prosedur bedah Jenis laparotomi diputuskan menurut jenis hepatektomi parsial dan konstitusi pasien .

Cholangiography pra operasi tidak biasanya dilakukan . Intraoperative ultrasonografi dilakukan untuk menentukan luasnya HCC dan garis parenkim transeksi . Parenkim transeksi dilakukan menggunakan dissector ultrasonik ( SonopTM 5000 , Aloka , Tokyo , Jepang ) dikombinasikan dengan bipolar elektrokauter . Pedikel Glisson ini dalam hati membedah dengan cara dissector ultrasonik yang pedikel diligasi dan kecil transected menggunakan logam klip . Untuk hemihepatectomies atau reseksi diperpanjang , hilus diseksi dilakukan untuk membagi cabang ipsilateral dari arteri hepatika dan vena portal . Hepatik saluran terkena dalam hati selama transeksi parenkim dan diikat atau oversewn menggunakan baik non - absorbable jahitan . Dalam hemihepatectomies atau reseksi hati diperpanjang , parenkim lintang biasanya dilakukan tanpa oklusi inflow vaskular . Untuk segmentectomies atau subsegmentectomies , Pedikel Glisson itu yang transected di hati hilus dan Pringle manuver intermiten adalah diterapkan selama transeksi parenkim . Intraoperatif kolangiografi dilakukan di pasien tertentu jika integritas saluran empedu berada di diragukan. Sebuah tes kebocoran empedu menggunakan kateter cholangiography juga dilakukan pada pasien tertentu jika sejumlah Pedikel Glisson yang terkena di bidang hati reseksi. Pada prinsipnya, dua tabung drainase perut yang diposisikan sesuai dengan jenis hepatektomi. Dalam hemihepatectomy, satu tabung drainase ditempatkan pada luka permukaan hati dan satu lagi di foramen Winslow. di subsegmentectomy dan Segmentectomy, satu tabung drainase ditempatkan pada permukaan potongan hati dan satu lagi di ruang subphrenic tepat. Dari tahun 2001 sampai 2005, terbuka sistem drainase dipekerjakan menggunakan 12-mm silikon Penrose saluran (Kaneka, Osaka, Jepang). Dari 2006 hingga 2010, sistem drainase tertutup digunakan dengan 24 Fr BLAKE silikon saluran (Johnson & Johnson, Somerville, New Jersey, USA). Saluran air yang dihapus ketika cairan drainase adalah serosa dan tidak mengandung empedu, yang biasanya sekitar 5 hari setelah operasi. Definisi kebocoran empedu dan organ / ruang infeksi bedah - situs Kebocoran empedu pascaoperasi didefinisikan sebagai drainase

empedu makroskopik dari bedah saluran air selama lebih dari 7 hari setelah operasi . Kebocoran empedu utama didefinisikan sebagai makroskopik empedu debit melebihi 100 ml / hari yang melakukan tidak menurun dari satu hari ke hari berikutnya . kebocoran empedu dianggap kecil jika tidak memenuhi definisi kebocoran empedu utama . Kebocoran empedu terselesaikan adalah didefinisikan sebagai kebocoran membutuhkan endoskopi retrograde empedu drainase ( ERBD ) atau percutaneous transhepatik empedu drainase ( PTBD ) selama manajemen pasca operasi . SSIS didefinisikan menurut Infeksi Nosokomial Nasional Surveillance System15 . Menggunakan kriteria ini , SSIS diklasifikasikan sebagai insisional ( superficial atau deep ) atau organ / ruang. Definisi organ / ruang SSI didasarkan temuan pasca operasi setidaknya salah satu dari berikut : drainase purulen dari cerat tanpa empedu makroskopik debit , atau intra - abdomen pengumpulan cairan purulen dikonfirmasi pada saat reoperation atau perkutan dihitung tomography - atau drainase ultrasonografi dipandu . Kebocoran empedu dianggap hadir jika intra - abdominal cairan pada saat reoperation atau perkutan drainase terkandung debit empedu makroskopik . Jika cairan purulen adalah dikeringkan pertama dan makroskopik empedu kebocoran selanjutnya menjadi jelas , ini didefinisikan sebagai kebocoran empedu . Sebaliknya, jika drainase cairan purulen masih diamati setelah penghentian kebocoran empedu makroskopik , organ / ruang SSI dianggap hadir .

