Isaku Okamoto

Therapeutic effects of a new photosensitizer for photodynamic therapy of early head and neck cancer in relation to tissue concentration.

OBJECTIVE Talaporfin sodium (Laserphyrin, Meiji Seika, Tokyo, Japan) is a second-generation photosensitizer developed in Japan. It is characterized by both mild and short-term skin photosensitivity. The objective of this study was to evaluate the efficacy and the pharmacokinetic characteristics in tumor tissues in patients with head and neck cancer. METHODS (1) Four hours after administration intravenous injection of talaporfin sodium (40 mg/m(2)), 100mg tissue specimens were taken from the central part of the tumor. The samples were analyzed by reverse phase liquid chromatography and concentrations were measured. (2) Four hours after intravenous injection of talaporfin sodium (40 mg/m(2)), we gave 60-150 J/cm(2) of 664 nm laser irradiation with a diode laser (PD laser, Panasonic, Japan). Biopsies were performed at 4 weeks and at 3 months after treatment and periodically thereafter to confirm the treatment efficacy of photodynamic therapy (PDT). RESULTS Of the 14 patients who grope informed consent, more than 1 microg/g of talaporfin sodium was found in the tumor tissues in 13. Moreover, in 9 patients, tumor-to-normal-tissue ratios ranged from 2.32:1 to 5.69:1, which indicates that more than double the amount of talaporfin sodium was maintained within the tumor than in normal tissues. We have enrolled 22 patients with head and neck cancer with no clinically recognizable metastases after obtaining written informed consent to participate in this study. PDT using talaporfin sodium exhibited the equivalent efficacy to that of conventional PDT using hematoporphyrin derivative (HpD). CONCLUSIONS The results using a combination of talaporfin sodium and PD laser achieved a primary treatment outcome equivalent to that of conventional PDT. This method has also proven to be advantageous because of the reduced incidence of side effects such as photosensitivity and local edema.

Rikkunshito improves globus sensation in patients with proton-pump inhibitor-refractory laryngopharyngeal reflux

AIM To investigate the effect of rikkunshito on laryngopharyngeal reflux (LPR) symptoms and gastric emptying in patients with proton-pump inhibitor (PPI)-refractory LPR. METHODS In total, 22 patients with LPR were enrolled. Following a 2-wk treatment with PPI monotherapy, PPI-refractory LPR patients were randomly divided into two treatment groups (rikkunshito alone or rikkunshito plus the PPI, lansoprazole). LPR symptoms were assessed using a visual analog scale (VAS) score, gastrointestinal symptoms were assessed using the gastrointestinal symptom rating scale (GSRS), and gastric emptying was assessed using the radio-opaque marker method prior to and 4 wk following treatments. RESULTS The 4-wk treatment with rikkunshito alone and with rikkunshito plus the PPI significantly decreased the globus sensation VAS scores. The VAS score for sore throat was significantly decreased following treatment with rikkunshito plus PPI but not by rikkunshito alone. Neither treatment significantly changed the GSRS scores. Rikkunshito improved delayed gastric emptying. We found a significant positive correlation between improvements in globus sensation and in gastric emptying (r² = 0.4582, P < 0.05). CONCLUSION Rikkunshito improved globus sensation in patients with PPI-refractory LPR, in part, because of stimulation of gastric emptying. Thus, rikkunshito is an effective treatment for PPI-refractory LPR.

Detection of passive movement of the arytenoid cartilage in unilateral vocal-fold paralysis by laryngoscopic observation: useful diagnostic findings

In a previous study of patients with unilateral vocal-fold paralysis (UVFP), three-dimensional computed tomography (3DCT) revealed passive movement during phonation, with the arytenoid cartilage on the paralyzed side pushed to the unaffected side and deviated upwards. The present work compares the 3DCT findings with those obtained by 2-dimensional endoscopy to visualize the vertical passive movement of the arytenoid cartilage. The study population consisted of 23 patients with UVFP and two with laryngeal deviation but normal movement of the vocal folds. Two endoscopic findings represented cranial deviation during phonation: posterior deviation of the arytenoid hump and lateral deviation of the muscular process. These two findings were classified into four grades, ranging from 0 (normal) to 3 (severe). Cranial displacement detected by 3DCT was also classified into four grades. Significant correlations were found between the 3DCT-determined grade of cranial displacement of the arytenoid cartilage and the grade assigned based on the two endoscopic findings. Moreover, lateral deviation of the muscular process was more significantly correlated with 3DCT grade than with endoscopic grade. Thus, endoscopic findings may be useful in the diagnosis of vocal-fold paralysis, and passive lateral deviation of the muscular process as an indicator of UVFP.

