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Hyperfractionated Radiotherapy and Concurrent Chemotherapy for Stage III Unresectable Non Small Cell Lung Cancer : Preliminary Report for Response and Toxicity (절제 불가능한 제 3기 비소세포성 페암의 다분할 방사선 치료와 MVP 복합 항암요법의 동시 치료에 대한 예비적 결과)

  • Choi, Eun-Kyung;Kim, Jong-Hoon;Chang, Hye-Sook;Kim, Sang-We;Suh, Cheol-Won;Lee, Kyoo-Hyung;Lee, Jung, Shin;Kim, Sang-Hee;Ko, Youn-Suk;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong;Song, Koun-Sik
    • Radiation Oncology Journal
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    • v.13 no.2
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    • pp.157-162
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    • 1995
  • Lung cancer study group at Asan Medical Center has conducted the second prospective study to determine the efficacy and feasibility of MVP chemotherapy with concurrent hyperfractionated radiotherapy for Patients with stage III unresectable non-small cell lung cancer(NSCLC). All eligible Patients with stage III unresectable NSCLC were treated with hyperfractionated radiotherapy(120 cGy/fx BID. 6480 cGy/54fx) and concurrent 2 cycles of MVP(Mitomycin C $6mg/m^2,$ d2 & d29.Vinblastine $6mg/m^2,$ d2 & d29, Cisplatin $60mg/m^2,$ dl & d28) chemotherapy. Between Aug. 1993 and Nov. 1994, 62 patients entered this study; $6(10\%)$ had advanced stage IIIa and $56(90\%)$ had IIIb disease including 11 with pleural effusion and 10 with supraclavicular metastases. Among 62 patients, $48(77\%)$ completed planned therapy. Fourteen patients refused further treatment during chemoradiotherapy. Of 46 patients evaluable for response, $34(74\%)$ showed major response including $10(22\%)$ with complete and $24(52\%)$ with partial responses. Of 48 patients evaluable for toxicity, $13(27\%)$ showed grade IV hematologic toxicity but treatment delay did not exceed 5 days Two patients died of sepsis during chemoradiotherapy. Severe weight loss(more than $10\%)$ occurred in 9 patients$(19\%)$ during treatment. Nine patients$(19\%)$ developed radiation pneumonitis Six of these patients had grade 1 (mild) Pneumonitis with radiographic changes within the treatment fields Three other patients had grade 11 Pneumonitis, but none of these patients had continuous symptoms after steroid treatment. Concurrent chemoradiotherapy for patients with advanced NSCLC was well tolerated with acceptable toxicity and achieved higher response rates than the first study, but rather low compliance $rate(77\%)$ in this study is worrisome. We need to improve nutritional support during treatment and to use G-CSF to improve leukopenia and if necessary. supportive care will be given as in patients, Longer follow-up and larger sample size is needed to observe survival advantage.

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Methylenetetrahydrofolate Reductase C677T Polymorphism in Gastric Cancer (위암에서 Methylenetetrahydrofolate Reductase C677T의 유전자 다형성)

  • Seo Won;Park Won Cheol;Lee Jeong Kyun;Kim Jeong Jung
    • Journal of Gastric Cancer
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    • v.5 no.1
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    • pp.10-15
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    • 2005
  • Purpose: Recently the role of vitamins, folate in particular, has been emphasized in the maintenance of health. Folate deficiency is known to give rise to developmental delay, immature vascular disease, neural tube defect, acute leukemia, atherosclerotic vascular disease, delivery defects, breast cancer, and particularly gastrointestinal neoplasia. Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in folate metaboism, and influences DNA synthesis and DNA methylation. Generally, folate deficiency is associated with gastrointestinal neoplasms. The amino-acid- changing and enzyme-activity-reducing nucleotide polymorphism (766C$\rightarrow$T/ Ala222Val) has been described in the MTHFR polymorphism and leads to low enzyme activity that may reduce the capacity of DNA methylation and possibly uracil mis-incorporation into DNA. These processes may be critical in the oncogenic transformation of human cells, especially in colorectal carcinomas. We investigated the relationship between the MTHFR polymorphism in gastric cancer and the tumor site, the smoking history, and the alcoholic history. Materials and Methods: Ninety-six (96) individuals with gastric cancer and 287 healthy persons were analyzed. Blood sampling was performed, PCR-RFLP was analyzed, and MTHFR polymorphism genotypes of C/C, C/T, and T/T were obtained and analyzed statistically for their correlation. Results: In the gastric cancer group there were 69 ($72\%$) males and 27 ($28\%$) females. There were also 58 cases ($60\%$) involving the gastric lower body, 20 cases ($21\%$) the gastric mid-body, and 18 cases ($19\%$) the gastric upper body. In the control group there were 169 ($59\%$) males and 118 ($41\%$) females. Among the gastric cancer, 56 ($61\%$) smoking patients, 40 ($39\%$) non-smoking patients, 45($47\%$) alcoholic patients, 51 ($53\%$) non-alcoholic patients. In the gastric cancer group, MTHER polymorphisms were C/C in 18 ($19\%$) cases, C/T in 59 ($61\%$) cases, T/T in 19 ($20\%$) cases. In the control group polymorphisms were C/C 116 ($40\%$) cases, C/T 103 ($36\%$) cases, and T/T 68 ($24\%$) cases (P=0.045). In cases of lower gastric body cancer, polymorphisms were C/C in 16 ($24\%$) C/C in 16 ($24\%$) cases and C/T or T/T in 42 ($72\%$) cases. In cases of upper and mid-body cancer, polymorphisms were C/C in 2 ($5\%$) cases and C/T or T/T 36 ($95\%$) cases (P=0.006). In the non-smoking patient group, polymorphisms were C/C in 5 (12%) cases and C/T or T/T in 35 ($88\%$) cases. In the smoking patient group, C/C in 13 ($23\%$) cases and C/T or T/T in 43 ($77\%$) cases (P=0.189). In the non-alcoholic patient group, polymorphisms were C/C in 6 ($12\%$) cases and C/T or T/T in 45 ($88\%$) cases. In the alcoholic patient group, polymorphisms were C/C in 12 ($26\%$) cases and C/T or T/T in 33 ($74\%$) cases (P=0.063) Conclusion: MTHFR polymorphisms are associated with gastric cancer and tumor site, but not with smoking and alcohol drinking.

