DOI QR코드

DOI QR Code

근관치료 실패와 관련된 Enterococcus faecalis 제거를 위한 치료 protocol의 재고찰

RECONSIDERATION OF TREATMENT PROTOCOL ON THE REDUCTION OF ENTEROCOCCUS FAECALIS ASSOCIATED WITH FAILED ROOT CANAL TREATMENT

  • 이우철 (서울대학교 치의학전문대학원 치과보존학교실) ;
  • 홍성태 (서울대학교 치의학전문대학원 치과보존학교실) ;
  • 손원준 (서울대학교 치의학전문대학원 치과보존학교실)
  • Lee, Woo-Cheol (Department of Conservative Dentistry, School of Dentistry, Seoul National University) ;
  • Hong, Seong-Tae (Department of Conservative Dentistry, School of Dentistry, Seoul National University) ;
  • Shon, Won-Jun (Department of Conservative Dentistry, School of Dentistry, Seoul National University)
  • 발행 : 2008.11.30

초록

본 review 논문의 목적은 통상의 근관치료로 해결되지 않는 persistent periapical lesion의 원인이 되는 주요 세균을 제거하고자 시행한 여러가지 실험을 비교분석하여 과연 (1) Enterococcus faecalis가 근관치료 실패의 주요 원인균인지 (2) 그리고 과연 그렇다면 근관치료에 실패한 증례에서 E. faecalis와 biofilm을 제거할 수 있는 치료 protocol이 있는 것인지를 확인하여 보다 나은 근관치료 성공을 위한 치료 protocol의 확립과 앞으로의 연구방향을 재조명하는 것이다. 지금까지 진행되어온 연구 결과에 대한 객관적인 분석이나 적절한 평가가 이루어지지 않은 가운데 어떤 특정한 연구를 통해 E. faecalis를 제거하는데 유의성있는 효과를 보인다고 알려진 세척액이나 약제를 막연한 기대감을 가지고 실제 임상에 사용하고 있는 실정에서 현재 진료실에서 사용하고 있는 치료 protocol에 대한 검증이 절실한 시점에서 review해 본 결과 현재까지 진행되어 왔던 여러 연구 결과를 통해 확신할 수 있는 것은 치료 protocol에 따라 현재 사용하고 있는 근관세척액이나 근관내 약제만으로도 E. faecalis나 그 biofilm을 대부분 제거할 수 있다는 사실이다. 하지만 이 그 protocol에 따라 근관치료 술식을 충실하게 이행한다 해도 근관치료가 100% 성공한다고 보장할 수는 없다. 물론 세균이 아닌 다른 요소에 의해 근관치료의 실패가 일어난다고도 할 수 있지만 그보다는 결국 체내의 면역반응에 저항하는 세균의 능력에 기인하는 것으로 보인다. 따라서 높은 수준의 치료 성공률을 지속적으로 유지하기 위해서는 위에서 언급된 바와 같은 제대로 된 치료 protocol을 따라 근관치료를 진행하면서 좀더 나은 결과를 얻기 위해 새로운 protocol을 개발하고 정립하는 과정이 계속되어야 한다.

Microorganism survived in the root canal after root canal cleaning and shaping procedure is a main cause of root canal treatment failure. There are several mechanisms for the bacteria to survive in the root canal after chemomechanical preparation and root canal irrigation. Bacteria organized as biofilm has been suggested as an etiology of persistent periapical lesion. Recent studies were focus on removal of Enterococcus faecalis biofilm due to the report that the persistence of this bacteria after root canal treatment may be associated with its ability to form biofilm. Several investigations demonstrated that current root canal treatment protocol including use of NaOCl, EDTA and Chlorhexidine as irrigants is quite effective in eliminating E. faecalis biofilm. However, this microorganism still can survive in inaccessible areas of root canal system and evade host immune response, suppress immune activity and produce biofilm. Up to date, there is no possible clinical method to completely get rid of bacteria from the root canal. Once the root canal treatment failure occurred, and conventional treatment incorporating current therapeutic protocol has failed, periapical surgery or extraction should be considered rather than prolong the in effected retreatment procedure.

