A Successful Case of Switching Treatment from Ketamine to Methadone for Complex Neuropathic Pain.

Background: Methadone is frequently used for the management of complex pain at the end of life by palliative care specialists. It is also used in low doses as an add-on therapy to chronic opioid treatment of cancer-related pain, usually with good effect, and without any reported severe adverse effects. However, there are few reports of switching from ketamine to methadone. Case: We report a case of a patient with rectal cancer and intractable pain. Switching from ketamine to methadone to maintain analgesia was successfully carried out without impacting activities of daily living. Established measurement tools, such as numerical rating scale, Douleur Neuropathique, Functional Independence Measure, and Barthel Index, were used. Conclusion: Switching from ketamine to methadone may be beneficial in relieving refractory cancer-related neuropathic pain without decreasing functioning.

Bulky cardiac metastasis of intracranial solitary fibrous tumor/hemangiopericytoma: Delayed metastasis after cranial tumor resection.

We report a case of bulky cardiac metastasis of intracranial solitary fibrous tumor/hemangiopericytoma (SFT/HPC). A 72-year-old woman developed a chief complaint of chest pain. Contrast-enhanced computed tomography revealed multiple enhanced masses in the heart, retroperitoneum, and femur. Initially, multiple metastases of cardiac primary angiosarcoma were suspected because the cardiac mass was the largest. However, it was diagnosed as SFT/HPC on the basis of biopsy and immunostaining for the retroperitoneal lesion. She had a history of resected brain tumor surgery for a meningioma 11 years earlier, and pathological reconfirmation revealed this was not a meningioma but rather a SFT/HPC. Thus, we found that the enhanced masses were extracranial metastases of an intracranial primary SFT/HPC. She died approximately 3 years after the onset of chest pain. Autopsy confirmed metastasis in the retroperitoneum, liver, lung, mesentery, skeletal muscle, and bone in addition to the heart. SFT/HPC has been reported to easily recur locally and to show systemic metastasis over the long term. Given that SFT/HPC has been recognized as a subtype of meningioma, the differential diagnosis for patients with a history of intracranial tumors, such as meningioma, should include SFT/HPC.

Quantification of DNA fragmentation in processed foods using real-time PCR.

DNA analysis of processed foods is performed widely to detect various targets, such as genetically modified organisms (GMOs). Food processing often causes DNA fragmentation, which consequently affects the results of PCR analysis. In order to assess the effects of DNA fragmentation on the reliability of PCR analysis, we investigated a novel methodology to quantify the degree of DNA fragmentation. We designed four real-time PCR assays that amplified 18S ribosomal RNA gene sequences common to various plants at lengths of approximately 100, 200, 400, and 800 base pairs (bp). Then, we created an indicator value, "DNA fragmentation index (DFI)", which is calculated from the Cq values derived from the real-time PCR assays. Finally, we demonstrated the efficacy of this method for the quality control of GMO detection in processed foods by evaluating the relationship between the DFI and the limit of detection.

Phase II study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer.

PURPOSE: S-1 is an oral fluoropyrimidine derivative that has demonstrated favorable antitumor activity in patients with metastatic pancreatic cancer. The aim of this study was to evaluate safety and efficacy of S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. METHODS AND MATERIALS: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day at a dose of 80 mg/m(2)/day from day 1 to 14 and 22 to 35. Two weeks after the completion of chemoradiotherapy, maintenance chemotherapy with S-1 was administered for 28 days every 6 weeks until progression. RESULTS: Thirty-four patients were enrolled in this study. The most common Grade 3 toxicities during chemoradiotherapy were anorexia (24%) and nausea (12%). The overall response rate was 41% (95% confidence interval, 25%-58%) and overall disease control rate (partial response plus stable disease) was 97%. More than 50% decrease in serum CA 19-9 was seen in 27 of 29 evaluable patients (93%). The median progression-free survival was 8.7 months. The median overall survival and 1-year survival rate were 16.8 months and 70.6%, respectively. CONCLUSIONS: Oral S-1 and concurrent radiotherapy exerted a promising antitumor activity with acceptable toxicity in patients with locally advanced pancreatic cancer. This combination therapy seems to be an attractive alternative to conventional chemoradiotherapy using 5-fluorouracil infusion.