antimikroba profilaksis Regimen antibiotik profilaksis adalah sebagai berikut. Pada awal hepatectomy parsial, cephalosporin generasi pertama disuntikkan secara intravena dalam waktu 30 menit sebelum insisi kulit. Pada pasien yang menjalani operasi berlangsung lebih lama dari 3 jam, agen antimikroba tambahan disuntik intravena setiap 3 jam, seperti yang direkomendasikan oleh Pusat Pengendalian Penyakit guidelines15. Agen ini juga diberikan sampai hari 2 setelah operasi. Dalam ulangi hepatektomi, cephalosporin generasi kedua disuntikkan intravena seperti dalam hepatectomy awal dan dilanjutkan sampai hari 3. Intervensi untuk methicillin-resistant Staphylococcus aureus Dengan pengecualian darurat, semua pasien mengalami evaluasi pra operasi untuk methicillin-resistant Staphylococcus aureus (MRSA), termasuk budaya hidung. Pada pasien di antaranya kolonisasi MRSA terdeteksi dari pra operasi budaya hidung, dekolonisasi dilakukan dengan menggunakan intranasal mupirocin terapi, diberikan dua kali sehari selama

3-5 hari sebelum operasi. Infus intravena profilaksis vankomisin tidak digunakan pada pasien dengan intranasal Kolonisasi MRSA. Analisis faktor risiko kebocoran empedu dan organ / ruang infeksi bedah - situs Demografi pasien , fungsi hati pra operasi , operasi dan faktor tumor dievaluasi untuk menentukan mereka berdampak pada terjadinya kebocoran empedu dan organ / ruang SSI . Faktor preoperatif termasuk usia pasien , jenis kelamin , etiologi penyakit hati , kelas Child-Pugh , indocyanine pewarna hijau tingkat retensi di 15 menit ( ICG - R15 ) , serum albumin , riwayat diabetes mellitus , frekuensi radio sebelumnya ablasi ( RFA ) dan chemoembolization transarterial sebelumnya ( TACE ) . The cut-off level untuk ICG - R15 yang ditetapkan sebesar 20 persen , karena seorang ICG - R15 kurang dari 20 persen telah dilaporkan sebagai aman untuk bisegmentectomy3 , 4,8 . Faktor Tumor termasuk jumlah lesi HCC dan diameter maksimum HCCs individu. cutoff level untuk HCC berdiameter ditentukan menurut Hasil dari laporan sebelumnya yang menganalisis faktor risiko morbiditas setelah hepatektomi parsial forHCC3 , 4,8,10 . bedah faktor dievaluasi adalah jenis hepatektomi parsial , jumlah hepatectomies parsial , waktu operasi , durasi hati parenkim transeksi , kehilangan darah , perlu untuk transfusi darah dan metode drainase perut . Berkenaan dengan jenis hepatektomi parsial , anterior segmentectomies dan medial ( S4 ) yang segmentectomies subgrouped untuk analisis . Cut-off point untuk waktu operasi dan durasi hati parenkim transeksi ditentukan dengan menganalisis karakteristik penerima operasi ( ROC ) kurva untuk kebocoran empedu . Optimal cut-off untuk durasi operasi adalah 302 menit ( sensitivitas dan spesifisitas 0.690 dan 0,687 masing-masing) , dan bahwa untuk durasi hati parenkim lintang adalah 82 menit ( sensitivitas dan spesifisitas 0,674 dan 0,668 ) . Akibatnya , 300 menit dan 80 menit ditetapkan sebagai tingkat cut-off untuk durasi operasi dan durasi hati transeksi parenkim masing-masing.
Investigasi kebocoran empedu terselesaikan Manajemen dan hasil diselidiki untuk pasien dengan kebocoran empedu pasca operasi. Indikasi untuk ERBD untuk mengobati kebocoran empedu pasca operasi didasarkan pada Temuan pasca operasi setidaknya salah satu dari berikut: jumlah debit empedu makroskopik dari bedah saluran air lebih dari 200 ml / hari pada 2 minggu setelah operasi, jumlah makroskopik empedu debit dari bedah saluran air melebihi

100 ml / hari pada 4 minggu setelah operasi, atau empedu makroskopik debit dari bedah saluran air masih berlangsung pada 6 minggu setelah operasi. PTBD ditunjukkan ketika pasca operasi kolangiografi dan drainase bilier oleh ERBD yang dianggap tidak praktis. Prosedur operasi, nomor dari hepatectomies parsial, waktu drainase bilier prosedur, situs kebocoran empedu dan kemungkinan penyebab kebocoran empedu dievaluasi pada pasien dengan empedu keras kebocoran yang memerlukan ERBD atau PTBD.