The efficiency and adverse events of radiotherapy with cetuximab for Japanese head and neck cancer patients

OBJECTIVES Radiotherapy with cisplatin (Chemoradiotherapy, CRT) has long been one of the standard treatments for head and neck squamous cell cancer (HNSCC). Approval of cetuximab for the treatment of HNSCC has made radiotherapy with cetuximab (Bioradiotherapy, BRT) a new treatment option for HNSCC. Reports of BRT in the Japanese written in English up to now is only the phase II study, though it includes only 22 patients. Also on the nature of the clinical Phase II trial, sampling bias of cases may exist. Here we report the treatment completion rate, response rate and frequency of adverse events of BRT in Japanese patients with HNSCC in English for the first time. In association with this, we examine the issues related to BRT in Japanese patients. PATIENTS AND METHODS The subjects consisted of patients with HNSCC who underwent BRT as the first curative treatment (45 cases). Their treatment completion rate, response rate and frequency of adverse events were examined. RESULTS Of the 45patients, 42 were male and 3 were female. The mean age of the patients was 64 (range from 40 to 86). Adverse events of Grade3 or more were 12 cases (27%) of dermatitis, 31 cases (69%) of mucositis/stomatitis, 6 cases (13%) of interstitial pneumonia. The complication rate of pulmonary emphysema in those who developed interstitial pneumonia and those who did not were 83% and 21%, respectively. The BRT completion rate was 78%, and the response rate was 84%. CONCLUSION BRT is sufficiently tolerable and have high response rate even for the Japanese, but we should recognize that BRT is not a minimally invasive and easily manageable treatment.

Chemoradiotherapy with generic cisplatin formulations for head and neck cancers

The use of generic drugs has been increasing. However, studies of the safety of generic cisplatin (CDDP) for the treatment of head and neck cancer (HNC) have not been reported. This study investigated the treatment completion rates and incidence of CDDP-related adverse events in patients with advanced HNC treated with concurrent chemoradiotherapy (CRT) using generic CDDP. This study included 72 patients who received concurrent CRT using generic CDDP. The number of courses of CDDP was 3 in 45 patients, 2 in 19 patients, and 1 in 8 patients. During 154 courses of 80 mg/m2 generic CDDP, grade 3/4 leukopenia in 21 (14%), neutropenia in 18 (12%), and hypochromia in 8 (5%) cases were reported. Grade 2 elevated serum creatinine occurred in 4 cases (3%), but no grade 3/4 elevated serum creatinine was reported. These results suggest that CRT using generic CDDP is well tolerated in patients with HNC.

Concomitant Extramedullary Plasmacytoma in the Oropharynx and Hypopharyngeal Squamous Cell Carcinoma

We report a rare case of hypopharyngeal squamous cell carcinoma occurring synchronously with extramedullary plasmacytoma (EPM) of the oropharynx in which radiotherapy was used as the curative treatment. A 73-year-old man presented with a sore throat that had persisted for 6 months. Examination revealed a superficial, smooth tumorous lesion at the base of his tongue with a red hue in the oropharynx. In addition, a protruding tumor was observed on the mucosal surface in the right piriform recess of the hypopharynx, and computed tomography revealed thickening of the pharyngeal wall at the right tongue base and in the right piriform recess of the hypopharynx. Because no definitive diagnosis could be reached for the lesion at the base of the tongue, the entire tongue-base tumor was resected by transoral surgery under endoscopy. Proliferation of plasma cells in the tumor was detected, and a bone marrow puncture test ruled out multiple myeloma leading to a definitive diagnosis of Stage I (cT1N0M0) squamous cell carcinoma in the right piriform recess of the hypopharynx and primary extramedullary plasmacytoma in the oropharynx. Radiotherapy was selected for curative treatment with a complete response for both cancers. No recurrences have been observed as of 12 months postoperatively.

