBDCA) infusion was used preoperatively, and intensity-modulated radiotherapy (IMRT) combined with high-dose cysplatin (CDDP) infusion chemotherapy was used from 2005 to 2007. The five-year overall survival rate (OS), five-year disease-free survival rate (DFS), and five-year local control rate (LC) of all patients were 80%, 72.6%, and 72.7%, respectively. The IMRT combined with high-dose CDDP infusion chemotherapy group had better OS than the other group, but it was not statistically significant.
TS-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: FT, a prodrug of 5FU; CDHP, an inhibitor of DPD, and Oxo, a reducer of gastro intestinal toxicity. TS-1 has safe and potent anti-tumor effects in oral cancer via these respective functions. TS-1 increased the effect of irradiation therapy for cancer. We report here a patient who had undergone hemodialysis because of chronic renal failure, with advanced upper gingival cancer in which preoperative concurrent chemoradiotherapy with TS-1was performed. The patient was a 62-year-old male who had a 40×25mm tumor mass around the left posterior buccal sulcus, which invaded to the pterygopalatine fossa (T4N1M0, Stage IVA). TS-1 therapy tends to increase the adverse events for patients with an impaired renal function due to excessively high blood concentration of 5FU, because CDHP is mainly excreted into the urine. The optimum dose of TS-1 for the treatment of upper gingival cancer in a chronic dialysis patient was estimated by monitoring the blood concentrations of 5FU (therapeutic drug monitoring (TDM)) during administration of TS-1. In this treatment protocol, TS-1 was administered 15 times at a daily dose of 25 mg every other day immediately after dialysis. Radiation was given for a total of 40Gy. The treatment could be safely continued without the development of any severe adverse events such as myelosuppression. After this treatment, PR was achieved. The tumor was responded to preoperative concurrent chemoradiotherapy, so curative resection was possible. Histological evaluation after surgery according to General Rules for Clinical Studies on Head and Neck Cancers classification showed grade II. The TS-1 combination with radiotherapy adjusted doses of TS-1 according to the results of pharmacokinetics studies may provide therapeutic safety and high efficacy in gingival carcinoma, in chronic dialysis patients.
In this study, we examined the oral flora in the saliva of head and neck cancer patients. We identified both the bacteria and its quantity in the flora as well as opportunistic pathogens in the saliva of 65 head and neck cancer patients. First, we counted the total number of bacteria in the saliva. Patients before the treatment had 1×107∼1×108cfu/ml of bacteria in their saliva. Second, we identified four bacilli in the oral flora. Streptococcus spp. was most prevalent in the saliva of head and neck cancer patients. The distribution of oral flora was not correlated with the primary site of the head and neck cancer. This data suggest that the primary site of cancer has no impact on the oral flora. On the other hand, the number of bacteria in patients with microvascular free flap was lower than in other patients. Next, we detected opportunistic pathogens in saliva. Oral cancer and oropharyngeal cancer patients had more opportunistic pathogens in their saliva than other head and neck cancer patients. The incidence of detection of opportunistic pathogens in patients who were scheduled for reconstruction with microvascular free flap was higher than the in other patients before the treatment. Moreover, opportunistic pathogens were detected with almost equal incidence in the patients who were scheduled for reconstruction with microvascular free flap and patients who had microvascular free flap. These findings indicate that cases with microvascular free flap can become highly complicated because of opportunistic infection. In conclusion, opportunistic pathogens have the potential to induce postoperative infection and pneumonia after reconstruction with micrvascular free flap, and oral care seems to be one possibility to prevent it.
We report a case of a 67-year-old man who underwent reconstruction surgery several times to place a metal plate on both sides of the DP flap after mandible and gingiva tumor excision by an oral surgeon in another hospital; however, it became infected and necrosis, and the mandible was lost. As a result, a huge tubed flap was made in the left thorax and the abdominal part; however, the patient opted for another treatment opinion and came to our hospital. The patient suffered a loss and was not able to close his mouth at all. We combined a free rectus abdominis muscle flap and ported tubed flap in the mandible and oral floor part and used them for efficient reconstruction of the mandible. After the surgery, the combined flap was completely engrafted and satisfactory results were obtained in terms of function and esthetic reconstruction.
