Dig Dis Sci (2011) 56:1201–1206 DOI 10.1007/s10620-010-1407-y
ORIGINAL ARTICLE
The Safety of Same-Day Endoscopy and Percutaneous Liver Biopsy Jonathan G. Stine • Gordon Liss • James H. Lewis
Received: 10 June 2010 / Accepted: 18 August 2010 / Published online: 21 September 2010 Ó Springer Science+Business Media, LLC 2010
Abstract Background and Aims The aim of this study was to review our experience with same-day endoscopy (SDE) plus percutaneous liver biopsy (PLB) and to evaluate its safety compared to PLB alone. Methods We retrospectively examined records of all patients who underwent PLB between January 2003 and September 2009 and identified those who underwent SDE and matched these patients to those undergoing PLB alone. Serious adverse events (SAEs) were analyzed using our endoscopic database (EndoPro, Pentax) and were divided into those occurring immediately post-procedure and those occurring after discharge. Results In the study, 479 patients underwent 507 PLBs and 52 patients (11%) were identified as having SDE. No statistical differences were apparent in terms of sex, age, baseline laboratory values, medical comorbidities, cirrhosis, or liver lesions. The most common indication for PLB was chronic hepatitis C (HCV). A total of 15 patients underwent upper endoscopy (EGD); 37 patients underwent colonoscopy (most for colorectal cancer screening). One (1.9%) SAE occurred in the SDE and PLB group. This patient experienced microperforation of the hepatic flexure secondary to abnormal anatomy and underwent immediate laparoscopic repair with an unremarkable post-op course.
J. G. Stine (&) G. Liss J. H. Lewis Department of Medicine, Georgetown University Hospital, 3800 Reservoir Rd NW, 2 Main, Washington, DC 20007, USA e-mail:
[email protected] G. Liss J. H. Lewis Division of Gastroenterology, Georgetown University Hospital, Washington, DC, USA
Four (0.88%) SAEs occurred with PLB alone, mostly prolonged pain from subcapsular hematoma, with no transfusions or surgery required. Conclusions At our institution, SDE with PLB is often performed and appears to be a safe method of practice. We believe that performance of EGD or colonoscopy on the same day as PLB optimizes medical resources and results in patient satisfaction without sacrificing safety. Keywords
Endoscopy Liver biopsy Safety Efficacy
Introduction Historically, endoscopy and percutaneous liver biopsy (PLB) have been performed on different days. Multiple reasons have been cited to explain this reluctance to do same-day endoscopy (SDE) with PLB, the most common being a potential risk of increased complications due to bowel distention [1–5]. Other reasons include the fact that fewer gastroenterologists/hepatologists are performing their own liver biopsies and most refer the patient to their radiology colleagues instead, as ultrasound is both costeffective when compared to non-image-guided PLB, and also significantly decreases the incidence of complications by avoiding major anatomic structures [1–3, 6–14]. Current recommendations from the American Association for the Study of Liver Diseases (AASLD) do not address performing PLB and endoscopy together [15]. As serious complications are rare, the current standard of care is to perform PLB on an outpatient basis. Only 0.5–3% of patients require hospitalization after PLB, the majority for severe bleeding. Mortality rates are of the order of 1 in 10–12,000 with most deaths related to complications of hemorrhage (Table 1) [2, 4–8, 15–22]. Less severe bleeding,
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Table 1 Complication rates in the literature for percutaneous liver biopsy (PLB) [15, 35–37]
Methods
Complication
Rate
Patient Identification
Pain
0.056–22
The Georgetown University Hospital (GUH) EndoPro database (Pentax Medical Equipment, Montvale, NJ) was searched to identify all patients who underwent both inpatient and outpatient PLB from January 2003 to September 2009. These patients were cross-referenced to identify those who underwent SDE with PLB and were then matched to a set of controls based on age, sex, baseline laboratory values (including liver function tests, coagulation studies, and serum creatinine), medical comorbidities (including cardiac, pulmonary, renal, diabetes, HIV, and malignancy) and the indication for PLB (chronic HCV, elevated liver associated enzymes (LAEs), primary biliary cirrhosis, hemochromatosis, methotrexate toxicity, autoimmune hepatitis, and orthotopic liver transplant rejection). All PLBs were performed according to the guidelines outlined by the AASLD and were of the liver parenchyma even in the presence of lesions on imaging [15].