키워드

참고문헌

  1. Imura N, Pinheiro ET, Gomes BPFA, Zaia AA, Ferraz CCR, Sauza-Filho FJ. The outcome of endodontic treatment : A retrospective study of 2000 cases performed by a specialist. J Endod 33:1278-82, 2007 https://doi.org/10.1016/j.joen.2007.07.018
  2. Swartz DB, Skidmore AE, Griffin Jr JA. Twenty years of endodontic success and failure. J Endod 9 :198-202, 1983 https://doi.org/10.1016/S0099-2399(83)80092-2
  3. Fred W. Benenati, Sharukh S. Khajotia. A Radiographic Recall Evaluation of 894 Endodontic Cases Treated in a Dental School Setting. J Endod 28:391-395, 2002 https://doi.org/10.1097/00004770-200205000-00011
  4. Gomes BP, Vianna ME, Sena NT, Zaia AA, Ferraz CCR, Souza-Filho FJ. In vitro evaluation of the antimicrobial activity of calcium hydroxide combined with chlorhexidine gel used as intracanal medicament. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102:544-50, 2006 https://doi.org/10.1016/j.tripleo.2006.04.010
  5. Siqueira JF, Araujo MCP, Garcia PF, Fraga RC, Dantas CJS. Histological evaluation of the effectiveness of five instrumentation techniques for cleaning the apical third of root canals. J Endod 23:499-502, 1997 https://doi.org/10.1016/S0099-2399(97)80309-3
  6. Friedman S, Abitbol S, Lawrence HP. Treatment outcome in endodontics : The Toronto study. Phase 1: initial treatment. J Endod 29:787-793, 2003 https://doi.org/10.1097/00004770-200312000-00001
  7. Farzaneh M, Abitbol S, Lawrence HP, Friedman S. Treatment outcome in endodontics : The Toronto study. Phase II: initial treatment. J Endod 30:302-309, 2004 https://doi.org/10.1097/00004770-200405000-00002
  8. Marquis VL, Dao T, Farzaneh M, Abitbol S, Friedman S. Treatment outcome in endodontics : The Toronto study. Phase III: initial treatment. J Endod 32:299-306, 2006 https://doi.org/10.1016/j.joen.2005.10.050
  9. de Chevigny C, Dao TT, Basrani BR, Marquis VL, Farzaneh M, Abitbol S, Friedman S. Treatment outcome in endodontics : The Toronto study. Phase 4: initial treatment. J Endod 34:258-263, 2008 https://doi.org/10.1016/j.joen.2007.10.017
  10. Strindberg LZ. The dependence of the results of pulp therapy on certain factors. An analytic study based on radiographic and clinical follow-up examinations. Acta Odontol Scand 14:1-175, 1956 https://doi.org/10.3109/00016355609007499
  11. Peciuliene V, Balciuniene I, Eriksen HM, Haapasalo M. Isolation of Enterococcus faecalis in previously rootfilled canals in a Lithuanian population. J Endod 26:593-5, 2000 https://doi.org/10.1097/00004770-200010000-00004
  12. Peciuliene V, Reynaud AH, Balciuniene I, Haapasalo M. Isolation of yeasts and enteric bacteria in root-filled teeth with chronic apical periodontitis. Int Endod J 34:429-34, 2001 https://doi.org/10.1046/j.1365-2591.2001.00411.x
  13. Hancock HH, Sigurdsson A, Trope M, Moiseiwitsch J. Bacteria isolated after unsuccessful endodontic treatment in a North American population. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 91: 579-86, 2001 https://doi.org/10.1067/moe.2001.113587
  14. Pinheiro ET, Gomes BPFA, Ferraz CCR, Sousa ELR, Teixeira FB, Souza-Filho FJ. Microorganisms from canals of root-filled teeth with periapical lesions. Int Endod J 36:1-11, 2003 https://doi.org/10.1046/j.1365-2591.2003.00603.x
  15. Evans M, Davies K, Sundqvist G, Figdor D. Mechanisms involved in the resistance of Enterococcus faecalis to calcium hydroxide. Int Endod J 35:221-8, 2002 https://doi.org/10.1046/j.1365-2591.2002.00504.x
