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Matthanja Bieze,1,2,* Annelotte Pauline van Haaps,3,4,* Leonardo Kapural,5 Sean Li,6 Kris Ferguson,7 Ralph de Vries,8 Michael E Schatman,9,10 Velja Mijatovic,3,4 Jan Willem Kallewaard1,11 1Department of Anesthesiology and Pain Management, Amsterdam UMC Location University of Amsterdam, Amsterdam, the Netherlands; 2Department of Anesthesia and Pain Management, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada; 3Department of Reproductive Medicine, Amsterdam University Medical Center location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; 4Amsterdam Reproduction and Development, Amsterdam University Medical Centers, Amsterdam, the Netherlands; 5Carolina’s Pain Institute and Center for Clinical Research, Winston Salem, North Carolina, USA; 6National Spine and Pain Centers, Shrewsbury, New Jersey, USA; 7Aspirus Langlade Hospital Pain Clinic, Antigo, Wisconsin, USA; 8Medical Library, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands; 9Department of Anesthesiology, Perioperative Care & Pain Medicine, NYU Grossman School of Medicine, New York, New York, USA; 10Department of Population Health – Division of Medical Ethics, NYU Grossman School of Medicine, New York, New York, USA; 11Department of Anesthesiology and Pain Management, Rijnstate Ziekenhuis, Arnhem, the Netherlands*These authors contributed equally to this workCorrespondence: Jan Willem Kallewaard, Department of Anaesthesiology and Pain Management, Amsterdam UMC location University of Amsterdam, Meibergdreef 9, Amsterdam, the Netherlands, Email j.w.kallewaard@amsterdamumc.nlAim: Visceral pain, characterized by pain that is diffuse and challenging to localize, occurs frequently and is difficult to treat. In cases where the pain becomes intractable despite optimal medical management, it can affect patients’ Quality of Life (QoL). Spinal Cord Stimulation (SCS) has emerged as a potential solution for intractable visceral pain.Purpose: In this narrative review, we collected all evidence regarding the efficacy of SCS for visceral pain across various underlying conditions.Methods: A comprehensive literature search was conducted in PubMed, Embase, and Web of Science in which articles published from October 1st, 1963 up to March 7th, 2023 were identified.Results: Seventy articles were included in this review of which most were retrospective cohort studies, case series and case reports. The studies, often with a small number of participants, reported on SCS for chronic pancreatitis, anorectal pain and bowel disorders, gynaecological diagnoses, visceral pelvic pain, urological disorders and finally general visceral pain. They found positive effects on pain and/or symptom relief, opioid consumption, anxiety and depression and QoL. Complications occurred frequently but were often minor and reversible.Conclusion: Better screening and selection criteria need to be established to optimally evaluate eligible patients who might benefit from SCS. A positive outcome of a sympathetic nerve block appears to be a potential indicator of SCS effectiveness. Additionally, women receiving SCS for endometriosis had a better outcome compared to other indications. Finally, SCS could also relief functional symptoms such as voiding problems and gastroparesis. Complications could often be resolved with revision surgery. Since SCS is expensive and not always covered by standard health insurance, the incorporation of cost-analyses is recommended. In order to establish a comprehensive treatment plan, including selection criteria for SCS, rigorous prospective, possibly randomized and controlled studies that are diagnosis-oriented, with substantial follow-up and adequate sample sizes, are needed.Keywords: neuromodulation, SCS, spinal cord stimulation, visceral pain, chronic pelvic pain, chronic pain