[Correlation of fat content and dioxins, total mercury and methyl mercury levels in tuna].

In this study, we analyzed the concentrations of mercury and dioxins in tuna with various fat contents (akami; the leaner meat, Chutoro; the belly area of the tuna along the side of the fish between the akami and the otoro. Otoro; the fattiest portion of the tuna) in wild and farmed bluefin tuna and farmed southern bluefin tuna. In the three kinds of tuna, average dioxins concentrations in Akami, chutoro and otoro were 1.7, 4.7 and 9.6 pg TEQ/g, respectively. The dioxins concentration in all three regions of tuna was in direct proportion to the fat content. In the farmed bluefin tuna, the dioxins concentration was almost the same as that of the wild tuna, but differed from that of the farmed southern bluefin tuna. Average total mercury concentration based on wet weight in akami was 0.42 µg/g, being higher than the values of 0.36 µg/g of chutoro and 0.31 µg/g of otoro, and in inverse proportion to the fat content. In all three regions, the total mercury concentration of the wild bluefin tuna was equal to that of the farmed tuna. The total mercury concentration in the latter was two to three times higher than that of the farmed southern bluefin tuna. If the Japanese intake is one fin of tuna (80 g) a day, the daily intake levels of dioxins and methyl mercury can be estimated as 0.48-37 pg TEQ/kg bw and 0.21-0.90 µg/kg bw, respectively.

Intrafractional gastric motion and interfractional stomach deformity during radiation therapy.

BACKGROUND AND PURPOSE: To evaluate intrafractional gastric motion and interfractional variability of the stomach shape during radiation therapy (RT) for gastric lymphoma. MATERIALS AND METHODS: For 11 patients with gastric lymphomas, we undertook fluoroscopic examinations at the time of the simulation, and once a week during RT to evaluate inter- and intrafractional gastric variations. We recorded anteroposterior and left to right X-ray images at inhale and exhale in each examination. We gave coordinates based on the bony landmarks in each patient, and identified the most superior, inferior, lateral, ventral, and dorsal points of the stomach on each film. The interfractional motion was assessed as the distance between a point at inhale and the corresponding point at exhale. We also analyzed interfractional variation based on each point measured. RESULTS: The intrafractional gastric motion was 11.7+/-8.3, 11.0+/-7.1, 6.5+/-6.5, 3.4+/-2.3, 7.1+/-8.2, 6.6+/-5.8mm (mean+/-SD) for the superior, inferior, right, left, ventral and dorsal points, respectively, which was significantly different between each point. The interfractional variability of stomach filling was -2.9+/-14.4, -6.0+/-13.4, 9.3+/-22.0mm for the superior-inferior (SI), lateral (LAT), and ventro-dorsal (VD) directions, respectively, and the differences of variabilities were also statistically significant. Thus, the appropriate treatment margins calculated from both systematic and random errors are 30.3, 41.0, and 50.8mm for the SI, LAT, and ventro-dorsal directions, respectively. CONCLUSIONS: Both intrafractional gastric motion and interfractional variability of the stomach shape were considerable during RT. We recommend regular verification of gastric movement and shape before and during RT to individualize treatment volume.

Postoperative radiotherapy for non-small-cell lung cancer: results of the 1999-2001 patterns of care study nationwide process survey in Japan.

