[A woman with an inguinal lump and lower abdominal pain]. / Een vrouw met buikpijn en een zwelling in de lies.

A 71-year-old female visited the gynaecology outpatient clinic with an inguinal lump and lower abdominal pain. Radiologic imaging of the abdomen demonstrated a pelvic mass with a diameter of 11 centimeters. Subsequent histopathologic analysis of the inguinal lump revealed a metastatic lesion of a gastrointestinal stromal tumour.

Accelerated Partial Breast Irradiation Using External Beam or Intraoperative Electron Radiation Therapy: 5-Year Oncological Outcomes of a Prospective Cohort Study.

PURPOSE: To evaluate the ipsilateral breast tumor recurrence (IBTR) after 2 accelerated partial breast irradiation (APBI) techniques (intraoperative electron radiation therapy [IOERT] and external beam APBI [EB-APBI]) in patients with early-stage breast cancer. METHODS AND MATERIALS: Between 2011 and 2016, women ≥60 years of age with breast carcinoma or Ductal Carcinoma In Situ (DCIS) of ≤30 mm and cN0 undergoing breast-conserving therapy were included in a 2-armed prospective multicenter cohort study. IOERT (1 × 23.3 Gy prescribed at the 100% isodose line) was applied in 1 hospital and EB-APBI (10 × 3.85 Gy daily) in 2 other hospitals. The primary endpoint was IBTR (all recurrences in the ipsilateral breast irrespective of localization) at 5 years after lumpectomy. A competing risk model was used to estimate the cumulative incidences of IBTR, which were compared using Fine and Gray's test. Secondary endpoints were locoregional recurrence rate, distant recurrence, disease-specific survival and overall survival. Univariate Cox regression models were estimated to identify risk factors for IBTR. Analyses were performed of the intention to treat (ITT) population (IOERT n = 305; EB-APBI n = 295), and sensitivity analyses were done of the per-protocol population (IOERT n = 270; EB-APBI n = 207). RESULTS: The median follow-up was 5.2 years (IOERT) and 5 years (EB-APBI). Cumulative incidence of IBTR in the ITT population at 5 years after lumpectomy was 10.6% (95% confidence interval, 7.0%-14.2%) after IOERT and 3.7% (95% confidence interval, 1.2%-5.9%) after EB-APBI (P = .002). The locoregional recurrence rate was significantly higher after IOERT than EB-APBI (12.1% vs 4.5%, P = .001). There were no differences between groups in other endpoints. Sensitivity analysis showed similar results. For both groups, no significant risk factors for IBTR were identified in the ITT population. In the per-protocol population, surgical margin status of the DCIS was the only significant risk factor for developing IBTR in both treatment groups. CONCLUSIONS: Ipsilateral breast tumor recurrences and locoregional recurrence rates were unexpectedly high in patients treated with IOERT, and acceptable in patients treated with EB-APBI.

Reprocessing filtering facepiece respirators in primary care using medical autoclave: prospective, bench-to-bedside, single-centre study.

OBJECTIVE: There are widespread shortages of personal protective equipment as a result of the COVID-19 pandemic. Reprocessing filtering facepiece particle (FFP)-type respirators may provide an alternative solution in keeping healthcare professionals safe. DESIGN: Prospective, bench-to-bedside. SETTING: A primary care-based study using FFP-2 respirators without exhalation valve (3M Aura 1862+ (20 samples), Maco Pharma ZZM002 (14 samples)), FFP-2 respirators with valve (3M Aura 9322+ (six samples) and San Huei 2920V (16 samples)) and valved FFP type 3 respirators (Safe Worker 1016 (10 samples)). INTERVENTIONS: All masks were reprocessed using a medical autoclave (17 min at 121°C with 34 min total cycle time) and subsequently tested up to three times whether these respirators retained their integrity (seal check and pressure drop) and ability to filter small particles (0.3-5.0 µm) in the laboratory using a particle penetration test. RESULTS: We tested 33 respirators and 66 samples for filter capacity. All FFP-2 respirators retained their shape, whereas half of the decontaminated FFP-3 respirators showed deformities and failed the seal check. The filtering capacity of the 3M Aura 1862 was best retained after one, two and three decontamination cycles (0.3 µm: 99.3%±0.3% (new) vs 97.0±1.3, 94.2±1.3% or 94.4±1.6; p<0.001). Of the other FFP-2 respirators, the San Huei 2920 V had 95.5%±0.7% at baseline vs 92.3%±1.7% vs 90.0±0.7 after one-time and two-time decontaminations, respectively (p<0.001). The tested FFP-3 respirator (Safe Worker 1016) had a filter capacity of 96.5%±0.7% at baseline and 60.3%±5.7% after one-time decontamination (p<0.001). Breathing and pressure resistance tests indicated no relevant pressure changes between respirators that were used once, twice or thrice. CONCLUSION: This small single-centre study shows that selected FFP-2 respirators may be reprocessed for use in primary care, as the tested masks retain their shape, ability to retain particles and breathing comfort after decontamination using a medical autoclave.