  16. Sundqvist G, Figdor D, Persson S, Sjogren U. Microbiologic analysis of teeth with failed endodontic treatment and the outcome of conservative re-treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 85:86-93, 1998 https://doi.org/10.1016/S1079-2104(98)90404-8
  17. Novais C, Vital C, Ribeiro G, Coque, Peixe LV. First characterization of vancomycin-resistant enterococci from a Portuguese hospital. J Antimicrob Chemother 49:215-7, 2002 https://doi.org/10.1093/jac/49.1.215
  18. Love RM, Enterococcus faecalis--a mechanism for its role in endodontic failure. Int Endod J 34:399-405, 2001 https://doi.org/10.1046/j.1365-2591.2001.00437.x
  19. Figdor D, Davies JK, Sundqvist G. Starvation survival, growth and recovery of Enterococcus faecalis in human serum. Oral Microbiol Immunol 18:234-9, 2003 https://doi.org/10.1034/j.1399-302X.2003.00072.x
  20. Rocas IN, Siqueira JF, Santos KR. Association of Enterococcus faecalis with different forms of periradicular diseases. J Endod 30:315-20, 2004 https://doi.org/10.1097/00004770-200405000-00004
  21. Gomes BP, Pinheiro ET, Sousa ELR, Jacinto RC, Zaia AA, Ferraz CCR, Souza-Filho FJ. Enterococcus faecalis in dental root canals detected by culture and by polymerase chain reaction analysis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102:247-53, 2006 https://doi.org/10.1016/j.tripleo.2005.11.031
  22. Jett BD, Huycke MM, Gilmore MS. Virulence of enterococci. Clin Microbiol Rev 7: 462-78, 1994 https://doi.org/10.1128/CMR.7.4.462
  23. Distel JW, Hatton JF, Gilespie MJ. Biofilm formation in medicated root canals. J Endod 28:689-93, 2002 https://doi.org/10.1097/00004770-200210000-00003
  24. Svensater G, Bergenholtz G. Biofilms in endodontic infections. Endod topics 9:27-36, 2004 https://doi.org/10.1111/j.1601-1546.2004.00112.x
  25. Duggan JM, Sedgley CM. Biofilm formation of oral endodontic Enterococcus faecalis. J Endod 33:815-8, 2007 https://doi.org/10.1016/j.joen.2007.02.016
  26. Dunavant TR, Regan JD, Glickman GN, Solomon ES, Honeyman AL. Comparative evaluation of endodontic irrigants against Enterococcus faecalis biofilms. J Endod 32:527-31, 2006 https://doi.org/10.1016/j.joen.2005.09.001
  27. Clegg MS, Vertucci FJ, Walker C, Belanger M, Britto LR. The effect of exposure to irrigant solutions on apical dentin biofilms in vitro. J Endod 32:434-7, 2006 https://doi.org/10.1016/j.joen.2005.07.002
  28. Kakehashi S, Stanley HR, Fitzgerald RJ. The Effects of Surgical Exposures of Dental Pulps in Germ-Free and Conventional Laboratory Rats. Oral Surg Oral Med Oral Pathol 20:340-9, 1965 https://doi.org/10.1016/0030-4220(65)90166-0
  29. Moller AJ, Fabricius L, Dahlen G, Ohman AE, Heyden G. Influence on periapical tissues of indigenous oral bacteria and necrotic pulp tissue in monkeys. Scand J Dent Res 89:475-84, 1981
  30. Sundqvist G. Bacteriologic studies of necrotic dental pulps, Dissertation. Umea University 1976
  31. Sjogren U, Figdor D, Persson S, Sundqvist G. Influence of infection at the time of root filling on the outcome of endodontic treatment of teeth with apical periodontitis. Int Endod J 30:297-306, 1997 https://doi.org/10.1111/j.1365-2591.1997.tb00714.x
  32. Lin LM, Pascon EA, Skribner J, G¨angler P, Langeland K. Clinical, radiographic, and histologic study of endodontic treatment failures. Oral Surg Oral Med Oral Pathol 71:603-11, 1991 https://doi.org/10.1016/0030-4220(91)90371-I
  33. Gomes BP, Pinheiro ET, Gade-Neto CR, Sousa ELR, Ferraz CCR, Zaia AA, Teixeira FB, Souza-Filho FJ. Microbiological examination of infected dental root canals. Oral Microbiol Immunol 19:71-6, 2004 https://doi.org/10.1046/j.0902-0055.2003.00116.x
