Background and study aims: Confocal endomicroscopy is a unique novel tool for in vivo histology in humans. Due to limitations imposed by the form of the equipment and by sterilization workflows, its use has been limited to the gastrointestinal tract so far. We have developed a rigid miniaturized probe for confocal endomicroscopy of the human liver during laparoscopy.
Patients and methods: To assess the feasibility and potential clinical value of this new system (diameter 6.3 mm), 25 patients with liver disease were examined during routine minilaparoscopy under conscious sedation.
Results: Subsurface serial images (from surface to 250 µm) were generated in real time after fluorescein injection, permitting visualization of hepatocytes, bile ducts, sinusoids, and collagen fibers in vivo. Typical appearances of liver diseases were identified. Confocal diagnosis of moderate-to-severe steatosis and pericellular fibrosis correlated well with histopathologic analysis of subsequent biopsies (83.3 % and 84.6 %, respectively). In addition, intra-abdominal structures such as gallbladder, omentum, and stomach were analyzed by endomicroscopy.
Conclusions: A miniaturized imaging system for confocal laparoscopy allowed in vivo microscopic analysis of healthy and diseased human liver for the first time during ongoing minilaparoscopy. Although such in vivo imaging does not yet compete with conventional histopathology, this novel confocal laparoscopy system may be of future relevance for immediate morphodynamic analysis in liver disease and the targeting of biopsies in vivo.
References
1
Ryder S D, Irving W L, Jones D A. et al .
Progression of hepatic fibrosis in patients with hepatitis C: a prospective repeat liver biopsy study.
Gut.
2004;
53
451-455
2
Loddenkemper C, Longerich T, Hummel M. et al .
Frequency and diagnostic patterns of lymphomas in liver biopsies with respect to the WHO classification.
Virchows Arch.
2007;
450
493-502
4
Bruno S, Battezzati P M, Bellati G. et al .
Long-term beneficial effects in sustained responders to interferon-alfa therapy for chronic hepatitis C.
J Hepatol.
2001;
34
748-755
8
Colloredo G, Guido M, Sonzogni A, Leandro G.
Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease.
J Hepatol.
2003;
39
239-244
9
Leroy V, De Traversay C, Barnoud R. et al .
Changes in histological lesions and serum fibrogenesis markers in chronic hepatitis C patients non-responders to interferon alpha.
J Hepatol.
2001;
35
120-126
10
Arun J, Jhala N, Lazenby A J. et al .
Influence of liver biopsy heterogeneity and diagnosis of nonalcoholic steatohepatitis in subjects undergoing gastric bypass.
Obes Surg.
2007;
17
155-161
11
Bedossa P, Poynard T, Naveau S. et al .
Observer variation in assessment of liver biopsies of alcoholic patients.
Alcohol Clin Exp Res.
1988;
12
173-178
13
Pagliaro L, Rinaldi F, Craxi A. et al .
Percutaneous blind biopsy versus laparoscopy with guided biopsy in diagnosis of cirrhosis. A prospective, randomized trial.
Dig Dis Sci.
1983;
28
39-43
14
Schneider A R, Benz C, Adamek H E. et al .
Minilaparoscopy versus conventional laparoscopy in the diagnosis of hepatic diseases.
Gastrointest Endosc.
2001;
53
771-775
15
Denzer U, Arnoldy A, Kanzler S. et al .
Prospective randomized comparison of minilaparoscopy and percutaneous liver biopsy: diagnosis of cirrhosis and complications.
J Clin Gastroenterol.
2007;
41
103-110
16
Helmreich-Becker I, Schirmacher P, Denzer U. et al .
Minilaparoscopy in the diagnosis of cirrhosis: superiority in patients with Child-Pugh A and macronodular disease.
Endoscopy.
2003;
35
55-60
17
Goetz M, Hoffman A, Galle P R. et al .
Confocal laser endoscopy: new approach to the early diagnosis of tumors of the esophagus and stomach.
Future Oncol.
2006;
2
469-476
18
Kiesslich R, Burg J, Vieth M. et al .
Confocal laser endoscopy for diagnosing intraepithelial neoplasias and colorectal cancer in vivo.
Gastroenterology.
2004;
127
706-713
19
Kiesslich R, Goetz M, Lammersdorf K. et al .
Chromoscopy-guided endomicroscopy increases the diagnostic yield of intraepithelial neoplasia in ulcerative colitis.
Gastroenterology.
2007;
132
874-882
20
Kiesslich R, Gossner L, Goetz M. et al .
In vivo histology of Barrett’s esophagus and associated neoplasia by confocal laser endomicroscopy.
Clin Gastroenterol Hepatol.
2006;
4
979-987
23
Kleiner D E, Brunt E M, Van Natta M. et al .
Design and validation of a histological scoring system for nonalcoholic fatty liver disease.
Hepatology.
2005;
41
1313-1321
24
Goetz M, Fottner C, Schirrmacher E. et al .
In-vivo confocal real-time mini-microscopy in animal models of human inflammatory and neoplastic diseases.
Endoscopy.
2007;
39
350-356
25
Goetz M, Memadathil B, Biesterfeld S. et al .
In vivo subsurface morphological and functional cellular and subcellular imaging of the gastrointestinal tract with confocal mini-microscopy.
World J Gastroenterol.
2007;
13
2160-2165
26
Timmers M, Vermijlen D, Vekemans K. et al .
Tracing DiO-labelled tumour cells in liver sections by confocal laser scanning microscopy.
J Microsc.
2002;
208
65-74
27
Goetz M, Vieth M, Kanzler S. et al .
In vivo confocal laser laparoscopy allows real time subsurface microscopy in animal models of liver disease.
J Hepatol.
2008;
48
91-97
28
Nikfarjam M, Muralidharan V, Malcontenti-Wilson C. et al .
Impact of blood flow occlusion on liver necrosis following thermal ablation.
ANZ J Surg.
2006;
76
84-91
29
Campo-Ruiz V, Lauwers G Y, Anderson R R. et al .
In vivo and ex vivo virtual biopsy of the liver with near-infrared, reflectance confocal microscopy.
Mod Pathol.
2005;
18
290-300
30
Yoneyama K.
Three-dimensional visualization and physiologic evaluation of bile canaliculi in the rat liver slice by confocal laser scanning microscopy.
Scanning.
2001;
23
359-365
31
Boon M E, Barlow Y, Marres E M. et al .
Analysis of three-dimensional architecture in Feulgen-stained fine-needle liver aspirates, using confocal scanning laser microscopy.
Diagn Cytopathol.
2000;
23
82-86