Abstract
Objective
The aim of the study was to compare the incidence of post-operative complications between those patients that received TachoSil® to the transection surface of the liver vs. those that received Surgicel®.
Methods
Retrospective study of a prospective database in a tertiary hospital. Primary endpoints were overall complications. Secondary endpoints were liver surgery-specific composite endpoint, major complications and hospital stay. Uni- and multivariate analysis of predictive factors for complications and subgroup analysis were performed.
Results
One hundred thirty-three liver resections were performed between 9 November 2007 and 2 November 2011: 64 with TachoSil® and 69 with Surgicel® application. Both groups were equivalent concerning demographic, clinical and major intra-operative data. No significant differences were observed in overall complication rate (62.5% vs. 62.3%), liver surgery-specific composite endpoint (12.5% vs. 18.8%), major complication rate (18.7% vs. 24.6%) and median hospital stay (13 vs. 10 days) for TachoSil® and Surgicel® application, respectively. Predictive factors for complications in multivariate analysis were: American Society of Anesthesiology Score ≥3 and duration of surgery >240 min. Subgroup analysis found a reduced complication rate with TachoSil® for major hepatectomy.
Conclusion
The results of the present study suggest that the routine use of TachoSil® after a liver resection does not reduce the overall complication rate compared with Surgicel® application. However, TachoSil® may be beneficial in a major hepatectomy.
Introduction
Liver resection is still an intervention with considerable morbidity in spite of intensive study.1,2 Liver-specific complications are observed in 10% to 20% of patients after a liver resection in high-volume centres.3 Resection surface-related complications such as a biliary fistula appear with a frequency of 4% to 12%4–6 and are associated with an increased rate of sepsis, liver failure, mortality and longer hospital stay.5 Peri-operative bleeding may require a transfusion and re-operation, increased mortality and prolonged hospital stay.7 Predictive factors for peri-operative complications after liver resection have been reported by several authors and include a high ASA (American Society of Anesthesiologists) score, low serum albumin, major liver resection, peri-operative transfusion, prolonged operative time, smoking, jaundice, major biliary procedures, extrahepatic procedures and prolonged ischaemic time.1,2,4–9
Topical haemostatic agents are widely used in liver surgery. A Dutch Survey showed that 49% of liver surgeons routinely used and 37% occasionally used topical haemostatic agents in liver resection. It is believed that topical haemostatic agents may reduce resection surface-related complications.10
Several techniques were studied for treating the liver resection surface. Fibrin glue sealant was studied by Figueras et al. in a large randomized trial and showed no efficacy for reducing overall- and liver-specific complications.11 Frilling et al. studied a carrier-bound fibrin sealant (TachoSil®) in a randomized trial and a shorter time to haemostasis was reported vs. argon beamer. However, the bile leakage and complication rate were not different between both groups.12 A prospective study by Briceno et al. found an advantage for carrier-bound fibrin sealants for reducing drain output, post-operative transfusion requirements and moderate-to-severe post-operative complications in major liver resections.13 Several authors suggested that fibrin sealants may reduce biliary fistulae.4,14–16 However, the available data about fibrin sealant use in liver resection are heterogenous and there is still a lack of evidence supporting its routine use.10,17
Two types of topical haemostatic agents are used in the authors' institution: TachoSil® (Nycomed Pharma) is a ready-to use fixed combination of a collagen sponge coated with a fibrinogen and thrombin layer and Surgicel®-Original (Ethicon) is an oxidized cellulose fleece providing a matrix for coagulation. The aim of the study was to compare the incidence of post-operative complications between those patients that received TachoSil® to the transection surface of the liver vs. those that received Surgicel®. A novelty of the present study was the analysis of the recently proposed liver surgery-specific composite endpoint3 and the comparison of two topical haemostatic agents.
Patients and methods
The study was performed in a single institution and included all patients who underwent a liver resection between 9 November 2007 and 2 November 2011. The data were retrieved from a prospective liver resection database and retrospectively analysed. Patients who required extrahepatic procedures such as a simultaneous colorectal resection or others were included in the study, as well as emergency interventions. All patients gave informed written consent for surgery and data collection. Ethics approvals were not required because of the retrospective monocentric study design and local data analysis without data transmission.18 Patients were followed-up for at least 3 months.