Investigasi karakteristik berkepanjangan hepatectomies Untuk memperjelas implikasi klinis dari sebuah operasi panjang, demografi pasien, fungsi hati pra operasi, faktor tumor dan bedah faktor swere dibandingkan antara kelompok dengan operasi berlangsung kurang dari 300 menit dibandingkan setidaknya 300 menit.

Analisis karakteristik organ / ruang infeksi bedah-situs Manajemen dan hasil diselidiki untuk pasien dengan organ / ruang SSI. Organ / ruang SSI diklasifikasikan menurut dimodifikasi Clavien system16. The penyebab bakteri diidentifikasi untuk kedua insisional dan organ / ruang SSIS. Pra operasi dan intraoperatif parameter, penyebab bakteri dan durasi tinggal di rumah sakit pasca operasi dibandingkan antara kelompok diklasifikasikan oleh jumlah hepatectomies parsial (awal dibandingkan ulangi) pada pasien dengan organ / ruang SSI.
analisis statistik Data kontinu disajikan sebagai rata-rata (sem) kecuali menunjukkan hal yang sebaliknya. Perbedaan dalam variabel kualitatif dinilai dengan menggunakan uji eksak Fisher atau 2 tes, dan kuantitatif variabel dianalisis dengan menggunakan Mann-Whitney U test. Univariat dan multivariabel analisis regresi logistik digunakan untuk mengidentifikasi risiko faktor empedu kebocoran dan organ / ruang SSI didasarkan pada 18 disebutkan di atas faktor klinis. Variabel dengan P 0.050 dalam analisis univariat dimasukkan dalam multivariabel analisis. Risiko relatif digambarkan oleh perkiraan odds ratio (OR) dengan 95 persen interval kepercayaan. Nilai P dua sisi dihitung dan P 0.050 adalah dianggap signifikan secara statistik. Semua analisa statistik dilakukan dengan menggunakan SPSS II

software statistik (IBM, Armonk, New York, USA). hasil Sebanyak 359 pasien dilibatkan dalam analisis ini , terdiri dari laki-laki 292 dan 67 wanita ( usia rata-rata 65 (kisaran 32-89 ) tahun ) . Etiologi penyakit hati pada 332 pasien dengan hepatitis kronis atau sirosis hati adalah hepatitis C virus ( 163 pasien ) , virus hepatitis B ( 122 ) , kedua hepatitis C virus dan virus hepatitis B ( 31 ) dan penyakit hati alkoholik ( 16 ) . Dua puluh tujuh pasien disajikan dengan HCC dalam hati yang normal . Beberapa 332 pasien memiliki Child-Pugh A dan 27 memiliki Child-Pugh fungsi hati B . Sebanyak 296 pasien ( 82,5 persen ) menjalani hepatectomy parsial anatomi termasuk subsegmentectomy . Ulangi hepatektomi adalah dilakukan pada 59 pasien ( 16,4 persen ) . laparotomi adalah dilakukan melalui sayatan berbentuk J di 287 pasien , Mercedes -jenis sayatan di 33 , sayatan garis tengah di 23 dan sayatan thoracoabdominal di 16 pasien . dengan pengecualian dua kasus darurat , 357 pasien menjalani evaluasi pra operasi untuk MRSA nasal menggunakan budaya . Sembilan ( 2,5 persen ) dari 359 pasien menunjukkan kolonisasi withMRSA pada masuk , dan dekolonisasi dilakukan . Faktor risiko kebocoran empedu Kebocoran empedu dikembangkan di 46 (12,8 persen) dari 359 pasien. Analisis univariat mengungkapkan beberapa faktor dikaitkan dengan peningkatan risiko kebocoran empedu (Tabel S1). Ulangi hepatektomi dikaitkan dengan peningkatan risiko kebocoran empedu, dengan Anor 3,78 dibandingkan dengan hepatectomy awal (P <0,001). Sebaliknya, tidak RFA sebelumnya norTACEhad dampak yang signifikan pada terjadinya kebocoran empedu. Waktu operasi setidaknya 300 menit dikaitkan dengan peningkatan risiko (OR 5.32, P <0,001), seperti kehilangan darah 2000 ml atau lebih (OR 4.12, P <0,001), transfusi darah (OR 3,66; P <0,001) dan durasi hati parenkim transeksi (OR 3.97, P <0,001). Analisis multivariabel dikonfirmasi ulangi hepatektomi (P <0,001) dan durasi operasi setidaknya 300 menit (P = 0,028) sebagai faktor risiko independen kebocoran empedu.

