Curcumin effects on age-related changes in oral immunity: an in vivo study.

The current study aimed to investigate the effects of ageing on oral immunity using ß-defensin (DEFB) 1/2 as a marker and evaluate the effects of curcumin (CUR) on these processes. The study sample included thirty male C57BL/6J mice divided into three groups based on the treatment method used. The young control (YC) and old control (OC) groups received 0·5 % methylcellulose-400 (CUR vehicle) orally for 5 days, whereas the CUR group of older mice received a CUR solution suspended in 0·5 % methylcellulose-400 (dose: 3·0 mg/kg body). DEFB1/2 and immune indicator levels were measured in the saliva and salivary glands post-treatment. The saliva volume and protein content were significantly reduced in the OC group compared with the YC group. CUR administration restored these parameters, decreased DEFB1 expression in the salivary gland and increased DEFB1/2 secretion and DEFB2 expression. These findings were supported by epigenetic gene regulation and partial cytokine activation from changes in WD40 repeat protein 5, TNF alpha and IL-1beta. CUR can partially restore age-related changes in oral immune responses and promote oral health, thereby preventing frailty in the older population through a nutritional therapeutic pathway.

Association of Geriatric Nutritional Risk Index With Adverse Event and Treatment Duration in Adjuvant Chemotherapy for Patients With Colorectal Cancer.

BACKGROUND/AIM: In recent years, the Geriatric Nutritional Risk Index (GNRI) has been reported as a predictor of prognosis in many patients with cancer. This study investigated the association of preoperative GNRI with the occurrence of adverse events and duration of treatment with capecitabine plus oxaliplatin (CAPOX), a postoperative adjuvant chemotherapy, in 59 patients with colorectal cancer from September 2019 to April 2022. PATIENTS AND METHODS: A cut-off value of 100.9 was used to categorize patients into high and low GNRI groups. RESULTS: The incidence of grade ≥2 leukopenia (p=0.03), and all grades peripheral neuropathy (p=0.04) were significantly more frequent in the low GNRI group. Analysis of factors influencing treatment duration by univariate and multivariate Cox regression proportional hazards models showed a significant difference in GNRI (p=0.0097). CONCLUSION: GNRI, a nutritional indicator assessed before the start of treatment, influences the occurrence of adverse events and duration of treatment with CAPOX as adjuvant chemotherapy. To complete CAPOX therapy, preoperatively, it is important to assess the patients' nutritional status using the GNRI and to actively intervene in nutritional therapy.

The 1-year continuation rate and discontinuation factors of vibegron and mirabegron: A retrospective comparative study in a rehabilitation hospital in Japan.

OBJECTIVES: To compare the 1-year continuation rate and discontinuation factors between vibegron and mirabegron in patients with neurogenic and nonneurogenic overactive bladder. METHODS: Continuation or discontinuation of the target drugs and reasons for discontinuation as well as patients' grounds and adverse effects were evaluated retrospectively from the medical records between September 2018 and December 2020. After selecting patients according to the inclusion and exclusion criteria, 180 cases taking mirabegron and 132 taking vibegron were adjusted for intergroup variability by propensity score matching. We performed Cox proportional hazards regression for the 1-year continuation rate and Fine-Gray proportional hazards regression for the 1-year cumulative incidence of discontinuation events. Subgroup analysis was also performed for the background factors related to the 1-year continuation rate. RESULTS: The 1-year continuation rate was 83.8% for vibegron and 58.2% for mirabegron, and the hazard ratio was 0.32 (95% CI: 0.18-0.57, P < .001) as for an incidence of discontinuation events of vibegron against mirabegron. The incidence of discontinuation due to an inadequate efficacy was 8.7% for vibegron and 29.1% for mirabegron, and similarly the hazard ratio was 0.26 (95% CI: 0.12-0.55, P < .001). The subgroup analysis indicated a similar tendency in each subgroup except for that of catheterization, and there was no significant interaction between the groups. CONCLUSIONS: It is suggested that vibegron is superior to mirabegron in the continuity of administration in neurogenic and nonneurogenic overactive bladder populations without catheterization with fewer discontinuations due to inadequate efficacy.

