2.Increase of hypoxia level induced by bevacizumab decreases the combined effect of bevacizumab and irradiation in CNI-H1441 xenografts in mice
Guangfei OU ; Itasaka SATOSHI ; Lihua ZENG ; Shibuya KEIKO ; Junlin YI ; Harada HIROSHI ; Hiraoka MASAHIRO
Chinese Journal of Radiation Oncology 2010;19(4):358-363
Objective To evaluate the impact of the hypoxia induced by bevacizumab on the antitumor effect in combining with irradiation in CNI-H441 xenografts in mice. Methods Bevacizumab of 5 mg/kg mouse for groups of control, bevacizumab alone, irradiation alone, earlier combination (EC), and later combination (LC) were initially injected peritoneally. Single irradiation of 14 Gy (122Sc γ-ray) was given at the 4th hour for the group of irradiation alone, 24th hour for EC group, and 72nd hour for LC group after the initial injection. Tumor hypoxia, micro vessels density and permeability of tumor vasculature,pathological responses, apoptosis, and tumor growth delay curve were evaluated after using bevacizumab and/or irradiation. Results Although it was lower than the control at the 24 hr after using bevacizumab (3. 1 × 106: 6.1 × 106 ;t = - 1.73 ,P > 0. 05), the HIF-1α rapidly increased to 3 - 4 times and 2 - 3 times of the control at day 3 (7.4 × 106: 20. 4 × 106; t = 2. 36, P < 0. 05) and lasted until day 10, which was consistent with the changes of tumor function vessels count. The count of residual micro vessel density count in LC group was higher than that in groups of EC and irradiation at day 3 after irradiation (9. 33: 3. 17;t =- 2. 43, P < 0. 05). The apoptotic count of tumor cells was lower in LC group than that in EC group (23.33: 43.83; t= 2.54, P< 0.05, at day 3 after radiation). Tumor growth delay time of LC groupwas shorter than that of EC groups (10. 5 days vs. 23. 0 days , t = 2. 67 , P < 0. 05) . Conclusions Hypoxia level induced by bevacizumab decreases the antitumor effect in later combination of bevacizumab and irradiaion. It shows a time window that determines whether the combination of bevacizumab and irradiation will be benefit or diverse.
3.Efficacy of palliative radiation for advanced gastric cancer patients
Shuji Hiramoto ; Ayako Kikuchi ; Akira Yoshioka ; Yuka Otsu ; Yasushi Kohigashi ; Yoko Goto ; Yurie Tsutsumi ; Masahiro Hiraoka ; Koji Ono
Palliative Care Research 2015;10(2):514-517
We have several choices against bleeding and obstruction in advanced gastric cancer patients such as surgical or endoscopic therapy. But we have few reports about palliative radiation. We conduct this study that we perform palliative radiation for unresectable advanced gastric cancer patients between April 2006 and March 2014 in single center. In the aim of the therapy, to stop gastric bleeding were 8, and to improve obstruction depend on gastric cancer were 4. Response rate of stop bleeding was 63%, and improve obstruction was 50%. Median duration of stop bleeding was 103 day, and improve obstruction was 52 day. Overall survival time was 567 day, survival time after the start of radiotherapy was 105days. Radiotherapy was limited in cases because onset time of response needed in comparison with surgical or endoscopic therapy. However, given minimally invasive therapy and a certain response, we can choice it so much more.
4.Dosimetric advantages and clinical outcomes of simultaneous integrated boost intensity-modulated radiotherapy for anal squamous cell carcinoma.