Faktor risiko untuk organ / ruang infeksi bedah - situs Organ / ruang SSI dikembangkan di 31 ( 8,6 persen ) dari 359 pasien . Analisis univariat mengungkapkan beberapa faktor

dikaitkan dengan peningkatan risiko mengembangkan organ / ruang SSI ( Tabel S2 ) . Ulangi hepatektomi dikaitkan dengan peningkatan risiko mengembangkan organ / ruang SSI , dengan OR sebesar 4,29 dibandingkan dengan hepatectomy awal ( P < 0,001 ) . Sebaliknya, baik RFA sebelumnya atau TACE punya dampak yang signifikan . Metode drainase perut ( Penrose saluran terbuka atau tertutup saluran hisap ) tidak memiliki pengaruh yang signifikan . Waktu operasi minimal 300 menit dikaitkan dengan peningkatan risiko organ / ruang SSI ( OR 2,99 , P < 0,001 ) , seperti durasi parenkim hati lintang ( OR 5.15 , P < 0,001 ) , kehadiran empedu kebocoran ( OR 3.16 , P < 0,001 ) dan darah kehilangan setidaknya 2000 ml ( OR 2.63 , P = 0,010 ) . analisis multivariabel dikonfirmasi ulangi hepatektomi ( P < 0,001 ) dan kehadiran empedu kebocoran ( P = 0,019 ) sebagai faktor risiko independen untuk organ / ruang SSI .

Surgical procedure The type of laparotomy was decided on according to the type of partial hepatectomy and the patients constitution. Preoperative cholangiography was not usually performed. Intraoperative ultrasonography was carried out to determine the extent of the HCC and the line of parenchymal transection. Parenchymal transection was done using an ultrasonic dissector (SonopTM 5000; Aloka, Tokyo, Japan) combined with bipolar electrocautery. Glissons pedicles in livers dissected by means of the ultrasonic dissector were ligated and small pedicles were transected using metal clips. For hemihepatectomies or extended resections, hilar dissection was performed to divide the ipsilateral branches of the hepatic artery and portal vein. The hepatic duct was exposed inside the liver during parenchymal transection and was ligated or oversewn using fine non-absorbable sutures. In hemihepatectomies or extended liver resections, parenchymal transection was usually performed without occlusion of vascular inflow. For segmentectomies or subsegmentectomies, Glissons pedicles were transected at the hepatic hilum and an intermittent Pringle manoeuvre was applied during parenchymal transection. Intraoperative cholangiography was undertaken in selected patients if the integrity of the bile duct was in doubt. A bile leakage test using a cholangiography catheter was also performed in selected patients if a number of Glissons pedicles were exposed in the plane of hepatic resection. In principle, two abdominal drainage tubes were positioned according to the type of hepatectomy. In hemihepatectomy, one drainage tube was placed on the cut surface of the liver and another at Winslows foramen. In subsegmentectomy and segmentectomy, one drainage tube was placed on the cut surface of the liver and another in the right subphrenic space. From 2001 to 2005, an open drainage system was employed using 12-mm silicone Penrose drains (Kaneka, Osaka, Japan). From 2006 to 2010, a closed drainage system was used with 24-Fr BLAKE silicone drains (Johnson & Johnson, Somerville, New Jersey, USA). Drains were removed when the drainage fluid was serous and contained no bile, which was usually around 5 days after surgery. Definition of bile leakage and organ/space surgical-site infection Postoperative bile leakage was defined as the drainage of macroscopic bile from surgical drains for more than 7 days after surgery. Major bile leakage was defined as macroscopic bile discharge exceeding 100 ml/day that did not decrease from one day to the next. Bile leakage was considered minor if it did not fulfil the definition for major bile leakage. Intractable bile leakage was defined as leakage requiring endoscopic retrograde biliary drainage (ERBD) or percutaneous transhepatic biliary drainage (PTBD) during postoperative management. SSIs were defined according to the National Nosocomial Infections Surveillance System15. Using these criteria, SSIs are classified as either incisional (superficial or deep) or organ/space. The definition of organ/space SSI was based on postoperative findings of at least one of the following: purulent drainage from a drain without macroscopic bile discharge; or intra-abdominal collection of purulent fluid confirmed at the time of reoperation or percutaneous computed tomography- or ultrasonography-guided drainage. Bile leakage was considered present if intra-abdominal

