Онкологія-

А.М.Гарін, І.С.Базін

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ВИСНОВОК

Рак підшлункової залози - трагічна глава клінічної онкологііпо смерті хвороби.

У стандартизованих показниках захворюваність РПЖ в Росії соответствуетзаболеваемості в інших Європейських країнах. Вражають отдаленниерезультати. Медіана виживання хворих з американським данним- 4,1 місяці, п`ять років виживають менше 5% хворих. Соотношеніепоказателей смертності до захворюваності за даними ВООЗ равняется0,99.

З результатів епідеміологічних досліджень найбільш важнифакти про зловісну роль куріння в етіології РПЖ, однозначні сужденіяо значенні дієти, зокрема, підвищеного споживання білкової м`яса.

Серед хімічних агентів найбільшу відповідальність несуть нітрозоаміни.

Сприятливими до РПЖ хворобами і станами вважаються діабет, хронічний панкреатит, операції на шлунку.

До генетичним аномалій при РПЖ відносять мутації генів р53, К-ras, DCC.

Найчастішою формою РПЖ є протоковая аденокарцинома.

Ранні симптоми РПЖ не специфічні і не до людей. Основниесімптоми, з якими приходять хворі РПЖ до онколога - болі мучітельногохарактера, жовтяниця, втрата ваги.

Серед методів діагностики найбільше значення мають ретрограднаяендоскопіческая холангиопанкреатография, комп`ютерна томографія, ультразонографія.

Серед маркерів основне значення надається рівню Са-19-9.

Єдино радикальний метод лікування хірургічний. Але всеголішь 5% хворих, які звертаються до онколога, резектабільни. 46% невозможновиполніть панкреатодуоденальную резекцію через місцеву інвазіісоседніх органів і лімфовузлів. 49% не проводиться операція через заотдаленних метастазів.

Остаточне рішення про резектабільності приймається на операціонномстоле.

До виконання радикальних операцій доцільно проведення желчеразгрузочнихоперацій, якщо у хворих є жовтяниця.

Панкреатодуоденальная резекції технічно дуже складні, операціідлятся більше 6,5 годин. Віддалений препарат зазвичай складається з общегожелчного протоки, жовчного міхура, головки, шийки і секреторнойчасті підшлункової залози, дванадцятипалої кишки, проксімальнойчасті тонкої кишки, дистальної половини шлунка. Але крім удаленіяорганов хірурги виконують також серію відновлювальних маніпуляцій (не менше 4 анастомозів).

До теперішнього часу тривають суперечки - чи потрібні ці операціііз високу післяопераційної летальності і поганих отдаленнихрезультатов?

У дев`яностих роках скоротилося число післяопераційних осложненійі підвищилися віддалені результати до 16%.

Велике значення мають паліативні хірургічні вмешательствадля контролю жовтухи і при здавленні пухлиною дванадцятипалоїкишки.

Клітини РПЖ радіочутливі. Зовнішнє опромінення (60 gy) приводитк виживання до протягом року близько 20% хворих з неректабільнимРПЖ. Медіана виживаності склала 29 тижнів. Для інтерстіціальнойлучевой терапії застосовують йод-125 та інші препарати. Средняявижіваемость при цьому - 11,6 місяців.

Використовується методика інтраопераційного опромінення (20-25 gy), як компонент комплексного лікування. Медіана виживання такіхбольних - 14 місяців.

Розпочато роботи по неоад`ювантної променевої терапії.

Хіміотерапія нерезектабільного раку в вісімдесятих роках опіраласьна використання фторурацилу, стрептозотоцином, митомицина, доксорубіцину, епірубіцину, іфосфаміду, нітрозосечовини. Ці препарати сохранілісвое значення і в наш час. Ефективність монотерапії НЕ превишает20%, при середній виживання - 20 тижнів.

У дев`яностих роках для характеристики ефекту при РПЖ пріняттакой параметр, як клінічне поліпшення. При цьому під вніманіепрінімалось якість життя, зниження споживання наркотиків, ослабленіеболей, збільшення ваги, поліпшення статусу Карновского.

Серед препаратів, які представляють особливі надії при лікуванні РПЖ, гемцитабін (вийшов на 1-шу лінію терапії) приводить до клінічного улучшеніюв діапазоні 48-66% хворих. Перспективні також нові інгібіторитіміділат синтетази (томудекс), таксани, комптотеціни.

Комбінування хіміопрепаратів має в якості основної задачіпродленіе життя хворих і поліпшення її якості. Перспектівникомбінаціі з включенням фторурацилу, гемзар, мітоміцину С і цисплатину.

Доведено доцільність ад`ювантної терапії РПЖ (опромінення + фторурацил, або фторураціловой комбінації).

Інтенсивно розробляються неоад`ювантної режими хіміотерапії (перед операціями або опроміненням).

Виклик, про який ми писали на початку книги, прийнятий онкологамі.Інтенсівное розвиток молекулярно-біологічних підходів, геннойтерапіі, поява нових лікарських та імунологічних препаратовпрібліжают до вирішення проблеми.

ЛІТЕРАТУРА

1. Цитовано по Douglass H.O., Kim S.Y., Meropol N.J. Neoplasmsof the exocrine pancreas. In "Cancer Medicine" Eds.HollandJ.F. et.al., 1997, Baltimore, pp.1989-2017.

2.Янішевскій В.І. Рак підшлункової залози, печінки, желчногопузиря і жовчних проток. В кн. "рання діагностікарака", М., 1948, 95-107.

3. Лепорський Н.І. Хвороби підшлункової залози. М., 1951.

4. Виноградов В.В. Пухлини і кісти підшлункової залози. М., 1959.

5. Людський А.Т. Хірургічні захворювання печінки і желчевиводящейсістеми М., 1963.

6. Шелагуров А.А. Хвороби підшлункової залози. М., 1970.

7. Вишневський А.А., Ульманис Я.Л., Гришкевич Е.В. Желчеотводящіеанастомози. М., 1972.

8. Шалімов А.А. Хвороби підшлункової залози і їх хірургіческоелеченіе. М., 1970.

9. Блохін М.М., Итин А.Б., Клименко А.А. Рак підшлункової железиі позапечінкових жовчних шляхів. М., 1982.

10. Parkin D.M., Pizani P., Ferlay J. Estimates of the worldwideincidence of eighteen major cancers in 1985. Int. J.Canc. 1993,54: 594-606.

11. Muir C., Waterhouse J., Mack T., et.al. Cancer Incidencein Five continents v.5, JARC Publ.88, 1988.

12. Facts and figures of cancer in the European community. EdsEsteve I., et.al., 1993, Lyon, p.26.

13. Wingo P.A., Tong T., Bolden S. Cancer statistics 1995. Can.j.clin., 1995- 45: 8-30.

14. сancer FACTS a: Figures - 1999. American Cancer Society

15.Трапезніков М.М., Аксель Е.М. Захворюваність злокачественниміновообразованіямі і смертність від них населення країн СНД в 1996 р. М., 1997..

16.Wynder E.L., Mabuchi K., Maruchi N. Et.al. Epidemiology ofcancer of the pancreas. J.Nat.Canc. Inst. 1973- 50: 645-667

17.Chadirian P., Simard A., Baillargeon J. Tabacco, alcohol andcoffee and cancer of the pancreas. Cancer 1991- 67: 2264-2270.

18.Bueno de Mesquita N.B., Maisonneuve P, Moerman C.J. Life-timehistory of smoking and exocrine carcinoma of the pancreas. A populationbased case-control study in the Netherlands. Int.j.Canc.- 1991 року, 49: 816.

19.Fraumeni J.F. Cancer of the pancreas and biliary tract: Epidemiologicalconsiderations. Canc.Res., 1975: 35: 3437-3446.

20.Wynder E.L. An epidemiological evaluation of the causes ofcancer of the pancreas. Canc.Res. 1975- 35: 2228-2233.

21. Kastan M.B., Onyekwere O., Sidransky D., et.al. Participationof p-53 protein in the cellular response to DNA damage. Canc.Res.1991-51: 6304-6311.

22. Hoffman D., Rivenson A., Chung F.L. et.al. Nicotine-derivedN-nitrosamines and their relevance in tobacco carci-nogenesis.Crit.Rev.Tox. 1991- 21: 305-311.

23.Falk R.T., Pickle R.W., Fontham E.T. et.al. Life-style riskfactors for pancreatic cancer in Louisiana: A case -control study.Am.j.Epid.1988, 128: 324-336.