Hemorrhage Overall
0.60
Intraperitoneal
0.03–0.07
Intrahepatic and/or subcapsular
0.059–0.2
Hemobilia
00.058–0.2
Bile peritonitis Sepsis
0.03–0.22 0.088
Pneumothorax
0.08–0.28
Hemothorax
0.18–0.49
Subcutaneous emphysema
0.014
AV fistula
5.4
Biopsy of other organs Lung
0.001–0.014
Gallbladder
0.034–0.117
Kidney
0.029–0.096
Colon
0.0038–0.0044
Mortality
0.0088–0.3
Procedural Technique
defined as that sufficient to cause pain, tachycardia, or hypotension without radiographic evidence of bleeding, occurs in roughly 1 in 500 patients [15]. The timing of pre-biopsy ultrasonography has been debated, but real-time sonographic marking of the biopsy site has not consistently demonstrated an increased diagnostic yield, nor has it led to a decreased complication rate compared to same-day pre-biopsy site marking [5, 11, 23]. As a result, either technique can be employed. While the timing of the ultrasound marking may not decrease complication rates, the experience of the gastroenterologist/ hepatologist performing the procedure may decrease complications, especially when more than 300 PLBs have been performed. However, a recent study by Seeff et al. failed to show any correlation between complication rate and operator experience, leaving this topic open to further debate [24, 25]. In their cohort study of 89 patients, Cook and Harrison demonstrated that SDE and PLB can be a safe, costeffective practice that increases patient satisfaction [1]. To our knowledge, this is the first attempt to rigorously investigate the simultaneous performance of SDE and PLB. However, no direct comparison has been made between PLB alone and PLB with preceding SDE. The purpose of this study was to retrospectively review this practice, which is often performed at our institution. While little has been written about the safety of this practice, the results confirm that PLB and SDE are safe in experienced hands.
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All of the procedures were performed using a standard protocol for the endoscopy suite at GUH. Sedation for the procedure was at the discretion of our anesthesiologists and attending gastroenterologist/hepatologist and included a combination of conscious sedation or monitored anesthesia care (MAC) given by attending anesthesiologists or nurse anesthetists. In cases where MAC with propofol was used, anesthesia was lightened after EGD or colonoscopy so that the patient could follow commands for PLB. The endoscopic procedures were done prior to PLB in all cases and were performed by an attending gastroenterologist, often with the assistance of a supervised gastroenterology fellow. Following the EGD or colonoscopy, careful attention was paid to removing air from the insufflated colon or stomach prior to PLB in order to avoid having over-distended small or large bowel loops. PLB was performed in the same room immediately after endoscopy. Pre-biopsy ultrasound site marking was performed either by our radiology department and discussed with the gastroenterologist/hepatologist performing the PLB, or by using a portable ultrasound unit at the bedside to identify a safe tract. An automatic Trucut type biopsy needle was used. In general, two passes were made as the patient maintained full but not forced expiration while lying in the supine position with their right hand and arm comfortably positioned behind their head. If an insufficient core specimen (\2 cm total) was obtained, a third pass was performed. The patient was left lying supine as there is no evidence that right side down positioning in the post biopsy period reduces the risk of post-PLB
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bleeding [3, 26, 27]. Patients were observed for at least 2 h after PLB to monitor for complications as this has been previously validated as a safe time limit [26, 27]. Vital signs were checked at least every 15 min for the first hour and every 30 min during the second hour. Post-PLB analgesia included the use of fentanyl, which was administered in post-anesthesia care unit (PACU) of the endoscopy suite. Safety The GUH Pentax EndoPro database was reviewed to identify SAEs. SAEs were divided between those that occurred immediately post procedure in the endoscopy suite (severe pain, suspected bleeding, need for hospitalization or other intervention) and those developing after discharge from the endoscopy suite PACU, e.g., unanticipated ER visit, physician office visit or hospital admission. An attempt was made to call the patient at home the day after PLB in order to check on their condition. This practice is performed by the endoscopy suite nursing staff and has been validated as an effective measure to appropriately assess post-procedural complications [28]. Pain specific to PLB was evaluated on the basis of analgesic use. It is important to note that complications were prospectively recorded and all patients were seen back in our liver clinic for a follow-up visit within 2 weeks after the procedure in order to capture delayed SAEs. Routine post-procedure
surveillance with imaging was not performed given that most post-procedure subcapsular hematomas detectable on ultrasound are largely asymptomatic [29]. Data and Statistical Analysis After cross-matching the patients, demographic characteristics were analyzed with a two-tailed t test and 95% confidence interval with alpha of 0.05. Mean values with standard deviations were calculated. This retrospective review was approved by the Georgetown University Institutional Review Board (#2010-183).