Risk prediction for new-onset atrial fibrillation using the Minnesota code electrocardiography classification system.

BACKGROUND: Few risk models are available to predict future onset of atrial fibrillation (AF) in workers. We aimed to develop risk prediction models for new-onset AF, using annual health checkup (HC) data with electrocardiogram findings. METHODS AND RESULTS: We retrospectively included 56,288 factory or office workers (mean age = 51.5 years, 33.0% women) who underwent a HC at a medical center and fulfilled the following criteria; age ≥ 40 years, no history of AF, and greater than 1 annual follow-up HC in 2013-2016. Using Cox models with the Akaike information criterion, we developed and compared prediction models for new-onset AF with and without the Minnesota code information. We externally validated the discrimination accuracy of the models in a general Japanese population cohort, the Hisayama cohort. During the median 3.0-year follow-up, 209 (0.37%) workers developed AF. Age, sex, waist circumference, blood pressure, LDL cholesterol, and γ-GTP were associated with new-onset of AF. Using the Minnesota code information, the AUC significantly improved from 0.82 to 0.84 in the derivation cohort and numerically improved from 0.78 to 0.79 in the validation cohort, and from 0.77 to 0.79 in the Hisayama cohort. The NRI and IDI significantly improved in all and male subjects in both the derivation and validation cohorts, and in female subjects in both the validation and the Hisayama cohorts. CONCLUSIONS: We developed useful risk model with Minnesota code information for predicting new-onset AF from large worker population validated in the original and external cohorts, although study interpretation is limited by small improvement of AUC.

Stereotactic body radiotherapy in patients with lung tumors composed of mainly ground-glass opacity.

We retrospectively reviewed the effect of stereotactic body radiation therapy (SBRT) in patients with stage I lung cancer whose lung tumor showed a nodular appearance of ground glass opacity, so-called ground glass nodule (GGN). A total of 84 patients (42 men, 42 women; mean age, 75 years) with stage I lung cancer with GGN accompanying a solid component <50% in diameter of the tumor and no metastases were studied. Concerning histology, 32 tumors were adenocarcinoma, 1 was squamous cell carcinoma, 2 were unclassified carcinoma and 49 cases were histology-unproven but increased in size or had a positive finding in 18F-FDG positron emission tomography (PET) examination. The median tumor size was 20 mm (range, 10-41 mm). All of the patients were treated with SBRT, and the total prescribed dose at the isocenter ranged between 48 Gy in four fractions and 84 Gy in ten fractions. Median follow-up duration was 33 months. No patient had local failure nor regional lymph node failure. The 3-year rate of distant failure was 2.6%. Two patients who experienced distant metastases had a past surgical history of initial lung cancer before SBRT. The rates of cause-specific and overall survival at 3 years were 98.2 and 94.6%, respectively. Treatment-related adverse events of ≥grade 4 were not reported. Although more cases and longer follow-ups are mandatory, SBRT may be one of the radical treatment options for patients with GGN.

ß-Lactamase-non-producing ampicillin-resistant Haemophilus influenzae is acquiring multidrug resistance.

BACKGROUND: Haemophilus influenzae strains with reduced susceptibilities to antimicrobial agents have emerged in Japan. Here, we aimed to investigate H. influenzae non-susceptibility to ß-lactams and non-ß-lactams. METHODS: A total of 260 H. influenzae isolates from patients in 2013-2016 were analysed. Antimicrobial susceptibilities were assessed by determining the minimum inhibitory concentration. Additionally, isolates with reduced susceptibility were analysed by both genetic and statistical methods. RESULTS: ß-Lactamase-non-producing ampicillin-resistant H. influenzae (BLNAR) strains increased significantly and accounted for more than 50% of all isolates from 2014. Additionally, the proportion of quinolone-low-susceptibility isolates increased significantly (P<0.05). Among these, three quinolone-non-susceptible isolates showed minimum inhibitory concentrations higher than the susceptibility breakpoint of levofloxacin. Moreover, one of the three isolates showing multidrug resistance was resistant to macrolides, ß-lactams, and quinolones. Low susceptibilities to non-ß-lactams were significantly associated with BLNAR. CONCLUSIONS: The present study indicates that BLNAR strains are increasing and tend to show multidrug resistance. Additionally, multidrug-resistant H. influenzae (MDRHI) has emerged. To prevent the further spread of MDRHI, the proportions of BLNAR strains should be evaluated.