  34. Siqueira JF, Rocas IN. Polymerase chain reactionbased analysis of microorganisms associated with failed endodontic treatment. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 97:85-94, 2004 https://doi.org/10.1016/S1079-2104(03)00353-6
  35. Molander A, Reit C, Dahlen G, Kvist T. Microbiological status of root-filled teeth with apical periodontitis. Int Endod J 31:1-7, 1998 https://doi.org/10.1046/j.1365-2591.1998.t01-1-00111.x
  36. Ercan E, Ozekinci T, Atakul F, Gul K. Antibacterial activity of 2% chlorhexidine gluconate and 5.25% sodium hypochlorite in infected root canal: in vivo study. J Endod 30:84-7, 2004 https://doi.org/10.1097/00004770-200402000-00005
  37. Vianna ME, Horz HP, Gomes BP, Conreds G. In vivo evaluation of microbial reduction after chemomechanical preparation of human root canals containing necrotic pulp tissue. Int Endo J 39:484-92, 2006 https://doi.org/10.1111/j.1365-2591.2006.01121.x
  38. Sassone LM, Fidel R, Fidel S, Vieira Hirata MR. The influence of organic load on the antimicrobial activity of different concentrations of NaOCl and chlorhexidine in vitro. Int Endod J 36:848-52, 2003 https://doi.org/10.1111/j.1365-2591.2003.00724.x
  39. Siqueira JF, Paiva SSM, Rocas IN. Reduction in the cultivable bacterial populations in infected root canals by a chlorhexidine-based antimicrobial protocol J Endod 33:541-7, 2007 https://doi.org/10.1016/j.joen.2007.01.008
  40. Ringel AM, Patterson SS, Newton CW, Miller CH, Mulhern JM. In vivo evaluation of chlorhexidine gluconate solution and sodium hypochlorite solution as root canal irrigants. J Endod 8:200-4, 1982 https://doi.org/10.1016/S0099-2399(82)80354-3
  41. Shabahang S, Torabinejad M. Effect of MTAD on Enterococcus faecalis-contaminated root canals of extracted human teeth. J Endod 29:576-9, 2003 https://doi.org/10.1097/00004770-200309000-00008
  42. Torabinejad, M., Cho Y, Khademi AA, Bakland LK. Shahrokh Shabahang The effect of various concentrations of sodium hypochlorite on the ability of MTAD to remove the smear layer. J Endod 29:233-9, 2003 https://doi.org/10.1097/00004770-200304000-00001
  43. Bystrom A, Claesson R, Sundqvist G. the antibacterial effect of camphorated para-monochlorophenol, camphorated phenol and calcium hydroxide in the treatment of infected root canals. Endod Dent Traumatol 1:170-5, 1985 https://doi.org/10.1111/j.1600-9657.1985.tb00652.x
  44. Sjogren U, Figdor D, Spangberg L, Sundqvist G. The antimicrobial effect of calcium hydroxide as a shortterm intracanal dressing. Int Endo J 24:119-25, 1991 https://doi.org/10.1111/j.1365-2591.1991.tb00117.x
  45. Sathorn C, Parashos P, Messer H. Antibacterial efficacy of calcium hydroxide intracanal dressing: a systematic review and meta-analysis. Int Endo J 40:2-4, 2007
  46. Haapasalo M, Orstavik D. In vitro infection and disinfection of dentinal tubules. J Dent Res 66:1375-9, 1987 https://doi.org/10.1177/00220345870660081801
  47. Lin YH, Mickel AK, Chogle S. Effectiveness of selected materials against Enterococcus faecalis: part 3. The antibacterial effect of calcium hydroxide and chlorhexidine on Enterococcus faecalis. J Endod 29:565-6, 2003 https://doi.org/10.1097/00004770-200309000-00006
  48. McHugh CP, Zhang P, Michalek S, Eleazer PD. pH required to kill Enterococcus faecalis in vitro. J Endod 30: 218-9, 2004 https://doi.org/10.1097/00004770-200404000-00008
