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1 대한내과학회지 : 제 75 권제 1 호 2008 감염경로에따른화농성농양의비교 원광대학교의과대학내과학교실 1, 가정의학교실 2 최창수 1 서검석 1 조은영 1 김기훈 1 서승오 1 오효정 1 신새론 2 김태현 1 최석채 1 김학철 1 Comparison of pyogenic liver abscesses based on the origin of infection Departments of Internal Medicine 1 and Family Medicin 2, Wonkwang University School of Medicine, Iksan, Korea Chang Soo Choi, M.D. 1, Geom Seog Seo, M.D. 1, Eun Young Cho, M.D. 1, Ki Hoon Kim, M.D. 1, Sung O Seo, M.D. 1, Hyo Jeong Oh, M.D. 1, Sae Ron Shin, M.D. 2, Tae Hyeon Kim, M.D. 1, Suck Chei Choi, M.D. 1 and Haak Cheoul Kim, M.D. 1 Background/Aims : The aim of this study was to evaluate the clinical features, radiologic findings, treatment modalities, and outcomes based on the origin of infection in patients with pyogenic liver abscesses. Methods : We retrospectively analysed the medical records of 118 patients who were treated for pyogenic liver abscesses between January 2004 and December Of the 118 patients, 56 patients had biliary risk factors. Results : The clinical characteristics were similar between the two groups, but the biliary risk group was characterized by an older age and the presence of jaundice. The size of the abscess was smaller in the group with biliary risk factors than in the cryptogenic group (p=0.02). Klebsiella pneumonia was the most common organism overall; however, Escherichia coli was more prevalent in the biliary risk group than in the cryptogenic group (p=0.03). Comparing the treatment modalities between the two groups, antibiotic therapy alone was more frequently used in the biliary group (p<0.01). The death rate was higher in the biliary group than in the non-biliary group (7.1 vs. 0.0%, p=0.04). The higher death rate in the biliary group was associated with multi-organ failure, absence of biliary drainage, and underlying diseases. Conclusions : There were differences between the two groups with respect to the size of the abscess, patient age, cultured organisms, and treatment modalities. The death rate was higher in the biliary group than the cryptogenic group. (Korean J Med 75:60-67, 2008) Key Words : Pyogenic liver abscess; Etiology; Biliary tract disease 서론간농양은발생원인에따라크게화농성과아메바성으로나뉘는데위생상태의개선으로아메바성간농양은현저하 게감소하였으며 1, 2), 화농간농양의가장흔한감염경로이었던일차적인복강내질환 (pyelophlebitis) 도항생제의도입이후감소하였다 3, 4). 그러나화농간농양의빈도는여전히줄지않고있으며 1, 2), 최근에는담도계원인이가장흔한감 Received : Accepted : Correspondence to : Haak Cheoul Kim, M.D. Department of Internal Medicine, College of Medicine, Wonkwang University Hospital, Sinyong-dong, Iksan , Korea hckimgold@wonkwang.ac.kr *This paper was supported by a grant from Wonkwang university (2006)