A Case of Septicemia due to Nonocclusive Mesenteric Ischemia Occurring in Induction Chemotherapy

In nonocclusive mesenteric ischemia (NOMI), mesenteric ischemia and intestinal necrosis occur despite the absence of organic blockage in mesenteric blood vessels. As abdominal pain is often absent and few characteristic findings are seen in blood biochemistry, imaging diagnosis or other examinations, discovery is often delayed. With a mortality rate of 56–79%, NOMI is a very serious disease. However, few reports have described this pathology in association with chemotherapy regimens such as those used for malignant head and neck tumors. We encountered a case of NOMI during induction therapy combining cisplatin, docetaxel, and 5-fluorouracil. The patient was a 74-year-old man receiving chemotherapy for T2N2bM0 stage IVA oropharyngeal carcinoma. Febrile neutropenia appeared on treatment day 8. An antibacterial agent and a granulocyte colony-stimulating factor were administered, but septic shock developed and he was transferred to the intensive care unit. Abdominal distension was present and contrast-enhanced computed tomography of the abdomen suggested NOMI. Emergency surgery on day 9 resected the necrotized small intestine and created a single-hole ileostomy. The patient subsequently recovered with 2 weeks of continuous hemodiafiltration and other intensive therapies. Otolaryngological surgeons seldom encounter intestinal diseases, which are thus easily overlooked. The present case report may help in achieving early diagnosis.

Parapharyngeal space tumor surgery using a modified cervical–parotid approach

Abstract Objectives: The cervical approach to parapharyngeal space tumors is blind in cases involving an approach to the vicinity of the skull base from below. We therefore devised a procedure to improve the safety of surgery in the vicinity of the skull base. Methods: With this surgical technique, the temporal branch from the main trunk is first identified, as in the case of parotid gland tumor surgery. We then approach the skull base by entering the posterior aspect of the parotid gland tissue from above the temporal branch and anterior auricular space, allowing clear visual confirmation of the upper part of the tumor. Combining this approach with the conventional cervical approach, which is used for the lower part, the tumor can be separated from top to bottom. Results: We have applied this combined approach in eight patients to date, and post-operative courses have been good, with no cases of facial paralysis. Conclusion: This modified cervical–parotid approach offers a very useful surgical procedure for parapharyngeal space tumors with respect to preservation of the facial nerve and tumor separation in the vicinity of the skull base.

Prevention of anastomotic leak using an advanced pectoral flap in total pharyngolaryngectomy and free jejunal reconstruction for hypopharyngeal or laryngeal carcinoma

Abstract Background: We devised an advanced pectoral flap (APF) to prevent anastomotic leak after total pharyngolaryngectomy (TPL) and free jejunal reconstruction (FJR) in patients with hypopharyngeal or laryngeal carcinoma. The APF alleviates tension on the skin in the neck, reduces the subcutaneous dead space, and promotes adhesion between the neck skin and the anastomosis. Objective: To investigate whether an APF is effective for prevention of anastomotic leak associated with TPL/FJR. Patients and methods: Anastomotic leak was compared between APF (n = 65) and non-APF groups (n = 25). Patients who had received preoperative radiotherapy or undergone tracheostomy or skin infiltration requiring neck reconstruction using a pedicle flap were excluded. Results: There were significantly fewer cases of anastomotic leak in the APF group than in the non-APF group (1.5% [1/65] vs. 16.0% [4/25]; p = .02). An APF could be created bilaterally within approximately 15 minutes. Unlike a deltopectoral flap, an APF does not require a skin graft. Conclusions: The postoperative anastomotic leak rate was 1.5% in patients who underwent TPL and FJR for hypopharyngeal or laryngeal carcinoma with an APF. Significance: An APF is easily created and can reduce the incidence of anastomotic leak after TPL and FJR.