Predicting procedure duration of colorectal endoscopic submucosal dissection at Western endoscopy centers.

Background and study aims Overcoming logistical obstacles for the implementation of colorectal endoscopic submucosal dissection (ESD) requires accurate prediction of procedure times. We aimed to evaluate existing and new prediction models for ESD duration. Patients and methods Records of all consecutive patients who underwent single, non-hybrid colorectal ESDs before 2020 at three Dutch centers were reviewed. The performance of an Eastern prediction model [GIE 2021;94(1):133-144] was assessed in the Dutch cohort. A prediction model for procedure duration was built using multivariable linear regression. The model's performance was validated using internal validation by bootstrap resampling, internal-external cross-validation and external validation in an independent Swedish ESD cohort. Results A total of 435 colorectal ESDs were analyzed (92% en bloc resections, mean duration 139 minutes, mean tumor size 39 mm). The performance of current unstandardized time scheduling practice was suboptimal (explained variance: R 2 =27%). We successfully validated the Eastern prediction model for colorectal ESD duration <60 minutes (c-statistic 0.70, 95% CI 0.62-0.77), but this model was limited due to dichotomization of the outcome and a relatively low frequency (14%) of ESDs completed <60 minutes in the Dutch centers. The model was more useful with a dichotomization cut-off of 120 minutes (c-statistic: 0.75; 88% and 17% of "easy" and "very difficult" ESDs completed <120 minutes, respectively). To predict ESD duration as continuous outcome, we developed and validated the six-variable cESD-TIME formula ( https://cesdtimeformula.shinyapps.io/calculator/ ; optimism-corrected R 2 =61%; R 2 =66% after recalibration of the slope). Conclusions We provided two useful tools for predicting colorectal ESD duration at Western centers. Further improvements and validations are encouraged with potential local adaptation to optimize time planning.

Outcome of Completion Surgery after Endoscopic Submucosal Dissection in Early-Stage Colorectal Cancer Patients.

T1 colorectal cancers (T1CRC) are increasingly being treated by endoscopic submucosal dissection (ESD). After ESD of a T1CRC, completion surgery is indicated in a subgroup of patients. Currently, the influence of ESD on surgical morbidity and mortality is unknown. The aim of this study was to compare 90-day morbidity and mortality of completion surgery after ESD to primary surgery. The completion surgery group consisted of suspected T1CRC patients from a multicenter prospective ESD database (2014-2020). The primary surgery group consisted of pT1CRC patients from a nationwide surgical registry (2017-2019). Patients with rectal or sigmoidal cancers were selected. Patients receiving neoadjuvant therapy were excluded. Propensity score adjustment was used to correct for confounders. In total, 411 patients were included: 54 in the completion surgery group (39 pT1, 15 pT2) and 357 in the primary surgery group with pT1CRC. Adverse event rate was 24.1% after completion surgery and 21.3% after primary surgery. After completion surgery 90-day mortality did not occur, though one patient died in the primary surgery group. After propensity score adjustment, lymph node yield did not differ significantly between the groups. Among other morbidity-related outcomes, stoma rate (OR 1.298 95%-CI 0.587-2.872, p = 0.519) and adverse event rate (OR 1.162; 95%-CI 0.570-2.370, p = 0.679) also did not differ significantly. A subgroup analysis was performed in patients undergoing rectal surgery. In this subgroup (37 completion and 136 primary surgery), these morbidity outcomes also did not differ significantly. In conclusion, this study suggests that ESD does not compromise morbidity or 90-day mortality of completion surgery.

Correction: Predicting procedure duration of colorectal endoscopic submucosal dissection at Western endoscopy centers.

[This corrects the article DOI: 10.1055/a-2122-0419.].