2 - Chang Soo Choi, et al : Comparison of pyogenic liver abscesses according to the infection origin - 염경로로보고되고있다 3, 4). 감염경로를모르는경우도증가추세를보이는데 1, 3, 5-7), 이러한변화들은동반질환, 원인질환의차이와고령화의증가와연관이있다 1, 6, 8). 최근진단율의향상, 효과적인항생제의조기도입, 배액술의발달로화농간농양의예후가향상되었으며 9-11), 국내간농양에의한사망률도 1990년초반에 7.8~17.1% 에서 2000년대에 2.1~12.8% 로감소하였지만여전히높은수준을나타내고있다 5, 6, 12, 13). 지금까지간농양환자들의감염경로에따른발생빈도에대한보고는있으나감염경로에따른원인적분류를통한비교는드물어 7), 저자는 2004년 1월부터 2006년 11월까지간농양으로치료받은 129명을대상으로원인적분류를시행하고후향적분석을시행하였다. 대상및방법 2004년 1월부터 2006년 11월까지원광대학병원에내원하여화농간농양을진단받은 129명의환자들중담도계질환이동반된경우와감염경로를모르는원발성으로진단된 118명환자들을대상으로하였다. 본연구기간동안아메바성이나진균성이원인인경우는없었으며간흡충소견을보인 8예, 게실염이나대장염과연관된경우로추정되는 2 예, 간세포암의경동맥화학색전술후발생한 1예는배제하였다. 자료수집은의무기록을중심으로후향적임상고찰을시행하였다. 화농간농양의진단기준은방사선학적진단하에경피적천자나배농이이루어진경우, 수술에의해간내농양강이확인된경우, 방사선학적진단후혈액배양검사로원인균이증명되었거나, 항생제치료후병변이소실된경우로정의하였다. 방사선학적진단은복부초음파, 전산화단층촬영또는자기공명촬영을이용하였다. Frey 분류를토대로방사선학적 ( 복부초음파, 복부전산화단층촬영, 내시경적역행성담췌관조영술 ), 임상적및수술소견에따라담도염또는담낭염의소견이보인경우, 간외담도이상이동반된경우, 담도계결석의존재, 악성담도계폐쇄가동반된경우를담도계원인으로하였다. 원인불명의감염경로는충수돌기염, 게실염및복강내감염등의감염경로가이학적, 방사선학적검사에서확인되지않은경우로하였다. 대상환자를감염경로에따라담도계질환이있는담관군과감염경로를알수없는원발군으로분류하고, 임상양상, 검사실소견, 세균학적검사, 동반질환, 영상진단, 농양의특징, 치료법, 합병증, 재원기간등을조사하고양군을 비교분석하였다. 결과분석에는정량분석의경우 t-test 또는 ANOVA test 를이용한단일회귀분석을, 정성분석의경우 Yates correction을동반한 Chi-square test 혹은 Fisher`s exact test를실시하여 p값 0.05 미만을통계적으로의미있게해석하였다. 결과 1. 환자군의임상적특징전체 118명에서담관화농간농양군은 56명, 원발군은 62 명이었고, 평균연령은각각 67.6세 ( ), 59.9세 ( ) 로담관군이연령이높았다 (p<0.01). 가장흔한증상은발열이었으며, 공막의황달이담관군에서원발군보다많았지만 (p=0.02), 그외임상증상및징후에서차이는없었다 ( 표 1). 2. 기왕력및동반질환기저질환으로담관군에서간경변환자가많았으며 (p=0.02), 그외기저질환에서차이는없었다 ( 표 1). 담관군에서담석에의한담낭절제술을시행받은환자가 15예, 담도계결석이 32예에서있었고, 이중 8예는담낭석과담도결석이동시에 24예는담도결석만이있었다. 악성종양에의한담도폐쇄는담관군에서 12예 ( 담도암 6예, 담낭암, 췌장암, 간암, 위암의담도침윤각각 3예, 1예, 1예, 1예 ) 있었으며원발군에서는동반된악성종양은없었다 ( 표 2). 3. 혈액검사소견혈액검사에서두군간의유의한차이는없었다 ( 표 3). 4. 농양의특징농양강의크기는방사선검사를통하여농양의가장큰직경을측정하였는데다발성인경우가장큰농양의직경을측정하였다. 담관군 (51.5±25.5 mm) 이원발군 (63.0±25.8 mm) 에비해농양강의크기가작았다 (p=0.02). 농양의양상은두군모두우엽에가장많이발생하였고, 단일농양이가장많았다. 담관군에서다발성농양의수가많은경향을보였으나유의한차이는없었으며 (p=0.07), 공기방울형성농양은차이가없었다 ( 표 4). 5. 세균학적검사혈액및농양배양검사를시행한 112예중 77예 (68.8%) 에