Anomalous Change in the de Haas-van Alphen Oscillations of CeCoIn_{5} at Ultralow Temperatures.

We perform de Haas-van Alphen (dHvA) measurements of the heavy-fermion superconductor CeCoIn_{5} down to 2 mK above the upper critical field. We find that the dHvA amplitudes show an anomalous suppression, concomitantly with a shift of the dHvA frequency, below the transition temperature T_{n}=20 mK. We suggest that the change is owing to magnetic breakdown caused by a field-induced antiferromagnetic (AFM) state emerging below T_{n}, revealing the origin of the field-induced quantum critical point (QCP) in CeCoIn_{5}. The field dependence of T_{n} is found to be very weak for 7-10 T, implying that an enhancement of AFM order by suppressing the critical spin fluctuations near the AFM QCP competes with the field suppression effect on the AFM phase. We suggest that the appearance of a field-induced AFM phase is a generic feature of unconventional superconductors, which emerge near an AFM QCP, including CeCoIn_{5}, CeRhIn_{5}, and high-T_{c} cuprates.

Suturing repair of subtotal iridodialysis.

PURPOSE: To report a case of subtotal iridodialysis that was repaired using suturing with the assistance of a guide needle. PATIENT AND METHODS: A 52-year-old man had subtotal iridodialysis of approximately 300° with massive hyphema and vitreous hemorrhage after blunt trauma. The patient was treated with pars plana vitrectomy, and then suturing repair of iridodialysis was performed. RESULTS: After the surgeries, the ratio of pupil area to corneal area is improved from 82.1 to 42.4%. The visual acuity improved to 30/20, and subjective symptoms of glare and monocular diplopia disappeared. There was no remarkable postoperative complication for up to 12 months. CONCLUSIONS: Suturing repair is useful for subtotal iridodialysis and may be an alternative for an iris implant.

Remnant extraction by using an intraocular lens injector with essential flow.

PURPOSE: To describe a new technique for remnant removal in cases of posterior capsular rupture during cataract surgery and Soemmering ring extraction during intraocular lens (IOL) removal. METHODS: An IOL injector, inserted into the anterior chamber, provides a new exit for residual lens fragments. Passive fluid flow, supplied by an anterior chamber maintainer or some ocular viscoelastic device (OVD) injection, delivers the residual fragments into a lumen of the injector in assistance with a second device such as a phaco-chopper and vitreous cutter. RESULTS: Soemmering rings can be removed safely through small incisions even when under the iris. Nucleus fragments in anterior chamber can be removed safely. Fragments that fall into the vitreous cavity can float up for removal by passive flow. CONCLUSIONS: This new technique, remnant extraction through lens injector with essential flow, has several practical advantages over existing methods including reduced OVD injection and smaller incision size. It may offer an alternative to existing methods of remnant removal in cases of posterior capsular rupture during cataract surgery and Soemmering ring extraction.

Long-term results of chemoradiotherapy for stage II-III thoracic esophageal cancer in a single institution after 2000 -with a focus on comparison of three protocols.