We analyzed stage III and IV advanced oral tongue cancer. A total of 59 patients were analyzed from 1987 to 2002 (Stage III 37 cases, stage IV 22 cases). The five-year survival rates were 81.1% (stage III) and 50.0% (stage IV). In stage III, a recurrence occurred in seven of 36 (19.4%) patients, only one patient was controlled. In stage IV, a recurrence occurred in eight of 19 (42.1%) patients, all were uncontrolled. Most recurrence occurred at the parapharyngeal space in stage III (cervical recurrence). In stage IV the recurrence sites were the deep site of the tongue, oropharyngeal mucosa, cervical skin, lung metastasis, systemic multiple metastasis. The effectiveness of post-operative adjuvant radiotherapy and/or chemotherapy were not presented clearly.
Epithelial dysplasia and local recurrence at the resected margins in 43 patients who underwent primary curative surgery for early stage oral squamous cell carcinoma (T1 or T2) without any preoperative treatment were discussed, respectively. Of the 43 patients, 19 had epithelial metaplasia at the resected margins, including seven in whom recurrence developed. Among the 24 patients with no epithelial dysplasia, one had recurrence. These results suggested that the presence of epithelial dysplasia the resection margins is closely related to recurrence. Among the 19 patients with epithelial dysplasia, there was no significant difference in the histologic malignancy grade of their primary tumors according to Anneroth's classification between patients with recurrence and those without recurrence. Patients with residual dysplasia who had recurrence of tongue cancer were analyzed according to the classification of squamous intraepithelial neoplasia (SIN) proposed by the “Guidelines for Tongue Cancer” Working Group, affiliated with the Japan Society for Oral Tumors. All of these patients met the criteria for SIN. This finding suggested that the classification of SIN is useful for the evaluation of epithelial dysplasia at the resection margins in patients with oral squamous cell cancer.
Objectives: We evaluated the cause and the duration of pharyngocutaneous fistula (PCF) after laryngectomy, placing special emphasis on radiotherapy and/or chemotherapy. Patients and methods: A total of 78 consecutive patients undergoing salvage total laryngectomy for squamous cell carcinoma of the larynx at Kanazawa University Hospital from 1990 to 2008 were reviewed. Forty-three of 78 had received primary total laryngectomy (PL). Sixteen patients underwent radiotherapy alone (SL-RT) and nine patients underwent concurrent systemic chemoradiotherapy (SL-SCRT1, 10 patients underwent concurrent arterio chemoradiotherapy (SL-ACRT) followed by salvage laryngectomy. Results: Overall, 23 of the 78 patients (29.4%) developed PCF after laryngectomy. Fisher's exact test showed a significant increase of PCF formation in salvage laryngectomy (45%) compared with PL (16%) (p = 0.0046). The Mann-Whitney U-test showed that the duration of PCF was significantly longer for SL (89.1 ± 104.2 days) compared with those for PL (54.9 ± 50.9 days) (p = 0.0146). Although we did not find a significant difference in the duration of PCF with respect to SL-SCRT and SL-ACRT (p = 0.1084), there were longer durations of PCF in SL-ACRT (143.8 ± 84.3 days) than SL-SCRT (41.4 ± 14.4 days). Conclusions: Radiotherapy has an impact on PCF information. Both radiotherapy and chemotherapy have an impact on PCF closure. We supposed that the dose of drug in the irradiation tissue has impact on PCF closure.
Forty-one cases with nasopharyngeal carcinoma (NPC) treated in our department between 1991 and 2007 were clinically analyzed. The mean age of the cases was 53 years old, and the male-to female ratio was 3.6:1. The most common chief complaint was ear symptoms followed by neck, eye, and nose symptoms. The most common histology was squamous cell carcinoma, followed by undifferentiated carcinoma, adenocarcinoma, and spindle cell carcinoma. More than half of the cases were classified as clinical stage IV. For squamous cell carcinoma, undifferentiated carcinoma, spindle cell carcinoma cases, concurrent chemoradiotherapy followed by adjuvant chemotherapy was applied. For adenocacinoma cases, transpalatal resection and postoperative radiotherapy was applied. The five-year overall survival rate was 64.1% and the disease-specific five-year survival rate was 71.2%. No significant statistical differences were seen between early stage (I, II) and late stage (III, IV), between I, II, III stage and IV stage. Recurrence occurred in 24.4% of the cases, and distant metastasis was more dominant than local recurrence. For the diagnosis and treatment of NPC, proper detection of NPC from variegated symptoms, and chemoradiotherapy for squamous cell carcinoma cases were considered to be important.
