A world-wide study on delirium assessments and presence of protocols.

BACKGROUND: Delirium is a common complication of older people in hospitals, rehabilitation and long-term facilities. OBJECTIVE: To assess the worldwide use of validated delirium assessment tools and the presence of delirium management protocols. DESIGN: Secondary analysis of a worldwide one-day point prevalence study on World Delirium Awareness Day, 15 March 2023. SETTING: Cross-sectional online survey including hospitals, rehabilitation and long-term facilities. METHODS: Participating clinicians reported data on delirium, the presence of protocols, delirium assessments, delirium-awareness interventions, non-pharmacological and pharmacological interventions, and ward/unit-specific barriers. RESULTS: Data from 44 countries, 1664 wards/units and 36 048 patients were analysed. Validated delirium assessments were used in 66.7% (n = 1110) of wards/units, 18.6% (n = 310) used personal judgement or no assessment, and 10% (n = 166) used other assessment methods. A delirium management protocol was reported in 66.8% (n = 1094) of wards/units. The presence of protocols for delirium management varied across continents, ranging from 21.6% (on 21/97 wards/units) in Africa to 90.4% (235/260) in Australia, similar to the use of validated delirium assessments with 29.6% (29/98) in Africa to 93.5% (116/124) in North America. Wards/units with a delirium management protocol [n = 1094/1664, 66.8%] were more likely to use a validated delirium test than those without a protocol [odds ratio 6.97 (95% confidence interval 5.289-9.185)]. The presence of a delirium protocol increased the chances for valid delirium assessment and, likely, evidence-based interventions. CONCLUSION: Wards/units that reported the presence of delirium management protocols had a higher probability of using validated delirium assessments tools to assess for delirium.

Delirium in the US: Results from 2023 cross-sectional World Delirium Awareness Day prevalence study.

IMPORTANCE: Delirium is an acute brain dysfunction associated with an increased risk of mortality and future dementia. OBJECTIVES: To describe the prevalence of clinically documented delirium in the United States on World Delirium Awareness Day 2023. DESIGN: Sub-analysis of a prospective, cross-sectional, online, international survey. SETTING: All healthcare settings were eligible with the exception of operating rooms and outpatient clinics. PARTICIPANTS: Healthcare clinicians, administrators, and researchers completed the survey. MAIN OUTCOME AND MEASURE: Prevalence of clinically documented delirium at 8:00 a.m. and 8:00 p.m. on March 15, 2023. Secondary outcomes were related to healthcare delivery. Descriptive statistics are reported. Differences between unit types (non-ICU vs ICU) were examined for all outcomes. RESULTS: Ninety-one hospital units reported on 1,318/1,213 patients. The prevalence of clinically documented delirium was 16.4% (n=216/1,318) at 8:00 a.m., 17.9% (n=217/1,213) at 8:00 p.m. (p= 0.316) and significantly differed between age groups, reported discipline, unit, and hospital types. Significant differences were identified between non-ICU and ICU settings in the use of delirium-related protocols, non-pharmacologic and pharmacologic management, educational processes, and barriers to evidence-based delirium care. CONCLUSION: To our knowledge, this is the first epidemiologic survey of clinically documented delirium across two time points in the U.S.. Delirium remains a significant burden and challenge for healthcare systems. The high percentage of units using delirium management protocols suggests administrator and clinician awareness of evidence-based strategies for its detection and mitigation. We provide recommendations for future studies and quality improvement projects to improve clinical recognition and management of delirium.

Enhancing European Management of Analgesia, Sedation, and Delirium: A Multinational, Prospective, Interventional Before-After Trial.