Surgical technique and peri-operative management
Briefly, a bilateral subcostal incision with an upper midline extension was used. Ultrasonography was performed routinely. Lymph node sampling or dissection was performed if indicated. A liver parenchyma transection was performed under intermittent portal triad clamping. A parenchyma transection was performed by the clamp crushing technique.19 Haemostasis and biliostasis was achieved by metallic clips, irrigated bipolar coagulation or ligatures. In a right or left hepatectomy, the corresponding pedicle was transected after clamping with a vascular clamp and a running suture with a non-absorbable monofilament was performed. During a right hepatectomy, the right hepatic vein was transected using a vascular stapler. A bile leakage test was routinely performed. Methylene-blue dyed saline solution was injected through the cystic duct and sites of bile leakage were repaired by fine sutures. Haemostasis was completed with bipolar coagulation. Finally, TachoSil® (Fig. 1) or Surgicel® (Fig. 2) was applied on the resection surface. In the first 2 years of the study, TachoSil® was quasi systematically (> 80%) used. Surgicel® was only occasionally used in minor liver resections. Since December 2009, the authors have changed their practice and Surgicel® was increasingly used for all liver resections and became the standard topical haemostatic agent in 2011. A multitubular silicon drain (Coloplast) was placed routinely in the resected space. In the cirrhotic liver drainage was not performed as it has been shown to increase post-operative morbidity.20 Blood loss was estimated by calculating the aspiration volume. A red blood cell transfusion was given when the haemoglobin level dropped below 8 g/dl and according to haemodynamic tolerance, pathology, age and co-morbidity.
Figure 1.
The liver resection surface after a left hepatectomy and lymph node dissection for intrahepatic cholangiocarcinoma sealed with two TachoSil® sponges (9.5 × 4.8 and 4.8 × 4.8 cm). The smaller sponge was divided in two. Cholangiography catheter was still in place. Post-operative hospital stay was 9 days and uneventful
Figure 2.
The liver resection surface after a right hepatectomy for intrahepatic cholangiocarcinoma with Surgicel® application (10 × 20 cm). The liver presented major steatosis. Cholangiography catheter was still in place. Post-operative hospital stay was 10 days and uneventful
Post-operatively patients were monitored in the intensive care unit for at least 24 h. Measurements of serum alanine aminotransferase, aspartate aminotransferase, bilirubin, albumin, prothrombin time, haemoglobin, creatinine and urea were recorded daily for at least 5 days. An abdominal computer tomography scan or ultrasound was performed routinely before hospital discharge for detection of complications and to provide a reference imaging for oncological follow-up. Abdominal drains were removed when the liquid was clear and the volume less than 50 ml/day. The bilirubin level was measured in the drainage liquid and compared with the serum level if bile leakage was suspected. Culture of the drainage liquid was performed if an infection was suspected.
Outcome measures
The primary endpoint was the overall complication rate. Secondary endpoints were a liver surgery-specific composite endpoint,3 major complications, bile leakage, 30- and 90-day mortality and hospital stay. Outcome data were prospectively recorded in the liver resection database.
Definitions
Overall complications were defined as any deviation from an uneventful post-operative course within 90 days after surgery and included: infectious complications (surgical site, pulmonary, venous catheter, urinary tract, cholangitis and sepsis), liver-specific complications and other complications (gastrointestinal, cardiopulmonary, thrombosis, confusion, etc). The severity of complications were defined according to the Clavien-Dindo classification.21
The liver-specific complications were defined according to the liver surgery-specific composite endpoint described by van den Broek et al.3 and included: ascites, liver failure, bile leakage, intra-abdominal hemorrhage, intra-abdominal abscess and mortality, all within 90 days after initial surgery and with a Clavien-Dindo grade ≥ 3.
A major hepatectomy was defined as the resection of 3 or more liver segments. The Brisbane terminology was used for classification of the type of liver resection.22 Bile leakage and hepatic insufficiency were defined according to the International Study Group of Liver Surgery (ISGLS).23,24 A repeat hepatectomy was defined as any liver resection performed in a patient who had previously undergone a partial hepatectomy. Extrahepatic procedures were defined as partial or total resection of other organs (colon, rectum, small intestine, stomach, pancreas, diaphragm and adrenal gland) and bilio-enteric anastomosis. A cholecystectomy, liver biopsy and lymph node sampling or dissection were not considered as extrahepatic procedures. Mortality was defined as death within 30 and 90 days after surgery. Hospital stay was defined as post-operative hospital stay.