Results Patient Characteristics A total of 479 patients were identified as having undergone PLB, all of which were performed by the same gastroenterologist/hepatologist (JHL). Of these, 52 underwent SDE with PLB and 427 had PLB alone, serving as the control group (Table 2). There were 27 females (52%) and 25 males (48%) for the SDE with PLB group. Mean age for the SDE and PLB group was 51.9 ± 2.09 (range 32–71) versus 51.4 ± 1.87 (range 34–66) for the PLB group. No statistical differences were apparent in terms of baseline
Table 2 Patient characteristics
PLB ? SDE
95% CI
PLB alone
95% CI
p-value
Age
51.9
2.1
51.4
1.9
0.73
Men
25
203
Women Total protein
27 7.1
0.4
224 7.6
0.3
1.00 0.60
Albumin
3.7
0.2
3.8
0.2
0.70
1.00
Total bilirubin
0.9
0.1
1.2
0.3
0.30
Direct bilirubin
0.1
0.1
0.2
0.2
0.41
Aspartate aminotransferase (AST)
63
22.8
78
31.3
0.66
Alanine aminotransferase (ALT)
64
21.1
71
28.0
0.87
Alkaline phosphatase
89
16.4
123
37.9
0.34
Prothrombin time (PT)
14.0
0.7
13.5
0.7
0.36
International normalized ration (INR)
1.1
0.1
1.1
0.1
0.86
Creatinine
1.1
0.1
1.1
0.4
0.27
Comorbidities Cardiovascular disease
18 (34.6%)
130 (30.4%)
0.33
Pulmonary disease
8 (15.4%)
82 (19.2%)
0.31
Renal disease
1 (1.9%)
34 (8.0%)
0.26
Rheumatologic disease
5 (9.6%)
49 (11.5%)
0.31
Diabetes Human immunodeficiency virus (HIV)
5 (9.6%) 3 (5.8%)
124 (29%) 19 (4.4%)
0.29 0.19
Malignancy
2 (3.8%)
17 (4.0%)
0.22
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laboratory values (liver function tests, coagulation studies, and serum creatinine), medical comorbidities, cirrhosis on imaging or the presence of liver lesions on imaging.
Table 4 Indications for percutaneous liver biopsy (PLB)
HCV
Indications for SDE A total of 52 patients underwent endoscopy prior to PLB. The endoscopic procedures included 15 EGDs and 37 colonoscopies (Table 3). None of the patients had both a triple procedure with EGD, colonoscopy, and PLB. The majority of EGDs (n = 9) were performed for dyspepsia; three for gastroesophageal reflux, one for Barrett’s surveillance, and one to evaluate esophageal thickening found on CT scan. Nearly three quarters (n = 28) of colonoscopies were performed for age-appropriate colon cancer screening. Other indications for colonoscopy included hematochezia (n = 6), work-up for anemia involving diagnosis of celiac disease (n = 2), and chronic constipation (n = 1). The use of pre-biopsy sedation is listed in Table 4.
Table 3 Endoscopic intervention with percutaneous liver biopsy Intervention
No. of patients (%)
Upper endoscopy
15 (28.8)
Biopsy Total
10 (66.7)
Esophagus
1 (6.7)
Gastric
4 (26.7)
Duodenum
5 (33.3)
Polypectomy Total
1 (6.7)
Esophagus
0 (0.0%)
Gastric
SDE ? PLB (%)
PLB alone (%)
34 (65.4)
312 (73.1)
Elevated LAE
8 (15.4)
41 (9.6)
PBC
4 (7.7)
16 (3.8)
AIH
3 (5.8)
25 (5.9)
Methotrexate toxicity
1 (1.9)
8 (1.9)
Transplant reject
1 (1.9)
24 (5.6)
Hemochromatosis
1 (1.9)
1 (0.2)
*All patients had platelet counts [75,000 and INR \1.5
Endoscopic Interventions Performed Of the 15 patients having EGD, 11 required intervention (ten biopsies, one polypectomy). Biopsies were taken from the esophagus, stomach, and duodenum. The lone polypectomy was performed on a single gastric polyp. Of the 37 colonoscopies, 16 required colonic biopsy. Eleven polypectomies were performed with the greatest number of polyps removed being four, with no polyp being larger than 1 cm. PLBs Performed A total of 479 PLBs were completed (one per individual patient), 52 of which immediately followed endoscopy. Ultrasound-guided marking was utilized in all cases,[90% performed prior to PLB in the radiology suite. Indications for PLB were statistically similar for both the PLB with SDE group and for those undergoing PLB alone (Table 4). Sufficient tissue samples were obtained in greater than 95% of patients with the standard two passes. An additional pass was needed \5% of the time.