BACKGROUND: To evaluate the long-term results of chemoradiotherapy (CRT) for stage II-III thoracic esophageal cancer mainly by comparing results of three protocols retrospectively. METHODS: Between 2000 and 2012, 298 patients with stage II-III thoracic esophageal cancer underwent CRT. Patients in Group A received two cycles of cisplatin (CDDP) at 70 mg/m(2) (day 1 and 29) and 5-fluorouracil (5-FU) at 700 mg/m(2)/24 h (day 1-4 and 29-32) with radiotherapy (RT) of 60 Gy without a break. Patients in Group B received two cycles of CDDP at 40 mg/m(2) (day 1, 8, 36 and 43) and 5-FU at 400 mg/m(2)/24 h (day 1-5, 8-12, 36-40 and 43-47) with RT of 60 Gy with a 2-week break. Patients in Group C received two cycles of nedaplatin at 70 mg/m(2) (day 1 and 29) and 5-FU at 500 mg/m(2)/24 h (day 1-4 and 29-32) with RT of 60-70 Gy without a break. Differences in prognostic factors between the groups were analyzed by univariate and multivariate analyses. RESULTS: The 5-year overall survival rates for patients in Group A, Group B and Group C were 52.4, 45.2 and 37.2%, respectively. The 5-year overall survival rates for patients in Stage II, Stage III (non-T4) and Stage III (T4) were 64.0, 40.1 and 22.5%, respectively. The 5-year overall survival rates for patients who received 1 cycle and 2 cycles of concomitant chemotherapy were 27.9 and 46.0%, respectively. In univariate analysis, stage, performance status and number of concomitant chemotherapy cycles were significant prognostic factors (p < 0.001, p = 0.008 and p < 0.001, respectively). In multivariate analysis, stage, protocol and number of concomitant chemotherapy cycles were significant factors (p < 0.001, p = 0.043 and p < 0.001, respectively). CONCLUSIONS: The protocol used in Group A may be an effective protocol of CRT for esophageal cancer. It may be important to complete the scheduled concomitant chemotherapy with the appropriate intensity of CRT.

Treatment outcomes of patients with FIGO Stage I/II uterine cervical cancer treated with definitive radiotherapy: a multi-institutional retrospective research study.

The purpose of this study was to analyze the patterns of care and outcomes of patients with FIGO Stage I/II cervical cancer who underwent definitive radiotherapy (RT) at multiple Japanese institutions. The Japanese Radiation Oncology Study Group (JROSG) performed a questionnaire-based survey of their cervical cancer patients who were treated with definitive RT between January 2000 and December 2005. A total of 667 patients were entered in this study. Although half of the patients were considered suitable for definitive RT based on the clinical features of the tumor, about one-third of the patients were prescribed RT instead of surgery because of poor medical status. The RT schedule most frequently utilized was whole-pelvic field irradiation (WP) of 30 Gy/15 fractions followed by WP with midline block of 20 Gy/10 fractions, and high-dose-rate intracavitary brachytherapy (HDR-ICBT) of 24 Gy/4 fractions prescribed at point A. Chemotherapy was administered to 306 patients (46%). The most frequent regimen contained cisplatin (CDDP). The median follow-up time for all patients was 65 months (range, 2-135 months). The 5-year overall survival (OS), pelvic control (PC) and disease-free survival (DFS) rates for all patients were 78%, 90% and 69%, respectively. Tumor diameter and nodal status were significant prognostic indicators for OS, PC and DFS. Chemotherapy has potential for improving the OS and DFS of patients with bulky tumors, but not for non-bulky tumors. This study found that definitive RT for patients with Stage I/II cervical cancer achieved good survival outcomes.

Inhibitory effect of black tea and its combination with acarbose on small intestinal α-glucosidase activity.

