呼吸运动对肺部肿瘤靶区受照剂量分布影响的研究

Objective To investigate the influence of respiratory motion on target dose distribution in radiotherapy for patients with lung tumors. Methods The Big Bore Brilliance CT with bellows system was used to gain the 4DCT sets and respiratory frequency information of the patients. The moving ranges of the tumors in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) directions were measured from the center coordinate values of gross tumor volume of ten time-phase CT sets in the treatment planning sys-tem. Then a breathing model was used to simulate the tumor motions due to respiration. A 4-dimensional motion table was used to mimic the motion of lung tumor in beams-eye-view (BEV). A 2-dimensional semi-conductor beams measurement system was fixed to the table to measure the 2-dimensional dose distribution of static and dynamic targets using the treatment beams at gantry angle of 0°. Finally, the differences of the dose distribution between the static and moving phantom were compared and analyzed with the statistical soft-ware R. Results When the amplitude (half of the moving rang) in the CC direction was 1 cm, the passing ratio of relative dose difference ≤4% in one beam field was minimal (1.1%), and there was 58% maximal relative dose absence. The 4% passing ratios media in the CC direction were 94.7%, 79.4%, 58.6% and 37.1% in <0.25, 0.25-<0.50, 0.50- <0.75 and ≥0.75 mm amplitude (X<'2>=29.20,P=0.000), but were all similar in the AP and LR directions. The mean value of the relative dose change in the high dose area was smaller than the low dose area in the 89% beam fields. When only the CC direction was consid-ered, the 4% passing ratio of 3.6 s and 8.2 s period was 72% and 60%, respectively. Conclusions The amplitude in the CC direction is a factor impacting the dose distribution of the moving target. The influence of respiratory motion on high dose area is more than that on low dose area. When the other respiratory param-eters are fixed, the motion of long period has more influence on the dose than that of short period. Special at-tention should be paid to the patients with tumor of more than 0.5 cm amplitude in the CC direction when planning the intensity modulated radiotherapy.     

呼吸运动对肺部肿瘤靶区受照剂量分布影响的研究

Objective To investigate the influence of respiratory motion on target dose distribution in radiotherapy for patients with lung tumors. Methods The Big Bore Brilliance CT with bellows system was used to gain the 4DCT sets and respiratory frequency information of the patients. The moving ranges of the tumors in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) directions were measured from the center coordinate values of gross tumor volume of ten time-phase CT sets in the treatment planning sys-tem. Then a breathing model was used to simulate the tumor motions due to respiration. A 4-dimensional motion table was used to mimic the motion of lung tumor in beams-eye-view (BEV). A 2-dimensional semi-conductor beams measurement system was fixed to the table to measure the 2-dimensional dose distribution of static and dynamic targets using the treatment beams at gantry angle of 0°. Finally, the differences of the dose distribution between the static and moving phantom were compared and analyzed with the statistical soft-ware R. Results When the amplitude (half of the moving rang) in the CC direction was 1 cm, the passing ratio of relative dose difference ≤4% in one beam field was minimal (1.1%), and there was 58% maximal relative dose absence. The 4% passing ratios media in the CC direction were 94.7%, 79.4%, 58.6% and 37.1% in <0.25, 0.25-<0.50, 0.50- <0.75 and ≥0.75 mm amplitude (X<'2>=29.20,P=0.000), but were all similar in the AP and LR directions. The mean value of the relative dose change in the high dose area was smaller than the low dose area in the 89% beam fields. When only the CC direction was consid-ered, the 4% passing ratio of 3.6 s and 8.2 s period was 72% and 60%, respectively. Conclusions The amplitude in the CC direction is a factor impacting the dose distribution of the moving target. The influence of respiratory motion on high dose area is more than that on low dose area. When the other respiratory param-eters are fixed, the motion of long period has more influence on the dose than that of short period. Special at-tention should be paid to the patients with tumor of more than 0.5 cm amplitude in the CC direction when planning the intensity modulated radiotherapy.     

