Euroasian journal of hepato-gastroenterology

Register      Login

VOLUME 8 , ISSUE 1 ( January-June, 2018 ) > List of Articles

RESEARCH ARTICLE

Diagnostic and Prognostic Role of Serum Interleukin-6 in Malignant Transformation of Liver Cirrhosis

Mustafa Yakut, Muhammed F Karakaya, Harun Erdal

Keywords : Cirrhosis, Diagnosis, Hepatocellular carcinoma, Interleukin-6, Prognostic role

Citation Information : Yakut M, Karakaya MF, Erdal H. Diagnostic and Prognostic Role of Serum Interleukin-6 in Malignant Transformation of Liver Cirrhosis. Euroasian J Hepatogastroenterol 2018; 8 (1):23-30.

DOI: 10.5005/jp-journals-10018-1253

License: CC BY-NC 4.0

Published Online: 01-08-2018

Copyright Statement:  Copyright © 2018; The Author(s).


Abstract

Aim: Alpha-fetoprotein (AFP) is still the most commonly used and the single most recommended marker in the diagnosis of hepatocellular carcinoma (HCC). Interleukin (IL)-6 is a circular cytokine and its role on carcinogenesis in various hematological and solid tumors is clearly documented. A combination of serum IL-6 and AFP may provide beneficial information regarding early diagnosis of HCC. In this study, the effect of plasma IL-6 level in the diagnosis of HCC was investigated. Materials and methods: A total of 130 patients with liver cirrhosis, together with 30 control cases were enrolled in the trial. A diagnosis of HCC was present in 75 patients (57.6%) in the liver cirrhosis group. Blood samples were obtained from the enrolled study and control cases. Alpha-fetoprotein was quantified by chemiluminescent method. Plasma IL-6 levels of samples obtained at –80°C were quantified by human IL-6 BMS213/2 BMS213/2TEN kit. Results: The HCC patients were older than the patients in the cirrhosis group (p = 0.016). On comparison of the HCC patients with the control group, AFP (p < 0.001) and IL-6 (p < 0.001) were significantly higher among the HCC patients. Comparison of HCC patients with liver cirrhosis cases with no diagnosis of HCC revealed significantly high AFP (p < 0.001) and IL-6 levels (p < 0.001) in HCC group. Cutoff value for IL-6 was calculated as 5.73 (pg/mL). No difference was detected in AFP (p = 0.600) and IL-6 (0.344) in all three subgroups. A total of 17 patients died during a mean follow-up period of 32.9 months. No correlation was found between mean AFP values and IL-6 values and survival rates. Conclusion: Plasma IL-6 level was found to be significant in the diagnosis of HCC. Alpha-fetoprotein and IL-6 provided no advantage in terms of early diagnosis of HCC and no correlation was observed between these markers and survival.


PDF Share
  1. Henry L, Lavabre-Bertrand T, Vercambre L, Ramos J, Carillo S, Guiraud I, Pouderoux P, Bismuth M, Valats J-C, Demattei C, et al. Plasma proteasome level is a reliable early marker of malignant transformation of liver cirrhosis. Gut 2009 Jun;58(6):833-838.
  2. Stroffolini T. Etiological factor of hepatocellular carcinoma in Italy. Minerva Gastroenterol Dietol 2005 Mar;51(1):1-5.
  3. Trinchet JC, Alperovitch A, Bedossa P, Degos F, Hainaut P, Beers BV. Epidemiology, prevention, screening and diagnosis of hepatocellular carcinoma]. Bull Cancer 2009 Jan;96(1): 35-43.
  4. Bhosale P, Szklaruk J, Silverman PM. Current staging of hepatocellular carcinoma: imaging implications. Cancer Imaging 2006 Jul;6(1):83-94.
  5. Sato Y, Nakata K, Kato Y, Shima M, Ishii N, Koji T, Taketa K, Endo Y, Nagataki S. Early recognition of hepatocellular carcinoma based on altered profiles of alpha-fetoprotein. N Engl J Med 1993 Jun;328:1802-1806.