Katsuyuki SAKANAKA ; Satoshi ITASAKA ; Yuichi ISHIDA ; Kota FUJII ; Takahiro HORIMATSU ; Takashi MIZOWAKI ; Yoshiharu SAKAI ; Masahiro HIRAOKA
Radiation Oncology Journal 2017;35(4):368-379
PURPOSE: The purpose of this study was to explore the dosimetric difference between simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) and three-dimensional conformal radiotherapy (3DCRT), and the clinical outcomes of anal squamous cell carcinoma (ASCC) chemoradiotherapy featuring SIB-IMRT. MATERIALS AND METHODS: This study included ten patients with ASCC who underwent chemoradiotherapy using SIB-IMRT with 5-fluorouracil and mitomycin C. SIB-IMRT delivered 54 Gy to each primary tumor plus metastatic lymph nodes and 45 Gy to regional lymph nodes, in 30 fractions. Four patients received additional boosts to the primary tumors and metastatic lymph nodes; the median total dose was 54 Gy (range, 54 to 60 Gy). We additionally created 3DCRT plans following the Radiation Therapy Oncology Group 9811 protocol to allow dosimetric comparisons with SIB-IMRT. Locoregional control, overall survival, and toxicity were calculated for the clinical outcome evaluation. RESULTS: Compared to 3DCRT, SIB-IMRT significantly reduced doses to the external genitalia, bladder, and intestine, delivering the doses to target and elective nodal region. At a median follow-up time of 46 months, 3-year locoregional control and overall survival rates were 88.9% and 100%, respectively. Acute toxicities were treated conservatively. All patients completed radiotherapy with brief interruptions (range, 0 to 2 days). No patient experienced ≥grade 3 late toxicity during the follow-up period. CONCLUSION: The dosimetric advantages of SIB-IMRT appeared to reduce the toxicity of chemoradiotherapy for ASCC achieving high locoregional control in the extended period.
Anus Neoplasms
;
Carcinoma, Squamous Cell*
;
Chemoradiotherapy
;
Epithelial Cells*
;
Fluorouracil
;
Follow-Up Studies
;
Genitalia
;
Humans
;
Intestines
;
Lymph Nodes
;
Mitomycin
;
Radiotherapy
;
Radiotherapy Planning, Computer-Assisted
;
Radiotherapy, Conformal
;
Radiotherapy, Intensity-Modulated*
;
Survival Rate
;
Treatment Outcome
;
Urinary Bladder
5.Fecal Immunochemical Test and Fecal Calprotectin Results Show Different Profiles in Disease Monitoring for Ulcerative Colitis.
Sakiko HIRAOKA ; Toshihiro INOKUCHI ; Asuka NAKARAI ; Shiho TAKASHIMA ; Daisuke TAKEI ; Yuusaku SUGIHARA ; Masahiro TAKAHARA ; Keita HARADA ; Hiroyuki OKADA ; Jun KATO
Gut and Liver 2018;12(2):142-148
BACKGROUND/AIMS: Both fecal immunochemical test (FIT) and fecal calprotectin (Fcal) results are useful biomarkers for ulcerative colitis (UC). However, the situations in which each marker should be used are largely unknown. METHODS: A total of 110 colonoscopy intervals of UC patients were assessed, and correlations between changes in colonoscopic findings and changes in the two aforementioned fecal markers were examined. RESULTS: Among patients with mucosal healing (MH) and negative FIT or Fcal results at the initial colonoscopy, FIT and Fcal findings exhibited accuracies of 93% (38/41) and 79% (26/33), respectively, for predicting the results of the subsequent examination. Among the 24 patients who showed endoscopic activity at the precedent colonoscopy and MH at the subsequent examination, positive-to-negative conversion of FIT and Fcal findings at the subsequent examination was observed in 92% (12/13) and 62% (8/13) of patients, respectively. Among the 43 patients who showed endoscopic activity at both the precedent and subsequent examinations, Fcal findings reflected the change in endoscopic activity better than FIT results (r=0.59, p<0.0001 vs r=0.30, p=0.054). CONCLUSIONS: The FIT is useful for confirming MH and the occurrence of relapse. In contrast, Fcal is useful for monitoring the mucosal status of patients with active inflammation.
Biomarkers
;
Colitis
;
Colitis, Ulcerative*
;
Colonoscopy
;
Humans
;
Inflammation
;
Leukocyte L1 Antigen Complex*
;
Recurrence
;
Ulcer*
6.An Elevated Platelet Count Increases the Risk of Relapse in Ulcerative Colitis Patients with Mucosal Healing.