BACKGROUND: The objective of this study was to analyze the impact of a structured educational intervention on the implementation of guideline-recommended pain, agitation, and delirium (PAD) assessment. METHODS: This was a prospective, multinational, interventional before-after trial conducted at 12 intensive care units from 10 centers in Germany, Austria, Switzerland, and the UK. Intensive care units underwent a 6-week structured educational program, comprising online lectures, instructional videos, educational handouts, and bedside teaching. Patient-level PAD assessment data were collected in three 1-day point-prevalence assessments before (T1), 6 weeks after (T2), and 1 year after (T3) the educational program. RESULTS: A total of 430 patients were included. The rate of patients who received all three PAD assessments changed from 55% (107/195) at T1 to 53% (68/129) at T2, but increased to 73% (77/106) at T3 (p = 0.003). The delirium screening rate increased from 64% (124/195) at T1 to 65% (84/129) at T2 and 77% (82/106) at T3 (p = 0.041). The pain assessment rate increased from 87% (170/195) at T1 to 92% (119/129) at T2 and 98% (104/106) at T3 (p = 0.005). The rate of sedation assessment showed no signficiant change. The proportion of patients who received nonpharmacological delirium prevention measures increased from 58% (114/195) at T1 to 80% (103/129) at T2 and 91% (96/106) at T3 (p < 0.001). Multivariable regression revealed that at T3, patients were more likely to receive a delirium assessment (odds ratio [OR] 2.138, 95% confidence interval [CI] 1.206-3.790; p = 0.009), sedation assessment (OR 4.131, 95% CI 1.372-12.438; p = 0.012), or all three PAD assessments (OR 2.295, 95% CI 1.349-3.903; p = 0.002) compared with T1. CONCLUSIONS: In routine care, many patients were not assessed for PAD. Assessment rates increased significantly 1 year after the intervention. Clinical trial registration ClinicalTrials.gov: NCT03553719.

Mobilization in the evening to prevent delirium: A pilot randomized trial.

BACKGROUND: Delirium is a common complication in patients in Intensive Care Units (ICU). Interventions such as mobilization are effective in the prevention and treatment of delirium, although this is usually completed during the daytime. AIM: The aim of this study was to assess the feasibility of mobilization in the evening to prevent and treat ICU patients from delirium by an additional mobility team over 2 weeks. METHODS: The design was a pilot, multi-centre, randomized, controlled trial in four mixed ICUs over a period of 2 weeks. The mobility team consisted of trained nurses and physiotherapists. Patients in the intervention group were mobilized onto the edge of the bed or more between 21.00 and 23.00. Patients in the control group received usual care. The primary outcome parameter was the feasibility of the study, measured as recruitment rate, delivery rate, and safety. Secondary outcomes were duration and incidence of delirium, mortality, duration of mechanical ventilation (MV), and hospital length of stay for 28 days follow-up, and power calculation for a full trial. RESULTS: Out of 185 patients present in the ICUs, 28.6% (n = 53) were eligible and could be recruited, of which 24.9% (n = 46, Intervention = 26, Control = 20) were included in the final analysis. In the intervention group, mobilization could be delivered in 75% (n = 54) of 72 possible occasions; mobilization-related safety events appeared in 16.7% (n = 9) without serious consequences. Secondary parameters were similar, with less delirium in the intervention group albeit not significant. With an association of Cramer's V = 0.237, a complete study reaching statistical significance would require at least 140 patients, last 6 weeks, and cost >30 000 €. CONCLUSIONS: In a mixed ICU population, mobilization in the evening was feasible in one-quarter of patients with a low rate of safety events. Future trials seem to be feasible and worth conducting.

Cholinesterases and Anticholinergic Medications in Postoperative Pediatric Delirium.

OBJECTIVES: To describe the relationships between anticholinergic drug exposure, cholinesterase enzyme activity, inflammation, and the development of postoperative delirium in children. DESIGN: Single-center prospective cohort study. SETTING: Twenty-two bed PICU in a tertiary-care academic medical center in Germany. PATIENTS: A consecutive cohort of children admitted after major elective surgery. INTERVENTIONS: Children were screened for delirium bid over 5 consecutive postoperative days. Acetylcholinesterase and butyrylcholinesterase plasma activity levels were measured prior to surgery and once daily during the 5 day study period. Number of anticholinergic drugs and Anticholinergic Drug Scale score were calculated for each patient. MEASUREMENTS AND MAIN RESULTS: Ninety-three children (age range, 0-17 yr) were included. The number of anticholinergic drugs as well as the Anticholinergic Drug Scale score were significantly correlated with development of postoperative delirium, independently of disease severity. Baseline cholinesterase enzyme levels did not differ between patients who did and did not develop postoperative delirium. Butyrylcholinesterase levels, but not acetylcholinesterase levels, dropped by 33% postoperatively, independent of the presence of postoperative delirium. Postoperative butyrylcholinesterase levels were inversely related to number of anticholinergic drugs, Anticholinergic Drug Scale score, and C-reactive protein levels. CONCLUSIONS: Anticholinergic drug exposure was related to development of postoperative delirium in this cohort, with demonstration of a dose-response relationship. As there are alternative options available for many of these medications, it may be reasonable to avoid anticholinergic exposure in the PICU whenever possible.