ETHNOPHARMACOLOGICAL RELEVANCE: It is said that black tea is effective against type 2 diabetes mellitus because it can help modulate postprandial hyperglycemia. However, the mechanism underlying its therapeutic and preventive effects on type 2 diabetes mellitus is unclear. In this study, we focused on the effect of black tea on the carbohydrate digestion and absorption process in the gastrointestinal tract. We examined whether black tea can modulate postprandial hyperglycemia. MATERIALS AND METHODS: The freeze-dried powder of the aqueous extract of black tea leaves (JAT) was used for in vitro studies of α-amylase activity, α-glucosidase activity, and glucose uptake by glucose transporters in Caco-2 cells; ex vivo studies of small intestinal α-glucosidase activity; and in vivo studies of oral sugar tolerance in GK rats, an animal model of nonobese type 2 diabetes mellitus. RESULTS: Half maximal inhibitory concentration values indicated that JAT significantly reduced α-glucosidase activity, but weakly reduced α-amylase activity. Kinetic studies of rat small intestinal α-glucosidase activity revealed that the combination of JAT and the α-glucosidase inhibitor, acarbose, showed a mixed-type inhibition. JAT had no effect on the uptake of 2'-deoxy-d-glucose by glucose transporter 2 (GLUT2) and the uptake of α-methyl-d-glucose by sodium-dependent glucose transporter 1 (SGLT1). In the oral sucrose tolerance test in GK rats, JAT reduced plasma glucose levels in a dose-dependent manner compared with the control group. The hypoglycemic action of JAT was also confirmed: JAT, in combination with acarbose, produced a synergistic inhibitory effect on plasma glucose levels in vivo. In contrast to the oral sucrose tolerance test, JAT showed no effect in the oral glucose tolerance test. CONCLUSIONS: JAT was demonstrated to inhibit the degradation of disaccharides into monosaccharides by α-glucosidase in the small intestine. Thereby indirectly preventing the absorption of the dietary source of glucose mediated by SGLT1 and GLUT2 transporters localized at the apical side of enterocytes in the small intestine. The results indicate that black tea could be useful as a functional food in the dietary therapy for borderline type 2 diabetes mellitus that could modulate postprandial hyperglycemia.

Evaluation of radiation-induced myocardial damage using iodine-123 ß-methyl-iodophenyl pentadecanoic acid scintigraphy.

We evaluated radiation-induced myocardial damage using iodine-123 ß-methyl-iodophenyl pentadecanoic acid (I-123 BMIPP) scintigraphy. Between May 2010 and April 2011 we performed I-123 BMIPP scintigraphy for patients who had maintained complete response to curative radiotherapy (RT) for esophageal cancer for more than six months. We compared the area of the myocardium in the RT fields with that of reduced I-123 BMIPP uptake using a 15-segment model that is based on axial computed tomography (CT) images. We classified the segments into three categories: segments receiving 40 Gy (Segment 40 Gy), segments receiving 60 Gy (Segment 60 Gy) and segments out of the radiation fields (Segment 0 Gy). A segment with reduced uptake in the RT fields was defined as positive. A total of 510 segments in 34 patients were used for analysis. The median interval from completion of RT to I-123 BMIPP scintigraphy was 22 months (range, 6-103 months). The numbers of Segment 0 Gy, Segment 40 Gy and Segment 60 Gy were 324, 133 and 53, respectively. Reduced uptake was detected in 42.9% (57/133) of Segment 40 Gy, 67.9% (36/53) of Segment 60 Gy and 13.3% (43/324) of Segment 0 Gy. The odds ratios of 40 Gy and 60 Gy compared with regions out of the RT fields were 5.2 (95% confidence interval [CI]: 3.7-7.4) and 15.4 (95% CI: 6.9-34.6), respectively. Reduced myocardial I-123 BMIPP uptake in RT fields, suggesting RT-induced myocardial damage, was frequently observed. I-123 BMIPP myocardial scintigraphy may be useful for identifying RT-induced myocardial damage.

Treatment outcome of high-dose image-guided intensity-modulated radiotherapy using intra-prostate fiducial markers for localized prostate cancer at a single institute in Japan.