Introduction: Acute Kidney Injury (AKI) following Liver Transplantation (LT) is associated with prolonged ICU and hospital stay, increased risk of chronic renal disease, and decreased graft survival. Intraoperative hypotension is a modifiable risk factor associated with postoperative AKI. We aimed to determine in which phase of LT hypotension has the strongest association with AKI: the anhepatic or neohepatic phase., Methods: This retrospective cohort study included adult patients undergoing LT between January 2010 and June 2022. Exclusion criteria were re-do or combined transplantations, preoperative dialysis, and early graft failure or death. Primary outcome was AKI as defined by KDIGO. Hypotension was Mean Arterial Pressure (MAP) below predefined thresholds in minutes. Risk adjusted logistic regression analysis considered hypotension in 3 periods: the total procedure, anhepatic phase, and neohepatic phase., Results: Our cohort included 1153 patients. The median MELD-NA score was 19 (IQR 11-28), and 412 (35.9%) were living-related donations. AKI occurred in 544 patients (47.2%). The unadjusted model showed an association with AKI for MAP < 60 mmHg (OR = 1.011 [1.0, 1.022], p = 0.047) and MAP < 55 mmHg (OR = 1.023 [1.002, 1.047], p = 0.040) in the anhepatic phase, and for MAP < 60 mmHg (OR = 1.032 [1.01, 1.056], p = 0.006) in the neohepatic phase. The adjusted model did not reach significance in the subgroups but did in the total procedure: MAP < 60 mmHg (OR = 1.005 [1.002, 1.008], p < 0.001) and MAP < 55 mmHg (OR = 1.008 [1.003-1.013], p = 0.004)., Conclusion: Intraoperative hypotension is independently associated with AKI following LT. This association is seen during the anhepatic phase. Maintaining MAP above 60 mmHg may improve kidney function after LT., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier España S.L.U.)

Introduction: Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively., Methods: Multicenter prospective nonrandomized pilot study included patients with moderate or severe pain (Numeric Rating Scale ≥ 4) associated with PDAC or CP in 5 Dutch centers. An intravenous lidocaine bolus of 1.5 mg/kg was followed by continuous infusion at 1.5 mg/kg/hr. The dose was raised every 15 minutes until treatment response (up to a maximum 2 mg/kg/hr) and consecutively administered for 2 hours. Primary outcome was the mean difference in pain severity, preinfusion, and the first day after (Brief Pain Inventory [BPI] scale 1-10). A BPI decrease ≥1.3 points was considered clinically relevant., Results: Overall, 30 patients were included, 19 with PDAC (63%) and 11 with CP (37%). The mean difference in BPI at day 1 was 1.1 (SD ± 1.3) points for patients with PDAC and 0.5 (SD ± 1.7) for patients with CP. A clinically relevant decrease in BPI on day 1 was reported in 9 of 29 patients (31%), and this response lasted up to 1 month. No serious complications were reported, and only 3 minor complications (vertigo, nausea, and tingling of mouth). Treatment with lidocaine did not impact quality of life., Discussion: Intravenous lidocaine in patients with painful PDAC and CP did not show an overall clinically relevant reduction of pain. However, this pilot study shows that the treatment is feasible in this patient group and had a positive effect in a third of patients which lasted up to a month with only minor side effects. To prove or exclude the efficacy of intravenous lidocaine, the study should be performed in a study with a greater sample size and less heterogeneous patient group., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Positron emission tomography (PET) using the cationic compound [ 18 F]fluoromethylcholine (FCH) enhances the sensitivity for noninvasive classification of hepatic tumors due to peculiar patterns of accumulation. The underlying transporters are not known. We aim to identify the carriers mediating uptake of FCH in liver and to correlate their expression pattern with PET intrahepatic signal distribution to clarify the role of membrane transporters in FCH accumulation. FCH transport was characterized in cells overexpressing organic cation transporters (OCTs). OCT mRNA levels were determined in different types of hepatic lesions and correlated with FCH PET signal intensity. Additionally, OCT1 and OCT3 protein was analyzed in a subset of patients by Western blotting. HEK293 cells overexpressing OCT1, OCT2, or OCT3 showed higher intracellular levels of FCH in comparison with wild-type cells. mRNA levels of OCT1 paralleled protein levels and were significantly downregulated in hepatocellular carcinoma (HCC), hepatocellular adenoma (HCA), and, to a lesser extent, in focal nodular hyperplasia compared with matched nontumor tissues. In three patients with HCA, the FCH PET signal intensity was reduced relative to normal liver. This correlated with the simultaneous downregulation of OCT1 and OCT3 mRNA. In another patient with HCA, lesion and surrounding tissue did not show a difference in signal, coinciding with downregulation of OCT1 and upregulation of OCT3. Therefore, OCT1 is very likely a key transporter for the accumulation of FCH in the liver. The data support the hypothesis that the varying expression levels of OCT1 and OCT3 in focal liver lesions determine FCH PET signal intensity., (Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.)