In this retrospective study, we report on 16 patients with hypopharyngeal squamous-cell carcinoma who underwent hypopharynx partial excision at the Department of Otolaryngology, Jikei University Hospital, between February 2005 and February 2009. Regarding postoperative staging, two patients were at stage I, four patients at stage II, three patients at stage III, and seven patients at stage IVA. Seven patients had a primary cancer lesion at the piriform sinus (PS), three patients at the posterior wall (PW), one patient at the post-cricoid area (PC), and two patients between PS and PW. We performed hypopharynx partial excision and reconstruction with free flap for all patients to preserve the larynx. No patients had trouble swallowing and phonation postoperatively. But four patients had a relapse in the cervical lymph node and one patient had a relapse in at a primary site. These patients underwent current chemoradiation and two patients died of the recurrence. The cause-specific two-year survival rate by Kaplan-Meier was 84% in all patients and 63% in stage IVA. We undertook hypopharynx partial excision for laryngeal preservation surgery and were able to obtain good results for the patients' post-operative function of swallowing and phonation. Moreover, only one of 16 patients relapsed at the primary site, and the cause-specific two-year survival rate was as high as 84%. Therefore, these results suggest that hypopharynx partial excision is suitable for patients with hypopharyngeal squamous-cell carcinoma as surgery for preservation of the larynx.
We evaluated the treatment outcome (prognosis, and the incidence and site of recurrent cancer in eight patients undergoing larynx preservation surgery for hypopharyngeal cancer in our department between 2004 and 2008. The overall five-year survival rate was 66.7%. The five-year disease-free survival rate of all cases was 50.0%. Recurrent cancer occurred in four (50.0%) patients. Lung metastasis occurred in one patient with pyriform sinus cancer at 12 months after treatment. Within seven months after treatment, the recurrence in the retropharyngeal lymph node or the mediastinal lymph node occurred in three patients with pN0 posterior wall cancer. Concomitant chemo-radio therapy was performed in three patients with lymph node recurrence. The overall response rate was 100%, CR in 2 patients and PR in one patient. We speculated that prophylactic postoperative radiotherapy was effective for regional lymph node recurrence based on our present study. However, we should investigate the therapeutic efficacy of adjuvant chemotherapy for prevention of lymph node recurrence without radiotherapy, because we will reserve radiotherapy as an therapeutic option for recurrent cancer or secondary cancer.
We studied 22 patients who underwent larynx-preserving partial hypopharyngo-laryngectomy with immediate reconstruction at our hospital between December 2004 and January 2009. The flaps used were the forearm flap in 16 patients, the anterolateral thigh flap in three patients, and the free jejunum in three patients. After the operation, removal of the speech cannulae was possible in 18 of 22 patients (81%). A normal diet was prescribed for 17 of 22 patients (77%), a full porridge or soft diet in four patients, and a mixer-processed/nutrient supplemented diet in one patient. Analysis of the relationship between the flap and diet consistency shows no significant difference between the forearm flap and the anterolateral thigh flap. The results of this study suggest that the extent of mucosal deficit is proportional to postoperative swallowing function. Functional preservation tended to be difficult when resection involved up to the pyriform sinus of the unaffected side and when more than half of the circumference of the cervical oesophagus was resected. Since one-stage plication of the harvesting site is possible, the anterolateral thigh flap may be a substitute for the forearm flap.
Free jejuna transfer has become a first choice for pharyngoesophageal reconstruction. We reviewed 90 consecutive patients who underwent pharyngoesophageal reconstruction with free jejunal transfer following total pharyngolaryngoesophagectomy in the Shizuoka Cancer Center from 2002 to 2008. Postoperative complications occurred in 48 of 90 (53%) patients. Tracheostomal stenosis (21%), stricture (13%) and small bowel obstruction (9%) were the most common complications. The rate of tracheostomal stenosis and stricture did not correlated with the perioperative radiation therapy. Minor jejunum-esopahageal anastmotic leakage occurred in two patients (2%). Graft loss occurred in one patient (1%). Although free jejunal transfer is a reliable procedure for pharyngoesophageal reconstruction, the rate of postoperative late complications is not small. A long-term follow up study must be carried out.