3 - 대한내과학회지 : 제 75 권제 1 호통권제 575 호 Table 1. Clinical characteristics of patients Variables N=62 (n, %) N=56 (n, %) Age (yr, mean SD) 59.9± ±11.0 <0.01 Gender (M/F) 42/20 32/24 Clinical manifestation Fever/Chills 57 (91.9%) 47 (83.9%) Abdominal pain 40 (64.5%) 35 (62.5%) Nausea/Vomiting 13 (21.0%) 15 (26.8%) Jaundice 10 (16.1%) 20 (35.7%) 0.02 Hypotension (sys. pr * <90 mmhg) 5 (8.9%) RUQ tenderness 40 (64.5%) 35 (62.5%) Diabetes mellitus 20 (32.3%) 15 (26.8%) Liver cirrhosis 0 (0.0%) 5 (8.9%) 0.02 * sys. pr, systolic pressure Table 2. Underlying diseases in the biliary group Variables (N=62,%) Gallbladder stones 20 (32.25%) Bile duct stones 32 (51.61%) GB and bile duct stone 8 (12.90%) Malignancy 12 (19.35%) 서균이배양되었고, 담관군에서 72.5% (37/51), 원발군에서 65.6% (40/61) 의배양양성율을보였다. 두군모두농양배양양성율 ( 담관군 75%, 원발군 67.2%) 이혈액배양양성율 ( 담관군 39.5%, 원발군 27.1%) 보다높았으며, 담관군에서혈액배양율이높은경향을보였다. 전체군에서 K. pneumonia 가 72.7% 로가장흔한원인균이었고, 양군을비교해보면담관군에서 E. coli 배양율이높았다 (p=0.03)( 표 5). 6. 치료의방법, 결과및재원기간의비교모든환자에서초기부터세팔로스포린, 페니실린계유도체, 아미노그라이코사이드, 메트로니다졸등의광범위항생제를정맥으로초기부터 10~14일간투여하였으며이후에복부초음파나전산화단층촬영을시행하여치료효과를판단하였다. 환자들은항생제단독치료, 초음파유도하경피적세침농양흡입술또는카테터농양배액술을시행하였고, 반응이없는경우수술을시행하였다. 항생제단독치료는담관군에서 16예 (28.6%), 원발군에서 4예 (6.5%) 로담관군에서높았다 (p<0.01). 항생제단독치료는농양의크기가 3 cm 이하로작고다발성인경우가 8예, 농양의미성숙으로 인한경우가 7예, 환자의시술거부 1예, 농양의크기가작고위치가접근하기어려운경우 4예에서시행하였다. 초음파유도하경피적세침농양흡입술또는카테터배액술은상기경우를제외하고는내원 24~72시간내에시행하였으며추적방사선검사에서농양강이남아있으면재시행을고려하였다. 흡인이나배액의병행은담관군에서 34예 (60.7%), 원발군에서 55예 (88.7%) 로후자에서시행빈도가높았다 (p<0.01). 수술적치료를시행한환자는담관군의경우 6예 (10.7%), 원발군의경우 3예 (4.8%) 였다. 수술적치료는다발성중격에의해배액이어려웠던경우 2예, 동반된담석이나종양의치료를위해수술한경우가 5예, 농양의복강내파열에의한 2예였다. 담관군의 20예에서방사선소견에서총담관결석이나찌꺼기가관찰되었으며이중 18예에서역행성담췌관조영술하에결석을제거하였다. 담관군의 9예에서총수담관및간내담관의감압을위해경피적담관배액술을시행하였다. 양군에서재원기간의유의한차이는없었으며전체사망은 4예 (3.4%) 로, 모두담관군에서발생하였다 (p=0.04)( 표 6). 사망한 4예중 3예에서농양에대한배액술이실시되었고, 1예를제외한 3예에서역행성담췌관조영술및경피적담관배액술을통한담도감압을시행받지않았다. 사망환자중 2예는담도계악성종양과연관이있었고, 2예는내원당시패혈증소견을보였으며다발성장기부전으로사망하였고, 이중 1예는기저질환으로간경화가있었다. 치료에따른입원기간의비교에서항생제단독치료군의경우재원일은 19.3±6.7일, 초음파유도하경피적세침농

4 - 최창수외 9 인 : 감염경로에따른화농성농양의비교 - Table 3. Laboratory findings in the biliary and cryptogenic groups Parameters (N=62, %) (N=56, %) WBC count (>10,000/mm 3 ) 52 (83.9%) 38 (67.9%) WBC count (<4000/mm 3 ) 2 (3.6%) Pletelet count (<150,000/mm 3 ) 13 (21%) 17 (30.4%) Serum albumin (<3.0 g/dl) 21 (33.9%) 21 (37.5%) AST (>35 IU/L) or ALT (>40 IU/L) 50 (80.6%) 48 (85.7%) ALP (>220 IU/L) 49 (79%) 51 (91.1%) TB (>1.4 g/dl) 20 (32.3%) 26 (46.4%) Hb (<10 g/dl) 8 (12.9%) 6 (10.7%) Serum Cr (>1.3 mg/dl) 15 (24.2%) 19 (33.9%) WBC, white blood cell; Hb, haemoglobin; Alb, albumin; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; TB, total