呼吸运动对肺部肿瘤靶区受照剂量分布影响的研究

Objective To investigate the influence of respiratory motion on target dose distribution in radiotherapy for patients with lung tumors. Methods The Big Bore Brilliance CT with bellows system was used to gain the 4DCT sets and respiratory frequency information of the patients. The moving ranges of the tumors in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) directions were measured from the center coordinate values of gross tumor volume of ten time-phase CT sets in the treatment planning sys-tem. Then a breathing model was used to simulate the tumor motions due to respiration. A 4-dimensional motion table was used to mimic the motion of lung tumor in beams-eye-view (BEV). A 2-dimensional semi-conductor beams measurement system was fixed to the table to measure the 2-dimensional dose distribution of static and dynamic targets using the treatment beams at gantry angle of 0°. Finally, the differences of the dose distribution between the static and moving phantom were compared and analyzed with the statistical soft-ware R. Results When the amplitude (half of the moving rang) in the CC direction was 1 cm, the passing ratio of relative dose difference ≤4% in one beam field was minimal (1.1%), and there was 58% maximal relative dose absence. The 4% passing ratios media in the CC direction were 94.7%, 79.4%, 58.6% and 37.1% in <0.25, 0.25-<0.50, 0.50- <0.75 and ≥0.75 mm amplitude (X<'2>=29.20,P=0.000), but were all similar in the AP and LR directions. The mean value of the relative dose change in the high dose area was smaller than the low dose area in the 89% beam fields. When only the CC direction was consid-ered, the 4% passing ratio of 3.6 s and 8.2 s period was 72% and 60%, respectively. Conclusions The amplitude in the CC direction is a factor impacting the dose distribution of the moving target. The influence of respiratory motion on high dose area is more than that on low dose area. When the other respiratory param-eters are fixed, the motion of long period has more influence on the dose than that of short period. Special at-tention should be paid to the patients with tumor of more than 0.5 cm amplitude in the CC direction when planning the intensity modulated radiotherapy.     

呼吸运动对肺部肿瘤靶区受照剂量分布影响的研究

Objective To investigate the influence of respiratory motion on target dose distribution in radiotherapy for patients with lung tumors. Methods The Big Bore Brilliance CT with bellows system was used to gain the 4DCT sets and respiratory frequency information of the patients. The moving ranges of the tumors in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) directions were measured from the center coordinate values of gross tumor volume of ten time-phase CT sets in the treatment planning sys-tem. Then a breathing model was used to simulate the tumor motions due to respiration. A 4-dimensional motion table was used to mimic the motion of lung tumor in beams-eye-view (BEV). A 2-dimensional semi-conductor beams measurement system was fixed to the table to measure the 2-dimensional dose distribution of static and dynamic targets using the treatment beams at gantry angle of 0°. Finally, the differences of the dose distribution between the static and moving phantom were compared and analyzed with the statistical soft-ware R. Results When the amplitude (half of the moving rang) in the CC direction was 1 cm, the passing ratio of relative dose difference ≤4% in one beam field was minimal (1.1%), and there was 58% maximal relative dose absence. The 4% passing ratios media in the CC direction were 94.7%, 79.4%, 58.6% and 37.1% in <0.25, 0.25-<0.50, 0.50- <0.75 and ≥0.75 mm amplitude (X<'2>=29.20,P=0.000), but were all similar in the AP and LR directions. The mean value of the relative dose change in the high dose area was smaller than the low dose area in the 89% beam fields. When only the CC direction was consid-ered, the 4% passing ratio of 3.6 s and 8.2 s period was 72% and 60%, respectively. Conclusions The amplitude in the CC direction is a factor impacting the dose distribution of the moving target. The influence of respiratory motion on high dose area is more than that on low dose area. When the other respiratory param-eters are fixed, the motion of long period has more influence on the dose than that of short period. Special at-tention should be paid to the patients with tumor of more than 0.5 cm amplitude in the CC direction when planning the intensity modulated radiotherapy.     