  6. Gupta S, Bent S, Kohlwes J. Test characteristics of alphafetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C. A systematic review and critical analysis. Ann Intern Med 2003 Jul;139(1):46-50.
  7. Porta C, De Amici M, Quaglini S, Paglino C, Tagliani F, Boncimino A, Moratti R, Corazza GR. Circulating interleukin-6 as a tumor marker for hepatocellular carcinoma. Ann Oncol 2008 Feb;19(2):353-358.
  8. £ukaszewicz M, Mroczko B, Szmitkowski M. Clinical significance of interleukin-6 (IL-6) as a prognostic factor of cancer disease. Pol Arch Med Wewn 2007 May- Jun;117(5-6):247-251.
  9. Ullmann CD, Schlom J, Greiner JW. Interleukin-6 increases carcinoembryonic antigen and histocompatibility leukocyte antigen expression on the surface of human colorectal carcinoma cells. J Immunother 1992 Nov;12(4):231-241.
  10. Ma W, Kantarjian H, Bekele B, Donahue AC, Zhang X, Zhang ZJ, O'Brien S, Estey E, Estrov Z, Cortes J, et al. Proteasome enzymatic activities in plasma as risk stratification of patients with acute myeloid leukemia and advancedstage myelodysplastic syndrome. Clin Cancer Res 2009 Jun;15(11):3820-3826.
  11. Di Bisceglie AM, Befeler AS. Tumors and cysts of the liver. In: Feldman M, editor. Sl azenger and Fordtran's gastrointestinal and liver disease. 9th ed. Saunders Elsevier Publishing; 2010. pp. 1569-1563.
  12. Gines P, Cardenas A, Arroyo V, Rodes J. Management of cirrhosis and ascites. N Engl J Med 2004;350:1646-1654.
  13. Trevisani F, D'Intino PE, Morselli-Labate AM, Mazzella G, Accogli E, Caraceni P, Domenicali M, De Notariis S, Roda E, Bernardi M. Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status. J Hepatol 2001 Apr;34(4):570-575.
  14. Ara T, Declerck YA. Interleukin-6 in bone metastasis and cancer progression. Eur J Cancer 2010 May;46(7):1223-1231.
  15. Wojcik E, Jacubowicz J, Skotnicki P, Sas-Korczynska B, Kulpa JK. IL-6 and VEGF in small cell lung cancer patients. Anticancer Res 2010 May;30(5):1773-1778.
  16. Ikeguchi M, Hatada T, Yamamoto M, Miyeka T, Matsunaga T, Fukumoto Y, Yamada Y, Fukuda K, Saito H, Tatebe S. Serum interleukin-6 and -10 levels in patients with gastric cancer. Gastric Cancer 2009;12(2):95-100.
  17. Meyer F, Saamson E, Duoville P, Duchesne T, Liu G, Bairati I. Serum prognostic markers in head and neck cancer. Clin Cancer 2010 Feb;16(3):1008-1015.
  18. Knüpfer H, Preiss R. Serum interleukin-6 levels in colorectal cancer patients—a summary of published results. Int J Colorectal Dis 2010 Feb;25(2):135-140.
  19. Napoli J, Bishop GA, McCaughan GW. Increased intrahepatic messenger RNA expression of interleukins 2, 6, and 8 in human cirrhosis. Gastroenterology 1994 Sep;107(3): 789-798.
  20. Kovalovich K, Li W, DeAngelis R, Greenbaum LE, Ciliberto G, Taub R. Interleukin-6 protects against Fasmediated death by establishing a critical level of anti-apoptotic hepatic proteins FLIP, Bcl-2, and Bcl-xL. J Biol Chem 2001 Jul; 276:26605-26613.
  21. Nagawa H, Maede S, Yoshida H, Tateishi R, Mazusaki R, Ohki T, Hayakawa Y, Kinoshita H, Yamakado M, Kato N, et al. Serum IL-6 levels and the risk for hepatocarcinogenesis in chronic hepatitis C patients: an analysis based on gender differences. Int J Cancer 2009 Nov;125(10):2264-2269.