1 (6.7) 37 (71.2)
Safety Endpoints
Total
16 (43.2)
Colon
16 (43.2)
There were no statistical differences in overall SAEs between patients undergoing PLB alone compared to those with PLB and SDE. A SAE occurred in a single patient (1.9%) in the PLB and SDE group who was diagnosed with a microperforation of the hepatic flexure secondary to unrecognized interposition of the colon between the abdominal wall and the liver, not detected on site marking performed in radiology. This patient required hospitalization for laparoscopic repair and had an unremarkable postop course, being discharged 4 days later. He suffered no long-term sequelae. Four of the 427 patients undergoing PLB alone experienced SAEs secondary to prolonged pain due to subcapsular hematoma, which did not necessitate transfusion or surgical intervention. Non-serious post-PLB pain was similar for both groups with approximately
Colonoscopy Biopsy
Ileum Polypectomy Total
0 (0.0%) 11 (29.7)
Polyp no. 1
8 (21.6)
2
1 (2.7)
3
1 (2.7)
4
1 (2.7)
Polyp size \5 mm
8 (21.6)
5–10 mm
3 (8.1)
[10 mm
0 (0.0)
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20% requiring post-procedure analgesia with additional fentanyl.
Discussion EGD and colonoscopy are typically performed on different days from PLB due to the theoretical risk of increased complications resulting from over-insufflation of the colon or small bowel. The resulting abdominal distention might predispose the patient to an increased chance for colonic perforation at the time of PLB. In our study, one patient experienced this complication and required surgical intervention. This patient was determined to have had unrecognized interposition of the colon between the abdominal wall and the liver, which resulted in inadvertent puncture of the hepatic flexure. The anatomic abnormality was not detected on pre-biopsy ultrasound. Our complication rate of 1.9% for SDE and PLB is comparable to that in the published literature for PLB alone [2, 6–8, 16–18]. Use of ultrasound to mark the biopsy site has been demonstrated to reduce post-biopsy complications [6, 7, 9]. Complications relate not only to whether preprocedure ultrasound marking was performed but also to the experience of the individual performing the procedure. Gilmore et al. showed that the rate of complications in PLB was 3.2% if the operator had performed fewer than 20 biopsies and only 1.1% if the operator had performed more than 100 biopsies [30]. Indeed, the European Board of Gastroenterology requires that 300 PLBs be performed prior to procedure credentialing to insure familiarity with the procedure and to minimize complications [31]. The AASLD recommends that the operator perform at least 40 biopsies in order to be considered adequately trained [15]. This number is consistent with the requirements for accreditation for advanced training in hepatology according to the American Gastroenterological Association’s (AGA) core curriculum [32]. We minimized interoperator bias by analyzing data from a single, experienced gastroenterologist/hepatologist. While our principal endpoint was safety, it has been demonstrated by others that SDE and PLB is also a costeffective practice and one that is preferred by patients, especially when taking into consideration the time needed for bowel preparation, travel time to the center, waiting time, procedure time, and onsite recovery time [33]. Pain after PLB was statistically similar when comparing the SDE/PLB and the PLB alone groups. It has previously been shown that patients with chronic HCV, a history of intravenous drug abuse, those requesting pain medications prior to biopsy, the presence of anxiety before the procedure, as well as the chronic use of addictive medications are all positive predictors of the need for pain medication
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after PLB [34]. In our limited data set, this appears to be true for chronic HCV patients. While our study is retrospective in nature, to our knowledge it is the first attempt to directly compare PLB alone to PLB combined with SDE. Cook and Harrison demonstrated that PLB with SDE can safely be performed together; however, no direct comparison was made with PLB alone. Another limitation of our study is the relatively small sample size from a single center study. With more and more liver biopsies being referred to and performed by our radiology colleagues, the opportunity to perform both PLB and endoscopy together appears to be shrinking. PLB appears to be well on its way to becoming a lost art among many gastroenterologists. Transplant hepatologists in general still perform their own PLBs; however, in our institution they rarely perform both PLB and endoscopy.
Conclusions At our institution, SDE and PLB are often performed together and this appears to be a safe method of practice. The single complication of colonic perforation occurred in a patient with abnormal anatomy, otherwise no significant differences were observed between the two groups in terms of SAEs. We believe that the performance of either EGD or colonoscopy on the same day as PLB optimizes patient care, medical resources, cost utilization, and patient preferences. Grant support
None.
Financial disclosures
None.
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