Endoscopic screening of the upper gastrointestinal tract for second primary tumors in patients with head and neck cancer in a Western country.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) can develop second primary tumors (SPTs) in the esophagus. Endoscopic screening could lead to detection of SPTs at early stages and improve survival. METHODS: We performed a prospective endoscopic screening study in patients with curably treated HNSCC diagnosed between January 2017-July 2021 in a Western country. Screening was performed synchronously (< 6 months) or metachronously (≥ 6 months) after HNSCC diagnosis. Routine imaging for HNSCC consisted of flexible transnasal endoscopy with positron emission tomography/computed tomography or magnetic resonance imaging, depending on primary HNSCC location. The primary outcome was prevalence of SPTs, defined as presence of esophageal high grade dysplasia or squamous cell carcinoma. RESULTS: 202 patients (mean age 65 years, 80.7 % male) underwent 250 screening endoscopies. HNSCC was located in the oropharynx (31.9 %), hypopharynx (26.9 %), larynx (22.2 %), and oral cavity (18.5 %). Endoscopic screening was performed within 6 months (34.0 %), 6 months to 1 year (8.0 %), 1-2 years (33.6 %), and 2-5 years (24.4 %) after HNSCC diagnosis. We detected 11 SPTs in 10 patients (5.0 %, 95 %CI 2.4 %-8.9 %) during synchronous (6/85) and metachronous (5/165) screening. Most patients had early stage SPTs (90 %) and were treated with curative intent with endoscopic resection (80 %). No SPTs in screened patients were detected with routine imaging for HNSCC before endoscopic screening. CONCLUSION: In 5 % of patients with HNSCC, an SPT was detected with endoscopic screening. Endoscopic screening should be considered in selected HNSCC patients to detect early stage SPTs, based on highest SPT risk and life expectancy according to HNSCC and comorbidities.

Endoscopic resection of upper gastrointestinal lesions using the colonic Ovesco full-thickness resection device: Retrospective observational case series of 22 cases.

Background and study aims The endoscopic full-thickness resection (EFRT) device (FTRD) has been shown to have acceptable outcomes in regard to efficacy and safety in the resection of colorectal lesions. Data on its use in the upper gastrointestinal tract are limited to small case series. Patients and methods All consecutive patients undergoing endoscopic full-thickness resection of gastric or duodenal lesions at our institutions were analyzed retrospectively for a primary endpoint of technical success. Results A total of 22 patients with duodenal and gastric lesions underwent EFTR between June 2018 and February 2022. Technical success was achieved in 20 of 22 (91 %) of the procedures. Indications for EFTR were: subepithelial tumor (n = 14), mucosal lesion (n = 5), scar resection (n = 2), and EFTR of endoscopic submucosal dissection (ESD) resection base (n = 1). The FTRD could be advanced to the lesion in all 22 cases (100 %). No dilation of the upper esophageal sphincter (UES) or pylorus was required to pass the device. There were 14 cases of gastric lesions and eight duodenal. One subepithelial lesion was too big for the cap and one scar could not be sucked into the cap. One lesion (gastrointestinal stromal tumor) was removed at second procedure with the ESD technique, including over-the-scope clip. The R0 resection rate for deployed clips was 90 % (18 of 20). There were two superficial esophageal tears from FTRD insertion that required no therapy. No bleeding occurred during the postoperative period. Conclusions Upper gastrointestinal EFTR using the colonic Ovesco FTRD is feasible without pre-dilation of the upper esophageal sphincter or pylorus. This study further confirms acceptable efficacy and safety in upper gastrointestinal use.

Relevance of polyp size for primary endoscopic full-thickness resection of suspected T1 colorectal cancers.