  22. Wong VW, Yu J, Cheng AS, Wong GL, Chan HY, Chu ES, Ng EK, Chan FK, Sung JJ, Chan HL. High serum interleukin-6 level predicts future hepatocellular carcinoma development in patients with chronic hepatitis B. Int J Cancer 2009 Jun;124(12):2766-2770.
  23. Lazarova DL, Chiaro C, Wong T, Drago E, Rainey A, O'Malley S, Bordonaro M. CBP activity mediates effects of the histone deacetylase inhibitor butyrate on WNT activity and apoptosis in colon cancer cells. J Cancer 2013 Jul 15;4(6):481-490.
  24. Kamitani H, Taniura S, Ikawa H, Watanabe T, Kelavkar UP, Eling TE. Expression of 15-lipoxygenase-1 is regulated by histone acetylation in human colorectal carcinoma. Carcinogenesis 2001 Jan;22(1):187-191.
  25. Worthley DL, Whitehall VL, Le Leu RK, Irahara N, Buttenshaw RL, Mallitt KA, Greco SA, Ramsnes I, Winter J, Hu Y, et al. DNA methylation in the rectal mucosa is associated with crypt proliferation and fecal short-chain fatty acids. Dig Dis Sci 2011 Feb;56(2):387-396.
  26. Munjal U, Glei M, Pool-Zobel BL, Scharlau D. Fermentation products of inulin-type fructans reduce proliferation and induce apoptosis in human colon tumour cells of different stages of carcinogenesis. Br J Nutr 2009 Sep;102(5): 663-671.
  27. Bajka BH, Clarke JM, Cobiac L, Topping DL. Butyrylated starch protects colonocyte DNA against dietary proteininduced damage in rats. Carcinogenesis 2008 Nov;29(11): 2169-2174.
  28. Rocca YS, Roberti MP, Arriaga JM, Amat M, Bruno L, Pampena MB, Huertas E, Loria FS, Pairola A, Bianchini M, et al. Altered phenotype in peripheral blood and tumorassociated NK cells from colorectal cancer patients. Innate Immun 2013 Feb;19(1):76-85.
  29. Zhang Z, Song Y, Wang XL. Inositol hexaphosphate-induced enhancement of natural killer cell activity correlates with suppression of colon carcinogenesis in rats. World J Gastroenterol 2005 Aug 28;11(32):5044-5046.
  30. Vannucci L, Fiserova A, Horvath O, Rossmann P, Mosca F, Pospisil M. Cancer evolution and immunity in a rat colorectal carcinogenesis model. Int J Oncol 2004 Oct;25(4):973-981.
  31. Bordonaro M. Crosstalk between Wnt signaling and RNA processing in colorectal cancer. J Cancer 2013;4(2):96-103.
  32. Lazarova DL, Wong T, Chiaro C, Drago E, Bordonaro M. p300 influences butyrate-mediated WNT hyperactivation in colorectal cancer cells. J Cancer 2013 Jul 18;4(6):491-501.
  33. Saitoh M, Ishihara K, Sekiya T, Araki T. Anticipation of uterine bleeding in placenta previa based on vaginal sonographic evaluation. Gynecol Obstet Invest 2002;54(1):37-42.
  34. Droste S, Keil K. Expectant management of placenta praevia: cost benefit analysis of outpatient treatment. Am J Obstet Gynecol 1994 May;170(5 pt 1):1254-1257.
  35. Mouer JR. Placenta praevia: antepartum conservative management, inpatient versus outpatient. Am J Obstet Gynecol 1994 Jun;170(6):1683-1686.
  36. Dola CP, Garite TJ, Dowling DD, Friend D, Ahdoot D, Asrat T. Placenta previa: does its type affect pregnancy outcome? Am J Perinatol 2003 Oct;20(7):353-360.
  37. Nelson JP. Interventions for suspected placenta praevia. Cochrane Database Syst Rev 2003;2:CD001998.
  38. Arias F. Cervical cerclage for the temporary treatment of patients with placenta previa. Obstet Gynecol 1988 Apr;71(4):545-548.
  39. Oyelese KO, Smulian JC. Placenta previa, placenta accreta, and vasa previa. Obstet Gynecol 2006 Apr;107(4):927-941.
  40. Bhide A, Thilaganathan B. Recent advances in the management of placenta previa. Curr Opin Obstet Gynecol 2004 Dec;16(6):447-451.