24.Mack T.M., Yu M.C., Hanisch R., et.al. Pancreas cancer andsmoking, beverage consumption, and past medical history. J.Nat.Canc.Inst.1986- 76: 49-68.

25.Raymond L., Infante F., Tuyns A.J. et.al. Alimentation etcancer du pancreas. Gastr.Clin.Biol. 1987-11: 488-492.

26.O`Connor T.P., Roebuck B.D., Peterson E., Campbell T.C. Effectof dietary intake of fish proteins on the development of L-azaserineinduced preneoplastic lesions in the pancreas. J.Nat.Canc. Inst.1985- 75: 959-962.

27. Norell S.E., Ahibom A., Erwarld R., et.al Diet and pancreaticcancer: A case-control study / Am.j.Epid.1986- 124: 894-902.

28. Heuch I., Kvale G., Jacobsen B.K.et.al. Use of alcohol, tobaccoand coffee and risk of pancreatic cancer. Br.j.Canc. 1983- 48: 637-643.

29. Hakulinen T., Lehtimaki L., Lehtonen M., et.al. Cancer morbidityamong two male cohorts with increased alcohol consumption in Finland.J.Nat.Canc.Inst. 1974- 52: 1711-1714.

30 .Monson R., Lyon J. Proportional mortality among alcoholics.Canc. 1975- 36: 1077-1079.

31. Okuda K., Ohishi K. Pancreatic cancer and alcohol. Clin.Gastr.1981- 10: 479-484.

32. Mills P.K., Beeson L., Abbey D.E., et.al. Dietary habitsand past medical history as related to fatal pancreas cancer riskamong adventists. Canc.1988- 61: 2578-2585.

33. Gold E.B., Gordis L., Diener M.D., et.al. Diet and otherrisk factors for cancer of the pancreas. Canc.1985- 55: 460-467.

34.Ahlgren J.D. Epidemiology and risk factors in pancreatic cancer.Sem.in Oncol. 1996- 23: 241-250.

35. MacMahon B., Yen S., Trichopoulos D., et.al. Coffee and cancerof the pancreas. N.Engl.j.Med.1981- 304: 630-633.

36. Binstock M., Krakow D., Stamler J., et.al. Coffee and pancreaticcancer: An analysis of international mortality data. Am j.Epid.1983- 118: 630-640.

37. Clavel F., Benhamon E., Auquier A., et.al. Coffee, alcohol, smoking and cancer of the pancreas: a case-control study. Int.j.Canc.1989- 43: 17-21.

38. Kinlen L.J., McPherson K Pancreas cancer and coffee and teaconsumption. A case-control study. Br.j.Canc. 1984- 49: 93-96.

39. Mancuso T., El-Attar A. Cohort study of workers exposed tobetanaphthylamine and benzidine. J.Occup.Med. 1967- 9: 277.

40. Li F.P., Fraumeni J.T., Mantel M.A., Miller R.W. Cancer mortalityamong chemists. J.Nat.Canc.Inst. 1969- 43: 1 159.

41`. Garabrani D.H., Held J., Langholz B., et.al. DDT and relatedcompounds and risk of pancreatic cancer. J.Nat.Canc.Inst. 1992-84: 764-771.

42. Lynch H.T. Genetics and pancreatic cancer. Arch.Surg. 1994-126: 266.

43. Chadirian P., Simard A., Baillargeon J. Familial aggregationof pancreatic cancer a population-based case -control study. Proc.ASCO1988- ab.257.

44. Gullo L., Pezzili R., Morselli-Labate A.M., et.al. Diabetesand the risk of pancreatic cancer. N.Engl.Med. 1994- 331: 81-84.

45.Karmody A., Kyle J. The association between carcinoma of thepancreas and diabetes mellitus. Br.j.Surg.1969- 56: 362-364.

46. Lowenfeis A.B., Maisonnerve P., Cavallini G., et.al. An InternationalPancreatitis Study Group. Pancretitis and the risk of pancreaticcancer. N.Engl.j.Med.1993- 328: 1 433.

47.Mainz D., Webster P.D. Pancreatic carcinoma - a review ofetiologic considerations. Am.j.Dig.Dis 1974- 19: 459-464.

48. Offerhaus G.J.A., Tersmette A.C., Tersmette K., et.al. Gastricpancreatic and colorectal carcinogenesis following remote pepticulcer surgery. Mod.Pathol. 1988- 1: 352-356.

49. Borch K., Kullman E., Hallhagen S., et.al. Increased incidenceof pancreatic neoplasia in pernicious anemia. World j.Surg. 1988-12: 866-867.

50.Upp J.R., Olson D., Poston G.J., et.al. Inhibition of growthof two human pancreatic adenocarcinoma in vivo by somatostatinanalog Sms 201-995. Am. J.Surg 1984- 142: 308-311.

51.Jansen J.B.M. Cholecystokinin and pancreatic cancer. Scand.j.Gastr.1988- 22 (suppl 154): 103-106.

52. Howatson A.G., Carter D.C. Pancreatic carcinogenesis - effectof secretin in the hamster- nitrosoamine model. J.N.Canc .Inst.1987- 78: 101-103.

53. Redston M.S., Caldas C., Seymour A.B., et.al. P-53 mutationsin pancreatic carcinoma and evidence of common involvement ofhomocopolymer tract in DNA microdeletions. Canc.Res. 1994- 54: 1005-1014.

54. Nakamori S., Yashima K., Murakami Y., et.al Association p-53gene mutations with short survival in pancreatic adeno-carcinoma.Jpn.j.Canc.Res. 1996-86: 174-181.

55. Moskaluk C., Kern S. Molecular genetics of pancreatic cancer.In "Pancreatic Cancer". Ed. Reber H. New.Jersey 1998 pp.3-20

56. Bos J.L. Ras oncogens in humar cancer a review. Canc.Res.1998-49: 4682-4689.

57. Motojima K., Urano T., Nogato Y., et.al. Detection of pointmutations in the kirsten-ras oncogene provides evidence for themulticentricity of pancreatic cancer. Ann.Surg. 1993- 217: 138.

58. Nakamori S., Okami J., Shiozaki K., et.al. K-ras gene mutationsin plasma DNA are potential prognostic indicators for patientswith pancreatic cancer. Proc.ASCO, 1999, ab. 967.

59. Satoh K., Sasano H., Shimosegawa T., et.al. An immunohistochemicalstudy of the C-erb. B-2 oncogene product in intraductal mucin-hypersecretiveneoplasms and in ductal cells of the pancreas. Canc. 1993- 72:51.

60. Alexandrow M.G., Moses H.L. Transforming growth factor betaand cell cycle regulation. Canc.Res. 1995- 55: 1452-1457.

61. Caldas C., Hahn S.A., da Costa L.T., et.al. Frequent somaticmutations and homozygous deletions of the p-16 (MTSI) gene inpancreatic adenocarcinoma Nat.Gen. 1994-8: 27-31

62. Yamanaka Y., Friess H., Kobrin H.S. Coexpression of epidermalgrowth factor receptor and liganda in human pancreatic canceris associated with enhanced tumor aggressiveness. Anticanc.Res.1993- 13: 565-570.

63. Ishiwata T., Bergman U., Kornmann M., et.al. Altered expressionof insulin-like growth factor II receptor in human pancreaticcancer. Pancreas 1997 15: 367-373.

64. Porschen R., Remy U., Bevers G., et.al Prognostic significanceof DNA ploidy in adenocarcinoma of the pancreas. A flow cytometriastudy of paraffin embedded specimens. Canc. 1993- 71: 3841.

65. Cubilla A.L., Fitzgerald P.J., Fortner J.C. Pancreas cancerductcell adenocarcinoma: survival in relation to site, size, stageand type of therapy. J.Surg.Oncol. 1978- 10: 465-482.

66. Morohoshi T., Held G., Kloppel G. Exocrine pancreatic tumorsand their histological classification: A study based оn 167 autopsyand 97 surgical cases. Histopath. 1983- 7: 64-66.

67. Brennan M.F., Kinsella T., Friedman M. Cancer of the pancreas.In "Cancer Principles a Practice of Oncology". Eds.DeVitaVT., Et.al. 1989, pp.800-836.

68. Wanabe T., Miyashita T., Ohishio G., et.al. Small carcinomaof the pancreas clinical and pathologic evaluation in 17 patients.Canc. 1988- 62: 135.

69. Wilentz R.E., Slebos R.J.C., Hruban R.H. Screening for pancreaticcancer using techniques to detect altered gene products. In "PancreaticCancer" Ed. Reber H.A., 1998, pp.113-136.