Asuka NAKARAI ; Jun KATO ; Sakiko HIRAOKA ; Shiho TAKASHIMA ; Toshihiro INOKUCHI ; Masahiro TAKAHARA ; Yuusaku SUGIHARA ; Keita HARADA ; Hiroyuki OKADA
Gut and Liver 2018;12(4):420-425
BACKGROUND/AIMS: Although mucosal healing (MH) has been considered a treatment goal for patients with ulcerative colitis (UC), the risk factors predictive of relapse in patients who achieve MH are unknown. Because the platelet count has been shown to be a marker of inflammation in inflammatory bowel diseases, this study aimed to assess whether the platelet count could predict relapse in UC patients with MH. METHODS: A prospective observational study was performed. UC patients with MH were consecutively enrolled in the study and monitored for at least 2 years or until relapse. The correlation between the incidence of relapse and the platelet count at the time of study enrollment was examined. RESULTS: In total, 43 patients were enrolled, and 14 patients (33%) relapsed. The median platelet count at the time of enrollment in the patients who relapsed significantly differed from that in the patients who did not relapse (27.2×104/μL vs 23.8×104/μL, respectively; p=0.016). A platelet count >25.0×104/μL was a significant risk factor for relapse based on a multivariate analysis (hazard ratio, 4.85; 95% confidence interval, 1.07 to 25.28), and according to the Kaplan-Meier analysis, this cutoff could identify patients susceptible to relapse (p=0.041, log-rank test). CONCLUSIONS: The platelet count could be used as a predictor of relapse in UC patients with MH.
Blood Platelets*
;
Colitis
;
Colitis, Ulcerative*
;
Humans
;
Incidence
;
Inflammation
;
Inflammatory Bowel Diseases
;
Kaplan-Meier Estimate
;
Multivariate Analysis
;
Observational Study
;
Platelet Count*
;
Prospective Studies
;
Recurrence*
;
Risk Factors
;
Ulcer*
7.The novel latex agglutination turbidimetric immunoassay system for simultaneous measurements of calprotectin and hemoglobin in feces
Sakiko HIRAOKA ; Shiho TAKASHIMA ; Toshihiro INOKUCHI ; Asuka NAKARAI ; Masahiro TAKAHARA ; Keita HARADA ; Yasuhiro SEKI ; Katsunori WATANABE ; Jun KATO ; Hiroyuki OKADA
Intestinal Research 2019;17(2):202-209
BACKGROUND/AIMS: Fecal calprotectin (Fcal) as well as the fecal immunochemical test (FIT) are useful biomarkers for detecting activity and mucosal healing in inflammatory bowel diseases. Here, we report the performance of simultaneous measurements of Fcal and FIT for ulcerative colitis (UC) patients using the newly-developed latex agglutination turbidimetric immunoassay (LATIA) system. METHODS: Fcal and hemoglobin were measured by the LATIA system in 152 UC patients who underwent colonoscopy. Fcal was also quantified with a conventional enzyme-linked immunosorbent assay (ELISA). Fecal markers were evaluated in conjunction with the mucosal status of UC, which was assessed via the Mayo endoscopic subscore (MES) classification. RESULTS: The LATIA system could quantify calprotectin and hemoglobin simultaneously with the same fecal samples within 10 minutes. The values of the Fcal-LATIA closely correlated with those of the Fcal-ELISA (Spearman rank correlation coefficient, r=0.84; P<0.0001). The values of Fcal for each assay and the FIT all significantly correlated with the MESs (Spearman rank correlation coefficient, Fcal-LATIA: r=0.58, Fcal-ELISA: r=0.55, and FIT: r=0.72). The mucosal healing predictability (determined by an MES of 0 alone) of the Fcal-LATIA, Fcal-ELISA, and FIT-LATIA with the cutoffs determined by receiver operating characteristic curve analysis was 0.79, 0.78, and 0.92 for sensitivity, respectively, and 0.78, 0.69, and 0.73 for specificity, respectively. CONCLUSIONS: The performance of the novel Fcal-LATIA was equivalent to that of the conventional Fcal assay. Simultaneous measurements with FITs would promote the clinical relevance of fecal biomarkers in UC.