BACKGROUND: En bloc local excision of suspected T1 colorectal cancer (CRC) provides optimal tumor risk assessment with curative intent. Endoscopic full-thickness resection (eFTR) with an over-the-scope device has emerged as a local excision technique for T1 CRCs, but data on the upper size limit for achieving a histological complete (R0) resection are lacking. We aimed to determine the influence of polyp size on the R0 rate. METHODS: eFTR procedures for suspected T1 CRCs performed between 2015 and 2021 were selected from the endoscopy databases of three tertiary centers. The main outcome was R0 resection, defined as tumor- and dysplasia-free margins (≥ 0.1 mm) for both the deep and lateral resection margins. Regression analysis was performed to identify risk factors for R1/Rx resection, mainly focusing on endoscopically estimated polyp size. RESULTS: 136 patients underwent eFTR for suspected T1 CRC (median size 15 mm [IQR 13-18 mm]; 83.1 % cancer). The rates of technical success and R0 resection were 87.5 % (119/136; 95 %CI 80.9 %-92.1 %) and 79.7 % (106/136; 95 %CI 72.1 %-85.7 %), respectively. Increasing polyp size was significantly associated with R1/Rx resection (risk ratio 2.35 per 5-mm increase, 95 %CI 1.80-3.07; P < 0.001). The R0 rate was 89.9 % (80/89) for polyps ≤ 15 mm, 71.4 % (25/35) for 16-20 mm, and 11.1 % (1/9) for those > 20 mm. CONCLUSIONS: eFTR is associated with a 90 % R0 rate for T1 CRCs of ≤ 15 mm. Performing eFTR for polyps 16-20 mm should depend on access, their mobility, and the availability of alternative resection techniques. eFTR for > 20-mm polyps results in a high R1 rate and should not be recommended.

Efficacy and safety of cap-assisted endoscopic mucosal resection for treatment of nonlifting colorectal polyps.

BACKGROUND : Suboptimal lifting increases complexity of endoscopic mucosal resection (EMR) for benign colorectal polyps. Cap-assisted EMR (EMR-C) may allow fibrotic polyp tissue to be captured in the snare. This study evaluated the efficacy and safety of EMR-C for benign nonlifting colorectal polyps. METHODS : This was a multicenter study, which prospectively registered all EMR-C procedures (2016-2018) for presumed benign nonlifting colorectal polyps. RESULTS : 70 nonlifting polyps with a median size of 25 mm (interquartile range [IQR] 15-40) were treated with EMR-C. Complete polyp removal was achieved in 68 (97.1 %), including 47 (67.1 %) with EMR-C alone. Overall, 66 polyps showed benign histology, and endoscopic follow-up after a median of 6 months (IQR 6-10) showed recurrence in 19.7 %. First (n = 10) and second (n = 2) benign recurrences were all treated endoscopically. Deep mural injury type III-V occurred in 7.4 % and was treated successfully with clips. CONCLUSION : EMR-C may be an alternative therapeutic option for removal of benign nonlifting polyp tissue. Although recurrence still occurs, repeat endoscopic therapy usually leads to complete polyp clearance.

Screening for synchronous esophageal second primary tumors in patients with head and neck cancer.

Patients with head and neck squamous cell carcinoma (HNSCC) have an increased risk of developing esophageal second primary tumors (ESPTs). We aimed to determine the incidence, stage, and outcome of synchronous ESPTs in patients with HNSCC in a Western population. We performed a prospective, observational, and cohort study. Patients diagnosed with HNSCC in the oropharynx, hypopharynx, any other sub-location in combination with alcohol abuse, or patients with two synchronous HNSCCs, between February 2019 and February 2020 underwent screening esophagogastroduodenoscopy (EGD). ESPT was defined as presence of esophageal squamous cell carcinoma (ESCC) or high grade dysplasia (HGD). Eighty-five patients were included. A lesion suspected for ESPT was detected in 14 of 85 patients, which was pathologically confirmed in five patients (1 ESCC and 4 HGD). The radiotherapy field was extended to the esophagus in two of five patients, HGD was treated with endoscopic resection in three of five patients. None of the ESPTs were detected on MRI and/or CT-scan prior to EGD. Of the remaining nine patients, three had low grade dysplasia on histology whereas the other six patients had benign lesions. Incidence of synchronous ESPT was 5.9% in our cohort of HNSCC patients. All ESPTs were diagnosed at an early stage and treated with curative intent. We recommend that screening for synchronous ESPTs should be considered in a selected group of patients with HNSCC.