bilirubin; BUN, blood urea nitrogen; Cr, creatinine Table 4. Characteristics of abscesses in the biliary and cryptogenic groups Variables (N=62)(%) (N=56)(%) Abscess size 63.0±25.8mm 51.5±25.5mm 0.02 Abscess location Right lobe 47 (75.8%) 36 (64.3%) Left lobe 9 (14.5%) 14 (25.0%) Both lobes 6 (9.7%) 6 (10.7%) Abscess number Single 53 (85.5%) 40 (71.4%) Multiple 9 (14.5%) 16 (28.6%) Gas forming abscess 4 (6.5%) 2 (3.6%) Ruptured abscess 2 (3.2%) 0 (0.0%) Multi-septated abscess 24 (38.7%) 20 (35.7%) 양흡입술또는카테터배액술병합치료군은 22.8±10.6일, 수술치료군은 34.3±15.2일로차이가있었다 (p<0.01)( 표 6). 고 찰 7. 합병증화농성간농양에의한합병증은담도계질환군에서 18예 (32.1%), 감염경로를모르는군에서 20예 (32.3%) 로두군간의차이는없었다. 합병증은담도계질환이있는경우폐렴 2예 (3.6%), 늑막삼출 13예 (23.2%), 패혈증 5예 (8.9%) 이었고, 감염경로를모르는군은폐렴 3예 (4.8%), 늑막삼출 19 예 (30.6%), 패혈증 3예 (4.8%), 농양파열 2예 (3.2%) 로두군간의유의한차이는없었다 ( 표 6). 화농간농양은담도계를통한감염이가장흔한경로이지만 3, 4) 감염경로를모르는경우도증가추세를보여, 1,3,5-7) 일부에서는가장흔한원인으로보고되어있다 5, 6, 13). 그러나영상진단및검사실의진단율의향상으로감염경로를모르는경우가 10~15% 로감소하였다는보고 14) 도있어화농성간농양의원인은보고마다차이가있고이를명확하게구분하기는어렵다. 본연구에서는담관군은 43.4%, 원발군은 48.06% 로감염경로를모르는간농양환자들의증가를확인할수있었다. 평균연령은담관군에서높았고, 이는연령이증가할수록종양및담도계질환의빈도증가와관련이있

5 - The Korean Journal of Medicine : Vol. 75, No. 1, Table 5. Result of bacteriologic cultures in the biliary and cryptogenic groups Variables (N=61, %) (N=51, %) Organism K. pneumonia 36 (59.0%) 21 (41.2%) E. coli 3 (4.9%) 9 (17.6%) 0.03 Pseudomonas spp. 2 (3.3%) 2 (3.9%) Stenotrophomonas maltophilia 1 (1.6%) 3 (5.9%) Multiple oragnisms 3 (4.9%) 7 (13.7%) Culture-positive 40/61 (65.6%) 37/51 (72.5%) Blood culture-positive 16/59 (27.1%) 17/43 (39.5%) Pus culture-positive 37/55 (67.2%) 30/40 (75.0%) Table 6. Treatment and outcome in the biliary and cryptogenic groups (N=62, %) (N=56, %) Treatment Antibiotics alone 4 (6.5%) 16 (28.6%) <0.01 PNA and/or PCD plus antibiotics 55 (88.7%) 34 (60.7%) <0.01 Operation 6 (10.7%) Length of hospital stay(days) 21.9± ±13.5 Death 0 4 (7.1%) 0.04 Complications 20 (32.3%) 18 (32.1%) Pneumonia 2 (3.6%) Pleural effusion 19 (30.6%) 13 (23.2%) Sepsis 5 (8.9%) Ruptured abscess 2 (3.2%) 0 (0.0%) PNA, percutaneous needle aspiration; PCD, percutaneous catheter drainge 을것으로추정된다. 발열은가장흔한증상이었으며담관군에서공막황달이흔하게동반되었지만그외임상양상의차이는없었다. 검사실소견에서두군간의의미있는차이는없었다. 담관군에서알부민감소, 혈소판감소, 크레아티닌증가빈도가높은경향을보여패혈증으로의진행이나장기부전등의중한경과를보일것으로추정되지만간경변이담관군에많이동반되어있어해석에주의를요한다. 단일검사로 ALP (alkaline phosphatase) 상승이담도계패쇄시유용한데 17) 본연구에서도담관군에서총빌리루빈및 ALP 상승의빈도가높음을확인하였다. 