fluid at the time of reoperation or percutaneous drainage contained macroscopic bile discharge. If purulent fluid was drained first and macroscopic bile leakage subsequently became apparent, this was defined as bile leakage. In contrast, if drainage of purulent fluid was still observed after the cessation of macroscopic bile leakage, organ/space SSI was considered present.

Antimicrobial prophylaxis Prophylactic antibiotic regimens were as follows. At the initial partial hepatectomy, a first-generation cephalosporin was injected intravenously within 30 min before skin incision. In patients who underwent operations lasting longer than 3 h, additional antimicrobial agents were injected intravenously every 3 h, as recommended by the Centers for Disease Control guidelines15. These agents were also administered up to day 2 after operation. In repeat hepatectomy, a second-generation cephalosporin was injected intravenously as in the initial hepatectomy and continued until day 3. Intervention for methicillin-resistant Staphylococcus aureus With the exception of emergencies, all patients underwent preoperative evaluation for methicillin-resistant Staphylococcus aureus (MRSA), including nasal culture. In patients in whom MRSA colonization was detected from preoperative nasal cultures, decolonization was performed using intranasal mupirocin therapy, administered twice daily for 35 days before operation. Prophylactic intravenous infusion of vancomycin was not used in patients with intranasal MRSA colonization. Analysis of risk factors for bile leakage and organ/space surgical-site infection Patient demographics, preoperative liver function, operative and tumour factors were evaluated to determine their impact on the occurrence of bile leakage and organ/space SSI. Preoperative factors included patient age, sex, aetiology of liver disease, ChildPugh grade, indocyanine green dye retention rate at 15 min (ICG-R15), serum albumin, history of diabetes mellitus, previous radiofrequency ablation (RFA) and previous transarterial chemoembolization (TACE). The cut-off level for ICG-R15 was set at 20 per cent, because an ICG-R15 of less than 20 per cent has been reported as safe for bisegmentectomy3,4,8. Tumour factors included the number of HCC lesions and the maximum diameter of individual HCCs. The cutoff level for HCC diameter was determined according to results from previous reports that analysed risk factors for morbidity after partial hepatectomy forHCC3,4,8,10. Surgical factors evaluated were the type of partial hepatectomy, number of partial hepatectomies, duration of operation, duration of liver parenchymal transection, blood loss, need for blood transfusion and method of abdominal drainage. With regard to the type of partial hepatectomy, anterior segmentectomies and medial (S4) segmentectomies were subgrouped for analysis. Cut-off points for operating time and duration of liver parenchymal transection were determined by analysing the receiver operating characteristic (ROC) curve for bile leakage. The optimal cut-off for duration of operation was 302 min (sensitivity and specificity 0690 and 0687 respectively), and that for duration of liver parenchymal transection was 82 min (sensitivity and specificity 0674 and 0668). As a result, 300 min and 80 min

were set as the cut-off levels for duration of operation and duration of liver parenchymal transection respectively.