Statistical analysis
Continuous variables were reported as median with range and compared with a non-parametric Mann–Whitney test. Categorical variables were compared with the χ2 or Fisher's exact test, as appropriate. All statistical tests were two-sided, and P < 0.050 was considered significant. To assess whether other parameters, apart from the main variable of the study (TachoSil® or Surgicel® application) may have influenced the development of complications, a uni- and multivariate analysis was performed. Subgroup analysis was performed to identify a group of patients who may benefit from fibrin sealant use. A power analysis was not performed owing to the retrospective study design.25
Results
One hundred thirty-three liver resections were performed in 108 patients between 9 November 2007 and 2 November 2011. Twenty-five (18.8%) repeat liver resections were performed: 24 for colorectal liver metastases and one for a recurrent hepatocellular carcinoma. No patient was excluded. Patients' characteristics are shown in Table 1. Surgical procedures are shown in Table 2. Intra-operative data are shown in Table 3. The median (range) number of TachoSil® sponges used per patient in the TachoSil® group was 1 (1–4) with a 102 patches in total used; however, for a large resection surface at least two patches (9.5 × 4.8 cm) were needed to cover the resection surface (Fig. 1). The median duration of surgery was 265 min in the first 66 patients and 240 min in the next 67 patients (P = 0.023). The median duration of all 133 liver resections was 240 min and was used for the quantalization of duration data.
Table 1.
General characteristics of patients in the ‘TachoSil®’ group (n = 64) and in the ‘Surgicel®’ group (n = 69)
| TachoSil® | Surgicel® | P | |
|---|---|---|---|
| n = 64 (%) | n = 69 (%) | ||
| Female gender | 17 (26.6%) | 24 (34.8%) | 0.350 |
| Median age (years) | 68 | 64 | 0.173* |
| Range | 23–86 | 27–84 | |
| Study period | |||
| First half (n = 66) | 43 (67.2%) | 23 (33.3%) | <0.001 |
| Second half (n = 67) | 21 (32.8%) | 46 (66.7%) | |
| Charlson's comorbidity index | |||
| Median | 6 | 6 | 0.865* |
| Range | 0–10 | 0–12 | |
| ASA Score ≥ 3 | 25 (39.1%) | 27 (39.1%) | 1 |
| Body mass index | |||
| Median | 25.5 | 26.2 | 0.718* |
| Range | 15–40 | 14–39 | |
| Albumin level < 35 g/dl | 8 (12.5%) | 13 (18.8%) | 0.350 |
| Liver disease | |||
| Cirrhosis | 6 (9.4%) | 7 (10.1%) | 1 |
| Fibrosis | 4 (6.2%) | 3 (4.3%) | 0.710 |
| Steatosis | 30 (46.9%) | 25 (36.2%) | 0.223 |
| Viral hepatitis | 3 (4.7%) | 8 (11.6%) | 0.210 |
| Diagnosis | |||
| Colorectal metastases | 39 (60.9%) | 38 (55.1%) | 0.598 |
| Hepatocellular carcinoma | 12 (18.7%) | 14 (20.3%) | 0.831 |
| Cholangiocarcinoma | 6 (9.4%) | 5 (7.2%) | 0.757 |
| Other diagnosis | 7 (10.9%) | 12 (17.4%) | 0.329 |
| Pre-operative chemotherapy | 19 (29.7%) | 26 (37.7%) | 0.363 |
| Emergency surgery | 1 (1.6%) | 4 (5.8%) | 0.367 |
Continuous variables* were compared using a Mann–Whitney test.
Categorical variables were compared using Fisher's exact test.
Variables with P < 0.050 are in bold.
ASA, American Society of Anesthesiology.
Table 2.