70. Cancer of the Pancreas Task Force: staging of cancer of thepancreas. Canc.1981-47: 1631.

71.Fortner J.G. Regional pancreatectomy for cancer of the pancreaticampulla with other related sites. Tumor staging and results. AnnSurg. 1984- 199, 418.

72. Horton J. Dominant symptoms and signs of pancreatic carcinoma.Curr.Conc. in Oncol. 1989- 1:37.

73.Go V.L.W., Taylor W.F., Di Magno E.P. Efforts at early diagnosisof pancreatic cancer. The Mayo Clinic Experience. Canc.1981- 47: 1698 Росія.

74.Fras J., Litin E.M., Pearson J.S. Comparison of psychiatricsymptoms in carcinoma of the pancreas with those in some otherintra-abdominal neoplasms. Am.j.Psych. 1967- 123: тисяча п`ятсот п`ятьдесят-три.

75.Kalsen M.H., MacIntyre J.M., Barkin J. Pancreatic cancer-assessmentof prognosis by clinical presentation. Castr. 1983- 84: 1202.

76. Fitzgerald P.J., Fortner J.G., Watson R.C. The value of diagnosticaids in detecting pancreatic cancer. Canc. 1978- 41: 868.

77. Neiderau C., Sonnenberg B., Muller J.E., et.al. Sonographicmeasurements of the normal liver, spleen, pancreas and portalvein. Radiol. 1983-149: 537.

78. Fernandez-del Castillo C., Warshaw A.L. Diagnosis and preoperativeevaluation of pancreatic cancer, with implications for management.Garstr.Clin.North.Am 1990-19: 915-933.

79. Frank B.B. Clinical evaluation of Jaundice: a guideline ofthe patient care committee of the American GastroenterologicalAssociation. Jama 1989, 262: 3031-3034.

80. Ward E.M., Stephens D.H., Sheedy P.F. Computed tomographiccharacteristics of pancreatic carcinoma: An analysis of 100 cases.Radiol. 1983- 3: 547-565.

81. Freeng P.C., Traverso L.W., Ryan J.A. Diagnosis and stagingof pancreatic adenocarcinoma with dynamic computed tomography.Am.j.Surg. 1993- 165: 600-606.

82. Toshifumi G., Matsui O., Kadoye M., et.al. Small pancreaticadenocarcinomas- efficacy of MK imaging with fat suppression andgadolinium enhancement. Radiol. 1994- 193: 683-688.

83. Hall T.J., Blackstone M.O., Cooper M.J.et.al. Prospectiveevaluation of endoscopic retrograde cholangiopancreatography inthe diagnosis of periampullary cancer. Ann.Surg. 1978- 187: 313.

84. Fockens P., Huibregtse K. Staging of pancreatic and ampullarycancer by endoscopy. Endosc., 1993- 25: 52-57.

85. Moossa A.R., Levin B. The diagnosis of "early"pancreatic cancer- the university of Chicago experience. Canc.1981- 47: 1688.

86. Cuesta M.A., Meijer S., Borgstein P.J. et.al. Laparoscopicultrasonography for hepatobiliary and pancreatic malignancy .Br.j.Surg. 1993- 80: 1571-1574

87. John T.G., Greig J.D., Crosbie J.L., et.al. Superior stagingof liver tumors with laparascopy and laparascopic ultrasound.Ann.Surg. 1994- 220: 711-719.

88. Hyoty M.K., Mattila J.J., Salo K., et.al. Intraoperativefine needle aspiration cytological examination of pancreatic lesions.Surg.Gyn.Obst. 1991- 173: 193-197.

89. Ferrari A.P., Lichtenstein D.R., Sivka A., et.al. Brush cytologyduring ERCP for the diagnosis of biliary and pancreatic malignancies.Gastr.Endogc. 1994- 40: 140.

90. Rollhauser C., Steinberg W. Tumor antigens in pancreaticcancer. In "Pancreatic Cancer" . Ed.Reber H.A., 1998Humane Press

91. Aziz D.C. Use and interpretation of laboratory tests in oncology1999, pp.55-56

92. Steinberg W. The clinical utility of the Ca-19-9 tumorassociatedantigen. Am j.Gastr. 1990- 85: 350-355.

93. Malesci A., Tommasini M.A., Bonato C., et.al. Determinationof Ca-19-9 antigen in serum and pancreatic juice for differentialdiagnosis of pancreatic adenocarcinoma from chronic pancreatitis.Gastroent. 1989- 92: 60-67.

94. Piantino P., Andriulli A., Gindro T., et.al. Ca-19-9 assayin differential diagnosis of pancreatic carcinoma from inflammatorypancreatic diseases. Am j.Gastr. 1986- 8: 346.

95. Steinberg W.M., Gelfand R., Anderson K.K., et.al. Comparisonof the sensitivity and specificity of the Ca-19-9 and carcinoembryonicantigen assays in detecting cancer of the pancreas. Gastroent.1986- 90: 343.

96. Haglund C., Roberts P.J., Jalanko H., Kuusela P. Tumor markersCA-19-9 and Ca 50 in digestive tract malignancies. Scand.j.Gastr.1992- 26: 169-173

97. Mahvi D.M., Meyers W.S., Bost R.C., et.al. Therapeutic efficacyas defined by a serodiagnostic test utilizing a monoclonal antibodyin carcinoma of the pancreas. Ann. Surg. 1985- 202-440.

98. Robles-Diaz G., Diaz-Sauchez V., Mendez J.P. et.al. Low Serumtestosterone / dihydrotestosterone ratio in pancreatic carcinoma.Pancreas 1987- 2: 684-687.

99. Gudjonsson B. Cancer of the pancreas: 50 years of surgery.Canc. 1987- 60: 2284-2303.

100. Nitecki S.S., Sarr M.G., Colby T.V., et.al. Long-term survivalafter resection for ductal adenocarcinona of the pancreas. Isit really improving? Ann Surg. 1995- 221: 59-66.

101. Yeo C.J., Cameron J.K., Lillemoe K.D., et.al. Pancreaticoduodenectomyfor cancer of the head of the pancreas: 201 patients. Ann.Surg.1995- 221: 721-733.

102. Trede M., Schwall G., Saeger H. Survival after pancreaticoduodenectomy: 118consecutive resections without an operative mortality. Ann.Surg.1990- 211: 447-458.

103. Norlander A., Kalin B., Sundblad R. Effect of percutaneoustranshepatic drainage upon liver function and postoperative mortality.Surg.Gyn.Obst. 1982- 155: 161.

104. Gundry S.R., Strodel W.E., Knol J.A., et.al. Efficacy ofpreoperative biliary tract decompression in patients with obstructivejaundice. Arch.Surg. 1984- 119: 703.

105. McPherson G.A., Benjamin I.S., Hodgson H.J., et.al. Preoperativepercutaneous transhepatic biliary drainage: The results of a controlledtrial. Br.j.Surg. 1984- 71: 371-375.

106. Pitt H.A., Gomes A.S., Lois J.F., et.al. Does preoperativepercutaneous biliary drainage operative risk or increase hospitalcost? Ann.Surg. 1985- 201: 545-553.

107. Pisters P.W.T., Lee J.A., Evans D.B. Standard forms of pancreaticresection. In "Pancreatic Cancer". Ed.Reber H.A., 1998, pp.181-199.

108. Fuhrman G.M., Leach S.D., Staley C.A., et.al. Rationalefor en bloc vein resection in the treatment of pancreatic adenocarcinomsadherent to the superior mesenteric- portal vein confluence. Ann.Surg.1996-223: 152-164.

109. Grace P.A., Pitt H.A., Longmire W.P. Pylorus preservingpancreaticoduodenectomy: an overview. Br.j.Surg. 1990- 77: 968-974.

110. Lillemoe K.D. Current management of pancreatic carcinoma.Ann.Surg.1995- 221: 133-148.

111. McGrath P.C., Sloan D.A., Kenady E. Surgical managementof pancreatic carcinoma. Sem.Oncol., 1996: 23: 2, 200-212.

112. Geer R.J., Brennan M.F. Prognostic indicators for survivalafter resection of pancreatic adenocarcinoma. Am.j.Surg. 1993-165: 68-73.

113. Патютко Ю.І., Котельников А.Г. Рак підшлункової залози: діагностика та хірургічне лікування на сучасному етапі. Анналихірург.гепатологіі 1998 3-1: 96-111

114. Kummerle F., Ruckert K., Surgical treatment of pancreaticcancer. World Surg. 1984- 8: 889-894.

115.Van Heerdan J.A., ReMine W.H., Weiland L.H., et.al. Totalpancreatectomy for ductal adenocarcinoma of the pancreas Mayoclinic experience. Am j.Surg. 1981- 142: 308-311.