  49. Tronstad L, Andreasen JO, Hasselgren G, Kristerson L, Riis I. pH changes in dental tissues after root canal filling with calcium hydroxide. J Endod 7:17-21, 1981 https://doi.org/10.1016/S0099-2399(81)80262-2
  50. Haapasalo HK, Siren EK, Waltimo TMT, Orstavik D, Haapasalo MPP. Inactivation of local root canal medicaments by dentine: an in vitro study. Int Endod J 33:126-31, 2000 https://doi.org/10.1046/j.1365-2591.2000.00291.x
  51. Portenier I, Haapasalo H, Rye A, Waltimo T, Orstavik D, Haapasalo M. Inactivation of root canal medicaments by dentine, hydroxylapatite and bovine serum albumin. Int Endod J 34:184-8, 2001 https://doi.org/10.1046/j.1365-2591.2001.00366.x
  52. Portenier I, Haapasalo H, Orstavik D, Yamauchi M, Haapasalo M. Inactivation of the antibacterial activity of iodine potassium iodide and chlorhexidine digluconate against Enterococcus faecalis by dentin, dentin matrix, type-I collagen, and heat-killed microbial whole cells. J Endod 28:634-7, 2002 https://doi.org/10.1097/00004770-200209000-00002
  53. Sukawat C, Srisuwan T. A comparison of the antimicrobial efficacy of three calcium hydroxide formulations on human dentin infected with Enterococcus faecalis. J Endod 28:102-4, 2002 https://doi.org/10.1097/00004770-200202000-00013
  54. Cwikla SJ, Belanger M, Giguere S, Progulske-Fox A, Vertucci FJ. Dentinal tubule disinfection using three calcium hydroxide formulations. J Endod 31:50-2, 2005 https://doi.org/10.1097/01.DON.0000134291.03828.D1
  55. Evans MD, Baumgartner JC, Khemaleelakul S, Xia T. Efficacy of calcium hydroxide: chlorhexidine paste as an intracanal medication in bovine dentin. J Endod 29:338-9, 2003 https://doi.org/10.1097/00004770-200305000-00005
  56. Gomes BP, Souza SF, Ferraz CC. Effectiveness of 2% chlorhexidine gel and calcium hydroxide against Enterococcus faecalis in bovine root dentine in vitro. Int Endo J 36:267-75, 2003 https://doi.org/10.1046/j.1365-2591.2003.00634.x
  57. Ercan E, Dalli M, Dulgergil CT. In vitro assessment of the effectiveness of chlorhexidine gel and calcium hydroxide paste with chlorhexidine against Enterococcus faecalis and Candida albicans. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102:e27-e31, 2006 https://doi.org/10.1016/j.tripleo.2006.02.022
  58. Garcez AS, Nunez SC, Lage-Marques JL, Jorge AOC, Ribeiro MS. Efficiency of NaOCl and laser-assisted photosensitization on the reduction of Enterococcus faecalis in vitro. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 102:e93-8, 2006 https://doi.org/10.1016/j.tripleo.2006.02.015
  59. Eldeniz AU, Ozer F, Hadimli HH, Erganis O. Bactericidal efficacy of Er,Cr:YSGG laser irradiation against Enterococcus faecalis compared with NaOCl irrigation: an ex vivo pilot study. Int Endod J 40:112-9, 2007 https://doi.org/10.1111/j.1365-2591.2006.01190.x
  60. Bergmans L, Moisiadis P, Huybrechts B, Van Meerbeek B, Quirynen M, Lambrechts P. Effect of photo- activated disinfection on endodontic pathogens ex vivo. Int Endod J 41:227-39, 2008 https://doi.org/10.1111/j.1365-2591.2007.01344.x
  61. Tronstad L, Barnett F, Cervone F. Periapical bacterial plaque in teeth refractory to endodontic treatment. Endod Dent Traumatol 6:73-7, 1990 https://doi.org/10.1111/j.1600-9657.1990.tb00394.x
  62. Larsen T. Susceptibility of Porphyromonas gingivalis in biofilms to amoxicillin, doxycyclin and metronidazole. Oral microbial Immunol 17:267-71, 2002 https://doi.org/10.1034/j.1399-302X.2002.170501.x