  41. Finberg HJ, Williams JW. Placenta accreta: prospective sonographic diagnosis in patients with placenta previa and prior cesarean section. J Ultrasound Med 1992 Jul;11(7): 333-343.
  42. O'Brien JM, Barton JR, Donaldson ES. The management of placenta percreta: conservative and operative strategies. Am J Obstet Gynecol 1996 Dec;175(6):1632-1638.
  43. Ouellet A, Sallout B, Oppenheimer LW. Outcomes of surgical versus conservative management of placenta accreta-percreta: systematic review of literature and case series. Am J Obstet Gynecol 2003 Dec;189(6):S130.
  44. Mazouni C, Gorincour G, Juhan V, Bretelle F. Placenta accreta: a review of current advances in prenatal diagnosis. Placenta 2006 Jul;28(7):599-603.
  45. Abramowicz JS, Sheiner E. Ultrasound of the placenta: a systematic approach. Part I: imaging. Placenta 2008 Mar;29(3):225-240.
  46. Wu S, Kocherginsky M, Hibbard JU. Abnormal placentation: twenty-year analysis. Am J Obstet Gynecol 2005 May;192(5):1458-1461.
  47. Gielchinsky Y, Rojansky N, Fasouliotis SJ, Ezra Y. Placenta accretae—summary of 10 years: a survey of 310 cases. Placenta 2002 Feb-Mar;23(2-3):210-214.
  48. Comstock CH. Antenatal diagnosis of placenta accreta: a review. Ultrasound Obstet Gynecol 2005 Jul;26(1):89-96.
  49. Shih JC, Palacios Jaraquemada JM, Su YN, Shyu MK, Lin CH, Lin SY, Lee CN. Role of three-dimensional power Doppler in the antenatal diagnosis of placenta accreta: comparison with gray-scale and color Doppler techniques. Ultrasound Obstet Gynecol 2009 Feb;33(2):193-203.
  50. Lax A, Prince MR, Mennitt KW, Schwebach JR, Budorick NE. The value of specific MRI features in the evaluation of suspected placental invasion. Magn Reson Imaging 2007 Jan;25(1):87-93.
  51. Lim PS, Greenberg M, Edelson MI, Bell KA, Edmonds PR, Mackey AM. Utility of ultrasound and MRI in prenatal diagnosis of placenta accreta: a pilot study. AJR Am J Roentgenol 2011 Dec;197(6):1506-1513.
  52. Baughman WC, Corteville JE, Shah RR. Placenta accreta: spectrum of US and MR imaging findings. Radiographics 2008 Nov-Dec;28(7):1905-1916.
  53. Stanojevic M, Antsaklis P, Kadic AS, Predojevic M, Vladareanu R, Vladareanu S, Neto RM. Is Kurjak antenatal neurodevelopmental test ready for routine clinical application? Bucharest Consensus Statement. DSJUOG 2015 Jan;9(3):260-265.
  54. Rosier-van Dunne FM, van Wezel-Meijler G, Bakker MP, Odendaal HJ, de Vries JI. Fetal general movements and brain sonography in a population at risk for preterm birth. Early Hum Dev 2010 Feb;86(2):107-111.
  55. Kurjak A, Stanojevic M, Andonotopo W, Scazzocchio-Duenas E, Azumendi G, Carrera JM. Fetal behavior assessed in all three trimesters of normal pregnancy by four-dimensional ultrasonography. Croat Med J 2005 Oct;46(5):772-780.
  56. Stanojevic M, Talic A, Miskovic B, Vasilj O, Shaddad AN, Ahmed B, Kadic AS, Predojevic M, Vladareanu R, Lebit D, Abu-Yaqoub S, et al. An attempt to standardize Kurjak's antenatal neurodevelopmental test: Osaka Consensus Statement. DSJUOG 2011 Oct-Dec;5(4):317-329.
  57. Low JA, Galbraith RS, Muir DW, Killen HL, Pater EA, Karchmar EJ. Factors associated with motor and cognitive deficits in children after intrapartum fetal hypoxia. Am J Obstet Gynecol 1984 Mar;148(5):533-539.