Types of liver resection according to the Brisbane terminology22 and extrahepatic procedures in the TachoSil® group (n = 64) and in the Surgicel® group (n = 69)
| TachoSil® | Surgicel® | P | |||
|---|---|---|---|---|---|
| n = 64 | (%) | n = 69 | (%) | ||
| Major hepatectomy | 20 | (31.2%) | 21a | (30.4%) | 1 |
| Right hepatectomy (+ segment 1) | 13 (0) | (20.3%) | 13 (2) | (18.8%) | 1 |
| Extended right hepatectomy | 0 | 1 | (1.4%) | 1 | |
| Left hepatectomy (+ segment 1) | 7 (0) | (10.9%) | 3 (1) | (4.3%) | 0.195 |
| Trisegmentectomy 4,5,8 | 0 | 1 | (1.4%) | 1 | |
| Minor hepatectomy | |||||
| Bisegmentectomy 2,3 | 5 | (7.8%) | 9 | (13.0%) | 0.402 |
| Bisegmentectomy (other) | 18 | (28.1%) | 19 | (27.5%) | 1 |
| Segmentectomy and limited resection | 21 | (32.8%) | 23 | (33.3%) | 1 |
| Resection involving segment 1 | 3 | (4.7%) | 5 | (7.2%) | 0.719 |
| Resection involving segment 4 | 28 | (43.7%) | 36 | (52.2%) | 0.386 |
| Repeat-hepatectomy | 12 | (18.7%) | 13 | (18.8%) | 1 |
| Extrahepatic procedures | |||||
| Total | 17 | (26.6%) | 28 | (40.6%) | 0.101 |
| Colorectal resection | 12 | (18.7%) | 17 | (24.6%) | 0.529 |
| Otherb | 5 | (7.8%) | 11 | (15.9%) | 0.186 |
In the Surgicel® group one patient had two bisegmentectomies (four resected segments) and two patients had a bisegmentectomy and uni-segmentectomy each (three resected segments) classifying those resections as a major hepatectomy.
Other extrahepatic procedures included: partial resection of the small intestine (n = 4), gastrectomy (n = 2), pancreatectomy (n = 2), partial resection of the right diaphragm (n = 3), right adrenalectomy (n = 2) and biliodigestive anastomosis (n = 3). Only the main extrahepatic procedure was included.
Categorical variables were compared using Fisher's exact test.
Table 3.
Intra-operative data of liver resection and extrahepatic procedures in the TachoSil® group (n = 64) and in the Surgicel® group (n = 69)
| TachoSil® | Surgicel® | P | |
|---|---|---|---|
| n = 64 (%) | n = 69 (%) | ||
| Duration of surgery (min) | |||
| >240 min | 39 (60.9%) | 30 (43.5%) | 0.056 |
| Median | 270 | 240 | 0.011* |
| Range | 110–630 | 110–480 | |
| Pringle clamping | |||
| Yes | 54 (84.4 %) | 55 (79.7 %) | 0.508 |
| Median clamping time (min) | 34 | 28 | 0.128* |
| Range | 10–82 | 8–61 | |
| Transfusion | |||
| Yes | 25 (39.1%) | 32 (46.4%) | 0.483 |
| Intra-operatively | 21 (32.8%) | 27 (39.1%) | 0.474 |
| Post-operatively | 11 (17.2%) | 13 (18.8%) | 0.825 |
| Median number of units | 3 | 3 | 0.711* |
| Range | 2–10 | 2–13 | |
| Estimated blood loss (ml) | |||
| Median | 300 | 300 | 0.841* |
| Range | 50–2500 | 30–2500 | |
Continuous variables* were compared using a Mann–Whitney test.
Categorical variables were compared using Fisher's exact test.
Variables with P < 0.050 are in bold.
Complications
Fifty patients (37.6%) had an uneventful post-operative course. Eighty-three patients (62.4%) had complications. Sixty patients (45.1%) had an infectious complication. Twenty-one patients (15.8%) had a liver-specific complication of at least grade 3 according to the Clavien-Dindo classification. Sixteen patients (12.0%) had other complications (no infection and no liver specific). Some patients had more than one complication. Twenty-nine patients (21.8%) had a major complication (Clavien-Dindo ≥3). Data are shown in Table 4.
Table 4.