본연구에서혈액이나농양강의배양양성율은 68.8% 이 며, 다른보고 3, 18, 19) 에서처럼혈액보다농양에서배양양성율이높았다. 혈액배양양성율은담관군이원발군에비해높거나 20) 비슷하다는보고가있으며 7) 본연구에서는담관군에서높은경향을보였다. 화농성간농양의원인균으로서 E. coli가 37~65% 로가장흔한균으로보고되었지만, 최근에는 K. pneumonia가증가추세를보인다 1, 6, 8, 14, 20). 본연구에서도 K. pneumonia 가가장흔한균으로최근원인균의변화와유사한양상을나타냈다. 그러나담관군에서 E coli, 원발군에서 K. pneumonia 가상대적인증가를보였는데이는원발군의당뇨환자가많이포함되어있다는점을고려해야할것이다. K. pneumonia는표면수용체의발현이낮아독성작용을일으키는것으로추정되는데당뇨병환자에서는호중

6 - Chang Soo Choi, et al : Comparison of pyogenic liver abscesses according to the infection origin - 구의화학주성과포식작용이방해를받게되어 Klebsiella K1과 K2 혈청형이간이나비장의대식세포포식작용이 78.4% 로간내대식세포에영향을주어간농양의발생에영향을주는것으로생각되고있다 22, 23). 농양강의특징에있어담관군에서다발성농양이많았지만 20, 24-26), 이와상반된결과도보고되어있다 7, 18). 본연구에서는담관군에서농양의크기가작았고다발성농양이많은경향을보였다. 농양강의위치는두군모두우엽에빈도가높았지만이는상부장간막정맥혈이우엽으로유입되고비장및하부장간막정맥은좌엽으로유입되는경향과관련이있을것으로생각된다 17, 11). 원발군에서농양의상대적인우엽의호발과담관군에서좌엽의상대적인호발은간내담석의발생과연관이있을것으로생각되지만관련기전은확인할수없었다. 농양의치료방법은예후에영향을줄수있는데항생제단독치료만으로는사망률이 59~100% 에이르지만 7, 25, 27), 배액술을병용한경우 90% 이상에서호전을보일수있어 5, 6, 12, 13) 치료방법의차이가예후에중요한영향을미치는것을알수있다. 그러나이와상반된결과로항생제단독치료환자에서치료율이높다는보고 28, 29) 가있는데, 이는 2 cm 이상의크기로성숙된농양의경우대부분배액을시행하고, 항생제단독치료는농양강의크기가작거나, 다발성소농양이거나, 임상경과가양호한환자에서시행되었기때문이라생각된다. 본연구에서항생제단독치료는농양의미성숙과다발성분포, 크기가작은경향을보인담관군에서많이시행되었다. 일반적으로간농양의치료에있어우선적으로조기배액을시도하고배액의필요성이없는경우에만항생제단독치료를시행해야예후를향상시킬수있다. 본연구에서담관군의사망률이높은이유를치료방법에있어항생제단독치료가많았다는점을고려해볼수있다. 그러나사망환자의 4명중 3명은농양배액술과항생제를병행하였던점을고려하면항생제단독치료가담관군에서많다는점은사망률에많은영향은주지않았을것으로생각된다. 이에담관군의내시경치료, 담관감압을위한배액, 기저질환, 동반질환의수술적치료의상황등을고려해야한다. 담관군의사망 4예는동반질환에대한담도감압이나배액은 1예에서만시행되었고, 이들이예후와연관이있을것으로생각된다. 그러므로담관군에서담도폐색이나담도염이동반되어있다면, 농양의배액뿐아니라내시경적, 경피적, 또는수술적담도감압을시행하는것이예후를향상시킬수있을것이다. 간농양으로인한사망은농양자체보다는기 저질환과연관이있다고보고하였으며 30), 본연구에서도사망환자중 2예는담도계종양, 1예는간경화가동반되어이들이예후에영향을주었을것으로생각된다. 간농양의합병증으로는패혈증, 폐렴, 늑막삼출, 급성신부전, 농양파열, 창상감염등이있는데본연구결과국내보고들보다합병증의발생이낮았으며 6, 12, 13) 이는최근항생제의조기사용, 조기진단, 배액술의발달등에의한것으로생각된다. 결론적으로두군을비교하여연령, 농양의크기, 황달의발생, 항생제단독치료빈도, E coli 균주의빈도, 사망율에서차이가있었다. 담관군이원발군에비해고령이고, 항생제단독치료만이가능한경우가많았으며, 패혈증으로진행하여사망에이르는중한경과를보였고이런경과는기저질환과연관이있었다. 화농성간농양환자의치료에있어가능하다면조기배농과담도감압을시행하고항생제를병행하는것이예후를향상시킬것으로생각된다. 요약목적 : 최근간농양에대한보고는원인적균주의변화나기저질환의분류에따른특징에대한내용이대부분으로, 감염경로의원인적분류에따른임상양상및경과, 농양의특징, 균주, 동반질환등의차이에대해알아보고자하였다. 방법 : 2004년1 월부터 2006년 11월까지병원에내원하여화농간농양을진단받은 118명의환자의대상으로임상양상, 방사선학적소견, 치료, 예후등을비교하였다. 결과 : 화농성간농양 118명의환자중담관군은 56예, 원발군은 62예였고, 담관군에서평균연령이 67.6세로원발군의 59.9세에비해의미있게높았다. 증상및징후에서대부분에서두군의차이는없었으나, 담관군에서황달의빈도가유의하게높았다 (p=0.02). 기저질환으로간경변이담관군에서높았다. 농양강의특징에서담관군에서다발성농양의빈도가높은경향을보였으며, 농양강의크기가의미있게작았다 (p=0.02). 원인균은두군에서모두 K. pneumonia 가가장많이검출되었고, 담관군에서상대적으로 E. coli의검출이유의하게높았다. 간농양의치료는담관군에서항생제단독치료가유의하게많았고, 원발군에서배액치료와항생제병용치료가유의하게많았다 (p<0.01). 합병증은두군간의차이는없었고, 사망은담관군에서유의하게높았다 (p=0.04). 결론 : 담관군은고령이며, 황달의발생이높고, 농양의크기, 기저질환, 원인균및치료적측면, 사망률등이원발