Background: Benign liver tumours (e.g., hepatocellular adenoma (HCA), focal nodular hyperplasia (FNH), and haemangioma) are occasionally resected for alleged symptoms, although data on long-term outcomes is lacking. The aim of this cross-sectional study was to assess long-term outcomes of surgical intervention., Methods: Forty patients with benign tumours (HCA 20, FNH 12, giant haemangioma 4, cysts 4) were included. Patients filled in Validated McGill Pain Questionnaires, preoperatively and after a median of 54 months after resection. Outcomes were evaluated using paired sample t-test and (M) ANOVA., Results: Relief of symptoms sustained in 30/40 patients, within a follow-up of 54 (24-148) months after resection. VAS scores were reduced from 5.5 preoperatively to 1.6 postoperatively (p < 0.001). Patients with left-sided tumours had higher postoperative Pain Rating Index (PRI), compared to patients with right-sided tumours: 15.3 vs. 5.8 (p = 0.018). If patients could reconsider undergoing surgery, 34/38 would again choose resection. Discomfort at the operative scar was the most common complaint: 8/40 patients, all after open surgery, of whom 3/40 had an incisional hernia. 7/40 patients had a laparoscopic resection., Conclusion: Resection relieved symptoms in 30/40 patients. The operative scar was a frequent source for remaining postoperative complaints, suggesting an advantage for a laparoscopic approach when feasible., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Unlabelled: Diagnosis of hepatocellular carcinoma (HCC) primarily involves imaging. The aim of this study was to assess the accuracy of (18) F-fluorocholine ((18) F-FCH) positron emission tomography (PET) for detection of HCC and evaluation of extent of disease. Patients with HCC >1 cm were included between 2009 and July 2011, and follow-up closed in February 2013. Diagnosis was based on American Association for the Study of Liver Diseases criteria, and all patients underwent (18) F-FCH PET/computed tomography (CT) at baseline before treatment, 6 underwent a second PET/CT posttreatment, and 1 a third during follow-up. Whole-body PET and low-dose CT imaging were performed 15 minutes after (18) F-FCH injection. Evaluation of imaging was done with standardized uptake value (SUV) ratios: SUV maximum of the lesion divided by the SUV mean of surrounding tissue. Statistical analyses included descriptive analyses, receiver operating characteristic curve, McNemar's test, and Kaplan-Meier's test at 5% level of significance. Twenty-nine patients revealed 53 intrahepatic lesions. In 48 of 53 lesions, (18) F-FCH PET was positive (SUVratio , 1.95 ± 0.66; sensitivity, 88%; specificity, 100%). PET/CT showed uptake in 18 extrahepatic lesions and no uptake in 3 lesions affirmed non-HCC lesions; all lesions were confirmed with additional investigation (accuracy, 100%). In 17 of 29 patients, additional lesions were found on PET/CT imaging, with implications for treatment in 15 patients. Posttreatment PET/CT showed identical results, compared with standard treatment evaluation., Conclusion: This study shows additional value of (18) F-FCH PET/CT for patients with HCC. (18) F-FCH PET/CT has implications for staging, management, and treatment evaluation because of accurate assessment of extrahepatic disease., (© 2014 by the American Association for the Study of Liver Diseases.)