To investigate the practice process of postoperative radiation therapy for non-small-cell lung cancer (NSCLC) in Japan. Between April 2002 and March 2004, the Patterns of Care Study conducted an extramural audit survey for 76 of 556 institutions using a stratified two-stage cluster sampling. Data on treatment process of 627 patients with NSCLC who received radiation therapy were collected. Ninety-nine (16%) patients received postoperative radiation therapy between 1999 and 2001 (median age, 65 years). Pathological stage was stage I in 8%, II in 17%, IIIA in 44%, and IIIB in 20%. The median field size was 9 cmx11 cm, and median total dose was 50 Gy. Photon energies of 6 MV or higher were used for 64 patients, whereas a cobalt-60 unit was used for five patients. Three-dimensional conformal treatment was used infrequently. Institutional stratification influenced several radiotherapy parameters such as photon energy and planning target volume. Smaller non-academic institutions provided worse quality of care. The study confirmed continuing variation in the practice of radiotherapy according to stratified institutions. Outdated equipment such as Cobalt-60 units was used, especially in non-academic institutions treating only a small number of patients per year.

Repair of potentially lethal damage in normal cells and ataxia telangiectasia cells; consideration of non-homologous end-joining.

When cell lines are held in a quiescent state after irradiation, survival rates are greater than those from cells that are stimulated to grow immediately after irradiation. These differences in survival rates correspond to rates of potentially lethal damage repair. The effects of confluent holding recovery after gamma-irradiation were investigated using normal human fibroblasts (AG1522) and ataxia telangiectasia fibroblasts (GM02052). Calyculin-A-induced premature chromosome condensation and fluorescent in situ hybridization were applied to study G2/M chromosomal aberrations. Survival results indicated normal capacity for PLDR in AG1522 cells but that PLDR was extremely compromised in GM02052 cells. The chromosomal aberration frequency decreased when AG1522 cells were allowed to repair for 24-h, whereas 24-hour incubation had little effect on the aberration frequency in GM02052 cells. Since the main mechanism for dsbs repair during G0/G1 phases of the cells cycle involve the non-homologous end-joining (NHEJ) process, our study indicates that for AG1522 cells the NHEJ repair process is more likely to induce accurate chromosome repair under quiescent G0 conditions than proliferating G1 phase, while in GM02052 cells the fidelity of NHEJ is similarly defective at either cell cycle phase. Reduced fidelity of NHEJ may be responsible for PLDR defect and its hyper-radiosensitivity in A-T cells.

Phase I study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer.

PURPOSE: The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. METHODS AND MATERIALS: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m(2)/day. RESULTS: Sixteen patients were enrolled in this study. Three patients received S-1 at 60 mg/m(2)/day, 3 at 70 mg/m(2)/day, and 10 at 80 mg/m(2)/day. Though 1 patient at the final dose level (80 mg/m(2)/day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively. CONCLUSIONS: The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m(2)/day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated.

A case of gastric lymphoma with marked interfractional gastric movement during radiation therapy.

Radiation therapy (RT) with or without chemotherapy has been a widely accepted treatment for patients with localized gastric lymphoma. We encountered a patient with gastric diffuse large B-cell lymphoma, whose stomach volume, and the position and location of the clips that had been endoscopically placed to define the gastric lesions clearly differed considerably at three simulation times. The positions of the clips moved between 5 and 35 mm (mean 24 mm) laterally on simulation films. The mean movement of these clips along the cephalocaudal directions was 8 mm (range 0-15 mm). There have been no published articles which systemically evaluated interfractional gastric motion between each treatment session. Therefore this is an important observation in the management of patients with gastric lymphoma with RT.

Dose-volume factors predicting radiation pneumonitis in patients receiving salvage radiotherapy for postlobectomy locoregional recurrent non-small-cell lung cancer.