7 - 대한내과학회지 : 제 75 권제 1 호통권제 575 호 군과유의한차이를보였다. 이는향후대규모전향적연구를통한평가가필요할것으로생각된다. 중심단어 : 화농성간농양 ; 원인 ; 담도계질환 REFERENCES 1) Lim SW, Lee EJ, Lee SW, Kim SM, Kim JH, Kim BJ, Jang BI, Kim TN, Chung MK. Clinical significance of Klebsiella pneumoniae in liver abscess. Korean J Gastroenterol 42: , ) Lee OJ, Kim YC. A clinical study on liver abscess. Korean J Gastroenterol 26: , ) Huang CJ, Pitt HA, Lipsett PA, Osterman FA Jr, Lillemoe KD, Cameron JL, Zuidema GD. Pyogenic hepatic abscess: changing trends over 42 years. Ann Surg 223: , ) Rahimian J, Wilson T, Oram V, Holzman RS. Pyogenic liver abscess: recent trends in etiology and mortality. Clin Infect Dis 39: , ) Jun DW, Moon JY, Baeg SH, Choi HS, Sohn JH, Lee OY, Yoon BC, Lee MH, Lee DH, Kee CS. A clinical study of pyogenic liver abscess at two different local hospitals. Korean J Hepatol 11: , ) Lee CJ, Jung DS, Jung SH, Baik JH, Lee JH, Cho YR, Go BS, Lee SW, Han SY, Lee DH. Comparison of liver abscess between diabetic patients and non-diabetic patients. Korean J Hepatol 11: , ) Chen SC, Yen CH, Tsao SM, Huang CC, Chen CC, Lee MC, Bell WR. Comparison of pyogenic liver abscesses of biliary and cryptogenic origin: an eight-year analysis in a University Hospital. Swiss Med Wkly 135: , ) Nah BK, Kim YS, Moon HS, Park KO, Kim SM, Lee YS, Yang HW, Seo SW, Kim SH, Lee BS, Kim NJ, Lee HY. Recent changes of organism and treatment in pyogenic liver abscess. Korean J Hepatol 9: , ) Cheng DL, Liu YC, Yen MY, Liu CY, Wang RS. Septic metastatic lesions of pyogenic liver abscess: their association with Klebsiella pneumoniae bacteremia in diabetic patients. Arch Intern Med 151: , ) Greenstein AJ, Lowenthal D, Hammer GS, Schaffner F, Aufses AH Jr. Continuing changing patterns of disease in pyogenic liver abscess: a study of 38 patients. Am J Gastroenterol 79: , ) Pitt HA, Zuidema GD. Factors influencing mortality in the treatment of pyogenic hepatic abscess. Surg Gynecol Obstet 140: , ) Kim DW, Han SP, Kim SJ, Cha BK, Ann GY, Jung SM, Kim SM, Do JH, Kim JG, Chang SK, Park SM. A clinical study on liver abscess over a recent 10 year period. Korean J Med 66: , ) Seo TJ, Park CH, Lee SH, Lee SJ, Park JH, Park JH, Lee WS, Joo YE, Kim HS, Choi SK, Rew JS, Kim SJ. A clinical study on liver