  58. Kurjak A, Miskovic B, Stanojevic M, Amiel-Tison C, Ahmed B, Azumendi G, Vasilj O, Andonotopo W, Turudic T, Salihagic- Kadic A. New scoring system for fetal neurobehavior assessed by three- and four-dimensional sonography. J Perinat Med 2008 Feb;36(1):73-81.
  59. Nelson C, Silverstein FS. Acute disruption of cytochrome oxidase activity in brain in a perinatal rat stroke model. Pediatr Res 1994 Jul;36(1 Pt 1):12-19.
  60. Visser GH, Mulder EJ, Tessa Ververs FF. Fetal behavioral teratology. J Matern Fetal Neonatal Med 2010 Oct;23(Suppl 3):14-16.
  61. Visser GH, Bekedam DJ, Mulder EJ, van Ballegooie E. Delayed emergence of fetal behavior in type-1 diabetic women. Early Hum Dev 1985 Nov;12(2):167-172.
  62. Aladjem S, Feria A, Rest J, Gull K, O'Connor M. Effect of maternal glucose load on fetal activity. Am J Obstet Gynecol 1979 Jun;134(3):276-280.
  63. Eller DP, Stramm SL, Newman RB. The effect of maternal intravenous glucose administration on fetal activity. Am J Obstet Gynecol 1992 Oct;167(4 Pt 1):1071-1074.
  64. Gelman SR, Spellacy WN, Wood S, Birk SA, Buhi WC. Fetal movements and ultrasound: effect of maternal intravenous glucose administration. Am J Obstet Gynecol 1980 Jun;137(4):459-461.
  65. Goodman JD. The effect of intravenous glucose on human fetal breathing measured by Doppler ultrasound. Br J Obstet Gynecol 1980 Dec;87(12):1080-1083.
  66. Miller FC, Skiba H, Klapholz H. The effect of maternal blood sugar levels on fetal activity. Obstet Gynecol 1978 Dec;52(6):662-665.
  67. Richardson B, Briggs ML, Toomey C, Burry KJ, O'Grady JP. The effect of maternal glucose administration on the specificity of the nonstress test. Am J Obstet Gynecol 1983 Jan;145(2):141-146.
  68. Allen CL, Kisilevsky BS. Fetal behavior in diabetic and nondiabetic pregnant women: an exploratory study. Dev Psychobiol 1999 Jul;35(1):69-80.
  69. Edelberg SC, Dierker L, Kalhan S, Rosen MG. Decreased fetal movements with sustained maternal hyperglycemia using the glucose clamp technique. Am J Obstet Gynecol 1987 May;156(5):1101-1105.
  70. Holden KP, Jovanovic L, Druzin ML, Peterson CM. Increased fetal activity with low maternal blood glucose levels in pregnancies complicated by diabetes. Am J Perinatol 1984 Jan;1(2):161-164.
  71. Bocking AD. Observations of biophysical activities in the normal fetus. Clin Perinatol 1989 Sep;16(3):583-594.
  72. Bocking A, Adamson L, Carmichael L, Patrick J, Probert C. Effect of intravenous glucose injection on human maternal and fetal heart rate at term. Am J Obstet Gynecol 1984 Feb;148(4):414-420.
  73. Bocking A, Adamson L, Cousin A, Campbell K, Carmichael L, Natale R, Patrick J. Effects of intravenous glucose injections on human fetal breathing movements and gross fetal body movements at 38 to 40 weeks’ gestational age. Am J Obstet Gynecol 1982 Mar;142(6 Pt 1):606-611.
  74. Reece EA, Hagay Z, Roberts AB, DeGennaro N, Homko CJ, Connolly-Diamond M, Sherwin R, Tamborlane WV, Diamond MP. Fetal Doppler and behavioral responses during hypoglycemia induced with the insulin clamp technique in pregnant diabetic women. Am J Obstet Gynecol 1995 Jan;172(1 Pt 1):151-155.