呼吸运动对肺部肿瘤靶区受照剂量分布影响的研究

Objective To investigate the influence of respiratory motion on target dose distribution in radiotherapy for patients with lung tumors. Methods The Big Bore Brilliance CT with bellows system was used to gain the 4DCT sets and respiratory frequency information of the patients. The moving ranges of the tumors in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) directions were measured from the center coordinate values of gross tumor volume of ten time-phase CT sets in the treatment planning sys-tem. Then a breathing model was used to simulate the tumor motions due to respiration. A 4-dimensional motion table was used to mimic the motion of lung tumor in beams-eye-view (BEV). A 2-dimensional semi-conductor beams measurement system was fixed to the table to measure the 2-dimensional dose distribution of static and dynamic targets using the treatment beams at gantry angle of 0°. Finally, the differences of the dose distribution between the static and moving phantom were compared and analyzed with the statistical soft-ware R. Results When the amplitude (half of the moving rang) in the CC direction was 1 cm, the passing ratio of relative dose difference ≤4% in one beam field was minimal (1.1%), and there was 58% maximal relative dose absence. The 4% passing ratios media in the CC direction were 94.7%, 79.4%, 58.6% and 37.1% in <0.25, 0.25-<0.50, 0.50- <0.75 and ≥0.75 mm amplitude (X<'2>=29.20,P=0.000), but were all similar in the AP and LR directions. The mean value of the relative dose change in the high dose area was smaller than the low dose area in the 89% beam fields. When only the CC direction was consid-ered, the 4% passing ratio of 3.6 s and 8.2 s period was 72% and 60%, respectively. Conclusions The amplitude in the CC direction is a factor impacting the dose distribution of the moving target. The influence of respiratory motion on high dose area is more than that on low dose area. When the other respiratory param-eters are fixed, the motion of long period has more influence on the dose than that of short period. Special at-tention should be paid to the patients with tumor of more than 0.5 cm amplitude in the CC direction when planning the intensity modulated radiotherapy.     

呼吸运动对肺部肿瘤靶区受照剂量分布影响的研究

Objective To investigate the influence of respiratory motion on target dose distribution in radiotherapy for patients with lung tumors. Methods The Big Bore Brilliance CT with bellows system was used to gain the 4DCT sets and respiratory frequency information of the patients. The moving ranges of the tumors in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) directions were measured from the center coordinate values of gross tumor volume of ten time-phase CT sets in the treatment planning sys-tem. Then a breathing model was used to simulate the tumor motions due to respiration. A 4-dimensional motion table was used to mimic the motion of lung tumor in beams-eye-view (BEV). A 2-dimensional semi-conductor beams measurement system was fixed to the table to measure the 2-dimensional dose distribution of static and dynamic targets using the treatment beams at gantry angle of 0°. Finally, the differences of the dose distribution between the static and moving phantom were compared and analyzed with the statistical soft-ware R. Results When the amplitude (half of the moving rang) in the CC direction was 1 cm, the passing ratio of relative dose difference ≤4% in one beam field was minimal (1.1%), and there was 58% maximal relative dose absence. The 4% passing ratios media in the CC direction were 94.7%, 79.4%, 58.6% and 37.1% in <0.25, 0.25-<0.50, 0.50- <0.75 and ≥0.75 mm amplitude (X<'2>=29.20,P=0.000), but were all similar in the AP and LR directions. The mean value of the relative dose change in the high dose area was smaller than the low dose area in the 89% beam fields. When only the CC direction was consid-ered, the 4% passing ratio of 3.6 s and 8.2 s period was 72% and 60%, respectively. Conclusions The amplitude in the CC direction is a factor impacting the dose distribution of the moving target. The influence of respiratory motion on high dose area is more than that on low dose area. When the other respiratory param-eters are fixed, the motion of long period has more influence on the dose than that of short period. Special at-tention should be paid to the patients with tumor of more than 0.5 cm amplitude in the CC direction when planning the intensity modulated radiotherapy.     