To reduce the incidence of Frey's syndrome after parotidectomy, the insertion of a sternocleidomastoideus flap in the parotid area has been performed intraoperatively, but the complete prevention of Frey's syndrome is impossible. In this report, we introduce a new parotid gland surgery for the prevention of Frey's syndrome. At raising of the skin flap, we don't separate the superficial parotid fascia from the subcutaneous tissue. Therefore, the sympathetic nerves controlling the sweat glands will be preserved. Accordingly, the misdirection of nerves never arises postoperatively. In 2008, 27 patients with a fresh parotid gland tumor received an operation in the Osaka Red Cross Hospital. The subjects were 23 out of the 27 patients who received an operation with skin flap elevation including the parotid fascia for the prevention of Frey's syndrome, and who could be followed up for over six months after surgery. Histpathological classification comprised 12 cases with Warthin's tumor, 10 cases with pleomorphic adenoma and one case with a cyst. There was no incidence of Frey's syndrome in all patients.
To assess the impact of modifications to radical neck dissection and radiotherapy on the postoperative quality of life, the study group “Study on Standardization of Treatment for Lymph Node Metastasis of Head and Neck Cancer” performed a multicenter cross-sectional study using our self-administered neck dissection questionnaire and arm abduction test. While sparing levels IV and V improved most postoperative symptoms, such as stiffness and constriction of the neck were avoided as long as the sternocleidmastoid muscle (SCM) and the spinal accessory nerve were preserved. Resection of the SCM and spinal accessory nerve resulted in a drop shoulder and neck pain, respectively. Irradiation with a total dose of 50 Gy or more worsened stiffness of neck and shoulder.
We investigated four patients with oropharyngeal cancer and 12 patients with hypopharyngeal cancer who underwent planned neck dissection (PND) after concurrent chemoradiotherapy (CCRT) from December 2001 to January 2005. We performed neck dissections in levels I to V or II to V. But we found that there was no residual cancer in the initially negative neck level. We conclude that we can limit the excision in the initially positive level in planned neck dissection.
In general, malignant melanoma in the head and neck (MMHN) provides a poor prognosis. The treatment for MMHN has mainly indicated radical excision. Other therapies are usually not effective. Nine MMHN patients were treated in our department from 1992 to 2008. Primary lesions were the in nasal cavity in four cases, in the paranasal sinus in four cases, and in the oral cavity in one case. The five-year overall survival rate was 55.6%. Seven patients were treated with radical surgery. In our current study, the relationship between satellite lesions around the primary site and the prognosis was examined. Three patients without satellite lesions survived with no recurrence, while all four patients with satellite lesions showed local and distant recurrence. Our study suggests that the prognosis of MMHN is influenced by the presence of satellite lesions around the primary site.
We investigated the efficacy and safety of concurrent chemoradiotherapy with CDGP/5-FU for 15 head and neck squamous cell carcinomas from July 2004 to March 2008. Seven patients were clinical stage III, six were stage IV A and two were stage IV B. Radiotherapy was 60-66 Gy and two courses of 5-FU 700mg/m2 on days 1-5 and CDGP 70mg/m2 on day five were administered concurrently with radiotherapy. The median follow-up period was 22 months (range 4-41 months). Eleven cases (73.3%) had a complete response to treatment in the primary lesions and three cases (20%) had a partial response. The three-year overall survival rate was 93% and the three-year local control rate was 79%. Grade 3 or greater acute adverse events were leucopenia in 33.3%, thrombocytopenia in 33.3% and pharyngeal mucositis in 26.6%. Concurrent chemoradiotherapy with CDGP/5-FU seemed to be effective for advanced head and neck squamous cell carcinomas.