Objectives: The clinical management of hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) is still subject to controversy, especially with respect to patient selection for surgery. The aim of this prospective cohort study was to assess the outcomes of surgical intervention., Methods: Between January 2008 and September 2012, patients diagnosed with FNH or HCA based on magnetic resonance imaging or computed tomography were enrolled in this prospective study. Resection was undertaken in patients with HCA of > 5 cm or symptomatic lesions. Lesion characteristics, extent of liver resection (minor: fewer than three segments; major: three or more segments), morbidity (by Dindo-Clavien class), mortality, postoperative length of stay and symptoms [McGill Pain Questionnaire, including a visual analogue scale (VAS)] were evaluated., Results: A total of 110 patients (106 female; median age: 39 years) were included; 51 patients had HCA and 59 had FNH. Of the 110 patients, 49 underwent resection (33 HCA patients; 16 FNH patients). Laparoscopic minor resection was performed in five HCA and five FNH patients; open minor resection was performed in 19 HCA and seven FNH patients, and open major resection was performed in nine HCA and four FNH patients. Severe postoperative complications were observed in four patients (Grade III, n = 3; Grade IV, n = 1). Median baseline scores on the VAS were 6 in FNH patients and 7 in HCA patients; the median VAS score after resection was 0 (P = 0.008)., Conclusions: If patients with HCA and FNH require surgery, limited resection can be carried out with low morbidity and without mortality. Patients with preoperative symptoms show a high rate of postoperative symptom relief., (© 2013 International Hepato-Pancreato-Biliary Association.)

A 44-year-old woman presented with symptoms of fatigue and increasing abdominal discomfort. MRI with the hepatobiliary contrast Gd-EOB-DTPA (Primovist) was performed showing a 6 cm lesion in segment 2/3 of the liver typical for focal nodular hyperplasia (FNH). Because of severe complaints attributed to the lesion, the patient was scheduled for resection. At laparotomy multiple small white lesions were found throughout the liver with enlarged locoregional lymph nodes. Macroscopically, the findings could be consistent with widespread metastases and the surgeon felt compelled to determine the nature of these lesions before continuing resection. Final diagnosis revealed multiple bile duct hamartomas and an FNH lesion as was expected.

Background: Staging laparoscopy (SL) is not regularly performed for patients with hepatocellular carcinoma (HCC). It may change treatment strategy, preventing unnecessary open exploration. An additional advantage of SL is possible biopsy of the nontumorous liver to assess fibrosis/cirrhosis. This study aimed to determine whether SL for patients with HCC still is useful., Methods: Patients with HCC who underwent SL between January 1999 and December 2011 were analyzed. Their demographics, preoperative imaging studies, surgical findings, and histology were assessed., Results: The 56 patients (34 men and 22 women; mean age, 60 ± 14 years) in this study underwent SL for assessment of extensive disease or metastases. For two patients, SL was unsuccessful because of intraabdominal adhesions. For four patients (7.1 %), SL showed unresectability because of metastases (n = 1), tumor progression (n = 1), or severe cirrhosis in the contralateral lobe (n = 2). An additional five patients did not undergo laparotomy due to disease progression detected on imaging after SL. Exploratory laparotomy for the remaining 47 patients showed 6 (13 %) additional unresectable tumors due to advanced tumor (n = 5) or nodal metastases (n = 1). Consequently, the yield of SL was 7 % (95 % confidence interval (CI), 3-17 %), and the accuracy was 27 % (95 % CI, 11-52 %). A biopsy of the contralateral liver was performed for 45 patients who underwent SL, leading to changes in management for 4 patients (17 %) with cirrhosis., Conclusions: The overall yield of SL for HCC was 7 %, and the accuracy was 27 %. When accurate imaging methods are available and additional percutaneous liver biopsy is implemented as a standard procedure in the preoperative workup of patients with HCC, the benefit of SL will become even less.