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Liability of the Compensation for Damage Caused by the International Passenger's Carrier by Air in Montreal Convention (몬트리올조약에 있어 국제항공여객운송인의 손해배상책임)

  • Kim, Doo-Hwan
    • The Korean Journal of Air & Space Law and Policy
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    • v.18
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    • pp.9-39
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    • 2003
  • The rule of the Warsaw Convention of 1929 are well known and still being all over the world. The Warsaw Convention is undoubtedly the most widely accepted private international air law treaty with some 140 countries. In the international legal system for air transportation, the Warsaw Convention has played a major role for more than half century, and has been revised many times in consideration of the rapid developments of air high technology, changes of social and economic circumstances, need for the protection of passengers. Some amendments became effective, but others are still not effective. As a result, the whole international legal system for air transportation is at past so complicated and tangled. However, the 'Warsaw system' consists of the Warsaw Convention of 1929 the Guadalajara Convention of 1961, a supplementary convention, and the following six protocols: (1) the Hague Protocol of 1955, (2) the Guatemala Protocol of 1971, (3) the Montreal Additional Protocols, No.1, (4) the Montreal Additional Protocol No.2, (5) the Montreal Additional Protocol No.3, and (6) the Montreal Additional Protocol No.4. of 1975. As a fundamental principle of the air carrier's liability in the international convention and protocols, for instance in the Warsaw Convention and the Hague Protocol, the principle of limited liability and a presumed fault system has been adopted. Subsequently, the Montreal Inter-carrier Agreement of 1966, the Guatemala City Protocol, the Montreal Additional Protocol No.3, and the Montreal Additional Protocol No. 4 of 1975 maintained the limited liability, but substituted the presumed liability system by an absolute liability, that is, strict liability system. The Warsaw System, which sets relatively low compensation limits for victims of aircraft accidents and regulates the limited liability for death and injury of air passengers, had become increasingly outdated. Japanese Airlines and Inter-carrier Agreement of International Air Transport Association in 1995 has been adopted the unlimited liability of air carrier in international flight. The IATA Inter-Carrier Agreement, in which airlines in international air transportation agree to waive the limit of damages, was long and hard in coming, but it was remarkable achievement given the political and economic realities of the world. IATA deserves enormous credit for bringing it about. The Warsaw System is controversial and questionable. In order to find rational solution to disputes between nations which adopted differing liability systems in international air transportation, we need to reform the liability of air carriers the 'Warsaw system' and fundamentally, to unify the liability system among the nations. The International Civil Aviation Organization(ICAO) will therefore reinforce its efforts to further promote a legal environment that adequately reflects the public interest and the needs of the parties involved. The ICAO Study Group met in April, 1998, together with the Drafting Committee. The time between the "Special Group on the Modernization and Consolidation of the 'Warsaw system'(SGMW)" and the Diplomatic Conference must be actively utilized to arrange for profound studies of the outstanding issues and for wide international consultations with a view to narrowing the scope of differences and preparing for a global international consensus. From 11 to 28 May 1999 the ICAO Headquarters at Montreal hosted a Diplomatic Conference convened to consider, with a view to adoption, a draft Convention intended to modernize and to integrate replace the instruments of the Warsaw system. The Council of ICAO convened this Conference under the Procedure for the Adoption of International Conventions. Some 525 participants from 121 Contracting States of ICAO attended, one non-contracting State, 11 observer delegations from international organizations, a total of 544 registered participants took part in the historic three-week conference which began on 10 May. The Conference was a success since it adopted a new Convention for the Unification of Certain Rules for International Carriage by Air. The 1999 Montreal Convention, created and signed by representatives of 52 countries at an international conference convened by ICAO at Montreal on May 28, 1999, came into effect on November 4, 2003. Representatives of 30 countries have now formally ratified the Convention under their respective national procedures and ratification of the United States, which was the 30th country to ratify, took place on September 5, 2003. Under Article 53.6 of the Montreal Convention, it enters into force on the 60th day following the deposit of the 30th instrument of ratification or acceptation. The United States' ratification was deposited with ICAO on September 5, 2003. The ICAO have succeeded in modernizing and consolidating a 70-year old system of international instruments of private international law into one legal instrument that will provide, for years to come, an adequate level of compensation for those involved in international aircraft