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    Koert De Jong

    ... Rafael & Gasthuisberg Leuven (Belgium) E-mail: gert. vanassche@ uz. kuleuven. ac. be Prof. dr. CGMI Baeten Department of Surgery University Medical Center Maastricht Maastricht (the Netherlands) E-mail: c. baeten@ surgery.... more
    ... Rafael & Gasthuisberg Leuven (Belgium) E-mail: gert. vanassche@ uz. kuleuven. ac. be Prof. dr. CGMI Baeten Department of Surgery University Medical Center Maastricht Maastricht (the Netherlands) E-mail: c. baeten@ surgery. azm. nl Prof. dr. ...
    Radiofrequency ablation (RFA) destroys liver tumours by the application of heat. A substantial number of patients with unresectable liver tumours can now be treated by local ablation, with or without partial liver resection. Another great... more
    Radiofrequency ablation (RFA) destroys liver tumours by the application of heat. A substantial number of patients with unresectable liver tumours can now be treated by local ablation, with or without partial liver resection. Another great advantage is the possibility of percutaneous RFA treatment, which has minimal morbidity. Although definite proofofits equivalence to other treatments is still lacking, RFA deserves a place in the spectrum of therapies for liver tumours.
    Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae... more
    Drain Amylase level are routinely determined to diagnose pancreatic fistula after Pancreatocoduodenectomy. Consensus is lacking regarding the cut-off value of amylase to diagnosis clinically relevant postoperative pancreatic fistulae (POPF). The present study proposes a model based on Amylase Value in the Drain (AVD) measured in the first three postoperative days to predict a POPF. Amylase cut-offs were selected from a previous published systematic review and the accuracy were validated in a multicentre database from 12 centres in 2 countries. The present study defined POPF the 2016 ISGPS criteria (3 times the upper limit of normal serum amylase). A learning machine method was used to correlate AVD with the diagnosis of POPF. Overall, 454 (27%) of 1638 patients developed POPF. Machine learning excluded a clinically relevant postoperative pancreatic fistulae with an AUC of 0.962 (95% CI 0.940–0.984) in the first five postoperative days. An AVD at a cut-off of 270 U/L in 2 days in the first three postoperative days excluded a POPF with an AUC of 0.869 (CI 0.81–0.90, p < 0.0001). A single AVD in the first three postoperative days may not exclude POPF after pancreatoduodenectomy. The levels should be monitored until day 3 and have two negative values before removing the drain. In the group with a positive level, the drain should be kept in and AVD monitored until postoperative day five.
    OBJECTIVE. To describe the experience with combined liver and kidney transplantation at the University Medical Centre Groningen, The Netherlands. DESIGN. Retrospective. Data were analysed from all patients who underwent combined liver and... more
    OBJECTIVE. To describe the experience with combined liver and kidney transplantation at the University Medical Centre Groningen, The Netherlands. DESIGN. Retrospective. Data were analysed from all patients who underwent combined liver and kidney transplantation in the University Medical Centre Groningen, in the period November 1994-December 2005. During the study period 582 orthotopic liver transplantations and 1026 isolated kidney transplantations were performed. 16 patients underwent combined liver and kidney transplantation: 4 were children (aged 17 months-16 years) and 12 were adults (aged 19-59 years). For all patients, both organs were obtained from the same post-mortem donor. Indications for combined liver and kidney transplantation were primary hyperoxaluria type I (n=6), polycystic liver and kidney disease (n=3) and unrelated liver and kidney failure (n=7). The 1- and 5-year survival rate was 88% (14/16), which was not significantly different from the results after isolated liver transplantation. Two patients died 11 days and 74 months after combined transplantation, due to complications from unsuccessful retransplantation of the liver for hepatic artery thrombosis and secondary biliary cirrhosis, respectively. A third patient died 51 days after combined transplantation due to sepsis. Combined liver and kidney transplantation was a life-saving intervention in this selected group of patients with combined liver and kidney failure. Patient survival was comparable to that of patients undergoing isolated liver transplantation.