116. Fortner J.C. Regional resection of cancer of the pancreas: a new surgical approach. Surg. 1973 73: 658-662.

117. Fortner J.G. Regional pancreatectomy for cancer of the pancreas, ampulla and other related sites. Ann Surg. 1984- 199: 418-425.

118. Manabe T., Ohshio G., Baba N., wt.al. Radical pancreatectomyfor ductal cell carcinoma of the head of the pancreas. Canc. 1989-64: 1132-1137.

119. Satake K., Nishiwaki H., Yokomatsu H. Et.al. Surgical curabilityand prognosis for standard versus extended resections for T-1carcinoma of the pancreas. Surg.Gyn. Obstr. 1992- 175: 259-265.

120. Geer R.J., Brennan M.F. Prognostic indicators for survivalafter resection of pancreatic adenocarcinoma. Am j.Surg. 1993-168: 68-73.

121. Singh S.M., Longmire W.P., Reber H.A. Surgical palliationfor pancreatic cancer. The UCLA experience. Ann Surg. 1990- 212: 132-139.

122. Забазний Р.П. Операції на органах біліопанкреатодуоденальнойзони у хворих, які перенесли лікування з приводу різних злокачественнихопухолей. Автореф. докт.дісс. М., 1999.

123. Wong R.C.K., Carr- Locke D.L. Endoscopic stents for palliationin patients with pancreatic cancer. In "Pancreatic Cancer"Ed.Reber H., 1998, pp.235-252.

124. Weaver D.W., Wiencek R.G., Bouwman D.L., et.al. Gastrojejunostomy: Isit helpful for patients with pancreatic cancer? Surg. 1987- 102: 608-613.

125. Wongsuwanporn T., Basse E. Palliative surgical treamentof sixty-eight patients with carcinoma of the head of the pancreas.Surg.Gyn.Obstr. 1993- 156: 73-75.

126. Malangoni M.A., McCoy M.D., Richardson J.D., et.al. Effectivepalliation of malignant biliary duct obstruction. Ann Surg. 1985-201: 554-559.

127. Smilanich R.P., Hafner G.H. Complications of biliary stentsin obstructive pancreatic malignancies. A case report and review.Dig.Dis.Sci. 1994- 39: 2645-2649.

128. Maetani I., Ogawa S., Hoshi H., et.al. Self-expanding metalstents for palliative treatment of malignant biliary and duodenalstenoses. Endosc. 1994-26: 703-704.

129 .Lillemoe K.D., Cameron J.L., Kaufman H.S., et.al. Chemicalsplanchnicectomy in patients with unresectable pancreatic cancer.A prospective randomized trial. Ann Surg. 1993- 217: 447-457.

130. Moertel C.G., Reitemeier R.J. Advanced Gastrointestinalcancer clinical management and chemotherapy NY, 1969, p.7.

131. Maity A., Kao G.D., Muschel R.J., McKenna W.G. Potentialmolecylar targets for manipulating the radiation response. Int.j.Rad.Oncol., Biol.Phys. 1997-37: 639-653.

132. Miller T.R., Fuller L.M. Radiation therapy of cancer ofthe pancreas. Report on 91 cases. Am j. Roentg. 1958- 80: 787-792.

133. Sindelar W.F., Kinsella T.J. Randomized trial of intraoperativetherapy in resected carcinoma of pancreas. Int.j.Rad.Oncol. Biol.Phys.1986- 12: 148.

134. Dowsett J.F., Russell R.C.G. Tumors of the pancreas. In"Oxford Textbook of oncology" Ed.Peckham et.al., 1996, pp.1177-1201

135. Rich T.L. Radiation therapy for pancreatic cancer. In "PancreaticCancer". Ed.Reber H.A .. Humane Press 1998 pp.281-294.

136. Coja L., Hoffman J., Scher R., et.al. Preoperative chemoradiationfor adenocarcinoma of the pancreas and duodenum. Int.Rad.Oncol.Biol.Phy. 1994- 30: 161-167.

137. Peretz T., Nori D., Hilaris B., et.al Treatment of primaryunresectable carcinoma of the pancreas with I-125 implantation.Int.j.Rad, Oncol. Biol.Phys.1989- 17: 931-935.

138. Abe M., Takahashi M., Yabumoto E., et.al. Clinical experienceswith intraoperative of locally advanced cancer. Canc. 1980 45: 40-48.

139. Roldan G.E., Gundersen L.L., Nagorney D.M., et.al. Externalbeam versus intraoperative and external beam irradiation for locallyadvanced pancreatic cancer. Canc. 1988- 61: 1110-1116.

140. Shibamoto Y., Manabe T., Baba N., et.al. High dose, externalbeam and intraoperative radiotherapy in the treatment of resectableand unresectable pancreatic cancer. Int.j..Rad.Oncol.Biol.Phys.1990- 19: 605-611.

141. Roldan G.E., Gunderson L.L., Nagorney D.M., et.al. Externalbeam versus intraoperative and external beam irradiation for locallyadvanced pancreatic carcinoma. Canc. 1989- 61: 1110 Отримати.

142. Lionetto R., Pugliese V., Bruzzi P., et.al. No standarttreatment is available for advanced pancreatic cancer. Eur.j.Canc.1995- 6: 882-887.

143. Climelius B., Hoffman K., Sjoden P.O., et.al. Chemotherapyimproves survival and quality of life in advanced pancreatic cancerand biliary cancer. Ann Oncol. 1996: 7: 593-600.

144. Гарін А.М., хлібні А.В. Довідник практичної хіміотерапііопухолей М., 1995.

145. Гарін А.М. Місце і значення антиметаболітів в хіміотерапіізлокачественних пухлин. М., 1999..

146.Moertel C.G. Chemotherapy of gastrointestinal cancer. Clin.Gastr.1976- 5: 777-793.

147.Carter S.K., Comis R.L. The integration of chemotherapy intoa combined modality approach for cancer treatment. Canc.Treat.Rev.1975-2: 193-214.

148. Schnall S., Macdonald J.S. Chemotherapy of adenocarcinomaof the pancreas. Sem.in Oncol. 1996- 23: 2,220-228.

149. Ahlgren J.D. Pancreatic cancer. In "Chemotherapy ofadvanced disease". Eds. Ahlgren J.a Macdonald J., 1992 pp.227-235.

150. Ardalan B., Singh G., Silberman H. A randomized phase Iand II study of short-term infusion of high-dose fluorouracilwith or without N- (phosphonacetyl) -L-asparatic. Acid in patientswith advanced pancreatic and colorectal cancer. J.clin.Oncol.1988-6: 1053-1058.

151.Guevara S., et.al. Ambulatory treatment with 5-FU in prolongedcontinuous infusion for advanced adenocarcinoma. Proc.ESMO 1996 ab.247.

152. Marsh R.D.W., Manyam V., Bewsher C., et.al. Circadian rhythmmodulated 5-FUDR infusion with megace in the treatment of advancedpancreatic cancer. J.Surg Oncol., 1994-57: 25-29.

153. Oman M., Blind P., Gustavsson B., et.al. Intraperitoneal5-fluorouracil treatment in patients with non resectable pancreaticcarcinoma. Proc. ECCO 9, ab.1280.

154.DeCaprio J.A., Mayer R.J., Gonin R., et.al. Fluorouraciland high-dose leucovorin in previously untreated patients withadvanced adenocarcinoma of the pancreas: Results of a phase IItrial. J.clin.Oncol. 1991- 9: 2128-2133.

155. Pozzo C .. The Modulation of 5-fluorouracil with S-Leucovorinin the treatment of advanced pancreatic cancer: Only an attemptto improve quality of life. Proc. ESMO 1996 року, ab.252.

156. Morrell L.M., Bach A., Richman S.P., et.al. A phase II multi-institutionaltrial of low-dose N- (phosphanacetyl) L-aspartate and high-dose5-fluorouracil as a short-term infusion in the treatment of adenocarcinomaof the pancreas. Canc. 1991- 67: 363-366.

157. Ardalan B., Sridhar K.S., Benedetto P., et.al. A phase I, II study of high-dose leucovorin with low-dose phosphonace-tyl-L-asparticacid in patients with advanced malignancies. Cancer 1991- 68: 1242-1246.