Post-operative outcome data: overall complications, severity of complications according to the Clavien-Dindo classification,21 liver surgery-specific composite endpoint according to van den Broek et al.,3 duration of drainage, re-operations, percutaneous radiological drainage and median hospital stay
| TachoSil® | Surgicel® | P | |
|---|---|---|---|
| n = 64 (%) | n = 69 (%) | ||
| Overall complication rate | 40 (62.5%) | 43 (62.3%) | 1 |
| Severity of overall complications | |||
| Clavien-Dindo 1 | 6 (9.4%) | 5 (7.2%) | 0.757 |
| Clavien-Dindo 2 | 22 (34.4%) | 21 (30.4%) | 0.711 |
| Clavien-Dindo 3 | 4 (6.2%) | 5 (7.2%) | 1 |
| Clavien-Dindo 4 | 5 (7.8%) | 7 (10.1%) | 0.765 |
| Clavien-Dindo 5 = 90-day mortality | 3 (4.7%) | 5 (7.2%) | 0.719 |
| Major complications (Clavien-Dindo 3, 4 and 5) | 12 (18.7%) | 17 (24.6%) | 0.529 |
| Liver surgery-specific composite endpoint3 | |||
| All grade of severity | 12 (18.7%) | 18 (26.1%) | 0.406 |
| Clavien-Dindo ≥ 3 | 8 (12.5%) | 13 (18.8%) | 0.350 |
| Bile leakage | 7 (10.9%) | 5 (7.2%) | 0.551 |
| Median duration of postoperative drainage (days) | 6 | 6 | 0.490* |
| Range | 2–50 | 2–45 | |
| ;Re-operation | 1 (1.6%) | 3 (4.3%) | 0.620 |
| Percutaneous radiological drainage | 4 (6.2%) | 5 (7.2%) | 1 |
| Median hospital-stay (days) | 13 | 10 | 0.096* |
| Range | 5–90 | 3–90 | |
Continuous variables* were compared using a Mann–Whitney test.
Categorical variables were compared using Fisher's exact test.
Bile leakage
Twelve patients (9.0%) had a bile leakage. One patient 0.7%) was re-operated as bile was leaking from the right subcostal incision: a multitubular silicon drain was placed for drainage and the laparotomy wound was closed. Three patients (2.2%) had percutaneous ultrasonography guided drainage and in 8 patients (6.0%) the intra-operatively placed drainage was left in place (duration of drainage 10–45 days) until the fistula subsided spontaneously. No patient with a bile leakage died.
Percutaneous radiological drainage
Nine patients (6.8%) had a percutaneous radiological drainage: biliary fistula (3 patients; 2.2%), infected pleural collections (2 patients; 1.5%) and infected intra-abdominal collections (4 patients; 3.0%).
Re-operation
Four patients (3.0%) were re-operated because of the following: 1 bile leakage in the TachoSil® group and 2 haemoperitoneum and 1 septicaemia in the Surgicel® group. The causes of haemoperitoneum were bleeding of the left hepatic artery, and bleeding of a small vein of the hepatic pedicle after lymph node dissection. In both patients no bleeding was observed from the liver resection surface.
Mortality
There were no intra-operative deaths. Four patients died within 30-days as a result of the following: 1 liver failure, 1 multi-organ failure owing to haemoperitoneum (emergency), 1 septic shock and 1 stroke. The overall 30-day mortality rate was 3.0% per procedure (4/133) and 3.7% per patients (4/108). The 30-day mortality rate for elective surgery was 2.3% (3/128) per procedure and 2.9% (3/103) per patients.
Another 4 patients (3.7%) died within 90-days after surgery because of the following: respiratory insufficiency in 2 patients (metastatic pleural effusions, pneumonia), 1 septic cerebral embolism as a result of endocarditis and 1 death at home. The overall 90-day mortality rate was 6.0% per procedure (8/133) and 7.4% per patients (8/108). The 90-day mortality rate for elective surgery was 4.7% (6/128) per procedure and 5.8% (6/103) per patients.
Factors related to complications
Because TachoSil® or Surgicel® application seemed to have no influence on post-operative complications, the data were further analysed to determine which factors were associated with post-operative complications, in order to detect potential bias because of the non-randomized study design.