BACKGROUND: Several studies have confirmed the advantages of delivering high doses of external beam radiotherapy to achieve optimal tumor-control outcomes in patients with localized prostate cancer. We evaluated the medium-term treatment outcome after high-dose, image-guided intensity-modulated radiotherapy (IMRT) using intra-prostate fiducial markers for clinically localized prostate cancer. METHODS: In total, 141 patients with localized prostate cancer treated with image-guided IMRT (76 Gy in 13 patients and 80 Gy in 128 patients) between 2003 and 2008 were enrolled in this study. The patients were classified according to the National Comprehensive Cancer Network-defined risk groups. Thirty-six intermediate-risk patients and 105 high-risk patients were included. Androgen-deprivation therapy was performed in 124 patients (88%) for a median of 11 months (range: 2-88 months). Prostate-specific antigen (PSA) relapse was defined according to the Phoenix-definition (i.e., an absolute nadir plus 2 ng/ml dated at the call). The 5-year actuarial PSA relapse-free survival, the 5-year distant metastasis-free survival, the 5-year cause-specific survival (CSS), the 5-year overall survival (OS) outcomes and the acute and late toxicities were analyzed. The toxicity data were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up was 60 months. RESULTS: The 5-year PSA relapse-free survival rates were 100% for the intermediate-risk patients and 82.2% for the high-risk patients; the 5-year actuarial distant metastasis-free survival rates were 100% and 95% for the intermediate- and high-risk patients, respectively; the 5-year CSS rates were 100% for both patient subsets; and the 5-year OS rates were 100% and 91.7% for the intermediate- and high-risk patients, respectively. The Gleason score (<8 vs. ≥ 8) was significant for the 5-year PSA relapse-free survival on multivariate analysis (p = 0.044). There was no grade 3 or 4 acute toxicity. The incidence of grade 2 acute gastrointestinal (GI) and genitourinary (GU) toxicities were 1.4% and 8.5%, respectively. The 5-year actuarial likelihood of late grade 2-3 GI and GU toxicities were 6% and 6.3%, respectively. No grade 4 GI or GU late toxicity was observed. CONCLUSIONS: These medium-term results demonstrate a good tolerance of high-dose image-guided IMRT. However, further follow-up is needed to confirm the long-term treatment outcomes.

Intraoperative radiotherapy for pancreatic cancer: 30-year experience in a single institution in Japan.

PURPOSE: To analyze retrospectively the results of intraoperative radiotherapy (IORT) with or without external beam radiotherapy (± EBRT) for localized pancreatic cancer in the past three decades and to analyze prognostic factors by multivariate analysis. METHODS AND MATERIALS: Records for 322 patients with pancreatic cancer treated by IORT ± EBRT in Tohoku University Hospital between 1980 and 2009 were reviewed. One hundred ninety-two patients who had no distant organ metastases or dissemination at the time of laparotomy were enrolled in the present study. RESULTS: Eighty-three patients underwent gross total resection (R0: 48 patients, R1: 35 patients), and 109 patients underwent only biopsy or palliative resection. Fifty-five patients underwent adjuvant EBRT, and 124 underwent adjuvant chemotherapy. The median doses of IORT and EBRT were 25 and 40 Gy, respectively. The median follow-up period was 37.5 months. At the time of the analysis, 166 patients had disease recurrence, and 35 patients had local failure. The 2-year local control (LC) and overall survival (OS) rates were 71.0% and 16.9%, respectively. Comparison of the results for each decade showed that OS was significantly improved decade by decade (2-year: 25.0% vs. 18.8% vs. 4.2%, p < 0.001). Multivariate analysis showed that degree of resection (R0-1 vs. R2, hazard ratio = 1.97, p = 0.001) and adjuvant chemotherapy (yes vs. no, hazard ratio = 1.54, p = 0.028) had significant impacts on OS. Late gastrointestinal morbidity of Common Terminology Criteria for Adverse Events version 3.0 grade 4 or 5 was observed in four patients. CONCLUSION: Excellent local control for pancreatic cancer with few cases of severe late toxicity was achieved by using IORT. OS of patients with pancreatic cancer treated by IORT ± EBRT improved significantly decade by decade. Multivariate analysis showed that degree of resection and adjuvant chemotherapy had significant impacts on OS.

Long-term results of radiochemotherapy for solitary lymph node metastasis after curative resection of esophageal cancer.