Clip placement to prevent delayed bleeding after colonic endoscopic mucosal resection (CLIPPER): study protocol for a randomized controlled trial.

BACKGROUND: Endoscopic mucosal resection (EMR) for large colorectal polyps is in most cases the preferred treatment to prevent progression to colorectal carcinoma. The most common complication after EMR is delayed bleeding, occurring in 7% overall and in approximately 10% of polyps ≥ 2 cm in the proximal colon. Previous research has suggested that prophylactic clipping of the mucosal defect after EMR may reduce the incidence of delayed bleeding in polyps with a high bleeding risk. METHODS: The CLIPPER trial is a multicenter, parallel-group, single blinded, randomized controlled superiority study. A total of 356 patients undergoing EMR for large (≥ 2 cm) non-pedunculated polyps in the proximal colon will be included and randomized to the clip group or the control group. Prophylactic clipping will be performed in the intervention group to close the resection defect after the EMR with a distance of < 1 cm between the clips. Primary outcome is delayed bleeding within 30 days after EMR. Secondary outcomes are recurrent or residual polyps and clip artifacts during surveillance colonoscopy after 6 months, as well as cost-effectiveness of prophylactic clipping and severity of delayed bleeding. DISCUSSION: The CLIPPER trial is a pragmatic study performed in the Netherlands and is powered to determine the real-time efficacy and cost-effectiveness of prophylactic clipping after EMR of proximal colon polyps ≥ 2 cm in the Netherlands. This study will also generate new data on the achievability of complete closure and the effects of clip placement on scar surveillance after EMR, in order to further promote the debate on the role of prophylactic clipping in everyday clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03309683 . Registered on 13 October 2017. Start recruitment: 05 March 2018. Planned completion of recruitment: 31 August 2021.

High practice variation in risk stratification, baseline oncological staging, and follow-up strategies for T1 colorectal cancers in the Netherlands.

Background and study aims Based on pathology, locally resected T1 colorectal cancer (T1-CRC) can be classified as having low- or high-risk for irradicality and/or lymph node metastasis, the latter requiring adjuvant surgery. Reporting and application of pathological high-risk criteria is likely variable, with inherited variation regarding baseline oncological staging, treatment and surveillance. Methods We assessed practice variation using an online survey among gastroenterologists and surgeons participating in the Dutch T1-CRC Working Group. Results Of the 130 invited physicians, 53 % participated. Regarding high-risk T1-CRC criteria, lymphangio-invasion is used by 100 %, positive or indeterminable margins by 93 %, poor differentiation by 90 %, tumor-free margin ≤ 1 mm by 78 %, tumor budding by 57 % and submucosal invasion > 1000 µm by 47 %. Fifty-two percent of the respondents do not perform baseline staging in locally resected low-risk T1-CRC. In case of unoperated high-risk patients, we recorded 61 different surveillance strategies in 63 participants, using 19 different combinations of diagnostic tests. Endoscopy is used in all schedules. Mean follow-up time is 36 months for endoscopy, 26 months for rectal MRI and 30 months for abdominal CT (all varying 3-60 months). Conclusion We found variable use of pathological high-risk T1-CRC criteria, creating risk for misclassification as low-risk T1-CRC. This has serious implications, as most participants will not proceed to oncological staging in low-risk patients and adjuvant surgery nor radiological surveillance is considered. On the other hand, oncological surveillance in patients with a locally resected high-risk T1-CRC who do not wish adjuvant surgery is highly variable emphasizing the need for a uniform surveillance protocol.

Measurement of liver function using hepatobiliary scintigraphy improves risk assessment in patients undergoing major liver resection.