In univariate analysis, 6 factors were associated with complications: ASA score ≥3, duration of surgery >240 min, pre-operative albumin level < 35 g/dl, right hepatectomy, blood loss and transfusion (Table 5). Multivariate logistic regression analysis found two independent risk factors for overall complications: ASA score ≥3 [P = 0.001; odds ratio (OR): 3.77; 95% confidence interval (CI): 1.64–8.63] and duration of surgery >240 min (P = 0.003; OR: 3.10; 95% CI: 1.44–6.67). The risk factors for complications were equally distributed between both groups (Tables 3).
Table 5.
Univariate analysis of predictive factors for overall post-operative complications
| Complicated | Uncomplicated | P | |
|---|---|---|---|
| n = 83 (%) | n = 50 (%) | ||
| Median age in years (range) | 67 (45–86) | 65 (23–85) | 0.180* |
| Female gender | 23 (27.7%) | 18 (36.0%) | 0.337 |
| First half of study (n = 66) | 43 (51.8%) | 23 (46.0%) | 0.592 |
| Second half of study (n = 67) | 40 (48.2%) | 27 (54.0%) | |
| Emergency surgery | 4 (4.8%) | 1 (2.0%) | 0.649 |
| Cancer | 77 (92.8%) | 44 (88.0%) | 0.533 |
| Charlson Comorbidity Index Score >6 | 32 (38.6%) | 14 (28.0%) | 0.260 |
| ASA Score ≥ 3 | 41 (49.4%) | 11 (22.0%) | 0.001 |
| Body Mass Index < 18.5 | 5 (6.0%) | 4 (8.0%) | 0.728 |
| Albumin level < 35 g/l | 19 (22.9%) | 2 (4.0%) | 0.005 |
| Creatinine >100 μmol/l | 11 (13.2%) | 8 (16.0%) | 0.798 |
| Hemoglobin level < 11 g/dl | 11 (13.2%) | 4 (8.0%) | 0.410 |
| Viral hepatitis | 6 (7.2%) | 5 (10.0%) | 0.746 |
| Cirrhosis | 8 (9.6%) | 5 (10.0%) | 1 |
| Fibrosis | 5 (6.0%) | 2 (4.0%) | 0.710 |
| Steatosis | 37 (44.6%) | 18 (36.0%) | 0.367 |
| Pre-operative chemotherapy | 30 (36.1%) | 15 (30.0%) | 0.571 |
| Colorectal liver metastases | 51 (61.4%) | 26 (52.0%) | 0.364 |
| Hepatocellular carcinoma | 16 (19.3%) | 10 (20.0%) | 1 |
| Cholangiocarcinoma | 5 (6.0%) | 6 (12.0%) | 0.329 |
| Other diagnosis | 11 (13.2%) | 8 (16.0%) | 0.798 |
| Repeat-hepatectomy | 19 (22.9%) | 6 (12.0%) | 0.168 |
| Major hepatectomy | 30 (36.1%) | 11 (22.0%) | 0.120 |
| Right hepatectomy | 22 (26.5%) | 5 (10.0%) | 0.026 |
| Left hepatectomy | 4 (4.8%) | 6 (12.0%) | 0.175 |
| Resection involving segment 1 | 6 (7.2%) | 2 (4.0%) | 0.493 |
| Resection involving segment 4 | 40 (48.2%) | 24 (48.0%) | 1 |
| Median clamping time in min (range) | 30 (8–61) | 30 (10–82) | 0.779* |
| TachoSil®sealing | 40 (48.2%) | 24 (48.0%) | 1 |
| Extrahepatic procedures | 31 (37.3%) | 14 (28.0%) | 0.344 |
| Median blood loss in ml (range) | 300 (30–2500) | 200 (30–2500) | 0.010* |
| Duration of surgery >240 min | 51 (61.4%) | 18 (36.0%) | 0.006 |
| Peri-operative transfusion | 43 (51.8%) | 14 (28.0%) | 0.010 |
Continuous variables* were compared using a Mann–Whitney test
Categorical variables were compared using Fisher's exact test.
ASA, American Society of Anesthesiology.
Variables with P < 0.1 were included in multivariate analysis.
Variables with P < 0.050 are in bold.