158. Rosvold E., Schilder R., Walczak J. et.al. Phase II trialof pala in combination with 5-fluorouracil in advanced pancreaticcancer. Canc.Chem.Pharm. 1992- 29: 305-308.

159. Pazdur R., Ajani J.J., Abbruzzese J.L., et.al. Phase IIevaluation of fluorouracil and recombinant 2a-interferon in pre-viouslyuntreated patients with pancreatic adenocarcinoma. Canc. 1992-70: 2073-2076.

160. Scheithauer W., Pfeffel F. ,, Komek G., et.al. A phase IItrial of 5-fluorouracil, leucovorin and recombinant alpha-2b-interferonin advanced adenocarcinoma of the pancreas. Canc. 1992- 70: 1864-1866.

161. Ikeda M., Okada S., Ueno H., et.al. A phase II study ofsequential methotrexate and 5-fluorouracil in metastatic pancreaticcancer. Proc. ASCO 1999 року, ab.1101.

162. Fiorentini G., Poddie D., Graziani G., et.al. Locoregionalchemotherapy with mitomycin C administered as intra-aortic stop-flowinfusion with hypoxic abdominal perfusion. Proc.ASCO 1997 ab.1024.

163. Moertel C.G., Schutt A., Reitemeier R.J., et.al. Therapyfor gastrointestinal cancer with the nitrosoureas alone and indrug combination. Canc. Treal.Rep. 1976- 60: 729-732.

164. Schein P.S., Lavin P.T., Moertel C.G., et.al. Randomizedphase II study clinical trial of adriamycin, methotrexate andactinomycin D in advanced measurable pancreatic carcinoma. Canc.1978-42: 19-26.

165. Yip D., Halford S., Karapetis C .. et.al. A phase II trialof callyx in the treatment of advanced pancreatic carcinoma. Proc.ASCO1999, ab.1177.

166. Gastrointestinal Tumor study Group Phase II trials of thesingle agents baker`s antifol, diaziguone and epirubicin in advancedpancreatic cancer. Canc.Treat.Rep. 1987- 71: 865-867.

167. Cersosimo R.J., Hong W.K. Epirubicin .A review of the pharmacology, clinical activity ang adverse effect of an adriamycin analogue.J.Clin.oncol. 1986- 4: 425-439.

168. Wils J., Bleiberg H., Blijham G., et.al. Phase II studyof epirubicin in advanced adenocarcinoma of the pancreas. Eur.j.Canc.Clin.Oncol.1985, 21: 191-194.

169. Hochser H., Green M.D., Speyer J.L., et.al. Activity ofepirubicin in pancreatic carcinoma. Canc.Treat.Rep. 1986, 70: 299-200.

170. Loehrer P.J., Williams S.D. Ifosfamide: An active drug inthe treatment of adenocarcinoma of the pancreas. J.clin.Oncol.1985- 3: 367-372.

171. Ajani J.A., Abbruzzese L., Goudeau P., et.al. Ifosfamideand Mesna: Marginally active in patients with advanced carcinomaof the pancreas. J.Clin.Oncol. 1988- 6: 1703-1707.

172. The Gastrointestinal Tumor study Group: Ifosfamide is aninactive substance in the treatment of pancreatic carcinoma. Canc.1989- 64: 2010-2013.

173. Cerny T., Martinelli G., Goldhirsch A., et.al. Continuous5-day infusion of ifosfamide with mesna in inoperable pancreaticcancer patients: A phase II study. J.Canc.Res.Clin.Oncol.1991-117: 135-138.

174. Wils J.A., Kok T., Wagener D.J.Th., et.al. Phase II trialwith ifosfamide in pancreatic cancer. Eur.J.Canc. 1993- 29: 290.

175. Judson I.R. Tomudex (raltitrexed) development: preclinical, phase I and II studies. Anticanc. drugs 1997 8: suppl.2: 5-9.

176. Pazdur R., Casper E.S., Meropol N.J., et.al. Phase II trialof tomudex a thymidilate synthase inhibitor in advanced pancreaticcancer. Proc.ASCO 1994- ab.613.

177. Pazdur R., Meropol N.J., Casper E.S., et.al. Phase II trialof zd один тисяча шістсот дев`яносто чотири (Tomudex) in patients with advanced pancreatic cancer.Invest.New Drugs 1995- 13 (4): 355-358.

178. Hanauske A.R. The development of new chemotherapeutic agents.Anticanc. Drugs 1996- 7 (2): 29-32.

179. Ota K., Taguchi T., Kimura K. Report on nationwide pooleddata and cohort investigation in UFT Phase II study. Canc.Chem.Pharm.1988: 22: 333-338.

180. Sadahiro S., Mukai M., Tokunaga N., et.al. Preliminary studyof the new optimal dosage schedule for oral UFT. Proc.ASCO 1997 ab.726.

181.Orita K., Tanaka N., Goehi A., et.al. Clinical trial of immunochemotherapywith OH-I preparation (1NF-a) and UFT (uracil-tegafur) in unresectablepancreatic cancer. Proc.ASCO, 1995 ab.339.

182. Ardalan B., Sparling L., Livingstone A., et.al. Phase IItrial of high-dose 24-hour infusion of 5-fluorodeoxyuridine inpatients with inoperable pancreatic cancer (previously failed5-FU and Gemzar). Proc.ASCO 1997, ab.999.

183. Wagener D.J., Verdonk H.E.R., Dirix L.Y., et.al. Phase IItrial of CPT-11 in patients with advanced pancreatic cancer. AnEORTC Early Clinical Trials Group Study. Ann Oncol.1995- 6: 102-104.

184. Sakata Y., Waku A., Nakao I., et.al. A late phase II studyof irinotecan in advanced pancreatic cancer. Proc. ASCO, 1993, ab.633.

185. Brown T., Tangen C., Fleming T., et.al. A phase II trialof taxol and granulocyte colony stimulating factor (G-CSF) inpatients with adenocarcinoma of the pancreas. Proc. ASCO 1993, ab.200.

186. Vеrweij J., Clavel N., Chevalier B. Paclitaxel (Taxol TN) and docetaxel (Taxotere) not simply two of a kind. Ann Oncol.1994-5: 495-505.

187. Okada S., Taguchi T. Phase II trial of docetaxel (taxotere) as first-line chemotherapy in patients with metastatic pancreaticcancer: a japanese cooperative study. Proc.ASCO 1998 ab.1019.

188. Rougier Ph., De Forni M., Adenis A., et.al. Phase II studyof taxotere in pancreatic adenocarcinoma. Proc.ASCO 1994- ab.587.

189. Kouroussis Ch., Kakolyris S., Samelis G., et.al. Treatmentof advanced pancreatic cancer with docetaxel. A multicenter phaseII study. Proc.ASCO 1998- ab.1021.

190. Preusser P., Niederle N., Harstrick A., et.al. Phase IIstudy of Docetaxel as first line chemotherapy in metastatic adenocarcinomaof the pancreas. Proc.ASCO 1999 року, ab.1142.

191. Heinemann V., Hertel L.W., Grindley G.B., et.al. Comparisonof the cellular pharmacokinetics and toxicity of 2`2`-difluorodeoxycytidineand 1-b-D arabinofuranosylcytosine. Canc. 1988- 48: 4024-4031.

192. Plunkett W., Huang P., Xu Y.Z., et.al. Gemcitabine: Metabolism, mechanism of action and self-potentiation. Sem.oncol. 1995 року, 22: 4 (suppl.11), 3-10.

193. Heinemann V., Schulz L., Issels R.D., Plunkett W. Gemcitabine: A modulator of intracellular nucleatide and deoxynucleotide metabolism.Sem.oncol., 1995- 22: 4 (suppl 11), 11-18.

194. Гарін А.М., Базин І.С. Гемцитабін - новий перспектівнийпрепарат з групи антиметаболітів М., 1999..

195. Peters G. Antimetabolites. In "Oxford textbook of oncology".Eds.Peckham M., et.al., 1995 v.1, pp.524-552.

196. Casper E.S., Kelsen D.P., Kresek T., Tarassoff P. Gemcitabine (2`2`-difluorodeoxycytidine): evidence of activity in patientswith adenocarcinoma of exocrine pancreas. Ann.Oncol. 1990- 1 (suppl): 35.

197. Casper E.C., Green M.R., Brown T.D. Phase II trial of gemcitabine (2`2`-difluorodeoxycytidine) in patients with pancreatic cancer.Proc.ASCO, 1991- ab.440.

198. Casper E.S., Green M.R., Kelsen D.P., et.al. Phase II trialof gemcitabine in patients with adenocarcinoma of the pancreas.Invest New Drugs. 1994- 12 (1): 29-34.