Agglutination
;
Biomarkers
;
Classification
;
Colitis, Ulcerative
;
Colonoscopy
;
Enzyme-Linked Immunosorbent Assay
;
Feces
;
Humans
;
Immunoassay
;
Inflammatory Bowel Diseases
;
Latex
;
Leukocyte L1 Antigen Complex
;
ROC Curve
;
Sensitivity and Specificity
8.Surgical Treatment for Takayasu Arteritis Complicated with Thoracic Aneurysm
Daisuke HIRAOKA ; Susumu MANABE ; Kazunobu HIROOKA ; Daiki HIRAYAMA ; Takashi YASUKAWA ; Sotaro KATSUI ; Hidetoshi UCHIYAMA ; Masahiro ONUKI
Japanese Journal of Cardiovascular Surgery 2018;47(6):289-292
Anti-inflammatory therapy is generally considered to be prior to surgery for Takayasu disease to achieve better outcomes. We report two Takayasu arteritis patients with thoracic aneurysm. Case 1 was a 19-year-old woman who presented acute trachyphonia for one month. CT revealed aortic arch aneurysm of which maximal diameter was 64 mm with partial cystic protrusion. We performed urgent total arch replacement before anti-inflammation therapy was induced. Postoperative course was uneventful and the patient discharged on steroid therapy. Case 2 was a 35-year-old woman who complained chest pain for two weeks. CT revealed a Valsalva aneurysm with maximal diameter 54 mm and the aortic wall of the arch including its branches was surrounded by thick low density area. As the FDG-PET confirmed inflammatory arteritis, initial steroid therapy was planned. However, one day before admission, the patient presented acute aortic dissection and did not respond to any resuscitation. We conclude that the right time of surgery or the initial induction of anti-inflammatory therapy for anuerysmal dilation by Takayasu arteritis is to be determined based not only on the inflammation level but also on aneurysmal size and the patient's severity of complaints.
9.Huge Syphilitic Aneurysm of the Thoracic Aorta Complicated with Airway Obstruction and Superior Vena Cava Syndrome
Takashi YASUKAWA ; Susumu MANABE ; Daiki HIRAYAMA ; Daisuke HIRAOKA ; Sotaro KATSUI ; Hidetoshi UCHIYAMA ; Masahiro ONUKI ; Kazunobu HIROOKA
Japanese Journal of Cardiovascular Surgery 2018;47(3):148-152
Today, syphilitic aortic aneurysm is rarely diagnosed due to widespread use of penicillin for early syphilis. Large aneurysms can be symptomatic by compressing on adjacent organs. We report a case of a huge syphilitic aneurysm of the thoracic aorta complicated with airway obstruction and superior vena cava syndrome. A 62-year-old man presented with acute severe dyspnea and distention of superficial veins. Contrast-enhanced computed tomography revealed an aneurysm of the ascending aorta extending to the transverse arch the diameter of which was 90 mm. The aneurysm compressed the bilateral main bronchi and superior vena cava. We performed an emergency operation because respiratory failure persisted despite the support of a ventilator. Since the aneurysm eroded the sternum, median sternotomy was performed under hypothermic circulatory arrest. Dissecting the aneurysm was complicated due to dense adhesion. Ascending aorta and partial arch replacement with reconstruction of the brachiocephalic trunk was successfully performed with antegrade cerebral perfusion. Postoperative computed tomography demonstrated that compression of the bilateral main bronchi was released. The result of preoperative syphilitic serologic test was strongly positive, and pathological findings of the aneurysm wall specimen was compatible with syphilitic aneurysm. Following treatment with benzyl penicillin for 14 days, the patient was discharged on the 19th postoperative day without specific complications.
10.Symptomatic Hypothyroidism after Aortic Valve Replacement in an Octogenarian
Daisuke HIRAOKA ; Susumu MANABE ; Daiki HIRAYAMA ; Takashi YASUKAWA ; Sotaro KATSUI ; Hidetoshi UCHIYAMA ; Masahiro ONUKI ; Kazunobu HIROOKA
Japanese Journal of Cardiovascular Surgery 2018;47(4):174-177
Surgical stress is closely associated with the activity of the thyroid hormone. Although many patients undergoing cardiac surgery revealed markedly low triiodothyronine (T3), few patients showed symptomatic hypothyroidism. This condition is generally recognized as “non thyroidal illness (NTI) ” which is characterized by a low T3 level, despite the normal function of hypothalamus-pituitary-thyroid system. NTI is generally considered as one of the biological defense mechanisms rather than a pathological condition, eliminating the requirement of medical intervention. Even if low T3 is observed in blood biochemical examination after open heart surgery, a cautious interpretation is required. We report an elderly case presenting severe fatigue and mild disorientation accompanied by significantly low thyroid hormone after aortic valve replacement. The morbidity was remarkably improved with medical treatment, suggesting hypothyroidism after cardiac surgery.