  75. Patrick J, Campbell K, Carmichael L, Natale R, Richardson B. Patterns of gross fetal body movements over 24-hour observation intervals during the last 10 weeks of pregnancy. Am J Obstet Gynecol 1982 Feb;142(4):363-371.
  76. Ornoy A, Ratzon N, Greenbaum C, Peretz E, Soriano D, Dulitzky M. Neurobehavior of school age children born to diabetic mothers. Arch Dis Child Fetal Neonatal Ed 1998 Sep;79(2):F94-F99.
  77. Wolf, A. Developmental evaluation on early school age children born to gestational diabetic mothers. Israel: Hebrew University; 1997.
  78. Mulder EJ, Leiblum DM, Visser GH. Fetal breathing movements in late diabetic pregnancy: relationship to fetal heart rate patterns and Braxton Hicks’ contractions. Early Hum Dev 1995 Nov;43(3):225-232.
  79. Schulte FJ, Michaelis R, Nolte R, Albert G, Parl U, Lasson U. Brain and behavioral maturation in newborn infants of diabetic mothers. I. Nerve conduction and EEG patterns. Neuropadiatrie 1969 Jan-Jul;1(1):24-35.
  80. Devoe LD, Youssef AA, Castillo RA, Croom CS. Fetal biophysical activities in third-trimester pregnancies complicated by diabetes mellitus. Am J Obstet Gynecol 1994 Aug;171(2):298-303.
  81. Dierker LJ Jr, Pillay S, Sorokin Y, Rosen MG. The change in fetal activity periods in diabetic and nondiabetic pregnancies. Am J Obstet Gynecol 1982 May;143(2):181-185.
  82. Doherty NN, Hepper PG. Habituation in fetuses of diabetic mothers. Early Hum Dev 2000 Aug;59(2):85-93.
  83. Kainer F, Prechtl HF, Engele H, Einspieler C. Assessment of the quality of general movements in fetuses and infants of women with type-1 diabetes mellitus. Early Hum Dev 1997 Nov;50(1):13-25.
  84. Mulder EJ, O'Brien MJ, Lems YL, Visser GH, Prechtl HF. Body and breathing movements in near-term fetuses and newborn infants of type-1 diabetic women. Early Hum Dev 1990 Nov;24(2):131-152.
  85. Mulder EJ, Visser GH. Growth and motor development in fetuses of women with type-1 diabetes. I. Early growth patterns. Early Hum Dev 1991 May;25(2):91-106.
  86. Mulder EJ, Visser GH. Growth and motor development in fetuses of women with type-1 diabetes. II. Emergence of specific movement patterns. Early Hum Dev 1991 May;25(2):107-115.
  87. Mulder EJ, Visser GH. Impact of early growth delay on subsequent fetal growth and functional development: a study on diabetic pregnancy. Early Hum Dev 1992 Dec;31(2):91-95.
  88. Mulder EJ, Visser GH, Bekedam DJ, Prechtl HF. Emergence of behavioral states in fetuses of type-1 diabetic women. Early Hum Dev 1987 Jul;15(4):231-251.
  89. Mulder EJ, Visser GH, Morssink LP, de Vries JI. Growth and motor development in fetuses of women with type-1 diabetes. III. First trimester quantity of fetal movement patterns. Early Hum Dev 1991 May;25(2):117-133.
  90. Aberg A, Westbom L, Kallen B. Congenital malformations among infants whose mothers had gestational diabetes or preexisting diabetes. Early Hum Dev 2001 Mar;61(2):85-95.
  91. Deregnier RA, Nelson CA, Thomas KM, Wewerka S, Georgieff MK. Neurophysiologic evaluation of auditory recognition memory in healthy newborn infants and infants of diabetic mothers. J Pediatr 2000 Dec;137(6):777-784.
  92. Nelson CA, Wewerka S, Thomas KM, Tribby-Walbridge S, deRegnier R, Georgieff M. Neurocognitive sequelae of infants of diabetic mothers. Behav Neurosci 2000 Oct;114(5):950-956.