To better understand ways to improve the content of explanations to patients while obtaining informed consent with respect to in-hospital mortality prior to head and neck cancer surgery, we did a retrospective analysis of in-hospital mortality of a total of 949 surgeries performed for head and neck cancer at Nippon Medical School Hospital, during the period from 1997 to 2008. Among them, 693 were male and 256 were female. The mean and standard deviation of age of these patients were 62.3±12.3. The in-hospital mortality rate in the total cases was 0.95%, that is nine cases out of a total of 949 cases. That after reconstructive surgery using the free flap was 1.82%, that is six cases out of a total of 329. Next, mid-level surgeries, including surgeries ranging from unilateral radical neck dissection to total laryngectomy with bilateral radical neck dissection, was 1.06%, that is three out of 289. No patient died due to any post-operative complication after smaller level surgeries, which included thyroid surgery, partial parotidectomy and microlaryngeal surgery. The major causes of in-hospital mortality were fistula formation followed by neck infection or airway disorders, based on complicated diseases.
Concurrent chemoradiotherapy for cancer of head and neck is becoming more popular as the treatment of choice. It is considered to maintain the QOL of patients better than operative treatments in terms of preserving the functions, organs, and figure, but recently we cannot necessarily say that it maintains the QOL of patients better than operative treatments because its complications after therapy disturb daily life. We report the results of a questionnaire survey about complications after therapy, problems during therapy, improvements, and satisfaction level directed at patients with cancer of the head and neck who received Concurrent chemoradiotherapy for the purpose of ascertaining if patients can actually maintain their QOL after therapy. As a result, the most controversial problem was mouth dryness, but the symptom improved as the follow-up duration got longer. As for the satisfaction level, “very-satisfied” and “almost-satisfied” were more than 90%, so we concluded that the QOL of patients is maintained after therapy, while there are still improvements to be made. We also concluded that we should continue to make improvement and try to improve the QOL of patients during and after therapy.
Postoperative swallowing dysfunction is thought to impair the quality of life (QOL) in patients with head and neck cancer surgery. However, few studies have thoroughly investigated the relationship among swallowing dysfunction, QOL and swallowing rehabilitation. This study evaluated the effect of postoperative swallowing rehabilitation on the postoperative swallowing function and QOL. The subjects were 27 patients who underwent surgery for head and neck cancer at the Tohoku University Hospital between 2006 and 2009. Thirteen patients who received postoperative swallowing exercises for two months served as the REHA group. Fourteen patients who did not receive postoperative swallowing exercises served as the Control group. Assessment of Frenchay Dysarthria Assessment test (FDA), speech intelligibility, swallowing function and The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire H&N35 (QLQ-H&N35) was conducted just before the operation (before the rehabilitation), and three months (after the rehabilitation) after surgery. In REHA group, FDA score improved significantly compared with the Control group. With regard to the QLQ-H&N35, the score for open mouth, pain, social contact score improved in the REHA group. Performing postoperative swallowing exercise produces improvements in the post-treatment swallowing function in patients with surgery for head and neck cancer. Postoperative rehabilitation, especially postoperative swallowing exercises may be effective in improving the swallowing dysfunction and QOL in patients with head and neck cancer surgery.
The therapeutic course is uncertain in patients with advanced head and neck cancer associated with severe psychiatric diseases, which poses a problem in determining the treatment options. We reviewed such patients seen during the five-year period from January 2004 to December 2008. The incidence of post-treatment complications was 75%. No deaths occurred due to complications. It was difficult to obtain the patient's cooperation with treatment because of underlying alcohol addiction or dementia, and their postoperative course was often problematic. We report herein a representative case. A 46-year-old male patient was found to have neck swelling during his stay in a neuropsychiatric hospital for atypical psychosis and was referred to our department for detailed examination. The patient was diagnosed with hypopharyngeal cancer (T2N3M0). He was treated with curative intent (total laryngectomy, partial pharyngectomy, and right cervical lymph node dissection in combination with skin excision). However, the patient developed multiple postoperative complications such as bleeding and pharyngocutaneous fistula. Four months after surgery, he was able to eat ordinary food. Delirium and other psychiatric disorders were treated in cooperation with the liaison team during hospitalization. Efforts were also made to gain cooperation of the patient's family members and social support after discharge from the hospital. When highly reliable healthcare is sought, we medical professionals are required to provide safe and efficient healthcare while striving to surpass therapeutic limitations. Cancer staging, general performance, and social backgrounds should be comprehensively evaluated to determine treatment options for patients with head and neck cancer.