In vivo dosimetry with MOSFETs and GAFCHROMIC films during electron IORT for Accelerated Partial Breast Irradiation.

PURPOSE: The purpose of this study was to compare the delivered dose to the expected intraoperative radiation therapy (IORT) dose with in vivo dosimetry. For IORT using electrons in accelerated partial breast irradiation, this is especially relevant since a high dose is delivered in a single fraction. METHODS: For 47 of breast cancer patients, in vivo dosimetry was performed with MOSFETs and/or GAFCHROMIC EBT2 films. A total dose of 23.33 Gy at dmax was given directly after completing the lumpectomy procedure with electron beams generated with an IORT dedicated mobile accelerator. A protection disk was used to shield the thoracic wall. RESULTS: The results of in vivo MOSFET dosimetry for 27 patients and GAFROMIC film dosimetry for 20 patients were analysed. The entry dose for the breast tissue, measured with MOSFETs, (mean value 22.3 Gy, SD 3.4%) agreed within 1.7% with the expected dose (mean value 21.9 Gy). The dose in breast tissue, measured with GAFCHROMIC films (mean value 23.50 Gy) was on average within 0.7% (SD = 3.7%, range -5.5% to 5.6%) of the prescribed dose of 23.33 Gy. CONCLUSIONS: The dose measured with MOSFETs and GAFROMIC EBT2 films agreed well with the expected dose. For both methods, the dose to the thoracic wall, lungs and heart for left sided patents was lower than 2.5 Gy even when 12 MeV was applied. The positioning time of GAFCHROMIC films is negligible and based on our results we recommend its use as a standard tool for patient quality assurance during breast cancer IORT.

Randomized Phase III Study to Assess Efficacy and Safety of Adjuvant CAPOX with or without Bevacizumab in Patients after Resection of Colorectal Liver Metastases: HEPATICA study.

Bevacizumab is a humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF). Recurrence after resection of colorectal liver metastases (CRLMs), presumably caused by VEGF-mediated outgrowth of micrometastases, might decrease when VEGF is inhibited. This study examines the efficacy and safety of adding bevacizumab to an adjuvant regimen of CAPOX in patients undergoing radical resection for their CRLMs. Patients with resected CRLMs were randomized after surgery to receive CAPOX and bevacizumab (arm A) or CAPOX alone (arm B) as adjuvant treatment. CAPOX was given in both arms for a total of eight cycles. Bevacizumab was administered for 16 cycles. The primary end point was disease-free survival (DFS). Secondary outcomes were overall survival (OS), toxicity, and quality of life (QoL). In total, 79 patients were randomized. At the time of analysis, 23 events were encountered in arm A and 20 in arm B. One-year DFS rate was 79% [95% confidence interval (CI): 68%-93%] and 68% (95% CI: 55%-85%) for arm A and B, respectively (P=.89). Toxicity was evaluated for 75 patients. No significant differences in toxicity between the two arms were found. QoL scores were higher in arm A, of which emotional functioning and global QoL scores were significant. Adding bevacizumab to a CAPOX regimen in patients undergoing a resection for their CLM is safe and showed higher QoL scores compared with CAPOX alone. Because of premature closure of the study, conclusions about the effect on DFS of additional VEGF inhibition in this setting could not yet be made.

Importance of patient reported outcome measures versus clinical outcomes for breast cancer patients evaluation on quality of care.