BACKGROUND: The correlation between treatment-related factors and lung toxicity has not been sufficiently evaluated in salvage radiotherapy. METHODS: Twenty-one patients with recurrent non-small-cell lung cancer (NSCLC) after lobectomy received salvage radiotherapy to a total dose of 46-60 Gy. The effects of radiotherapy parameters on the development of radiation pneumonitis (RP) were examined using dose-volume histograms. RESULTS: Grade 1 RP was observed in 4, grade 2 in 2, and grade 3 in 1 patient. Patients who developed RP had a significantly higher value in V dose (V13, V20) parameters and mean lung dose (MLD) than those who did not develop RP. Concerning G2 or higher RP, 3 patients who developed > or = G2 RP had a significantly higher value in V20, V13, and MLD than the remaining patients with P values of 0.01, 0.015, and 0.016, respectively. The mean V20, V13, and MLD in these 3 patients were 27%, 29.3%, and 14.8 Gy, respectively, whereas the mean V20, V13, and MLD in the remaining 18 patients were 15.8%, 18.3%, and 8.8 Gy, respectively. Three of 6 patients with a V20 > or = 20% developed > or = G2 RP whereas this did not occur in the remaining patients (P = 0.015). Similarly, 3 of 6 patients with a V13 > or = 23% developed > or = G2 RP whereas this did not occur in the remaining patients (P = 0.015). CONCLUSIONS: These data suggest that a somewhat lower V dose value or MLD, as compared with the setting of definitive radiotherapy, could be a surrogate for RP in patients undergoing salvage radiotherapy for recurrent NSCLC.

Extranodal natural killer/T-cell lymphoma, nasal type: the significance of radiotherapeutic parameters.

BACKGROUND: The objective of this study was to investigate the correlation between local recurrence and radiotherapeutic parameters, including dose and RT radiotherapy (RT) field. METHODS: The current study included 35 patients who were diagnosed with immunohistochemically confirmed nasal natural killer (NK)/T-cell lymphoma between 1976 and 2004. There were 21 males and 14 females, and they ranged in age from 18 years to 76 years (median, 51 yrs). The primary tumor originated in the nasal cavity in 28 patients, and 32 patients had Stage I disease. Seventeen patients received treatment solely with RT, and the remaining 18 patients received a combination of chemotherapy and RT. The median tumor dose was 50 grays (Gy) (range, 22-60 Gy). Twenty-seven patients received RT to include all macroscopic lesions, all paranasal sinuses, the palate, and the nasopharynx. Eight patients received RT to all macroscopic lesions with generous margins. RESULTS: A complete remission (CR) or a CR/unconfirmed was achieved in 28 patients (80%). The 5-year overall survival (OAS) rate, disease-free survival (DFS) rate, and local control probability (LCP) were 47.3%, 42.9%, and 65.2%, respectively. Patients who received RT only to macroscopic lesions fared less well in terms of LCP (LCP 5 years, 71.9% vs. 41.7%; P=0.007). The difference in RT field also affected both the OAS rate and the DFS rate. Patients who received RT doses>or=50 Gy tended to achieve favorable local control. CONCLUSIONS: In the management of nasal NK/T-cell lymphoma, the RT field affected treatment outcomes. RT doses>or=50 Gy resulted in favorable local control.

Preoperative chemotherapy and radiation therapy for squamous cell carcinoma of the maxillary sinus.

OBJECTIVE: This study was undertaken to assess the prognostic factors for the management of squamous cell carcinoma (SCC) of the maxillary sinus, who received preoperative chemotherapy and radiation therapy (RT). We also elucidated the appropriate sequence of chemotherapy. METHODS: A total of 124 patients (median age 62 years) with SCC of the maxillary sinus were analysed retrospectively. T3 or T4 disease was found in 93% of the patients. Thirty-nine patients received neoadjuvant chemotherapy (NA), 38 patients received concurrent chemoradiotherapy (CRT) and 47 patients received NA followed by CRT. The median dose of RT was 60 Gy. Maxillectomy was undertaken in 98 patients. RESULTS: The 5 year overall survival (OAS) and local control probability (LCP) were 56.6 and 73.7%, respectively. On univariate analysis, surgery (P < 0.0001) and T classification (P < 0.04) were significant prognostic factors for OAS and LCP. Histological grade and nodal status were also related to OAS. However, any chemotherapy sequence was not associated with the treatment outcome. On multivariate analysis, surgery (P < 0.0005) and T classification (P < 0.05) were identified as significant prognostic factors for LCP and OAS. CONCLUSIONS: This study suggests that both surgery and T stage are important prognostic factors for LCP and OAS in the management of SCC of the maxillary sinus. The appropriate sequence of chemotherapy remains to be elucidated in the future study.