  93. Reece EA, Homko CJ. Infant of the diabetic mother. Semin Perinatol 1994 Oct;18(5):459-469.
  94. Reece EA, Homko CJ. Why do diabetic women deliver malformed infants? Clin Obstet Gynecol 2000 Mar;43(1):32-45.
  95. Rizzo T, Metzger BE, Burns WJ, Burns K. Correlations between antepartum maternal metabolism and intelligence of offspring. N Engl J Med 1991 Sep;325(13):911-916.
  96. Rizzo TA, Metzger BE, Dooley SL, Cho NH. Early malnutrition and child neurobehavioral development: insights from the study of children of diabetic mothers. Child Dev 1997 Feb;68(1):26-38.
  97. Schwartz R, Teramo KA. Effects of diabetic pregnancy on the fetus and newborn. Semin Perinatol 2000 Apr;24(2):120-135.
  98. Vaarasmaki MS, Hartikainen A, Anttila M, Pramila S, Koivisto M. Factors predicting peri- and neonatal outcome in diabetic pregnancy. Early Hum Dev 2000 Jul;59(1):61-70.
  99. Robertson SS, Dierker LJ. Fetal cyclic motor activity in diabetic pregnancies: sensitivity to maternal blood glucose. Dev Psychobiol 2003 Jan;42(1):9-16.
  100. Accardo PJ, Blondis TA, Whitman BY. Disorders of attention and activity level in a referral population. Pediatrics 1990 Mar;85(3 Pt 2):426-431.
  101. Ornoy A, Uriel L, Tennenbaum A. Inattention, hyperactivity and speech delay at 2-4 years of age as a predictor for ADDADHD syndrome. Isr J Psychiatry Relat Sci 1993;30(3):155-163.
  102. Smyth TR. Impaired motor skill (clumsiness) in otherwise normal children: a review. Child Care Health Dev 1992 Sep-Oct;18(5):283-300.
  103. Petersen MB, Pedersen SA, Greisen G, Pedersen JF, Mølsted- Pedersen L. Early growth delay in diabetic pregnancy: relation to psychomotor development at age 4. Br Med J (Clin Res Ed) 1988 Feb;296(6622):598-600.
  104. Sells CJ, Robinson NM, Brown Z, Knopp RH. Long-term developmental follow-up of infants of diabetic mothers. J Pediatr 1994 Jul;125(1):S9-S17.
  105. Vladareanu R, Lebit D, Constantinescu S. Ultrasound assessment of fetal neurobehaviour in high risk pregnancies. DSJUOG 2012 Apr-Jun;6(2):132-147.
  106. Talic A, Kurjak A, Ahmed B, Stanojevic M, Predojevic M, Kadic AS, Di Renzo GC. The potential of 4D sonography in the assessment of fetal behavior in high-risk pregnancies. J Matern Fetal Neonatal Med 2011 Jul;24(7):948-954.
  107. Bekedam DJ, Visser GH, de Vries JJ, Prechtl HF. Motor behaviour in the growth retarded fetus. Early Hum Dev 1985 Nov;12(2):155-165.
  108. Cioni G, Prechtl HF. Preterm and early postterm motor behaviour in low-risk premature infants. Early Hum Dev 1990 Sep;23(3):159-191.
  109. Seme-Ciglenecki P. Predictive value of assessment of general movements for neurological development of highrisk preterm infants: comparative study. Croat Med J 2003 Dec;44(6):721-727.
  110. Abo-Yaqoub S, Kurjak A, Mohammed AB, Shadad A, Abdel-Maaboud M. The role of 4-D ultrasonography in prenatal assessment of fetal neurobehaviour and prediction of neurological outcome. J Matern Fetal Neonatal Med 2012 Mar;25(3):231-236.
  111. Athanasiadis AP, Mikos T, Tambakoudis GP, Theodoridis TD, Papastergiou M, Assimakopoulos E, Tarlatzis BC. Neurodevelopmental fetal assessment using KANET scoring system in low and high-risk pregnancies. J Matern Fetal Neonatal Med 2013 Mar;26(4):363-368.
  112. Fauser BC, Tarlatzis BC, Rebar RW, Legro RS, Balen AH, Lobo R, Carmina E, Chang J, Yildiz BO, Laven JS, et al. Consensus on women's health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-Sponsored 3rd PCOS Consensus Workshop Group. Fertil Steril 2012 Jan;97(1):28-38.e25
  113. Sirmans SM, Pate KA. Epidemiology, diagnosis and management of polycystic ovary syndrome. Clin Epidemiol 2014; 6:1-13.