INTRODUCTION: Given increasing numbers of breast cancer survivors, there is an increased focus on quality of life and quality of care. This study aims to investigate whether clinical or patient reported outcomes are most important for perceived quality of care by breast cancer patients. METHODS: Overall, 606 patients aged 18 years or older, who underwent breast cancer surgery 9-18 months ago in five hospitals in the Netherlands, were invited to complete an internet-based questionnaire. Patients were asked to judge a random selection of 24 patient profiles and choose which of 2 presented patients had received the best quality of care, using conjoint analysis. The individual relative importance (RI) for each outcome was estimated using Hierarchical Bayes Estimation, and averaged over all patients to assess which outcomes were most important. RESULTS: Complete data were available for 350 patients (58%). Avoiding severe breast symptoms was most important for good quality of care according to patients (RI 23.22 [95% Confidence Interval (95% CI) 22.32-24.12]), followed by a 2 year longer disease free survival (18.30 [17.38-19.22]). However, the importance differed by age: younger patients (<50 years) assigned higher importance to longer disease free survival (21.99 [19.52-24.46]) than older patients (65 + years) (15.03 [13.88-16.18]). CONCLUSION: Avoiding severe breast symptoms rather than 2 year longer disease free survival is considered most important in our population of breast cancer patients for evaluation of quality of care. These data should thus be included in both information provision prior to treatment choices and post treatment quality of care evaluation.

[Breast-conserving surgery and radiotherapy as a one-day procedure]. / Borstsparende ingreep en bestraling in dagbehandeling.

A single dose of irradiation to the lumpectomy cavity alone after breast-conserving surgery in breast cancer patients has been available in the Netherlands since 2011. This new treatment modality is used in the Haaglanden Medical Centre in The Hague and in the Catharina Hospital in Eindhoven. The goal of intraoperative radiation therapy is to limit the patient burden caused by whole breast irradiation, while maintaining excellent local tumour control. The technique is used only in patients with a low probability of recurrent disease in the breast. Approximately 150 patients receive intraoperative radiation therapy each year In the Netherlands, an estimated 4,000 breast cancer patients were eligible in 2013 for this new treatment technique or another method of partial breast irradiation. In both hospitals the results are closely monitored. Only 15 of the first 200 patients experienced a side effect within a period of 3 months after intraoperative radiation therapy. These side effects were successfully treated either with antibiotics or with surgery.

[A woman with a painful toe]. / Een vrouw met een pijnlijk stekende teen.

A 64-year-old woman visited the surgeon because of an infected right hallux. After investigation we concluded she had myiasis caused by an infestation with Lucilia Sericata. This usually occurs in tropical regions in patients with low standards of hygiene, but is sometimes found in non-tropical countries, in patients with minor underlying lesions.

[Chewing gum to prevent postoperative ileus]. / Kauwgom kauwen ter preventie van postoperatieve ileus.

Postoperative ileus is a commonly occurring complication after abdominal surgery. Reduced well-being and ileus related complications lead to extension of hospital stay. An early commencement of postoperative feeding to stimulate the digestive system is not always achievable in practice. Recent studies suggest that use of chewing gum can be effective in preventing postoperative ileus by a similar mechanism of action to early postoperative feeding. However, these studies were small in size and of varying quality. Recently the "Chewing gum study" ("Kauwgomstudie") to investigate the effect of general use of chewing gum after abdominal surgery has been started in the Netherlands.

A randomized two arm phase III study in patients post radical resection of liver metastases of colorectal cancer to investigate bevacizumab in combination with capecitabine plus oxaliplatin (CAPOX) vs CAPOX alone as adjuvant treatment.

BACKGROUND: About 50% of patients with colorectal cancer are destined to develop hepatic metastases. Radical resection is the most effective treatment for patients with colorectal liver metastases offering five year survival rates between 36-60%. Unfortunately only 20% of patients are resectable at time of presentation. Radiofrequency ablation is an alternative treatment option for irresectable colorectal liver metastases with reported 5 year survival rates of 18-30%. Most patients will develop local or distant recurrences after surgery, possibly due to the outgrowth of micrometastases present at the time of liver surgery. This study aims to achieve an improved disease free survival for patients after resection or resection combined with RFA of colorectal liver metastases by adding the angiogenesis inhibitor bevacizumab to an adjuvant regimen of CAPOX. METHODS/DESIGN: The Hepatica study is a two-arm, multicenter, randomized, comparative efficacy and safety study. Patients are assessed no more than 8 weeks before surgery with CEA measurement and CT scanning of the chest and abdomen. Patients will be randomized after resection or resection combined with RFA to receive CAPOX and Bevacizumab or CAPOX alone. Adjuvant treatment will be initiated between 4 and 8 weeks after metastasectomy or resection in combination with RFA. In both arms patients will be assessed for recurrence/new occurrence of colorectal cancer by chest CT, abdominal CT and CEA measurement. Patients will be assessed after surgery but before randomization, thereafter every three months after surgery in the first two years and every 6 months until 5 years after surgery. In case of a confirmed recurrence/appearance of new colorectal cancer, patients can be treated with surgery or any subsequent line of chemotherapy and will be followed for survival until the end of study follow up period as well. The primary endpoint is disease free survival. Secondary endpoints are overall survival, safety and quality of life. CONCLUSION: The HEPATICA study is designed to demonstrate a disease free survival benefit by adding bevacizumab to an adjuvant regime of CAPOX in patients with colorectal liver metastases undergoing a radical resection or resection in combination with RFA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00394992.