Toxicities and effects of involved-field irradiation with concurrent cisplatin for unresectable carcinoma of the pancreas.

PURPOSE: To evaluate local effects and acute toxicities of involved field irradiation with concurrent cisplatin (CDDP) for unresectable pancreatic carcinoma. MATERIALS AND METHODS: Thirty-three patients with unresectable pancreatic carcinoma were treated with chemoradiotherapy. Sixteen were Stage IVA; 17 were Stage IVB. The total prescribed dose of radiotherapy was 50 Gy/25 fractions or 50.4 Gy/28 fractions, using a three-dimensionally determined involved-field that included only the primary tumor and clinically enlarged lymph nodes. Twelve patients received a daily i.v. infusion of CDDP; 21 patients received a combination of CDDP and 5-fluorouracil either i.v. or through the proper hepatic artery. RESULTS: Twenty-seven (82%) patients completed planned chemoradiotherapy. Nausea was the most frequent complaint. No patient experienced Grade 4 toxicities. More than half achieved pain relief. As for the primary site, only 4 patients (12%) achieved a partial response at 4 weeks; however, 3 additional patients attained >50% tumor reduction thereafter. The most frequent site of disease progression was the liver, and only 3 patients developed local progression alone. No regional lymph nodal progression outside the treatment field was seen. Median survival time and survival at 1 year were 7.1 months and 27%, respectively, for the entire group. Difference in overall survival between patients with and without distant metastases was significant (p = 0.01). CONCLUSIONS: Involved-field irradiation with concurrent daily CDDP was well tolerated without compromising locoregional effects.

Weekly cisplatin administration concurrent with radiation therapy for locoregionally advanced nasopharyngeal carcinoma.

Radiation therapy (RT) with concurrent and adjuvant chemotherapy has been a widely accepted treatment for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). We administered 40 mg/m2 cisplatin (CDDP) weekly, concurrently with RT, to six consecutive patients with locoregionally advanced NPC to evaluate its toxicity and efficacy. The median number of courses of CDDP administration was 4.5 and the median radiation dose was 69.7 Gy. Grade 3 leukopenia was observed in three patients. All but one patient experienced grade 3 or 4 skin reactions, pharyngitis, or dysphagia. All but one patient achieved a complete response, and the remaining patient received radical neck dissection for persistent cervical lymphadenopathies, which contained no cancer cells. All six patients were disease-free at last contact, with a median follow up of 23.5 months. This regimen is well tolerated in patients with locoregionally advanced NPC.

[Determination of isophorone in foods].

Isophorone (ISP) is used widely as a solvent of natural and synthetic resins, wax, printing ink, pesticides and paints. In this study, the level of ISP in various foods (93 samples) was analyzed. ISP was collected from samples by steam distillation after the addition of an internal standard, deuterium-labeled ISP, then extracted with dichloromethane, cleaned up on a silica gel column, and determined by GC/MS. ISP was barely detected in fish, meat and vegetable samples, but it was detected in rice, wheat, beans and their processed products, miso, soy sauce and fermented soybeans (natto). The maximum level was 8.9 ng/g in miso. The packaging materials of the foods contained little ISP, and so the source of ISP in the foods could not be clarified.

Hyperfractionated radiation therapy for locoregionally advanced nasopharyngeal cancer.