accidents. An international diplomatic conference on air law by ICAO of 1999 succeeded in adopting a new regime for air carrier liability, replacing the Warsaw Convention and five other related legal instruments with a single convention that provided for unlimited liability in relation to passengers. Victims of international air accidents and their families will be better protected and compensated under the new Montreal Convention, which modernizes and consolidates a seventy-five year old system of international instruments of private international law into one legal instrument. A major feature of the new legal instrument is the concept of unlimited liability. Whereas the Warsaw Convention set a limit of 125,000 Gold Francs (approximately US$ 8,300) in case of death or injury to passengers, the Montreal Convention introduces a two-tier system. The first tier includes strict liability up to l00,000 Special Drawing Rights (SDR: approximately US$ 135,000), irrespective of a carrier's fault. The second tier is based on presumption of fault of a carrier and has no limit of liability. The 1999 Montreal Convention also includes the following main elements; 1. In cases of aircraft accidents, air carriers are called upon to provide advance payments, without delay, to assist entitled persons in meeting immediate economic needs; the amount of this initial payment will be subject to national law and will be deductable from the final settlement; 2. Air carriers must submit proof of insurance, thereby ensuring the availability of financial resources in cases of automatic payments or litigation; 3. The legal action for damages resulting from the death or injury of a passenger may be filed in the country where, at the time of the accident, the passenger had his or her principal and permanent residence, subject to certain conditions. The new Montreal Convention of 1999 included the 5th jurisdiction - the place of residence of the claimant. The acceptance of the 5th jurisdiction is a diplomatic victory for the US and it can be realistically expected that claimants' lawyers will use every opportunity to file the claim in the US jurisdiction - it brings advantages in the liberal system of discovery, much wider scope of compensable non-economic damages than anywhere else in the world and the jury system prone to very generous awards. 4. The facilitation in the recovery of damages without the need for lengthy litigation, and simplification and modernization of documentation related to passengers. In developing this new Montreal Convention, we were able to reach a delicate balance between the needs and interests of all partners in international civil aviation, States, the travelling public, air carriers and the transport industry. Unlike the Warsaw Convention, the threshold of l00,000 SDR specified by the Montreal Convention, as well as remaining liability limits in relation to air passengers and delay, are subject to periodic review and may be revised once every five years. The primary aim of unification of private law as well as the new Montreal Convention is not only to remove or to minimize the conflict of laws but also to avoid conflict of jurisdictions. In order to find a rational solution to disputes between nations which have adopted differing liability systems in international air transport, we need fundamentally to reform their countries's domestic air law based on the new Montreal Convention. It is a desirable and necessary for us to ratify rapidly the new Montreal Convention by the contracting states of lCAO including the Republic of Korea. According to the Korean and Japanese ideas, airlines should not only pay compensation to passengers immediately after the accident, but also the so-called 'condolence' money to the next of kin. Condolence money is a gift to help a dead person's spirit in the hereafter : it is given on account of the grief and sorrow suffered by the next of kin, and it has risen considerably over the years. The total amount of the Korean and Japanese claims in the case of death is calculated on the basis of the loss of earned income, funeral expenses and material demage (baggage etc.), plus condolence money. The economic and social change will be occurred continuously after conclusion of the new Montreal Convention. In addition, the real value of life and human right will be enhanced substantially. The amount of compensation for damage caused by aircraft accident has increased in dollar amount as well as in volume. All air carrier's liability should extend to loss of expectation of leisure activities, as well as to damage to property, and mental and physical injuries. When victims are not satisfied with the amount of the compensation for damage caused by aircraft accident for which an airline corporation is liable under the current liability system. I also would like to propose my opinion that it is reasonable and necessary for us to interpret broadly the meaning of the bodily injury on Article 17 of the new Montreal Convention so as to be included the mental injury and condolence. Furthermore, Korea and Japan has not existed the Air Transport Act regulated the civil liability of air carrier such as Air Transport Act (Luftverkehrsgestz) in Germany. It is necessary for us to enact "the Korean Air Transport Contract Act (provisional title)" in order to regulate the civil liability of air carrier including the protection of the victims and injured persons caused by aircraft accident.

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