Added value of positron emission tomography imaging in the surgical treatment of colorectal liver metastases.

OBJECTIVE: [F-18]-Fluorodeoxyglucose-positron emission tomography (FDG-PET) is used increasingly in the work-up to surgery for patients with potentially resectable colorectal liver metastases. This study evaluates the clinical effectiveness, impact on health care resources and cost-effectiveness of adding FDG-PET to the diagnostic algorithm alongside a randomized clinical trial from a health care perspective. METHODS: In a randomized clinical trial, the net monetary benefit (NMB) of FDG-PET added to conventional diagnostic work-up (CWU) was determined in patients with colorectal liver metastases. Seventy-five patients were included in each arm. Change in clinical management, futile laparotomies, preoperative findings and all relevant health care consumption were prospectively documented during 3 years. To assess health-related quality of life European Quality of Life-5 Dimensions was administered at the time of randomization, 3 and 6 weeks postoperatively, and every 3 months postoperatively for 3 years. Quality-adjusted life years (QALYs) were calculated based on European Quality of Life-5 Dimensions outcomes. RESULTS: In adding FDG-PET, diagnostic performance increased and futile laparotomies were reduced by 38%. Both health-related quality of life and QALYs showed no significant difference between the CWU and PET groups. For CWU and PET groups costs were euro 92,836 and euro 81,776, respectively, accumulated in 3 years after randomization. NMB ranged from euro 1004 to euro 11,060 depending on the monetary value given to a QALY. When costs for chemotherapy were disregarded, costs amounted to euro 15,874 for CWU and euro 18,664 for PET group. CONCLUSION: Additional costs of FDG-PET in the diagnostic work-up of patients with potentially resectable colorectal liver metastases were compensated by a reduction in futile laparotomies. The NMB analysis showed savings over a relevant range of willingness to pay for a QALY.

Improved selection of patients for hepatic surgery of colorectal liver metastases with (18)F-FDG PET: a randomized study.

UNLABELLED: With the increasing possibilities for surgical treatment of colorectal liver metastases, careful selection of patients who may benefit from surgical treatment becomes critical. The addition of PET to (18)F-FDG may significantly improve conventional staging by CT. Up to now, definitive evidence that the addition of (18)F-FDG PET to conventional staging leads to superior clinical results and improved clinical management in these patients has been lacking. In this randomized controlled trial in patients with colorectal liver metastases, we investigated whether the addition of (18)F-FDG PET is beneficial and reduces the number of futile laparotomies. METHODS: A total of 150 patients with colorectal liver metastases selected for surgical treatment by imaging with CT were randomly assigned to CT only (n = 75) or CT plus (18)F-FDG PET (n = 75). Patients were followed up for at least 3 y. The primary outcome measure was futile laparotomy, defined as any laparotomy that did not result in complete tumor treatment, that revealed benign disease, or that did not result in a disease-free survival period longer than 6 mo. RESULTS: Patient and tumor characteristics were similar for both groups. The number of futile laparotomies was 34 (45%) in the control arm without (18)F-FDG PET and 21 (28%) in the experimental arm with (18)F-FDG PET; the relative risk reduction was 38% (95% confidence interval, 4%-60%, P = 0.042). CONCLUSION: The number of futile laparotomies was reduced from 45% to 28%; thus, the addition of (18)F-FDG PET to the work-up for surgical resection of colorectal liver metastases prevents unnecessary surgery in 1 of 6 patients.

Value of intraoperative radiotherapy in locally advanced rectal cancer.

PURPOSE: This study was designed to analyze the results of a multimodality treatment using preoperative radiotherapy, followed by surgery and intraoperative radiotherapy in patients with primary locally advanced rectal cancer. METHODS: Between 1987 and 2002, 123 patients with initial unresectable and locally advanced rectal cancer were identified in our prospective database, containing patient characteristics, radiotherapy plans, operation notes, histopathologic reports, and follow-up details. An evaluation of prognostic factors for local recurrence, distant metastases, and overall survival was performed. RESULTS: All patients were treated preoperatively with a median dose of 50 Gy radiotherapy. Surgery was performed six to ten weeks after radiotherapy. Twenty-seven patients were treated with intraoperative radiotherapy because margins were incomplete or

Factors influencing the local failure rate of radiofrequency ablation of colorectal liver metastases.