PURPOSE: To evaluate the long-term efficacy and toxicity of definitive radiochemotherapy for solitary lymph node metastasis after curative surgery of esophageal cancer. METHODS AND MATERIALS: We performed a retrospective review of 35 patients who underwent definitive radiochemotherapy at Tohoku University Hospital between 2000 and 2009 for solitary lymph node metastasis after curative esophagectomy with lymph node dissection for esophageal cancer. Radiotherapy doses ranged from 60 to 66 Gy (median, 60 Gy). Concurrent chemotherapy was platinum based in all patients. The endpoints of the present study were overall survival, cause-specific survival, progression-free survival, irradiated-field control, overall tumor response, and prognostic factors. RESULTS: The median observation period for survivors was 70.0 months. The 5-year overall survival was 39.2% (median survival, 39.0 months). The 5-year cause-specific survival, progression-free survival, and irradiated-field control were 43.3%, 31.0% and 59.9%, respectively. Metastatic lesion, size of the metastatic lymph node, and performance status before radiochemotherapy were significantly correlated with prognosis. Complete response and partial response were observed in 22.9% and 57.1% of the patients, respectively. There was no Grade 3 or higher adverse effect based on the Common Terminology Criteria for Adverse Events (CTCAE v3.0) in the late phase. CONCLUSIONS: Based on our study findings, approximately 40% of patients with solitary lymph node metastasis after curative resection for esophageal cancer have a chance of long-term survival with definitive radiochemotherapy.

Carbon ion radiation therapy improves the prognosis of unresectable adult bone and soft-tissue sarcoma of the head and neck.

PURPOSE: To evaluate the safety and efficacy of carbon ion radiotherapy (C-ion RT) with 70.4 GyE for unresectable bone and soft-tissue sarcoma of the adult head and neck. METHODS AND MATERIALS: Twenty-seven patients (mean age, 46.2 years) were enrolled in this prospective study on C-ion RT with 70.4 GyE/16 fractions (fr) between April 2001 and February 2008. The primary end points were acute and late reactions of normal tissues, local control rate, and overall survival rate. The secondary end point was efficacy of the treatment in comparison to historical results with 57.6 or 64.0 GyE/16 fr. RESULTS: The 3-year local control rate and overall survival rate for all patients were 91.8% (95% confidence interval [CI] = 81.0-100%) and 74.1% (95% CI = 57.5-90.6%), respectively. Acute reaction of Grade 3 or more was observed in only 1 patient. With regard to late reactions, visual loss was observed in 1 patient and a Grade 3 reaction of the maxillary bone was observed in 4 patients. A comparison with historical results revealed that the local control rate with 70.4 GyE was significantly higher than that with 57.6 or 64.0 GyE (3-year, 91.8% vs. 23.6%, p < 0.0001). Furthermore, the overall survival with 70.4 GyE tended to be higher than that with 57.6 or 64.0 GyE (3-year, 74.1% vs. 42.9%, p = 0.09). CONCLUSION: C-ion RT with 70.4 GyE/16 fr for bone and soft-tissue sarcoma of the adult head and neck appears to be effective with acceptable toxicities in comparison to conventional RT and C-ion RT with lower doses.

Impact of pathological tumor stage for salvage radiotherapy after radical prostatectomy in patients with prostate-specific antigen < 1.0 ng/ml.