Liver hemangiomas are the most common benign liver tumors and are usually incidental findings. Liver hemangiomas are readily demonstrated by abdominal ultrasonography, computed tomography or magnetic resonance imaging. Giant liver hemangiomas are defined by a diameter larger than 5 cm. In patients with a giant liver hemangioma, observation is justified in the absence of symptoms. Surgical resection is indicated in patients with abdominal (mechanical) complaints or complications, or when diagnosis remains inconclusive. Enucleation is the preferred surgical method, according to existing literature and our own experience. Spontaneous or traumatic rupture of a giant hepatic hemangioma is rare, however, the mortality rate is high (36-39%). An uncommon complication of a giant hemangioma is disseminated intravascular coagulation (Kasabach-Merritt syndrome); intervention is then required. Herein, the authors provide a literature update of the current evidence concerning the management of giant hepatic hemangiomas. In addition, the authors assessed treatment strategies and outcomes in a series of patients with giant liver hemangiomas managed in our department.

Hepatoblastoma is a rare carcinoma mostly seen in children. Neoadjuvant chemotherapy followed by resection and adjuvant chemotherapy is the optimal treatment. We present the case of an 18-year-old woman who presented with abdominal pain, nausea, bloating, and fatigue. MRI showed 3 hepatic lesions with high signal intensity on arterial phase T1-weighted images and slight washout on the late phase, suggestive for hepatocellular carcinoma. Laboratory examinations revealed plasma α-feto-protein of 114,245 μg/L. Subsequent baseline and posttreatment F-fluoromethyl choline PET/CT were performed to possibly evaluate extent of the disease and assess disease response after neoadjuvant chemotherapy.

Introduction: Diagnosis of focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) using conventional imaging techniques can be difficult; however, it is important to differentiate between them as these benign liver tumors require different therapeutic strategies. The aim of our study was to prospectively evaluate the use of PET/computed tomography (CT) with F-fluoromethylcholine (F-FCH) as a novel diagnostic approach in the differentiation between HCA and FNH., Materials and Methods: Fifty-six consecutive patients with a suspicion of one or multiple HCAs or FNHs larger than 2 cm were prospectively included after written informed consent was obtained from them. All the patients underwent a PET/CT with F-FCH. Histopathology of the lesions was the standard of reference. The ratio of the standardized uptake value (SUV) of the lesions compared with normal liver uptake within the same patient was calculated. Statistical tests were evaluated at the 95% confidence interval., Results: Forty-nine patients with 60 lesions and histopathological diagnosis of FNH or HCA completed the study and were analyzed. The mean SUV ratio for FNH was 1.67±0.31 (mean±SD, n=28), resulting in a positive likelihood ratio of 32.3 for PET-positive FNH. The mean SUV ratio for HCA was 0.82±0.17 (n=32), with a likelihood ratio of ∼100 for PET-negative HCA. Receiver operating characteristic curve analysis revealed an optimal SUV ratio cutoff value of 1.13, which reached 100% sensitivity and 97% specificity in differentiating FNH from HCA., Conclusion: This prospective study shows that PET/CT with F-FCH can accurately differentiate FNH from HCA and may become a valuable diagnostic tool when conventional imaging techniques fail to do so.

We present five cases in whom two rare entities were simultaneously found within the liver, i.e. hepatocellular adenomas (HCAs) and granulomas. Coexistence of both entities confuses diagnosis. Our aim is to disclose the association between HCA and hepatic granulomas. Five patients presented with HCA for which they underwent resection. During laparotomy or at pathological examination, granulomas were found in tumorous and non-tumorous tissue. No specific cause for the granulomas was found. Immunohistochemistry showed overexpression of C-reactive protein and serum amyloid A in 4/5 patients, classifying these lesions as inflammatory HCA. HCA and especially the inflammatory subtype may cause formation of granulomas in (peri-)tumorous tissue as a local response to persistent inflammation and/or the presence of a tumor. Both HCA and hepatic granulomas have also been associated with oral contraceptive use. In conclusion, HCAs associated with hepatic granulomas derive from a local response to (inflammatory) HCA or neoplasm, chronic use of oral contraceptives, or a combination of these factors.