呼吸运动对肺部肿瘤靶区受照剂量分布影响的研究

Objective To investigate the influence of respiratory motion on target dose distribution in radiotherapy for patients with lung tumors. Methods The Big Bore Brilliance CT with bellows system was used to gain the 4DCT sets and respiratory frequency information of the patients. The moving ranges of the tumors in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) directions were measured from the center coordinate values of gross tumor volume of ten time-phase CT sets in the treatment planning sys-tem. Then a breathing model was used to simulate the tumor motions due to respiration. A 4-dimensional motion table was used to mimic the motion of lung tumor in beams-eye-view (BEV). A 2-dimensional semi-conductor beams measurement system was fixed to the table to measure the 2-dimensional dose distribution of static and dynamic targets using the treatment beams at gantry angle of 0°. Finally, the differences of the dose distribution between the static and moving phantom were compared and analyzed with the statistical soft-ware R. Results When the amplitude (half of the moving rang) in the CC direction was 1 cm, the passing ratio of relative dose difference ≤4% in one beam field was minimal (1.1%), and there was 58% maximal relative dose absence. The 4% passing ratios media in the CC direction were 94.7%, 79.4%, 58.6% and 37.1% in <0.25, 0.25-<0.50, 0.50- <0.75 and ≥0.75 mm amplitude (X<'2>=29.20,P=0.000), but were all similar in the AP and LR directions. The mean value of the relative dose change in the high dose area was smaller than the low dose area in the 89% beam fields. When only the CC direction was consid-ered, the 4% passing ratio of 3.6 s and 8.2 s period was 72% and 60%, respectively. Conclusions The amplitude in the CC direction is a factor impacting the dose distribution of the moving target. The influence of respiratory motion on high dose area is more than that on low dose area. When the other respiratory param-eters are fixed, the motion of long period has more influence on the dose than that of short period. Special at-tention should be paid to the patients with tumor of more than 0.5 cm amplitude in the CC direction when planning the intensity modulated radiotherapy.     

呼吸运动对肺部肿瘤靶区受照剂量分布影响的研究

Objective To investigate the influence of respiratory motion on target dose distribution in radiotherapy for patients with lung tumors. Methods The Big Bore Brilliance CT with bellows system was used to gain the 4DCT sets and respiratory frequency information of the patients. The moving ranges of the tumors in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) directions were measured from the center coordinate values of gross tumor volume of ten time-phase CT sets in the treatment planning sys-tem. Then a breathing model was used to simulate the tumor motions due to respiration. A 4-dimensional motion table was used to mimic the motion of lung tumor in beams-eye-view (BEV). A 2-dimensional semi-conductor beams measurement system was fixed to the table to measure the 2-dimensional dose distribution of static and dynamic targets using the treatment beams at gantry angle of 0°. Finally, the differences of the dose distribution between the static and moving phantom were compared and analyzed with the statistical soft-ware R. Results When the amplitude (half of the moving rang) in the CC direction was 1 cm, the passing ratio of relative dose difference ≤4% in one beam field was minimal (1.1%), and there was 58% maximal relative dose absence. The 4% passing ratios media in the CC direction were 94.7%, 79.4%, 58.6% and 37.1% in <0.25, 0.25-<0.50, 0.50- <0.75 and ≥0.75 mm amplitude (X<'2>=29.20,P=0.000), but were all similar in the AP and LR directions. The mean value of the relative dose change in the high dose area was smaller than the low dose area in the 89% beam fields. When only the CC direction was consid-ered, the 4% passing ratio of 3.6 s and 8.2 s period was 72% and 60%, respectively. Conclusions The amplitude in the CC direction is a factor impacting the dose distribution of the moving target. The influence of respiratory motion on high dose area is more than that on low dose area. When the other respiratory param-eters are fixed, the motion of long period has more influence on the dose than that of short period. Special at-tention should be paid to the patients with tumor of more than 0.5 cm amplitude in the CC direction when planning the intensity modulated radiotherapy.     