OBJECTIVE: The purpose of this study is to clarify the efficacy and toxicity of hyperfractionated radiation therapy (RT) for patients with nasopharyngeal cancer (NPC). METHODS: Twenty-two patients with NPC treated at our hospital between April 1994 and December 2002 were the subjects of this study. They received hyperfractionated RT with a fraction size of 1.2 Gy, with a median tumor dose of 72 Gy (range 64.8-80.4). During this study period, our institutional strategy for locoregionally advanced NPC included neoadjuvant or concurrent chemotherapy combined with hyperfractionated RT, and 17 patients received some forms of cisplatin-containing chemotherapy. RESULTS: With a median follow-up of 59 months, the estimated 5-year disease-free survival rate and overall survival rate were 72.7 and 85.2%, respectively. Acute hematological toxicities were acceptable and manageable. However, >50% of patients required nutritional support, and experienced severe pharyngitis, skin reaction and body weight loss. With regard to late sequelae, one patient developed grade 3 osteomyelitis, and one patient each developed grade 4 passage disturbance and laryngeal edema. No patients experienced any grades of optic nerve injury or temporal lobe necrosis. CONCLUSIONS: Hyperfractionated RT using 1.2 Gy per fraction, for a total dose of 72 Gy, produces a comparable treatment outcome. Although deleterious neurological sequelae were not observed in this study, caution should be exercised regarding other late sequelae, such as osteomyelitis and passage disturbance.

Efficacy and toxicities of concurrent chemoradiation for elderly patients with esophageal cancer.

BACKGROUND: To evaluate the efficacy and toxicity of concurrent chemoradiation in patients with esophageal cancer aged 75 and older. PATIENTS AND METHODS: Twenty-two elderly patients were treated with concurrent chemoradiation. Seventeen received a combination of cisplatin/carboplatin and 5-fluorouracil, 5 received daily 5-fluorouracil. Total doses of radiotherapy ranged from 50 to 65 Gy. RESULTS: Nineteen out of 22 patients completed the planned chemoradiation. Five in 8 patients (63%) with T1-2 lesion and 1 in 14 patients (7o%) with T3-4 lesion achieved complete response (p=0.011). Only 2 patients experienced grade 3 toxicities. Grade 2 or worse hematological toxicities were less frequently observed in patients who received local-field radiotherapy (p=0.006). There was no isolated lymph node recurrence. The median survival time was 9 months. CONCLUSION: This study showed the potential for chemoradiation in elderly patients. A planning target volume of radiotherapy should include only clinically involved lesions in this setting.

Radiation therapy for idiopathic orbital myositis: two case reports and literature review.

We report two cases of idiopathic orbital myositis treated with radiation therapy (RT). Both patients visited our hospital with complaints of orbital pain on eye movement and eyelid swelling. There was no history of thyroid disease or trauma, and no signs of infection, neoplasm, or collagen disease. The laboratory investigations, including a thyroid function test, showed no abnormalities in either woman. They were initially treated with a combination of corticosteroids (CS) and nonsteroidal anti-inflammatory drugs (NSAIDs), however, they became dependent on or refractory to oral CS therapy, and received 20 Gy in 10 fractions of RT to the orbit. Their symptoms decreased immediately, and both patients were able to reduce the dosage of oral CS after RT. One patient could completely withdraw oral CS thereafter. However, they both experienced recurrence at eight months after RT, and have been receiving oral CS to control their symptoms. RT at doses of 20 Gy in 10 fractions for patients with idiopathic orbital myositis appears to be effective in palliating symptoms, but long-term control is not satisfactory.

A case of bronchiolitis obliterans organizing pneumonia syndrome with preceding radiation pneumonitis after breast-conserving therapy.

Recent case series have demonstrated that bronchiolitis obliterans organizing pneumonia (BOOP) after radiation therapy to the breast is a distinct clinicopathological entity. Most of the investigators speculated that radiation may prime the development of BOOP through an unidentified immunological process; however, none of them showed the relationship between direct radiation injury and BOOP. We report herein a case of a 67-year-old female with BOOP following direct radiation damage confined to the irradiated area after breast-conserving therapy. This is the first case demonstrating that BOOP after breast-conserving therapy arises from direct radiation injury.