Objective: The purpose of this article is to prospectively determine the sensitivity of hepatobiliary phase gadoxetate disodium-enhanced MRI combined with standard MRI in differentiating focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA)., Subjects and Methods: Patients suspected of having FNH or HCA larger than 2 cm underwent gadoxetate disodium-enhanced MRI. Standard MRI was evaluated separately from the additional hepatobiliary phase by two blinded radiologists. For the largest lesion in each patient, findings were compared with histologic diagnosis. Sensitivity, positive predictive value (PPV), and distinctive features were analyzed using McNemar and analysis of variance tests., Results: Fifty-two patients completed the study. Histologic diagnosis revealed 24 HCAs and 28 FNHs. Characterization on standard MRI was inconclusive in 40% (21/52) and conclusive in 60% (31/52) of lesions. The sensitivity of standard MRI for HCA was 50% (12/24) with a PPV of 100% (12/12). The sensitivity for FNH was 68% (19/28) with a PPV of 95% (18/19). After review of hepatobiliary phase, the sensitivity for HCA improved to 96% (23/24) with a PPV of 96% (23/24). The sensitivity for FNH improved to 96% (27/28) with a PPV of 96% (27/28). Features with significant predictive value for diagnosis in HCA included bleeding (p < 0.001), fat (p = 0.010), and glycogen (p = 0.024). The presence of a central scar was predictive for FNH (p < 0.001)., Conclusion: This study shows high sensitivity of gadoxetate disodium-enhanced MRI when standard series are combined with the hepatobiliary phase for differentiation of FNH and HCA in lesions larger than 2 cm.

A liver haemangioma is a benign, usually small tumour comprised of blood vessels, which is often discovered coincidentally; giant haemangiomas are defined as haemangiomas larger than 5 cm. The differential diagnosis includes other hypervascular tumours, such as hepatocellular adenoma, hepatocellular carcinoma, metastasis of a neuro-endocrine tumour or renal cell carcinoma.- The diagnosis is based on abdominal ultrasonography and can be confirmed by a CT or MR scan. A wait-and-see approach is justified in patients without symptoms or with minimal symptoms, even in the presence of a giant haemangioma. Surgical resection of a giant haemangioma is only necessary when the preoperative diagnosis is inconclusive, or when the haemangioma leads to mechanical symptoms or complications. Extirpation is the only effective form of treatment of the giant haemangioma; enucleation is preferred over partial liver resection. A known complication of a giant haemangioma is the occurrence of disseminated intravascular coagulation, the Kasabach-Merritt syndrome; intervention is then demanded.

The aim of this pilot study was to evaluate the use of PET/CT with (18)F-fluorocholine in the differentiation of hepatocellular adenoma (HCA) from focal nodular hyperplasia (FNH). Patients with liver lesions larger than 2 cm suspicious for HCA or FNH were prospectively included. All patients underwent PET/CT with (18)F-fluorocholine and histopathological diagnosis was obtained by either liver biopsy or surgery. The ratios between the maximum standardized uptake value (SUV) of the lesion and the mean SUV of normal liver parenchyma were calculated and a receiver operating characteristic (ROC) curve analysis was performed. Ten patients with FNH and 11 with HCA were included. The mean SUV ratio was 1.68±0.29 (±SD) for FNH and 0.88±0.18 for HCA (p<0.001). An SUV ratio cut-off value between 1.12 and 1.22 differentiated patients with FNH from those with HCA with 100% sensitivity and 100% specificity. This pilot study showed that PET/CT with (18)F-fluorocholine can differentiate HCA from FNH.