呼吸运动对肺部肿瘤靶区受照剂量分布影响的研究

Objective To investigate the influence of respiratory motion on target dose distribution in radiotherapy for patients with lung tumors. Methods The Big Bore Brilliance CT with bellows system was used to gain the 4DCT sets and respiratory frequency information of the patients. The moving ranges of the tumors in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) directions were measured from the center coordinate values of gross tumor volume of ten time-phase CT sets in the treatment planning sys-tem. Then a breathing model was used to simulate the tumor motions due to respiration. A 4-dimensional motion table was used to mimic the motion of lung tumor in beams-eye-view (BEV). A 2-dimensional semi-conductor beams measurement system was fixed to the table to measure the 2-dimensional dose distribution of static and dynamic targets using the treatment beams at gantry angle of 0°. Finally, the differences of the dose distribution between the static and moving phantom were compared and analyzed with the statistical soft-ware R. Results When the amplitude (half of the moving rang) in the CC direction was 1 cm, the passing ratio of relative dose difference ≤4% in one beam field was minimal (1.1%), and there was 58% maximal relative dose absence. The 4% passing ratios media in the CC direction were 94.7%, 79.4%, 58.6% and 37.1% in <0.25, 0.25-<0.50, 0.50- <0.75 and ≥0.75 mm amplitude (X<'2>=29.20,P=0.000), but were all similar in the AP and LR directions. The mean value of the relative dose change in the high dose area was smaller than the low dose area in the 89% beam fields. When only the CC direction was consid-ered, the 4% passing ratio of 3.6 s and 8.2 s period was 72% and 60%, respectively. Conclusions The amplitude in the CC direction is a factor impacting the dose distribution of the moving target. The influence of respiratory motion on high dose area is more than that on low dose area. When the other respiratory param-eters are fixed, the motion of long period has more influence on the dose than that of short period. Special at-tention should be paid to the patients with tumor of more than 0.5 cm amplitude in the CC direction when planning the intensity modulated radiotherapy.     

重复CT扫描提高运动靶区勾画范围准确性研究

Objective To find a method to improve the range accuracy of moving target such as peripheral lung tumors, since a single CT snapshot may not be accurate during the treatment process.Methods A simple harmonic motion phantom, embedded with a cube and a circular ball, was used to simulate the tumor motion. Individualized moving targets were scanned 24 times with different amplitudes and frequencies. Then the images were fused from every 1, 2 or 3 sets of CT scans. The GTV volume variation of circular target and the length variation of the cube target along the z axis were contoured and analyzed. Results As motion amplitude increased, the maximum of both circular target volume and cube target length was increased, while the minimum of the factors was decreased. Motion frequency affected the target volume less than amplitude. For a cube target with the length of 3.3 cm at stationary phase, when motion frequencies was 20 and motion amplitude was 2 cm, the maximal length was 2. 4 times of the minimal length (5. 1 cm vs. 2. 1 cm). When it came to the cube target groups fused from every 1,2 and 3 sets of CT scans, the average length and standard deviation were (3.77 ± 1.20) cm, (4.18 ±0. 91)cm and (4.52 ±0. 59) cm, respectively. With the increase of fused scan number, targets became bigger, the standard deviation decreased, and the change of center positions was decreased. Conclusions The motion amplitude, frequency and the number of CT scans are the main factors affecting target definition, though, the optimized scanning phase is not certained. When 4DCT and respiration gating technique are not available,the efficient and practical method to solve this problem is to scan the target three or more times and fuse them in planning system, which will generate a larger, more reproducible GTV volume for moving targets.     

Pharmacogénétique des fluoropyrimidines. La méthylènetétrahydrofolate réductase

Résumé: Lefficacité optimale des fluoropyrimidines nécessite des concentrations élevées en 5-10 méthylènetétrahydrofolate (CH₂FH₄), contrôlées par la méthylènetétrahydrofolate réductase (MTHFR) qui convertit irréversiblement le CH₂FH₄ en 5-méthyltétrahydrofolate (CH₃FH₄). Les polymorphismes 677CT et 1298AC du gène MTHFR sont associés à une baisse dactivité de lenzyme. Les tumeurs «MTHFR mutées» devraient donc être plus sensibles aux fluoropyrimidines que les tumeurs «MTHFR sauvages». Les études expérimentales et cliniques publiées à ce jour tendent à montrer une plus grande sensibilité au 5-FU (associé ou non à lacide folinique) dans les tumeurs MTHFR mutées par rapport aux tumeurs sauvages. Ces résultats montrent la nécessité de poursuivre ces recherches afin de confirmer limpact de ces polymorphismes sur lefficacité des fluoropyrimidines.     

Oncogénétique et psycho-oncologie, une collaboration recommandée...