  114. Fauser BC, Diedrich K, Bouchard P, Domínguez F, Matzuk M, Franks S, Hamamah S, Simón C, Devroey P, Ezcurra D, et al. Contemporary genetic technologies and female reproduction. Human Reproduction Update 2011 Nov;17(6):829-847.
  115. Balen A, Conway G, Kaltsas G. Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients. Hum Reprod 1995 Aug;10(8):2107-2111.
  116. Azziz R, Sanchez L, Knochenhauer ES, Moran C, Lazenby J, Stephens KC, Taylor K, Boots LR. Androgen excess in women: experience with over 1000 consecutive patients. J Clin Endocrinol Metab 2004 Feb;89(2):453-462.
  117. Wild S, Pierpoint T, McKeigue P, Jacobs H. Cardiovascular disease in women with polycystic ovary syndrome at longterm follow-up: a retrospective cohort study. Clin Endocrinol (Oxf) 2000 May;52(5):595-600.
  118. Hollinrake E, Abreu A, Maifeld M, Van Voorhis BJ, Dokras A. Increased risk of depressive disorders in women with polycystic ovary syndrome. Fertil Steril 2007 Jun;87(6): 1369-1376.
  119. Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome. In: Givens JHF, Merriman G, editors. The polycystic ovary syndrome. Cambridge, MA: Blackwell Scientific; 1992. p. 377-384.
  120. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril 2004 Jan;81(1):19-25.
  121. Azziz R, Carmina E, DeWailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, et al. Position statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006 Nov;91(11):4237-4245.
  122. Lujan ME, Jarrett BY, Brooks ED, Reines JK, Peppin AK, Muhn N, Haider E, Pierson RA, Chizen DR. Updated ultrasound criteria for polycystic ovary syndrome: reliable thresholds for elevated follicle population and ovarian volume. Hum Reprod 2013 May;28(5):1361-1368.
  123. Badawy A, Elnashar A. Treatment options for polycystic ovary syndrome. Int J Womens Health 2011 Feb;3:25-35.
  124. ACOG Committee on Practice Bulletins—Gynecology. ACOG Practice Bulletin No 108: Polycystic ovary syndrome. Obstet Gynecol 2009 Oct;114(4):936-949.
  125. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group Consensus on infertility treatment related to polycystic ovary syndrome. Fertil Steril 2008 Mar;89(3): 505-522.
  126. Balen AH. Ovulation induction in the management of anovulatory polycystic ovary syndrome. Mol Cell Endocrinol 2013 Jul;373(1-2):77-82.
  127. Berridge DL, Winter TC. Saline infusion sonohysterography: technique, indications, and imaging findings. J Ultrasound Med 2004 Jan;23(1):97-112.
  128. Allison SJ, Horrow MM, Kim HY, Lev-Toaff AS. Salineinfused sonohysterography: tips for achieving greater success. Radiographics 2011 Nov-Dec;31(7):1991-2004.
  129. O'Neill MJ. Sonohysterography. Radiol Clin North Am 2003 Jul;41(4):781-797.
  130. Bonnamy L, Marret H, Perrotin F, Body G, Berger C, Lansac J. Sonohysterography: a prospective survey of results and complications in 81 patients. Eur J Obstet Gynecol Reprod Biol 2002 Apr;102(1):42-47.
  131. Lindheim SR, Adsuar N, Kushner DM, Pritts EA, Olive DL. Sonohysterography: a valuable tool in evaluating the female pelvis. Obstet Gynecol Surv 2003 Nov;58(11):770-784.
  132. Lindheim SR, Sprague C, Winter TC. Hysterosalpingography and sonohysterography: lessons in technique. AJR Am J Roentgenol 2006 Jan;186(1):24-29.
  133. Jeanty P, Besnard S, Arnold A, Turner C, Crum P. Air-contrast sonohysterography as a first step assessment of tubal patency. J Ultrasound Med 2000 Aug;19(8):519-527.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.