199. Carmichael J., Russel R.G., Spittle M.F., et.al. Phase IIstudy of gemcitabine in chemonaive patients with pancreatic cancer.Ann.Oncol 1992 3 (suppl 5): 190.

200. Fink U., Russel R.C., Spittle M.F., et.al. Phase II studyof gemcitabine in patients with advanced pancreatic cancer. Eur.j.canc.1993-29 (suppl.6): 101.

201. Carmichael J., Fink U., Russell R.G., et.al. Phase II studyof gemcitabine in patients with advanced pancreatic cancer. Br.j.Canc.1996- 73: 1, 101-105.

202.Rothenberg H.A., Burris H.A., Andersen J.S. Gemcitabine: palliative therapy for pancreas cancer patients failing 5-FU.Proc.ASCO, 1995, ab.470.

203. Andersen J.S., Burris H.A., Casper E., et.al. Developmentof a new system for assessing clinical benefit for patients withadvanced pancreatic cancer. Proc, ASCO, 1994, ab.1600.

204. Moore M., Andersen J., Burris H., et.al. A randomized trialof gemcitabine versus 5-FU as first line therapy in advanced pancreaticcancer. Proc.ASCO, 1995, ab.473.

205. Rothenberg M.L., Moore M.J., Cripps M.C., et.al. A phaseII trial of gemcitabine in patients with 5-FU-refractory pancreascancer. Ann of oncol. 1996- 7: 4, 347-353.

206. Storniolo A.M., Enas N.H., Brown C.A., Schilsky R. Treatmentinvestigation new drug program for gemzar in patients with pancreaticcancer. Proc. ASCO, 1997 ab.1088.

207. Tempero M., Plunkett W., van Haperen V.R. Randomized phaseII trial of dose intense gemcitabine by standard infusion vs fixedrate in metastatic pancreatic adenocarcinoma. Proc.ASCO 1999 року, ab.1048.

208. Weissmann L., Ludwig H. Intraarterial gemcitabine for treatmentof inoperably pancreatic and cholongiocarcinoma. Proc. ASCO 1999 року, ab.1170.

209. Spagnuolo P., Roversi R., Rossi G., et.al. Phase II studyof gemcitabine as locoregional treatment of advanced pancreaticcancer. Proc. ASCO 1999 року, ab.1153.

210. Rosemurgy L., Buckels J., Charnley R., et.al. A randomizedstudy comparing marimastat to gemcitabine es first line therapyin patients with non-resectable pancreatic cancer. Proc. ASCO1999, ab. 1005.

211. Evans T.R.J., Mansi J.L., Lofts F.J., et.al. EB-1089 (secalcitol) in pancreatic cancer. Preliminary results of an open uncontrolledphase II study. Proc. ASCO, ab.1085

212. Macdonald J.S., Wooley P.V., Smythe T., et.al. 5-fluorouracil, adriamycin and mitomycin C (FAM) combination chemotherapy in thetreatment of advanced gastric cancer. Canc. 1979- 44: 42-47.

213. Smith F.P., Hoth D.F., Levin B., et.al. 5-fluorouracil, adriamycin and mitomycin C (FAM) chemotherapy for advanced adenocarcinomaof pancreas. Cancer 1980 46: 2014-2018.

214. Bitran J.D., Desser R.K., Kozloff M.F., et.al. The treatmentof metastatic pancreatic and gastric adenocarcinoma with 5-fluorouracil, adriamycin and mitomycin C (FAM). Canc.Treat.Rep. 1979-63: 2049-2051.

215. The Gastrointestinal Tumor Study Group: Phase II studiesof drug combinations in advanced pancreatic carcinoma fluorouracilplus doxorubicin + mitomycin C and two regimens of streptozotocinplus mitomycin C plus fluorouracil. J.Clin.Oncol 1986- 41: 1794-1798.

216. Oster M.W., Gray R., Panasci L., et.al. Chemotherapy foradvanced pancreatic cancer. Canc. 1986- 57: 29-33.

217. Bukowski R.M., Schacter L.P., Groppe C.W., et.al. PhaseII trial of 5-fluorouracil, adriamycin, mitomycin C and strepto-zotocin (FAMS) in pancreatic carcinoma. Canc. 1982- 50: 197-200.

218. Bukowski R.M., Fleming T.R., Macdonald J.S., et.al. Evaluationof combination chemotherapy and phase II agents in pancreaticadenocarcinoma. A Southwest Oncology Group Study. Canc. 1993-71: 322-325.

219. Karlin D.A., Strochlein J.R., Bennets R.W., et.al. PhaseI-II study of the combination of 5-FU, doxorubicin, mitomycinC and semustine (FAMMC) in the treatment of adenocarcinoma of thestomach, gastroesophagel junction, and pancreas. Canc. Treat.Rep.1982- 66: 1613-1617.

220. Wiggans R.G., Wooley P.V., Macdonalds J.S., et.al. PhaseII trial of streptozotocin, mitomycin C and 5-fluorouracil (SMF) in the treatment of advanced pancreatic cancer. Canc. 1978- 41: 387-391.

221. Bukowski R.M., Balcerzoc S.P., O`Bryan R.M., et.al. Randomizedtrial of 5-FU and mitomycin C with or without streptozotocin foradvanced pancreatic cancer. Canc. 1983- 52: 1577-1582.

222. Mallinson C.N., Rake M.O., Cocking J.B., et.al. Chemotherapyin pancreatic cancer: results of a controlled, prospective andrandomized trial. Br.Med.j. 1980- 281: 1589-1591.

223. Cullinan S., Moertel C.G., Wieand H.S., et.al. A phase IIItrial on the therapy of advanced pancreatic carcinoma. Canc. 1990-65: 2207-2212.

224. Kovach J.S., Moertel C.G., Schutt A., et.al. A controlledstudy of combined 1,3-bis- (2-chlorethyl) -1-nitrosourea and 5-fluorouraciltherapy for advanced gastric and pancreatic cancer. Canc. 1974-33: 563.

225. Buroker T., Kim P.N., Croppe C., et.al. 5-FU infusion withmitomycin C v.s. 5-FU infusion with methyl-CCNU in the treatmentof advanced upper gastrointestinal cancer. Canc. 1979- 44: 1215-1221.

226. Horton J., Gelber R., Engstrom P., et.al. Trials of singleagent and combination chemotherapy for advanced cancer of thepancreas. Canc.Treat.Rep. 1981- 65: 65-68.

227. Bremer K. Primary treatment of advanced gastric and pancreaticadenocarcinomas with 5-fluorouracil, folinic acid and mitomycinC. Second international conference on biology, prevention andtreatment of gastrointestinal malignancies- 1995- ab, 57.

228. Maiello E., Gebbia V., Giuliani F., et.al. ELFE (etoposide, folinic acid, 5-fluorouracil and epirubicin, regimen in the treatmentof advanced pancreatic cancer (APC). Proc.ECCO 9, 1997 p.280-ab.1270.

229. Di Costanzo F. Fluorouracil plus folinic acid vs 5-FU, FAand ifosfamide in advanced pancreatic cancer: a randomized phaseII trial of the italian oncology group for clinical research.Proc.Second Int.Conf. Biol.Prev.Treat.Gastr.Malign., 1995- p.88

230. Ahmed F.Y., Michels J., Nicolson M.C. Preliminary resultsof a phase II study of infusional chemotherapy regimen MCF (mitomycinC., Cisplatin and continuous infusional 5-fluorouracil) for pancreaticcancer. Proc. ASCO 1999 року, ab. +1059.

231. Moertel C.G., Rubin J., O`Connell M.J., et.al. A phase IIstugy of combined 5-fluorouracil, doxorubicin and cisplatin inthe treatment of advanced upper gastrointestinal adenocarcinoma.J.Clin.Oncol, 1986- 4: 1053-1057.

232. Rougier Ph., Zarba J., Ducreux M., et.al. Efficacy of combined5-FU and CDDP in advanced pancreatic adenocarcinoma. Int.Conf.Biol.Treat.Gastrointest.Malign., 1992 p.70

233. Rothman H., Cantrell J.E., Lokich J., et.al. Continuousinfision 5-fluorouracil plus weekly cisplatin for pancreatic carcinoma.Canc. 1991- 68: 264-268.

234. Charles A., Heider A., Steffens F., et.al. 5-Fluorouracil | cisplatinin the treatment of advanced pancreatic cancer. Proc. ASCO 1999 року, ab.1076.