    Background/aims: The purpose of this study was to investigate whether differences existed in demography and outcome after resection for hepatocellular carcinoma (HCC) in patients with a normal liver compared to patients with a diseased... more
    Background/aims: The purpose of this study was to investigate whether differences existed in demography and outcome after resection for hepatocellular carcinoma (HCC) in patients with a normal liver compared to patients with a diseased liver. Methodology: Twenty-seven Caucasian patients with HCC in a histologically proven normal liver (NL group) in the Netherlands and 141 Asian patients with HCC in a diseased liver (DL group) in Japan underwent a curative liver resection. Patient and tumor characteristics, post-resectional disease-free, overall survival rates and pattern of recurrence were investigated. Results: HCC's in the NL group were found to be larger, in a more advanced stage and needed more extended resections compared to HCC's in the DL group. Microvascular invasion was similar in both groups, while capsule formation was observed less in the NL group. Overall survival and disease-free survival after curative resection were not statistically different between both groups. Also even after stratification for T-stage, there was no difference in survival. Although the rate of recurrence was similar in both groups, a significantly higher number of extrahepatic metastases was observed in the NL group. Conclusions: Distinct demographic differences existed between patients with HCC in the NL group compared to patients in the DL group. Extrahepatic recurrences were more frequent after curative resection for HCC in a normal liver. No difference in survival was demonstrated between both groups.
    Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are two hepatic nodular lesions of different etiologies. FNH, a polyclonal lesion, is assumed to be a regenerative reaction following a vascular injury, whereas HCA is a... more
    Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are two hepatic nodular lesions of different etiologies. FNH, a polyclonal lesion, is assumed to be a regenerative reaction following a vascular injury, whereas HCA is a monoclonal, benign neoplastic lesion. In addition to features that are predominantly found in either FNH or HCA (e.g., dystrophic vessels in FNH and single arteries in HCA), FNH and HCA share morphological vascular abnormalities such as dilated sinusoids. We hypothesized that these anomalous vascular features are associated with altered expression of growth factors involved in vascular remodeling. This was based on reports of morphologically abnormal hepatic vasculature and nodular lesions in transgenic models of hepatocytic overexpression of angiopoietin-1 (Ang-1), a member of the angiopoietin family, which is crucially involved in vascular morphogenesis and homeostasis. We investigated gene and protein expression of members of the angiopoietin system and vascular endothelial growth factor A (VEGF-A) and its receptors in 9 FNH samples, 13 HCA samples, and 9 histologically normal livers. In comparison with normal samples, a significant increase in Ang-1 was found in FNH (P < 0.01) and HCA (P < 0.05), whereas no significant changes in Ang-2, receptor tyrosine kinase with immunoglobulin-like and EGF-like domains 2, VEGF-A, or vascular endothelial growth factor receptor 2 (VEGFR-2) were observed. Because of the different etiological contexts of a preceding vascular injury in FNH and a neoplastic growth in HCA, Ang-1 might exert different effects on the vasculature in these lesions. In FNH, it could predominantly stimulate recruitment of myofibroblasts and result in dystrophic vessels, whereas in HCA, it may drive vascular remodeling that produces enlarged vessels and arterial sprouting that generates single arteries.