BACKGROUND: (99m)Tc-mebrofenin-hepatobiliary-scintigraphy (HBS) enables measurement of future remnant liver (FRL)-function and was implemented in our preoperative routine after calculation of the cut-off value for prediction of postoperative liver failure (LF). This study evaluates our results since the implementation of HBS. Additionally, CT-volumetric methods of FRL-assessment, standardized liver volumetry and FRL/body-weight ratio (FRL-BWR), were evaluated. METHODS: 163 patients who underwent major liver resection were included. Insufficient FRL-volume and/or FRL-function <2.7%/min/m(2) were indications for portal vein embolization (PVE). Non-PVE patients were compared with a historical cohort (n = 55). Primary endpoints were postoperative LF and LF related mortality. Secondary endpoint was preoperative identification of patients at risk for LF using the CT-volumetric methods. RESULTS: 29/163 patients underwent PVE; 8/29 patients because of insufficient FRL-function despite sufficient FRL-volume. According to FRL-BWR and standardized liver volumetry, 16/29 and 11/29 patients, respectively, would not have undergone PVE. LF and LF related mortality were significantly reduced compared to the historical cohort. HBS appeared superior in the identification of patients with increased surgical risk compared to the CT-volumetric methods. DISCUSSION: Implementation of HBS in the preoperative work-up led to a function oriented use of PVE and was associated with a significant decrease in postoperative LF and LF related mortality.

Physiological and biochemical basis of clinical liver function tests: a review.

OBJECTIVE: To review the literature on the most clinically relevant and novel liver function tests used for the assessment of hepatic function before liver surgery. BACKGROUND: Postoperative liver failure is the major cause of mortality and morbidity after partial liver resection and develops as a result of insufficient remnant liver function. Therefore, accurate preoperative assessment of the future remnant liver function is mandatory in the selection of candidates for safe partial liver resection. METHODS: A MEDLINE search was performed using the key words "liver function tests," "functional studies in the liver," "compromised liver," "physiological basis," and "mechanistic background," with and without Boolean operators. RESULTS: Passive liver function tests, including biochemical parameters and clinical grading systems, are not accurate enough in predicting outcome after liver surgery. Dynamic quantitative liver function tests, such as the indocyanine green test and galactose elimination capacity, are more accurate as they measure the elimination process of a substance that is cleared and/or metabolized almost exclusively by the liver. However, these tests only measure global liver function. Nuclear imaging techniques ((99m)Tc-galactosyl serum albumin scintigraphy and (99m)Tc-mebrofenin hepatobiliary scintigraphy) can measure both total and future remnant liver function and potentially identify patients at risk for postresectional liver failure. CONCLUSIONS: Because of the complexity of liver function, one single test does not represent overall liver function. In addition to computed tomography volumetry, quantitative liver function tests should be used to determine whether a safe resection can be performed. Presently, (99m)Tc-mebrofenin hepatobiliary scintigraphy seems to be the most valuable quantitative liver function test, as it can measure multiple aspects of liver function in, specifically, the future remnant liver.

Travel health preparation and travel-related morbidity of splenectomised individuals.

Asplenic or hyposplenic patients are at an increased risk of encapsulated bacterial and intraerythrocytic parasitic infections, which are endemic at many travel destinations. With proper travel health advice and preparation splenectomised individuals could have comparable travel-related morbidity as healthy control subjects. We conducted a prospective case-control study with 21 travel pairs. Each pair consisted of a splenectomised patient (case) and a healthy, non-splenectomised travel companion (control) in order to match for travel destination, duration and potential exposures to travel-related health risks. All participants filled out a questionnaire detailing travel health preparation including vaccination and malaria prophylaxis as well as travel-related morbidity. Cases and controls were comparable for age and gender. Cases received significantly more information about on demand use of antibiotics in case of fever. Immunisation coverage against encapsulated bacteria and adherence to malaria prophylaxis guidelines was suboptimal. There were no significant differences in the occurrence of travel-related ailments nor differences in severity of ailments. The immunisation coverage against encapsulated bacteria and adherence to malaria prophylaxis guidelines was suboptimal in some splenectomised patients and should be improved. Strict adherence to national travel health advice guidelines and specific guidelines for asplenic patients is advisable. However, with regard to travel-related morbidity there are no significant differences in morbidity between splenectomised patients and healthy controls, at least in the setting of short-term travel.

