Acetylcholine released by efferent vagus nerves inhibits macrophage activation. Here we show that the anti-inflammatory action of nicotinic receptor activation in peritoneal macrophages was associated with activation of the transcription factor STAT3. STAT3 was phosphorylated by the tyrosine kinase Jak2 that was recruited to the alpha7 subunit of the nicotinic acetylcholine receptor. The anti-inflammatory effect of nicotine required the ability of phosphorylated STAT3 to bind and transactivate its DNA response elements. In a mouse model of intestinal manipulation, stimulation of the vagus nerve ameliorated surgery-induced inflammation and postoperative ileus by activating STAT3 in intestinal macrophages. We conclude that the vagal anti-inflammatory pathway acts by alpha7 subunit-mediated Jak2-STAT3 activation.

No significant differences in diagnostic accuracy among the imaging techniques were observed. Because patients with IBD often need frequent reevaluation of disease status, use of a diagnostic modality that does not involve the use of ionizing radiation is preferable.

The transporter specificity of (99m)Tc-mebrofenin and ICG partially overlaps as both compounds are transported by OATP1B3. (99m)Tc-mebrofenin is also taken up by OATP1B1, whereas ICG is additionally transported by NTCP. Accepted ManuscriptTransporters involved in the hepatic uptake of 99m Tc-mebrofenin and indocyanine green This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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.

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Background99mTc-mebrofenin hepatobiliary scintigraphy (HBS) was used as a quantitative method to evaluate liver function. The aim of this study was to compare future remnant liver function assessed by 99mTc-mebrofenin hepatobiliary scintigraphy with future remnant liver volume in the prediction of liver failure after major liver resection.MethodsComputed tomography (CT) volumetry and 99mTc-mebrofenin hepatobiliary scintigraphy were performed prior to major resection in 55 high-risk patients, including 30 patients with parenchymal liver disease. Liver volume was expressed as percentage of total liver volume or as standardized future remnant liver volume. Receiver operating characteristic (ROC) curve analysis was performed to identify a cutoff value for future remnant liver function in predicting postoperative liver failure.ResultsPostoperative liver failure occurred in nine patients. A liver function cutoff value of 2.69%/min/m2 was calculated by ROC curve analysis. 99mTc-mebrofenin hepatobiliary scintigraphy demonstrated better sensitivity, specificity, and positive and negative predictive value compared to future remnant liver volume. Using 99mTc-mebrofenin hepatobiliary scintigraphy, one cutoff value suffices in both compromised and noncompromised patients.ConclusionPreoperative 99mTc-mebrofenin hepatobiliary scintigraphy is a valuable technique to estimate the risk of postoperative liver failure. Especially in patients with uncertain quality of the liver parenchyma, 99mTc-mebrofenin HBS proved of more value than CT volumetry.

Hyposplenic patients are at risk of overwhelming post-splenectomy infection (OPSI), which carries mortality of up to 70%. Therefore, preventive measures are warranted. However, patients with diminished splenic function are difficult to identify. In this review we discuss immunological, haematological and scintigraphic parameters that can be used to measure splenic function. IgM memory B cells are a potential parameter for assessing splenic function; however, more studies are necessary for its validation. Detection of Howell–Jolly bodies does not reflect splenic function accurately, whereas determining the percentage of pitted erythrocytes is a well-evaluated method and seems a good first-line investigation for assessing splenic function. When assessing spleen function, 99mTc-labelled, heat-altered, autologous erythrocyte scintigraphy with multimodality single photon emission computed tomography (SPECT)-CT technology is the best approach, as all facets of splenic function are evaluated. In conclusion, although scintigraphic methods are most reliable, they are not suitable for screening large populations. We therefore recommend using the percentage of pitted erythrocytes, albeit suboptimal, as a first-line investigation and subsequently confirming abnormal readings by means of scintigraphy. More studies evaluating the value of potentially new markers are needed.

Preoperative evaluation of future remnant liver (FRL) function is crucial in the determination of whether a patient can safely undergo liver resection. Although dynamic 99m Tc-mebrofenin hepatobiliary scintigraphy (HBS) is used to measure FRL function, 2-dimensional planar images lack the ability to assess segmental liver function. Modern SPECT/CT cameras combine dynamic 99m Tc-mebrofenin HBS with additional SPECT and the anatomic information of the CT scan. The aim of this study was to evaluate the additional value of 99m Tc-mebrofenin SPECT for the measurement of segmental liver function and liver functional volume. Methods: Preoperative CT volumetry and 99m Tc-mebrofenin HBS with SPECT were performed in 36 patients undergoing liver resection. In 18 patients, postoperative 99m Tc-mebrofenin HBS with SPECT was performed within 3 d after operation. Dual-head dynamic acquisitions were used to calculate FRL function using anterior and geometric mean (Gmean) datasets. Total and FRL functional liver volumes were measured by SPECT. Results: Because of the anatomic position of the liver, the anterior projection resulted in an underestimation of FRL function in patients undergoing left hemihepatectomy. In patients with normal liver parenchyma, total functional liver volume was comparable to total liver volume measured by CT volumetry, indicating that 99m Tc-mebrofenin SPECT is an accurate method to measure hepatic volume. In compromised livers, compared with normal livers, FRL function per cubic centimeter of liver volume was significantly less. In addition, liver function was not distributed homogeneously, with the segments to be resected relatively more affected. FRL function, measured by a combination of SPECT and dynamic HBS, was able to accurately predict actual postoperative remnant liver function. Conclusion: The Gmean dataset is recommended for the assessment of hepatic function by dynamic planar 99m Tc-mebrofenin HBS. The combination of SPECT data with the dynamic uptake function measured by planar HBS provides valuable visible and quantitative information regarding segmental liver function and is an accurate measure for FRL function.