BACKGROUND: The prognosis of patients with colorectal cancer is poor, especially when there is distant metastatic disease. Local ablation of tumor by radiofrequency ablation (RFA) has emerged as a safe and effective new treatment modality, but its long-term efficacy may be hindered by renewed local tumor growth at the site of RFA. The objectives of this study were to identify risk factors for local RFA failure and to define exclusion criteria for RFA treatment of colorectal liver metastases. METHODS: A total of 199 lesions in 87 patients were ablated with RFA. Factors influencing local failure rates were identified and compared with data from the literature. RESULTS: The local failure rate was 47.2%, and the average time to local disease progression was 6.5 months. Factors that significantly correlated with increased failure rates were metachronous occurrence of liver metastases, large mean lesion size, and central tumor location. CONCLUSIONS: Because accurate electrode placement is pivotal in achieving adequate tumor necrosis, RFA should not be performed percutaneously when electrode placement is impaired. We suggest that lesions >5 cm and lesions located near great vessels or adjacent organs should be treated with open RFA, thus allowing vascular inflow occlusion and complete mobilization of the liver. Lesions that are difficult to reach by electrodes should be approached by an open procedure.

The feeding route (enteral or parenteral) affects the plasma response of the dipetide Ala-Gln and the amino acids glutamine, citrulline and arginine, with the administration of Ala-Gln in preoperative patients.

Enhancement of depressed plasma concentrations of glutamine and arginine is associated with better clinical outcome. Supplementation of glutamine might be a way to provide the patient with glutamine, and also arginine, because glutamine provides the kidney with citrulline, from which the kidney produces arginine when plasma levels of arginine are low. The aim of the present study was to investigate the parenteral and enteral response of the administered dipeptide Ala-Gln, glutamine, citrulline and arginine. Therefore, seven patients received 20 g Ala-Gln, administered over 4 h, parenterally or enterally, on two separate occasions. Arterial blood samples were taken before and during the administration of Ala-Gln. ANOVA and a paired t test were used to test differences (P<0.05). Ala-Gln was undetectable with enteral administration, whereas Ala-Gln remained stable at a plasma concentration of 268 micromol/l throughout parenteral infusion and rapidly decreased towards zero after infusion was stopped. The highest level of glutamine was observed with parenteral infusion of the dipeptide, although enteral infusion also significantly increased plasma levels of glutamine. The highest plasma response of citrulline was observed with the enteral administration of the dipeptide, although parenteral administration also increased plasma levels of citrulline. Plasma arginine increased significantly with parenteral infusion, but not with enteral administration of Ala-Gln. In conclusion, administrations of Ala-Gln, parenteral or enteral, resulted in an increased plasma glutamine response, as compared with baseline. Interestingly, in spite of the high availability of citrulline with enteral administration of the dipeptide, only parenteral infusion of Ala-Gln increased plasma arginine concentration.

Macrophages direct tumour histology and clinical outcome in a colon cancer model.

Macrophages generally constitute a major component of the tumour stroma. Although conventionally considered to be cytotoxic effector cells, macrophages have recently been described as promoters of tumour progression. The present study shows that selective depletion of peritoneal or liver macrophages prior to CC531 tumour cell inoculation resulted in highly differentiated tumours in rats. In contrast, tumours from control rats, in which macrophages are abundantly present, showed a desmoplastic stromal reaction with hallmark features of malignancy, such as neovascularization and matrix remodelling, indicating that the presence of macrophages is associated with malignant histopathological differentiation. Remarkably, macrophage-depleted rats, bearing highly differentiated tumours, had a worse prognosis, as they displayed a higher tumour load and poorer survival. Thus, while macrophages direct tumours towards malignant tumour histology, their role in anti-tumour defence is important. The selective inhibition of macrophage functions involved in malignant progression without interfering with cytotoxic ability may therefore identify important new targets for cancer therapy.

Sentinel lymph node tumor load: an independent predictor of additional lymph node involvement and survival in melanoma.