abscess for recent 15 years in Gwangju- Chonnam province. Korean J Med 68;26-38, ) Seeto RK, Rockey DC. Pyogenic liver abscess: changes in etiology, management, and outcome. Medicine 75:99-113, ) Rustgi AK, Richter JM. Pyogenic and amebic liver abscess. Med Clin North Am 73: , ) Nah BK, Kim YS, Moon HS, Park KO, Kim SM, Lee YS, Yang HW, Seo SW, Kim SH, Lee BS, Kim NJ, Lee HY. Recent changes of organism and treatment in pyogenic liver abscess. Korean J Hepatol 9: , ) Rubin RH, Swartz MN, Malt R. Hepatic abscess: changes in clinical, bacteriologic and therapeutic aspects. Am J Med 57: , ) Alvarez JA, Gonzalez JJ, Baldonedo RF, Sanz L, Carreno G, Jorge JI. Single and multiple pyogenic liver abscesses: etiology, clinical course, and outcome. Dig Surg 18: , ) Koneru S, Peskin GW, Sreenivas V. Pyogenic hepatic abscess in a community hospital. Am Surg 60: , ) Wang JH, Liu YC, Lee SS, Yen MY, Chen YS, Wang JH, Wann SR, Lin HH. Primary liver abscess due to Klebsiella pneumoniae in Taiwan. Clin Infect Dis 26: , ) Yang CC, Chen CY, Lin XZ, Chang TT, Shin JS, Lin CY. Pyogenic liver abscess in Taiwan: emphasis on gas-forming liver abscess in diabetics. Am J Gastroenterol 88: , ) Cohen JL, Martin FM, Rossi RL, Schoetz DJ Jr. Liver abscess: the need for complete gastrointestinal evaluation. Arch Surg 124: , ) Gyorffy EJ, Frey CF, Silva J Jr, McGahan J. Pyogenic liver abscess: diagnostic and therapeutic strategies. Ann Surg 206: , ) Chou FF, Sheen-Chen SM, Chen YS, Chen MC. Single and multiple pyogenic liver abscesses: clinical course, etiology, and results of treatment. World J Surg 21: , ) McDonald MI, Corey GR, Gallis HA, Durack DT. Single and multiple pyogenic liver abscesses: natural history, diagnosis and treatment, with emphasis on percutaneous drainage. Medicine 63: , ) Tazawa J, Sakai Y, Maekawa S, Ishida Y, Maeda M, Marumo F, Sato C. Solitary and multiple pyogenic liver abscesses: characteristics of the patients and efficacy of percutaneous drainage. Am J Gastroenterol 92: , ) Johannsen EC, Sifri CD, Madoff LC. Pyogenic liver abscesses. Infect Dis Clin North Am 14: , ) Herbert DA, Fogel DA, Rothman J, Wilson S, Simmons F,

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386-390.hwp 386 HANYANG MEDICAL REVIEWS Vol. 29 No. 4, 2009 우리나라 미숙아의 통계와 의료비용 Statistics and Medical Cost of Preterm in Korea 윤혜선 을지대학교 노원을지병원 소아청소년과학교실 Hye Sun Yoon, M.D., Ph.D., Department of Pediatrics, Nowon