Résumé: La possibilité depuis 1994, de connaître la probabilité individuelle de développer certains cancers a permis de proposer de nouvelles modalités de prévention, de traitements et contribué au développement actuel de loncogénétique. Une meilleure connaissance des répercussions psychologiques tant pour les patients que pour les apparentés est désormais possible et limplication des psycho-oncologues dans ce cadre de la réalisation des tests prédictifs, recommandée. La mission de «messager» qui incombe au «cas-index» doit faire lobjet dune attention particulière. La complexité de linformation et la dimension paradoxale que peut avoir parfois la communication à propos des choix, rend difficile lévaluation de la qualité du consentement. La situation particulièrement délicate dune aide à la décision à légard de la chirurgie prophylactique, exige une collaboration étroite des généticiens et des psycho-oncologues.Les soins de support en oncologie     

The role of papillomaviruses in human cancers

This review comprehensively evaluates the influence of gene-gene, gene-environment and multiple interactions on the risk of colorectal cancer (CRC). Methods of studying these interactions and their limitations have been discussed herein. There is a need to develop biomarkers of exposure and of risk that are sensitive, specific, present in the pathway of the disease, and that have been clinically tested for routine use. The influence of inherited variation (polymorphism) in several genes has been discussed in this review; however, due to study limitations and confounders, it is difficult to conclude which ones are associated with the highest risk (either individually or in combination with environmental factors) to CRC. The majority of the sporadic cancer is believed to be due to modification of mutation risk by other genetic and/or environmental factors. Micronutrient deficiency may explain the association between low consumption of fruit/vegetables and CRC in human studies. Mitochondrial modulation by dietary factors influences the balance between cell renewal and death critical in colon mucosal homeostasis. Both genetic and epigenetic interactions are intricately dependent on each other, and collectively influence the process of colorectal tumorigenesis. The genetic and environmental interactions present a good prospect and a challenge for prevention strategies for CRC because they support the view that this highly prevalent cancer is preventable.     

Antifungal combination therapy in localized candidosis

A mouse model of localized candidosis in air-filled subcutaneous cysts imitating thrush has been developed. We have now tested various antifungal combinations in this animal model. Flucytosine (5-FC) + amphotericin B (Amph B) showed the highest efficacy, a clear additive or even synergistic effect was seen. The combination of 5-FC + imidazole or triazole derivative was less efficacious, an additive effect was rare. The combination of 5-FC + Amph B was also tested against Candida albicans strains showing various degrees of 5-FC-resistance. A significant reduction in 5-FC-resistant mutants was seen after the treatment with the combination.     

Les génériques en cancérologie: à molécule identique, médicaments identiques? Les biosimilaires, des super-génériques?

Résumé: Les biosimilaires vont bientôt voir leur apparition en Europe. Comment un laboratoire peut-il aborder le développement de son dossier dAMM? Quelles sont les bases légales et les recommandations officielles? Comment la similarité et/ou le caractère générique peuvent-ils être démontrés? Les règles sont-elles identiques à celles des produits chimiques conventionnels pour lesquels, notamment en cancérologie, il existe des médicaments génériques? Comment faire pour que la sécurité et lefficacité des médicaments biosimilaires soient assurées pour les patients?     

PSA-Test zur Früherkennung des Prostatakarzinoms

Zusammenfassung Prostatakrebs ist hierzulande seit einigen Jahren die häufigste Krebserkrankung bei Männern. Da über die Ätiologie wenig gesichertes Wissen vorliegt und daher kaum Möglichkeiten zur primären Prävention bestehen, konzentrieren sich die Anstrengungen auf die Suche nach wirksamen Verfahren zur sekundären Prävention. Hierbei gilt die Verwendung des PSA-Tests zur Früherkennung des Prostatakarzinoms als derzeit aussichtsreichstes Verfahren. Bevor ein neues Früherkennungsverfahren zur breiten Anwendung empfohlen oder in das gesetzliche Früherkennungsprogramm aufgenommen wird, muss jedoch seine Wirksamkeit in hierfür geeigneten wissenschaftlichen Untersuchungen nachgewiesen werden. Bis jetzt gibt es bereits eine ganze Reihe epidemiologischer Studien zur Effektivität des PSA-Screenings, doch konnte ein Wirksamkeitsnachweis bisher nicht erbracht werden. Zwei große randomisierte Studien in Europa und den USA lassen für die Jahre 2005–08 erste Ergebnisse erwarten. Da epidemiologische Arbeiten belegen, dass durch PSA-Screening eine nicht unerhebliche Überdiagnostik und Übertherapie eintritt, d. h. Schaden angerichtet werden kann, ist das Ergebnis der genannten randomisierten Studien vor weitergehenden Entscheidungen unbedingt abzuwarten. Bis dahin sollte von der Anwendung des PSA-Tests zur Prostatakrebsfrüherkennung unmissverständlich abgeraten werden. Da für den Test bereits ausgiebig Werbung betrieben wurde, kommt einer gründlichen ärztlichen Aufklärung von an dem Test interessierten Personen eine Schlüsselrolle zu.     