Liver function testing with nuclear medicine techniques is coming of age.

Liver function is a broad term, as the organ participates in a multitude of different physiological and biochemical processes, including metabolic, synthetic, and detoxifying functions. However, it is the function of the hepatocyte that is central to sustaining normal life and dealing with disease states. When the liver begins to fail in severely ill patients, it forecasts a terminal outcome. However, unlike the glomerular filtration rate which clearly quantifies the key renal function, at most practice sites, there is no clinically available quantitative test for liver function. Although it is commonplace to assess indirect evidence of that function (by measuring blood levels of its end products and by-products) and to detect an acute injury (by following rising transaminases), a widely available test that would directly measure hepatocellular function is lacking. This article reviews current knowledge on liver function studies and focuses on those nuclear medicine tests available to study the whole liver and regional liver function. The clinical application driving these tests, prediction of remnant liver function after partial hepatectomy for primary liver malignancy or metastatic disease, is addressed here in detail. The test was recently validated for this specific application and was shown to be better than the current standard of practice (computed tomography volumetry), particularly in patients with hepatic comorbidities like cirrhosis, steatosis, or cholestasis. Furthermore, early assessment of regional liver function increase after preoperative portal vein embolization becomes possible with this technology. The limiting factor to a wider acceptance of this test is based on the lack of clinical software that would allow calculation of liver function parameters. This article provides information that enables a clinical nuclear medicine facility to provide this test using readily available equipment. Furthermore, it addresses emerging clinical applications that are under investigation.

Systemic lidocaine does not attenuate hepatic dysfunction after liver surgery in rats.

BACKGROUND: Lidocaine has been shown to attenuate ischemia-reperfusion (I/R) injury in the heart, lung, and brain, potentially due to modulation of inflammatory responses and apoptotic signaling pathways. Because hepatic I/R injury after liver surgery still poses a significant risk for postoperative liver dysfunction or even failure, we investigated whether systemic lidocaine would also positively affect hepatocellular damage and overall liver function after hepatic I/R injury. In addition the potential underlying mechanisms of action were studied. METHODS: A standardized rat model of 70% I/R injury was used to assess the effects of systemic lidocaine on hepatocellular damage after 60 minutes of ischemia and subsequent reperfusion. To better mimic the clinical situation, we combined 45 minutes of ischemia with partial hepatectomy in a second model. Systemic lidocaine was administered continuously, starting 30 minutes before the ischemic insult until 20 minutes of reperfusion. Hepatocellular function was assessed using different variables of liver synthesis, cellular integrity, and metabolism. Inflammation was evaluated by measuring leukocyte influx and apoptosis detected using TUNEL staining and a caspase-3 assay. RESULTS: In both models, I/R injury resulted in a significant increase in biochemical and histological hepatocellular damage with comparable values in control and lidocaine-treated animals. Postoperative liver function was significantly impaired secondary to ischemia, yet no significant differences between control and lidocaine groups could be observed. Likewise, there was no significant difference between control and lidocaine-treated animals with respect to I/R injury-induced leukocyte influx, as a marker for inflammatory response. CONCLUSION: Systemic lidocaine in therapeutic concentrations neither attenuated hepatocellular damage nor improved postoperative liver function after hepatic I/R injury.

Quantitative assessment of liver function after ischemia-reperfusion injury and partial hepatectomy in rats.