Subgroup analysis
The data were further analysed to determine whether TachoSil® was more effective in reducing complications in patients with extrahepatic procedures, repeat hepatectomy or major hepatectomy. Subgrouping was performed according to the definitions given in the patients and methods section. Demographic, clinical and intra-operative data for the subgroups are shown in Table 6. A difference between the subgroups was a higher number of patients with colorectal liver metastases in repeat hepatectomy and extrahepatic procedures vs. major hepatectomy.
Table 6.
Characteristics of subgroups concerning demographic, clinical and intra-operative data
| Major | Repeat | Extrahepatic | |
|---|---|---|---|
| Hepatectomy | Hepatectomy | Procedure | |
| n = 41 | n = 25 | n = 45 | |
| Median age in years (range) | 65 (28–84) | 61 (28–84) | 67 (27–86) |
| Charlson's Comorbidity Index Score >6 | 14 | 9 | 23 |
| ASA Score ≥ 3 | 18 | 12 | 18 |
| Albumin level < 35 g/l | 9 | 3 | 10 |
| Colorectal liver metastases | 24 | 24 | 35 |
| Median blood loss in ml (range) | 500 (100–2500) | 600 (200–2500) | 300 (50–2000) |
| Median duration of surgery in min (range) | 270 (150–540) | 285 (160–435) | 290 (180–630) |
| Peri-operative transfusion | 27 | 16 | 24 |
| Repeat hepatectomy* | 13 | 25 | 7 |
| Major hepatectomy* | 41 | 13 | 12 |
Statistical comparison of subgroups was not performed as subgroups overlap (see lines*).
Results of the subgroup analysis for TachoSil® vs. Surgicel® application are shown in Table 7. The overall complication rate and the liver surgery-specific composite endpoint were significantly reduced for the TachoSil® group in major liver resection.
Table 7.
Subgroup analysis of the TachoSil® vs. Surgicel® application for post-operative complication after liver resection
| Subgroup | Overall complicationsa | Surgicel® | Odds ratio (95% CI) for TachoSil® use | P |
|---|---|---|---|---|
| TachoSil® | ||||
| Extrahepatic procedure (n = 45) | 11/17 | 20/28 | 0.733 (0.20–2.66) | 0.743 |
| Repeat hepatectomy (n = 25) | 9/12 | 10/13 | 0.9 (0.14–5.64) | 1 |
| Major hepatectomy (n = 41) | 11/20 | 19/21 | 0.128 (0.02–0.70) | 0.014 |
| Subgroup | Liver surgery-specific composite endpointa | Surgicel® | Odds ratio (95% CI) for TachoSil® use | P |
|---|---|---|---|---|
| TachoSil® | ||||
| Extrahepatic procedure (n = 45) | 2/17 | 9/28 | 0.281 (0.05–1.50) | 0.164 |
| Repeat hepatectomy (n = 25) | 3/12 | 4/13 | 0.75 (0.12–4.35) | 1 |
| Major hepatectomy (n = 41) | 1/20 | 7/21 | 0.105 (0.01–0.95) | 0.044 |
The first number represents the number of patients with complications and the second number represents the total number of patients in the respective group.
Variables with P < 0.050 are in bold.
CI, confidence interval for the odds ratio. P, Fisher's exact test.
Discussion
The aim of this study was to compare the incidence of post-operative complications between those patients that received TachoSil® to the transection surface of the liver vs. those that received Surgicel®. The present study suggests that routine use of a carrier-bound fibrin sealant after liver resection does not reduce the overall complication rate compared with oxidized cellulose application. However, subgroup analysis found that TachoSil® may be beneficial in major hepatectomy, as the liver surgery-specific composite endpoint and overall complications were reduced in the TachoSil® group.