235. Rougier P., Ducreux M., Douillard J.Y., et.al. Efficacyof 5-FU + cisplatin compared to bolus 5-FU in advanced pancreaticcarcinoma: a randomized trial from the French anticancer centersdigestive group. Proc. ASCO, 1999. ab.1050

236.Munzone E., Nole F., De Brand E., et.al. ECF (epirubicin, cisplatin, fluorouracil) in pancreatic carcinoma: a promisingapproach. Proc. ASCO 1997 ab.1062.

237. Underhill C.R., Highley M.S., Parnis F.X., et.al. Epirubicin, cisplatin and infusional 5-FU (ECF) - an active regimen in pancreaticcarcinoma. Proc.ASCO 1996- ab.453.

238. Cantore A., Cavazzini G., Aitine E., et.al. Intra-arterialchemotherapy for advanced carcinoma of the pancreas. Proc. ASCO1996- ab.455.

239. Liu J.M., Chao Y., Tin G.M., et.al. Biweekly continuousinfusion chemotherapy (M-FLEEP) plus megestrol acetate for pancreaticcancer. Proc. ASCO 1999 року, ab.1119.

240. Dougherty J.B., Kelsen D., Kemeny N., et.al. Advanced pancreaticcancer. A phase I-II trial of cisplatin, high-dose cytarabineand caffeine. J.Nat.Canc.Inst. 1989- 81: 1735-1738.

241. Hidalgo M., Paz-Ares L., Hitt R., et.al. Phase I-II studyof gemcitabine combined with continuous infusion 5-fluorouracilas first-line chemotherapy in locally advanced and metastaticpancreatic cancer. Proc. ASCO 1997, ab.1030.

242. Gutzler F., Moehler M. ,, Hosch W.P., et.al. A phase I studyof gemcitabine in combination with 5 days 5 fluorouracil and folinicacid in patients with advanced adenocarcinomas of pancreas orbile duct. Proc. ASCO 1999 року, ab.1097.

243. Louvet C., Hammel P., Andre T., et.al. Multicenter phaseII study in advanced pancreatic adenocarcinoma patients treatmentwith a combination of leucovorin, 5-FU bolus and infusion andgemcitabine (FOLFUGEM). Proc. ASCO 1999 року, ab.1054.

244.Oettle H., Pelzer U., Hochmuth K., et.al. Phase II trialof gemcitabine with 24-hour infusion of 5-fluorouracil and folinicacid in patients with advanced pancreatic cancer. Proc. ASCO 1999 року, ab. +1132.

245. Alabiso O., Grosso M., Buosi R., et.al. Locoregional chemotherapyfor advanced pancreatic cancer: a phase I study. Proc. ASCO 1999 року, ab.1061.

246.Rodriguez-Lescure A., Carrato A., Massuti B., et.al. PhaseI-II study of gemcitabine and weekly 48 hour continuous infusionif high dose 5-fluorouracil in advanced exocrine pancreatic cancer.Proc. ASCO 1999 року, ab.1145.

247. Villa E., Reni M. PEF-6 (cisplatin, epirubicin, 5-fluorouracilcontinuos infusion, gemcitabine): A new combination in advancedpancreatic adenocarcinoma: Phase II study. Proc. ASCO 1999 року, ab.1033.

248. Heinemann V., Wilke H., Possinger K., et.al. Gemcitabineand cisplatin: combination treatment for advanced and metastaticpancreatic carcinoma. Proc. ASCO, 1996, ab. 623.

249. Heintmann V., Wilke H., Possinger K., et.al. Activity andtolerability of gemcitabine plus cisplatin in advanced metastaticpancreatic carcinoma. Proc. ECCO, 1997, ab.1240.

250. Heinemann V., Wilke H., Possinger K., et.al. Gemcitabineand cisplatin in the treatment of advanced and metastatic pancreaticcancer. Final results of a phase II study. Proc. ASCO 1999 року, ab.1052.

251. Philip P.A., Zalupski M., Vaitkevicius V.K., et.al. PhaseII study of gemcitabine and cisplatin in advanced or metastaticpancreatic cancer. Proc. ASCO 1999 року, ab. 1053.

252. Colucci G., Riccardi F., Giuliani F., et.al. Randomizedtrial of gemcitabine alone or with cisplatin in the treatmentof advanced pancreatic cancer: A phase II Multicenter Study ofthe Southern Italy Oncology Group. Proc. ASCO 1999 року, ab. 961.

253. Kakolyris S., Stathopoulos G., Tsavaris N., et.al. Firstline with docetaxel and gemcitabine in patients with advancedpancreatic cancer: a multicenter phase II study. Proc. ASCO 1999 року, ab.960.

254. Jacobs A.D., Otero H., Picozzi V., et.al. Gemcitabine andTaxotere in patients with unresectable pancreatic carcinoma. Proc.ASCO 1999 року, ab. 1103.

255. Muller H. Angiogenesis inhibition and intra-arterial chemotherapy-A new modality treatment for advanced and metastatic pancreaticcarcinoma. Proc.ECCO 9, 1997 ab.215.

256. Garcia A.L., Leichman A.A., Baranda J., et.al. Phase IIstudy of trimetrexate (neutrexin), 5-fluorouracil and leucovorinin advanced pancreatic. Proc. ASCO 1999 року, ab.971.

257. Lersch C., Fckel F., Schutte-Flohlinde E., et.al. PhaseII trial of cyclophosphamide, folinic acid, 5-fluorouracil, tamoxifenand gemcitabine in advanced pancreatic cancer. Proc. ASCO 1999 року, ab.1115

258. Brierley J., Oza A., Patnaik A., et.al. A phase I studyof radiation therapy and gemcitabine in patients with locallyadvanced pancreatic carcinoma. Proc. ASCO 1999 року, ab.713.

259. McGinn C.J., Shureiqi I., Robertson J.M., et.al. A phaseI trial of radiation dose escalation with full dose gemcitabinein patients with pancreatic cancer. Proc. ASCO 1999 року, ab.1051.

260.Kurtz J.E., Jung G.M., Rohr S., et.al. Combined Modalitytreatment for unresectable pancreatic cancer. Proc. ASCO 1999 року, ab. 1112

261. De Brand F., Orlando L., Drecchia R., et.al. Combined modalitytreatment for locally advanced pancreatic carcinoma ECF (epirubicin, cisplatin, fluorouracil as continuous infusion) plus concomitantthree dimensional conformal radiotherapy. Proc. ASCO 1999 року, ab.1125.

262.Childs H., Spenser S., Raben D., et.al. Phase I study ofcombined UFT plus leucovorin and radiation therapy in pancreaticcancer. Proc. ASCO 1999 року, ab. 956.

263. Brunson C.Y., Baron P., Leveen P., et.al. Phase I studyof escalating tamoxifen, weekly low dose cisplatin and conformalradiation therapy in patients with locally advanced / unresectablepancreatic cancer. Proc. ASCO 1999 року, ab.788.

264. Osteen R.T., Zinner M.J., Fuchs C.S., et.al. Phase I trialof concurent gemcitabine, infusional 5-fluorouracil and radiationtherapy in patients with locolized unresectable pancreatic adenocarcinoma.Proc. ASCO 1999 року, ab. 1091.

265.Safor A.M., Atamira P.S., Recht A. Phase I trial of gemcitabine, cisplatin and external beam radiation therapy for pancreaticcancer. Proc. ASCO 1999 року, ab.874.

266.Andren-Sandberg A., Johonsson S. Recurrence after total pancreatectomyin exocrine pancreatic cancer - liver metastases or local recurrence? Pancreas 1988- 3: 590.

267. Tepper J., Nardi G., Sutt H. Carcinoma of the pancreas: Review of MGH experience from 1963 to 1973 Analysis of surgicalfailure and implications for radiation therapy. Canc. 1976- 37: 1579.

268. Foo M.L., Gunderson L.L., Nagorney D.M., et.al. Patternsof failure in grossly resected pancreatic ductal adenocarcinomatreated with adjuvant irradiation + 5-fluorouracil. Int.j.Rad.Oncol.Biol.Phys.1993-26: 483-489.

269. Whittington R., Bryer M.P., Haller D.G. Adjuvant therapyof resected adenocarcinoma of the pancreas. Int. j.Rad.Oncol.Biol.Phys.1991- 21: 1137-1143.

270. Gastrointestinal Tumor Study Group: Pancreatic cancer. Adjuvantcombined radiation and chemotherapy following curative resection.Arch.Surg.1985- 120: 899-903.