    BACKGROUND In thermal ablation of malignant liver tumors, ablation dimensions remain poorly predictable. This study aimed to investigate factors influencing volumetric ablation dimensions in patients treated with stereotactic microwave... more
    BACKGROUND In thermal ablation of malignant liver tumors, ablation dimensions remain poorly predictable. This study aimed to investigate factors influencing volumetric ablation dimensions in patients treated with stereotactic microwave ablation (SMWA) for colorectal liver metastases (CRLM). METHODS Ablation volumes from CRLM ≤3 cm treated with SMWA within a prospective European multicentre trial were segmented. Correlations between applied ablation energies and resulting effective ablation volumes (EAV) and ablation volume irregularities (AVI) were investigated. A novel measure for AVI, including minimum enclosing and maximum inscribed ellipsoid ablation volumes, and a surrogate parameter for the expansion of ablation energy (EAV per applied energy), was introduced. Potential influences of tumor and patient-specific factors on EAV per applied energy and AVI were analyzed using multivariable mixed-effects models. RESULTS A total of 116 ablations from 71 patients were included for analyses. Correlations of EAV or AVI and ablation energy were weak to moderate, with a maximum of 25% of the variability in EAV and 13% in AVI explained by the applied ablation energy. On multivariable analysis, ablation expansion (EAV per applied ablation energy) was influenced mainly by the tumor radius (B = -0.03, [CI -0.04, -0.007]). AVI was significantly larger with higher applied ablation energies (B = 0.002 [CI 0.0007, 0.002]]); liver steatosis, KRAS mutation, subcapsular location or proximity to major blood vessels had no influence. CONCLUSIONS This study confirmed that factors beyond the applied ablation energy might affect volumetric ablation dimensions, resulting in poor predictability. Further clinical trials including tissue sampling are needed to relate physical tissue properties to ablation expansion.
    BACKGROUND Hepatocellular adenomas (HCA) are benign liver tumors at risk of hemorrhage. The influence of pregnancy on HCA growth and potential bleeding remains unclear. This study investigates HCA-associated behavior and bleeding... more
    BACKGROUND Hepatocellular adenomas (HCA) are benign liver tumors at risk of hemorrhage. The influence of pregnancy on HCA growth and potential bleeding remains unclear. This study investigates HCA-associated behavior and bleeding complications during or shortly after pregnancy. METHODS (I) Single center retrospective cohort study of HCA during and after pregnancy (II) Systematic literature review. RESULTS The retrospective study included 11 patients, of which 4 with HCA ≥5 cm. In only two patients HCA showed growth during pregnancy. In this local cohort, no HCA-related hemorrhages occurred during median follow-up of 34 months (interquartile range 19-58 months). The systematic review yielded 33 studies, totaling 90 patients with 99 pregnancies. Of 73 pregnancies without prior HCA-related intervention, 39 HCA remained stable (53.4%), 11 regressed (15.1%), and 23 (31.5%) progressed. Fifteen HCA-related hemorrhages occurred in HCA measuring 6.5-17.0 cm. Eight patients experienced bleeding during pregnancy, two during labor and five postpartum. CONCLUSION Although hemorrhage of HCA during or shortly after pregnancy is rare and only reported in HCA ≥6.5 cm, it can be fatal. Pregnancy in women with HCA, regardless of size, warrant a close surveillance strategy. Observational studies on behavior and management of HCA ≥5 cm during and immediately after pregnancy are needed.
    Tumour-bearing rats were randomized to a 70% partial hepatectomy or a sham operation. At days 1, 3 or 14, portal and systemic serum was obtained and colon carcinoma cells were cultured in the presence of 5, 10, 20 or 50% serum.... more
    Tumour-bearing rats were randomized to a 70% partial hepatectomy or a sham operation. At days 1, 3 or 14, portal and systemic serum was obtained and colon carcinoma cells were cultured in the presence of 5, 10, 20 or 50% serum. Proliferation and epidermal growth factor receptor (EGFr) expression was measured in tumour cells. Proliferation was 25–40% higher in tumour cells cultured with portal serum after hepatectomy than after sham operation when using serum obtained at day 3, but not days 1 and 14 after operation. In cultures with serum obtained at day 14 after operation CC 531 cells showed a 30% higher proliferation rate with systemic hepatectomy serum than CC 531 cells with sham systemic serum. These effects were not mediated by a change in EGFr mRNA and protein levels as the used colon carcinoma cells did not reveal EGFr activity by any of the three detection methods used.
    Precision-cut liver slices (PCLSs) model provides a unique platform to investigate the different immune responses of healthy versus cirrhotic livers in humans. Our data show that cirrhotic PCLSs exhibit excessive inflammatory response... more
    Precision-cut liver slices (PCLSs) model provides a unique platform to investigate the different immune responses of healthy versus cirrhotic livers in humans. Our data show that cirrhotic PCLSs exhibit excessive inflammatory response accompanied by a lower anti-inflammatory cytokine release in response to LPS; a better understanding of this alteration may guide the novel therapeutic approaches to mitigate the excessive inflammation during the onset of acute-on-chronic liver failure.