  63. Nair PNR. Light and electron microscopic studies on root canal flora and periapical lesions. J Endod 13:29-39, 1987 https://doi.org/10.1016/S0099-2399(87)80089-4
  64. Noiri Y, katsumoto T, Azakami H, Ebisu S. Effects of Er:YAG laser irradiation on biofilm-forming bacteria associated with endodontic pathogens in vitro. J Endod 34:826-829, 2008 https://doi.org/10.1016/j.joen.2008.04.010
  65. George S, Kishen A, Song KP. The role of environmental changes on monospecies biofilm formation on root canal wall by Enterococcus faecalis. J Endod 31:867-72, 2005 https://doi.org/10.1097/01.don.0000164855.98346.fc
  66. Chai WL, Hamimah H, Cheng SC, Sallam AA, Abdullah M. Susceptibility of Enterococcus faecalis biofilm to antibiotics and calcium hydroxide. J Oral Sci 49:161-6, 2007 https://doi.org/10.2334/josnusd.49.161
  67. Lima KC, Fava LRG, Siqueira JF. Susceptibilities of Enterococcus faecalis biofilms to some antimicrobial medications. J Endod 27:616-9, 2001 https://doi.org/10.1097/00004770-200110000-00004
  68. Spratt DA, Pratten J, Wilson M, Gulabivala K. An in vitro evaluation of the antimicrobial efficacy of irrigants on biofilms of root canal isolates. Int Endo J 34:300-7, 2001 https://doi.org/10.1046/j.1365-2591.2001.00392.x
  69. Chavez de paz L. Redefining the persistent infection in root canals: possible role of biofilm communities. J Endod 33:652-62,2007 https://doi.org/10.1016/j.joen.2006.11.004
  70. Shenker BJ, McArthur WP, Tsai CC. Immune suppression Induced by Actinobacillus actinomycetemcomitans. I. Effects on human peripheral blood lymphocyte responses to mitogens and antigens. J Immunol 128:148-54, 1982
  71. Korostoff J, Wang JF, Kieba I, Miller M, Shenker BJ, Lally ET. Actinobacillus actinomycetemcomitans leukotoxin induces apoptosis in HL-60 cells. Infect Immun 66:4474-83, 1998
  72. Yoshida H, Jontell M, Sundqvist G, Bergenholtz G. Effect of sonicated material from Fusobacterium nucleatum on the functional capacity of accessory cells derived from dental pulp. Oral Microbiol Immunol 10:208-12, 1995 https://doi.org/10.1111/j.1399-302X.1995.tb00144.x
  73. Shenker BJ, Datar S. Fusobacterium nucleatum inhibits human T-cell activation by arresting cells in the mid-G1 phase of the cell cycle. Infect Immun 63:4830-6, 1995
  74. Lee W, Pankoski L, Zekavat A, Shenker BJ. Treponema denticola immunoinhibitory protein induces irreversible G1 arrest in activated human lymphocytes. Oral microbiol Immunol 19:144-9, 2004 https://doi.org/10.1111/j.0902-0055.2004.00129.x
  75. Lee W, Lim S, Son H, Bae K. Sonicated extract of Enterococcus faecalis induces irreversible cell cycle arrest in phytohemagglutinin-activated human lymphocytes. J Endod 30: 209-12, 2004 https://doi.org/10.1097/00004770-200404000-00006
  76. Shon W, Lim S, Bae K, Baek S, Lee W. The expression of alpha4 integrins by human polymorphonuclear neutrophils in response to sonicated extracts of Enterococcus faecalis. J Endod 31: 369-72, 2005 https://doi.org/10.1097/01.don.0000145420.29539.78
  77. Giardino L, Ambu E, Savoldi E, Rimondini R, Cassanelli C, Debbia EA. Comparative evaluation of antimicrobial efficacy of sodium hypochlorite, MTAD, and tetraclean against Enterococcus faecalis biofilm. J Endod 33:852-5, 2007 https://doi.org/10.1016/j.joen.2007.02.012
  78. Sena NT, Gomes BPFA, Vianna ME, Berber VB, Zaia AA, Ferraz CCR, Souza-Filho FJ. In vitro antimicrobial activity of sodium hypochlorite and chlorhexidine against selected single-species biofilms. Int Endo J 39:878-85, 2006 https://doi.org/10.1111/j.1365-2591.2006.01161.x