Investigation of intractable bile leakage Management and outcomes were investigated for patients with postoperative bile leakage. Indications for ERBD to treat postoperative bile leakage were based on postoperative findings of at least one of the following: amount of macroscopic bile discharge from surgical drains more than 200 ml/day at 2 weeks after surgery; amount of macroscopic bile discharge from surgical drains exceeding 100 ml/day at 4 weeks after surgery; or macroscopic bile discharge from surgical drains still continuing at 6 weeks after surgery. PTBD was indicated when postoperative cholangiography and biliary drainage by ERBD were considered impractical. The operative procedure, number of partial hepatectomies, timing of biliary drainage procedures, sites of bile leakage and possible causes of bile leakage were evaluated in patients with intractable bile leakage necessitating ERBD or PTBD. Investigation of characteristics of prolonged hepatectomies To clarify the clinical implications of a prolonged operation, patient demographics, preoperative liver function, tumour factors and surgical factorswere compared between groups with an operation lasting less than 300 min versus at least 300 min. Analysis of characteristics in organ/space surgical-site infection Management and outcomes were investigated for patients with organ/space SSI. Organ/space SSI was classified according to the modified Clavien system16. The causative bacteria were identified for both incisional and organ/space SSIs. Preoperative and intraoperative parameters, causative bacteria and duration of postoperative hospital stay were compared between groups classified by the number of partial hepatectomies (initial versus repeat) in patients with organ/space SSI. Statistical analysis Continuous data are presented as mean(s.e.m.) unless indicated otherwise. Differences in qualitative variables were assessed using Fishers exact test or the 2 test, and quantitative variables were analysed using the MannWhitney U test. Univariable and multivariable logistic regression analyses were used to identify risk factors for bile leakage and organ/space SSI based on the 18 above-mentioned clinical factors. Variables with P 0050 in univariable analysis were included in the multivariable analysis. Relative risk was described by the estimated odds ratio (OR) with 95 per cent confidence interval. Two-sided P values were computed and P 0050 was considered statistically significant. All statistical analyses
were performed using SPSSII statistical software (IBM, Armonk, New York, USA).
Results

A total of 359 patients were included in this analysis, comprising 292 men and 67 women (mean age 65 (range 3289) years). The aetiology of liver disease in 332 patients with chronic hepatitis or liver cirrhosis was hepatitis C virus (163 patients), hepatitis B virus (122), both hepatitis C virus and hepatitis B virus (31) and alcoholic liver disease (16). Twenty-seven patients presented with HCC in a normal liver. Some 332 patients had ChildPugh A and 27 had ChildPugh B liver function. A total of 296 patients

(825 per cent) underwent anatomical partial hepatectomy including subsegmentectomy. Repeat hepatectomy was performed in 59 patients (164 per cent). Laparotomy was performed through a J-shaped incision in 287 patients, a Mercedes-type incision in 33, a midline incision in 23 and a thoracoabdominal incision in 16 patients. With the exception of two emergency cases, 357 patients underwent preoperative evaluation for MRSA using nasal culture. Nine (25 per cent) of the 359 patients showed colonization withMRSA on admission, and decolonization was carried out.

Risk factors for bile leakage Bile leakage developed in 46 (128 per cent) of the 359 patients. Univariable analysis revealed several factors associated with an increased risk of developing bile leakage (Table S1). Repeat hepatectomy was associated with an increased risk of bile leakage, with anOR of 378 compared with the initial hepatectomy (P < 0001). In contrast, neither previous RFA norTACEhad any significant impact on the occurrence of bile leakage. An operating time of at least 300 min was associated with an increased risk (OR 532; P < 0001), as were blood loss of 2000 ml or more (OR 412; P < 0001), blood transfusion (OR 366; P < 0001) and duration of liver parenchymal transection (OR 397; P < 0001). Multivariable analysis confirmed repeat hepatectomy (P < 0001) and duration of operation of at least 300 min (P = 0028) as independent risk factors for bile leakage. Risk factors for organ/space surgical-site infection Organ/space SSI developed in 31 (86 per cent) of the 359 patients. Univariable analysis revealed several factors associated with an increased risk of developing organ/space SSI (Table S2). Repeat hepatectomy was associated with an increased risk of developing organ/space SSI, with an OR of 429 compared with initial hepatectomy (P < 0001). In contrast, neither previous RFA nor TACE had any significant impact. The method of abdominal drainage (open Penrose drains or closed suction drains) had no significant influence. An operating time of at least 300 min was associated with an increased risk of organ/space SSI (OR 299; P < 0001), as was duration of liver parenchymal transection (OR 515; P < 0001), the presence of bile leakage (OR 316; P < 0001) and blood loss of at least 2000 ml (OR 263; P = 0010). Multivariable analysis confirmed repeat hepatectomy (P < 0001) and presence of bile leakage (P = 0019) as independent risk factors for organ/space SSI.