BACKGROUND: Even though 60% to 80% of melanoma patients with a positive sentinel lymph node (SLN) have no positive additional lymph nodes (ALNs), all these patients are subjected to an ALN dissection (ALND) with its associated morbidity. The aim of this study was to predict the absence of ALN metastases in patients with a positive SLN by using features of the primary melanoma and SLN tumor load. METHODS: Of 71 SLN-positive patients, 52 had metastasis limited to the SLN (group 1), and 19 had > or =1 positive ALN after ALND (group 2). The tumor load of the SLN was assessed by measuring the total surface area by computerized morphometry. Breslow thickness, ulceration and lymphatic invasion of the primary tumor, and total SLN metastatic area were tested as covariates predicting the absence of positive ALNs. RESULTS: The mean SLN metastatic area was 1.18 mm(2) (group 1) and 3.39 mm(2) (group 2) (P = .003) and was the only significant and independent factor after multivariate analysis (P = .02). None of the patients with both a Breslow thickness <2.5 mm and an SLN metastatic area <.3 mm(2) had a positive ALN. CONCLUSIONS: SLN metastatic area can be used to predict the absence of positive ALNs in melanoma patients. In this study, patients with a Breslow thickness <2.5 mm and an SLN tumor load <.3 mm(2 )seemed to have no positive ALN and had excellent survival. We hypothesize that this subgroup might not benefit from ALND. Prospective larger trials, using this model and randomizing between ALND and no ALND, should confirm this hypothesis.

Preoperative radiotherapy improves outcome in recurrent rectal cancer.

PURPOSE: When local recurrent rectal cancer is diagnosed without signs of metastases, a potentially curative resection can be performed. This study was designed to compare the results of preoperative radiotherapy followed by surgery with surgery only. METHODS: Between 1985 and 2003, 117 patients with recurrent rectal cancer were prospectively entered in our database. Ninety-two patients were suitable for resection with curative intent. Preoperative radiation with a median dosage of 50 Gy was performed in 59 patients; 33 patients did not receive preoperative radiotherapy. The median age of the patients was respectively 66 and 62 years. RESULTS: The median follow-up of patients alive for the total group was 16 (range, 4-156) months. Tumor characteristics were comparable between the two groups. Complete resections were performed in 64 percent of the patients who received preoperative radiation and 45 percent of the nonirradiated patients. A complete response after radiotherapy was found in 10 percent of the preoperative irradiated patients (n = 6). There were no differences in morbidity and reintervention rate between the two groups. Local control after preoperative radiotherapy was statistically significantly higher after three and five years (P = 0.036). Overall survival and metastases-free survival were not different in both groups. Complete response to preoperative radiotherapy was predictive for an improved survival. CONCLUSIONS: Preoperative radiotherapy for recurrent rectal cancer results in a higher number of complete resections and an improved local control compared with patients treated without radiotherapy. Preoperative radiotherapy should be standard treatment for patients with recurrent rectal cancer.

The human liver clears both asymmetric and symmetric dimethylarginine.

Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) inhibit production of nitric oxide. The concentration of both dimethylarginines is regulated by urinary excretion, although ADMA, but not SDMA, is also subject to degradation by dimethylarginine dimethylaminohydrolase, which is highly expressed in the liver but also present in the kidney. The exact roles of the human liver and kidney in the metabolism of dimethylarginines are currently unknown. Therefore, we aimed to investigate renal and hepatic handling of ADMA and SDMA in detail in 24 patients undergoing hepatic surgery. To calculate net organ fluxes and fractional extraction (FE) rates, blood was collected from an arterial line, the portal vein, hepatic vein, and renal vein, and blood flow of the hepatic artery, portal vein, and renal vein was determined using Doppler ultrasound techniques. Results showed a significant net uptake (median [IQR]) of ADMA in both the liver (9.6 nmol/min [5.6-13.2]) and the kidney (12.1 nmol/min [1.3-17.1]). SDMA uptake was present not only in the kidney (12.7 nmol/min [3.5-25.4]), but also in the liver (7.7 nmol/min [2.8-16.4]). FE rates of ADMA for the liver and kidney were 5.0% (3.5%-7.4%) and 8.4% (1.3%-13.9%), respectively. For SDMA, hepatic and renal FE rates were 3.4% (2.1%-7.5%) and 12.5% (3.6%-16.2%), respectively. In conclusion, this study gives a detailed description of the hepatic and renal elimination of dimethylarginines and shows that the clearing of SDMA is not only confined to the kidney, but the human liver also takes up substantial amounts of SDMA from the portal and systemic circulation.