    Background Post-therapy [90Y] PET/CT-based dosimetry is currently recommended to validate treatment planning as [99mTc] MAA SPECT/CT is often a poor predictor of subsequent actual [90Y] absorbed dose. Treatment planning software became... more
    Background Post-therapy [90Y] PET/CT-based dosimetry is currently recommended to validate treatment planning as [99mTc] MAA SPECT/CT is often a poor predictor of subsequent actual [90Y] absorbed dose. Treatment planning software became available allowing 3D voxel dosimetry offering tumour-absorbed dose distributions and dose-volume histograms (DVH). We aim to assess dose–response effects in post-therapy [90Y] PET/CT dosimetry in SIRT-treated HCC patients for predicting overall and progression-free survival (OS and PFS) and four-month follow-up tumour response (mRECIST). Tumour-absorbed dose and mean percentage of the tumour volume (V) receiving ≥ 100, 150, 200, or 250 Gy and mean minimum absorbed dose (D) delivered to 30%, 50%, 70%, and 90% of tumour volume were calculated from DVH’s. Depending on the mean tumour -absorbed dose, treated lesions were assigned to a < 120 Gy or ≥ 120 Gy group. Results Thirty patients received 36 SIRT treatments, totalling 43 lesions. Median tumour-a...
    3562 Background: Decision on optimal treatment strategy for CRLM remains complex because uniform (un)resectability criteria are lacking. We hypothesize that the use of an expert panel can improve the identification of patients with... more
    3562 Background: Decision on optimal treatment strategy for CRLM remains complex because uniform (un)resectability criteria are lacking. We hypothesize that the use of an expert panel can improve the identification of patients with potentially resectable CRLM. The Dutch Colorectal Cancer Group (DCCG) Expert Panel was established in conjunction with the CAIRO5 study (Huiskens J et al. BMC Cancer 2015), a multicenter, randomized, phase-3 trial, investigating optimal systemic induction treatment in patients with initially unresectable CRLM. Here, we present the feasibility of this panel. Methods: The DCCG Expert Panel consists of 13 liver surgeons and 4 radiologists. Consensus was reached on predefined (un)resectability criteria at baseline. An online platform allowed resectability-assessment by 3 surgeons in case of inter-surgeon agreement, and 5 surgeons if they disagreed. CRLM were assessed as 1) resectable 2) potentially resectable, or 3) permanently unresectable. Patients with ini...
    1. The influence of short-term cold storage in University of Wisconsin organ preservation solution (UW) on the ability to metabolize lidocaine, testosterone and 7-ethoxycoumarin in isolated human and cynomolgus monkey (Macaca... more
    1. The influence of short-term cold storage in University of Wisconsin organ preservation solution (UW) on the ability to metabolize lidocaine, testosterone and 7-ethoxycoumarin in isolated human and cynomolgus monkey (Macaca fascicularis) hepatocytes and liver slices has been investigated. 2. The human liver tissue was obtained from two different sources, i.e. healthy liver tissue from patients undergoing partial hepatectomy because of metastases of colorectal carcinoma (PH livers) and donor tissue remaining as surgical waste after reduced size or split liver transplantation (Tx livers). Tx livers were perfused in situ with ice-cold UW avoiding warm ischaemia. This in contrast with PH livers, where the operation caused warm ischaemia for 5-90 min. 3. Liver slices and hepatocytes from cynomolgus monkey liver showed comparable metabolic rates for the substrates tested, indicating that all hepatocytes in the slice are participating in the biotransformation of the substrates. These monkey liver preparations can be stored up to 18 h with only a slight loss of their metabolic capacity. 4. Liver slices and isolated hepatocytes from the Tx livers as well as isolated cells from the PH livers could also be stored up to 18 h without losing metabolic capacity. However, for liver slices prepared from PH livers cold storage is not recommended, because metabolic function was reduced by approximately 40% after 18 h.

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