BACKGROUND: Liver function after hepatic ischemia-reperfusion (I/R) injury and partial liver resection (PHx) is influenced by the extent of PHx, hepatocellular damage, and liver regeneration. This study investigates the effect of minor PHx with increasing degrees of I/R-induced damage on postoperative liver function parameters and compares the indocyanine green (ICG) clearance test with (99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) for quantitative measurement of hepatic function in a standardized rat model. METHODS: Rats were subjected to 70% partial liver I/R combined with resection of the nonischemic lobes. Various degrees of hepatic damage were induced by 0, 15, 30, 45, and 60 min ischemia. Prothrombin time and bilirubin were used as indirect parameters of liver function. (99m)Tc-mebrofenin HBS and ICG clearance were used as dynamic quantitative liver function tests. RESULTS: After 24 h reperfusion hepatocellular damage increased with prolonged ischemia times. Hepatocellular damage and liver regeneration were closely interrelated. Moderate I/R-induced damage enhanced regeneration, while extensive damage debilitates the regenerative capacity. PHx alone resulted in no significant decrease in liver uptake function measured by HBS or ICG. Increasing severity of hepatic I/R injury had a differential effect on ICG clearance and (99m)Tc-mebrofenin uptake and excretion. CONCLUSIONS: The specific impact of 30% PHx combined with progressive ischemia times is different for each liver function test. Albeit (99m)Tc-mebrofenin HBS and the ICG clearance test provide complementary quantitative information to biochemical parameters, they only quantify one or two components of liver function. ICG and (99m)Tc-mebrofenin uptake profiles differed significantly, suggesting that the specific hepatic transporters may be distinct.

The emerging role of transport systems in liver function tests.

Liver function tests are of critical importance for the management of patients with severe or terminal liver disease. They are also used as prognostic tools for planning liver resections. In recent years many transport systems have been identified that also transport substances employed in liver function tests. Such substances include endogenous bilirubin or exogenously administered indocyanine green, agents for magnetic resonance imaging, agents for single photon emission computed tomography or agents for breath tests. The increasing functional and molecular information on the respective transport systems should improve the management and as a result the outcome of patients scheduled for liver surgery or transplantation. To achieve the latter goal, clinical studies that assess individual patients' liver function over the course of their disease with liver function tests are needed to firmly establish and validate recently introduced and novel liver function markers.

Quantitative assessment of hepatic function during liver regeneration in a standardized rat model.

UNLABELLED: Reliable assessment of hepatic function during liver regeneration is crucial after liver surgery or liver transplantation. (99m)Tc-galactosyl human serum albumin ((99m)Tc-GSA) scintigraphy, (99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS), the indocyanine green (ICG) clearance test, and the galactose elimination capacity (GEC) are common quantitative liver function tests. However, to our knowledge, comparative analysis between these tests has never been performed during liver regeneration. The aim of this study was therefore to compare (99m)Tc-GSA scintigraphy, (99m)Tc-mebrofenin HBS, the ICG clearance test, and GEC in the assessment of hepatic function during liver regeneration in rats. METHODS: Rats were subjected to 70% partial hepatectomy (PHx). Liver function and functional volume were determined at predefined times after PHx and expressed as a percentage of baseline (pre-PHx) values. RESULTS: During liver regeneration, functional liver volume measured by (99m)Tc-GSA SPECT correlated strongly with conventional liver volume based on wet weight. One day after 70% PHx, conventional liver volume overestimated liver function as measured by (99m)Tc-mebrofenin uptake and excretion rates, (99m)Tc-GSA uptake rate, and ICG clearance. On days 5 and 7, (99m)Tc-mebrofenin uptake and ICG clearance had recovered to levels similar to conventional liver volume, whereas (99m)Tc-GSA uptake reflected a reduced liver function in relation to conventional liver volume and (99m)Tc-mebrofenin uptake. The GEC measurements consistently overestimated liver function during regeneration. CONCLUSION: Volumetric assessment of the liver should be complemented by liver function-specific assays. Functional regeneration is impaired, compared with volumetric regeneration, in the early phase of liver regeneration. In later stages of liver regeneration, (99m)Tc-GSA uptake underestimates hepatic regeneration in comparison to liver volume and (99m)Tc-mebrofenin uptake. GEC is of less value because it is only minimally affected by 70% PHx and is influenced by factors not related to liver function. (99m)Tc-mebrofenin HBS has the advantage of providing visual and quantitative information regarding both uptake and excretory liver function.