Cancer immunotherapy

Unprecedented progress has seen made in the last decade in the field of cancer immunotherapy. The recent approval of nivolumab （Opdivo）, the first anti-programmed cell death-1 （PD-1） antibody, for metastatic melanoma in Japan, marked a milestone in the rapidly advancing field of cancer immunotherapy. Nivolumab together with ipilimumab （Yervoy）, the anti-cytotoxic T-lymphocyte-associated antigen-4 （CTLA-4） antibody, are the first 2 drugs in the class of ＂immune checkpoint inhibitors＂ that have delivered impressive responses in patients with metastatic melanoma and renal cell cancer （RCC） as well as a variety of solid tumors.     

异基因造血干细胞移植后患者肝损害病因与临床特征分析

 【摘要】　目的　总结异基因造血干细胞移植（allo-HSCT）后患者肝损害的发生率、发生原因、诊断方法与治疗选择。方法　回顾性分析郑州大学附属肿瘤医院2006～2010年接受allo-HSCT的83例良、恶性血液病患者中Ⅱ～Ⅳ级肝损害的发生率、各种病因的构成比、临床表现以及诊断方法,分析移植后不同时期肝损害病因的差异、治疗方法、疗效。结果　83例allo-HSCT患者中,发生Ⅱ～Ⅳ级肝损害45例（54.2 %）。按肝损害致病病因分类,预处理化疗所致7例,环孢素所致9例,肝静脉闭塞病（HVOD）所致2例,肝脏移植物抗宿主病（GVHD）所致24例,乙型肝炎病毒再激活所致2例,多器官衰竭所致1例。发生于移植后1个月内者20例（44.4 %）,以药物性肝损害为主,1个月～100 d者13例（28.9 %）,101 d～1年者12例（26.7 %）,均以肝脏GVHD为主。经减停肝损害药物、抗排异、保肝等治疗后,27例治愈,10例好转,2例未愈,6例死于原发病复发或移植相关并发症。结论　肝损害是allo-HSCT后常见的并发症,药物及肝脏GVHD是其最主要的致病原因,肝损害与其发生时间的相关性可作为肝损害病因学诊断的参考依据。根据肝损害的病因选择针对性的治疗方法,可取得较好的疗效。     

Pharmacokinetics and dosage of fluconazole in continuous hemofiltration (CAVH, CVVH) and hemodialysis (CAVHD, CVVHD)

Continuous haemofiltration (CAVH, CVVH) and haemodialysis (CAVHD, CVVHD) are increasingly used in patients with acute renal failure (ARF). The elimination rates of fluconazole vary considerably among the different procedures. In CVVHD, the elimination rate is, depending on the combined dialysate/ultrafiltrate flow rate, the most marked compared to CVVH and intermittent dialysis with a fluconazole clearance exceeding the values of healthy persons in CVVHD 2 L/h. To achieve therapeutic plasma levels during continuous renal replacement therapy, the same loading dose as in patients without renal failure should be applied, followed by the adjusted maintenance dose for anuric patients multiplied by a factor taking the extracorporeal elimination of the absorbed dose into account (CAVH, CVVH: x 2.2, ultrafiltrate flow 0.5 L/h; CAVHD, CVVHD: x 3.8, combined dialysate/ultrafiltrate flow 1.5 L/h). Despite the broad therapeutic margin of fluconazole, drug monitoring is recommended with respect to the very limited number of investigations with relatively low dosages up to 200 mg/day and--which is of paramount importance--to achieve therapeutic drug levels in vital indications.