These findings were in agreement with the study of Briceno et al.13 who showed a reduction of Clavien-Dindo grade 3 complications for major liver resections in the fibrin sealant group. In the present study, TachoSil® sealing did not reduce the bile leakage rate. These findings were in agreement with other reports.12,13
Surgical outcome in the present study was comparable to published data: the overall major complication rate of 21.8% (29/133) was similar to 19.6 % reported by Aloia et al.2 and 23.3% reported by Figueras et al.11 The 30-day mortality rate for elective surgery observed in the present study of 2.3% (per procedure) or 2.9% (per patient) was similar to the mortality rate of 2.5% to 3.1% reported by other authors.1,2,11 The liver surgery-specific composite endpoint (Clavien-Dindo ≥ grade 3) was registered in 15.8% of all resections (21/133) and was within the range of data published for the Maastricht cohort (19.2%) and the Strasbourg cohort (10.7%), where extrahepatic procedures were excluded.3
In the present study, ASA score ≥3 and duration of surgery >240 min were risk factors for complications in multivariate analysis. The ASA classification of physical status (ASA score) was introduced in 1941 and revised in 1963.26 The ASA score indicates a patient's anaesthetic risk based on comorbidities. A higher ASA score was a predictive factor for post-operative complications in abdominal and vascular surgery.27 Aloia et al. in a large multicenter study of 2313 patients2 and Belgithi et al. in a study of 747 consecutive liver resections28 have shown a correlation of a higher ASA score with post-operative complications after liver resections. Recently, Tzeng et al. reported that an ASA score ≥3, an operation time >222 min and the extent of liver resection were associated with an increased risk for venous thromboembolism.29 In the present study, the median duration of surgery was 240 min and was increased for a major hepatectomy (270 min), repeat hepatectomy (285 min) and extrahepatic procedures (290 min; Table 6). A longer operation time probably reflects a more complex or technically more difficult procedure. Median operation time was 25 min longer for the first 66 patients (43 with TachoSil®) vs. the next 67 patients (46 with Surgicel®). A learning curve effect can not be excluded here. It is intuitive that a longer operation time could increase the peri-operative risk. This observation was confirmed by other authors.1,2,27,29
The main limitation of the present study was the absence of randomization. In 2007, the initial choose of TachoSil® for liver resection was motivated by the authors surgical training, technical habits and literature data.4,11,12 Surgicel® was already used in the authors institution for thyroid, pancreatic and digestive surgery. The Surgicel® Original 10 × 20 cm fleece is a ready to use haemostatic agent and adheres well to the liver resection surface after application with gentle pressure (Fig. 2). The main advantage of Surgicel® over TachoSil® was the lower cost. No patient required TachoSil® sealing for failure of haemostasis with Surgicel® application.
A controversial detail of the present study was the routine use of drainage (except in the cirrhotic liver). Indeed a meta-analysis by Petrowsky et al. based on three studies with a total of 304 patients showed a higher rate of infected intra-abdominal collections after liver resection in the drainage group vs. the group without drainage (ORs: 2.83; CI: 0.82–9.71). However, the difference was not significant (P = 0.70).30 Intra-peritoneal drainage was widely used after liver resection.11,13,30,31 In the authors institution drainage was used after liver resection and digestive surgery for the detection of postoperative bleeding, bile leakage or a digestive fistula. In the present study, infected intra-abdominal collections were registered in four patients (3.0%). Bile leakage subsided with retention of the drain in 8 out of 12 patients. This finding was in agreement with the study of Kyoden et al.31 who studied the value of prophylactic drainage in 1269 consecutive liver resections. However, only a randomized, sufficiently powered trial could show if routine drainage is really worthwhile after liver resection.
In the present study, subgroup analysis found a reduction of the liver surgery-specific composite endpoint and overall complications after major hepatectomy for the TachoSil® group. Why TachoSil® seems to be more efficient in major vs. minor hepatectomy remains questionable. A more efficient sealing of a large transection surface in major hepatectomy may be an explication. However, the transection surface was not measured in the present study. Subgroup analysis should be regarded with caution, as unidentified bias may be present and because of the small numbers. Therefore, these findings should be confirmed by a larger randomized trial.
Conclusion
The present study showed no reduction in the overall complication rate, bile leakage rate and hospital stay for routine TachoSil® sealing vs. Surgicel® application after liver resection. However, TachoSil® application seems to be beneficial after a major hepatectomy. Further studies are necessary to confirm these findings.
Acknowledgments
The authors express their gratitude to their collaborators Sebastian Dan, MD and Pierre Barsotti, MD who provided and cared for study patients and critically reviewed the study.
Authorship
T.Z.: conception and study design; T.Z. and N.F.: acquisition of data, analysis and interpretation of data, drafting and revision of the manuscript and final approval.
Conflicts of interest
None declared.
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