BACKGROUND: To evaluate prognostic factors in salvage radiotherapy (RT) for patients with pre-RT prostate-specific antigen (PSA) < 1.0 ng/ml. METHODS: Between January 2000 and December 2009, 102 patients underwent salvage RT for biochemical failure after radical prostatectomy (RP). Re-failure of PSA after salvage RT was defined as a serum PSA value of 0.2 ng/ml or more above the postradiotherapy nadir followed by another higher value, a continued rise in serum PSA despite salvage RT, or initiation of systemic therapy after completion of salvage RT. Biochemical relapse-free survival (bRFS) was estimated using the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression model. RESULTS: The median follow-up period was 44 months (range, 11-103 months). Forty-three patients experienced PSA re-failure after salvage RT. The 4-year bRFS was 50.9% (95% confidence interval [95% CI]: 39.4-62.5%). In the log-rank test, pT3-4 (p < 0.001) and preoperative PSA (p = 0.037) were selected as significant factors. In multivariate analysis, only pT3-4 was a prognostic factor (hazard ratio: 3.512 [95% CI: 1.535-8.037], p = 0.001). The 4-year bRFS rates for pT1-2 and pT3-4 were 79.2% (95% CI: 66.0-92.3%) and 31.7% (95% CI: 17.0-46.4%), respectively. CONCLUSIONS: In patients who have received salvage RT after RP with PSA < 1.0 ng/ml, pT stage and preoperative PSA were prognostic factors of bRFS. In particular, pT3-4 had a high risk for biochemical recurrence after salvage RT.

Predicting the severity of acute urinary toxicity after brachytherapy with iodine-125 for localized prostate cancer.

Prostate cancer is one of the common cancers in the world. In Japan, prostate brachytherapy (PB) with iodine-125 has become a treatment option for localized prostate cancer since 2003. Nevertheless, severe acute urinary toxicity (AUT) remains as one of the intractable side effects. We assessed AUT and the changes in international prostate symptom score (IPSS) before and after PB for localized prostate cancer. IPSS is a questionnaire tool for tracking the subjective urinary symptoms. Between 2006 and 2009, 104 eligible patients underwent PB with iodine-125 were analyzed. AUT was graded with the radiation therapy oncology group (RTOG) scale. Eligible patients filled out IPSS questionnaires before and after PB. Clinical and treatment-related factors were examined for correlation with the severity of AUT and the interval to IPSS resolution. AUT of RTOG Grade 0 (no changes) and Grade 2 was detected in one and 96 patients, respectively, whereas seven patients (6.7%) experienced AUT of Grade 3. Thus, the incidence of severe AUT (Grade 3) after PB was low. A greater number of needles (p = 0.012) were associated with AUT of RTOG Grade 3 on the univariate analysis. The median interval to IPSS resolution was 6 months (7 ± 6 months). Greater post-implant maximal IPSS (p < 0.001) was associated with slower IPSS resolution, whereas higher pre-implant IPSS (p < 0.001) was associated with faster IPSS resolution on the multivariate analysis. In conclusion, reducing the number of needles in PB may be helpful for decreasing the rate of severe AUT.

Malignant mucosal melanoma treated with carbon ion radiotherapy with concurrent chemotherapy: prognostic value of pretreatment apparent diffusion coefficient (ADC).

BACKGROUND AND PURPOSE: To evaluate the potential of apparent diffusion coefficient (ADC) value before carbon ion radiotherapy (C-ion RT) for malignant mucosal melanoma (MMM) to predict prognosis. MATERIALS AND METHODS: We recruited 37 patients with MMM in the head and neck treated by C-ion RT with concomitant chemotherapy. Univariate and multivariate analyses of minimum ADC, mean ADC, tumor volume, age, PS, and gender were performed to identify prognostic factors. RESULTS: The 3-year local control rate, distant metastasis-free survival rate and overall survival rate of all patients were 81.1%, 37.6% and 65.3%, respectively, with a median follow-up period of 19.0 months. In univariate analyses, lower minimum ADC (≤0.6380 × 10(-3) mm(2)/s) and lower mean ADC (≤1.1523 × 10(-3) mm(2)/s) were unfavorable prognostic factors for distant metastasis (p=0.029 and p=0.014, respectively), and lower minimum ADC was an unfavorable prognostic factor for overall survival (p=0.019). However, there was no significant prognostic factor of local control including ADC value. In multivariate analyses, only minimum ADC was selected as a prognostic factor of distant metastasis-free survival and overall survival (p=0.015 and p=0.006, respectively). CONCLUSION: Minimum ADC can be a prognostic factor of MMM in the head and neck after C-ion RT.