271. Klinkenbijl J., Sahmoud T., van Pel R., et.al. Radiotherapyand 5-FU after curative resection for the cancer of the pancreasand peri ampullary region: A phase III trial of the EORTC GITCCG.Proc.ECCO 9 1997- ab.1239.

272. Kalser M.H., Ellenberg S.S. Pancreatic cancer: Adjuvantcombined radiation and chemotherapy following curative resection.Arch.Surg.1985- 120: 899-903.

273. Yeo C.J., Cameron J.L., Lillemore K.D., et.al. Pancreaticoduodenectomyfor cancer of the head of the pancreas- 201 patients. Ann.Surg.1995-221: 721-733.

274. Amano H., Takada T., Kato H., et.al. Five-year results ofa randomized study of postoperative adjuvant chemotherapy forresected pancreatic biliary carcinomas. Proc. ASCO 1999 року, ab.1049.

275. Spitz F., Abbruzzese J., Lee J., et.al. Preoperative andpostoperative chemoradiation strategies in patients treated withpancreaticoduodenectomy for adenocarcinoma of the pancreas. J.Clin.Oncol.1997- 15: 928-937.

276. Thomas P.R.M. Radiotherapy for carcinoma of the pancreas.Sem.Oncol. 1996- 23: 2,213-219.

277. Seydel H.G., Stablein D.M., Leichman L.P., et.al. Hyperfractionatedradiation and chemotherapy for unresectable localized adenocarcinomaof the pancreas. The gastrointestinal tumor study group experience.Canc. 1990- 65: 1478-1482.

278. Pilepich M.V., Miller M.H. Predoperative irradiation incarcinoma of the pancreas. Canc. 1980 45: +1945.

279. Wanebo H.J., Posner M., Glicksman A., et.al. Integratedmodality protocol for carcinoma of the pancreas pilot.program.Proc.ASCO 1991 року, ab.499.

280. Hoffman J.P., Weese J.L., Solin L.J., et.al. Preoperativechemoradiation for patients with resectable pancreatic adenocarcinoma: An Eastern Cooperative Oncology Group (ECOG) phase II study. Proc.ASCO 1995- ab.201.

281. Staley C.A., Lee J.E., Cleary K.R., et.al. Preoperativechemoradiation, pancreaticoduodenectomy, and intraoperative radiationtherapy for adenocarcinoma of the pancreatic head. Am.j.Surg.1996- 171: 118-125.

282. Tyler D.S., Evans D.B. Reoperative pancreatoduodenectomy.Ann j.Surg. 1995-169: 7-139.

283. Garton G.R., Gunderson L., Nagorne D.M., et.al. High dosepreoperative external beam and IORT for locally advanced pancreaticcancer. Int.j.Rad.Oncol. Biol.Phys. 1993- 27-1153.

284. Bruckner H., Snady H., Dalton J., et.al. Split course radiotherapyeffectively downstage and facilitate resection of unresectablepancreatic cancer. Proc.Eighth International congress on anti-cancertreatment 1997, ab.97.

285. Jessup J.M., Steele G., Mayer R.J., et.al. Neoadjuvant therapyfor unresectable pancreatic adenocarcinoma. Arch.Surg. 1993- 128: 559.

286. Scheithauer W., Pfeffel F., Koznek G., et.al. A phase IItrial of 5-flourouracil, leucovorin and recombinant alpha-2b-interferonin advanced adenocarcinoma of the pancreas. Canc.70,1992- 1864-1866.

287. Jessup J.M., Mayer R.J., Posner M., et.al. Phase I / II neoadjuvanttrials for locally advanced pancreas adenocarcinoma. Second intern.conf. on biol., prev. and treatment of gastrointestinal malign.1995- ab 61.

288. Berns T. Prott F.J., Preusser P., et.al. Feasibility andphase II study of combined modality treatment with acceleratedradiotherapy and chemotherapy in patients with localy advancedinoperable carcinoma of pancreas. Proc.ECCO 9 1997- ab. 1251.

289. Lorenz M., Janshon G., Heinrich S., et.al. Aorticstop-flow-infusion (ASF) in patients with unresectable pancreatic cancer. Proc. ECCO9 1997 ab.1251.

290. Benz C., Hollander C., Miller B. Endocrine-responsive pancreaticcarcinoma: steroid binding and cyto-toxicity studies in humantumor cell lines. Canc.Res.1986- 46: 2276-2281.

291. Andren-Sandberg A., Borg A., Dawiskiba S., et.al. Estrogenreceptors and esrogen-binding protein in pancreatic cancer. Digest1982- 35:12.

292. Lhoste E.T., Roebuck B.D., Brinck-Johsen T., et.al. Effectof castration and normal replacement on azaserin-induced pancreaticcarcinogenesis in male and female Fisher rats. Carcinog. 1987-8: 696-704.

293. Huguier M., Samama G., Testart J., et.al. Treatment ofadenocarcinoma of the pancreas with somatostatin and gonadoliberin (luteinizing hormone-releasing hormone). Am j.Sur. 1992- 164: 348-353.

294. Allegretti A., Lionetto R., Saccomanno S., et.al. LH-RHanalogue treatment in adenocarcinoma of the pancreas. A phaseII study. Oncol. 1993- 50: 77-80.

295. Philip P.A., Carmichael J., Tonkin K., et.al. Hormonal treatmentof pancreatic carcinoma: a phase II study of LHRH agonist goserelinplus hydrocortisone. Br.j.Canc. 1993- 67: 379-282.

296. Wong A., Chan A. Survival benefit of tamoxifen therapy inadenocarcinoma of pancreas. Canc. 1993- 71: 2200-2203.

297. Bakkevold K.E., Pettersen A., Arnesjo B., et.al. Tamoxifentherapy in inresectable adenocarcinoma of the pancreas and thepapilla of vater. Br.j.Surg. 1990- 77: 725-730.

298. Keating J.J., Johnson P.J., Cochrane A.M.G., et.al. A prospectiverandomized trial of tamoxifen and cyproterone acetate in pancreaticcarcinoma. Br. J.Canc. 1989- 60: 789-792.

299. Klijn J.C., Hoff A.M., Planting A.S., et.al. Treatment patientswith metastatic pancreatic and gastrointestinal tumours with thesomatostatin analogue sandostatin. A phase II study includingendocrine effects. Br.j.Canc. 1990- 62: 623-630.

300. Friess H., Buchler M., Beglinger C., et.al. Low-dose octreotidetreatment is not effective in patients with advanced pancreaticcancer. Pancr. 1993- 8: 540-545.

301. Caillouette C., Hammond C.L., Razvillas B., et.al. A phaseI / II trial of SMS 201-995 pa Lar (SMS pa LAR) and gemcitabinein patients with advanced pancreatic cancer. Proc. ASCO 1999 року, ab.1071.

302. Abbruzzese J.L., Levin B., Ajani J.A., et.al. A pilot phaseII trial recombinant human interferon-gamma and recombinant tumornecrosis factor in patients with advanced gastrointestinal malignancies: Results of a trial terminal by excessive toxicity. J.Biol.Resp.Mod.1990- 9: 522-527.

303. Tempero M.A., Sivinski C., Steplewski Z., et.al. Phase IItrial of interferon gamma and monoclonal antibody 17-1A in pancreaticcancer: Biological and clinical effects. J.Clin.Oncol.1990- 8: 2019-2026.

304. Gottlinger H.G., Funke I., Johnson J.P. et.al. The epithelialcell surface antigen 17-1A, a target for antibody-mediated tumortherapy: its biochemical nature, tissue distribution and recognitionby different monoclonal antibodies. Int.j.Canc. 1986- 38: 47-53.

305. Buchler M., Friess H., Schultheiss K.M., et.al. A randomizedcontrolled trial of adjuvant immunotherapy (murine monoclonalantibody 494 (3L) in resectable pancreatic cancer. Canc. 1991-68: 1507-1512.

СПИСОК СКОРОЧЕНЬ

РПЖ - рак підшлункової залози
TNM - класифікація пухлин (Т- первинна пухлина, N -регіонарниелімфоузли, М- віддалені метастази)
Са-19-9 - маркер
КТ - комп`ютерна томографія
gy- грей
СЕА - маркер
FU - фторафур
ММС - мітоміцін З
Szt- стрептозотоцин
ADM - доксорубіцин
EPI- епірубіцин
IFO- ифосфамид
Том - томудекс
DPD- фермент дигідропіримідини деідрогеназа
CPt-11- кампто
Тах- паклітаксол
Тхt- доцетаксел
Gem; гемзар