Intrahepatic biliary strictures after liver transplantation are morphologically similar to primary sclerosing cholangitis but immunologically distinct.

OBJECTIVE: Biliary strictures are an important cause of morbidity and mortality in primary hepatic disease and after liver transplantation (LT). We aimed to characterize inflammatory cytokines in biliary fluids in biliary strictures to investigate their immunological origin. METHODS: We conducted a retrospective study on 72 patients with strictures after LT, eight patients with primary sclerosing cholangitis (PSC) and 15 patients with secondary sclerosing cholangitis (SSC). We measured cytokines interleukin (IL)-2, -4, -6, -10, -17, monocyte chemoattractant protein (MCP)-1, fibroblast growth factor (FGF)-2 and interferon (IFN)-γ as well as biochemical components such as protein and phospholipids in biliary fluid obtained from endoscopic retrograde cholangiography (ERC). Cell viability assays were performed on human cholangiocytes (H69) after being treated with IL-6, IL-4 and IFN-γ. RESULTS: Bile of patients with diffuse strictures after LT or due to SSC showed low values of all measured cytokines except for IL-6 levels, which were largely elevated in patients with diffuse strictures after LT. Patients high in biliary IL-6 showed an increase in profibrotic markers FGF-2 and MCP-1. In contrast, PSC bile was dominated by a Th1/Th17 profile with elevated IL-2, IL-17 and IFN-γ. In LT patients with biliary strictures, biliary IL-6 negatively predicted retransplantation-free survival after ERC. CONCLUSION: PSC patients showed a biliary Th1/Th17 cytokine profile, while SSC and diffuse strictures showed low values of cytokines except IL-6. In diffuse intrahepatic strictures after LT, biliary IL-6 is strongly associated with retransplantation-free survival after ERC.

[Detection of delirium in three steps - From Screening to Verification to Etiology]. / Delir erkennen in 3 Schritten.

BACKGROUND: Clinicians are commonly confronted with the differential diagnosis of altered mental status, impaired cognition and altered level of consciousness in hospitalized patients including those admitted to medical, geriatric, emergency, intensive and post-operative care units. Although delirium is the most common acute neuropsychiatric condition in the acute hospital setting this diagnosis is commonly delayed, made too late or missed altogether. DIFFICULTIES AND IMPORTANCE OF TIMELY DIAGNOSIS: The causes of delirious states are manifold. Both, direct damage to the brain tissue as well as encephalopathy as a result of other medical diseases, can be the cause of delirium. Depending on the predisposition delirious syndromes can be provoked by minor medical interventions. Clinical presentation is very variable, but remains largely independent of the triggering mechanisms. Purely catatonic, hypoactive, hyperactive and excitatory types as well as mixed forms can be distinguished.Immediate diagnosis of a delirious syndrome and rapid elucidation of its causes are keys for the implementation of curative therapy. There is a need to act fast because delirious phases are associated with significantly longer hospital stay and increased morbidity as a result of long-term cognitive deficits as well as increased mortality. As negative outcome is closely linked to the duration of a delirious episode, early diagnosis and rapid termination of the delirium constitute a significant positive predictor of outcome. In this respect, delirium represents an emergency, with or without concomitant cerebral or extracerebral symptoms.

Routine Liver Elastography Could Predict Actuarial Survival after Liver Transplantation.

BACKGROUND AND AIMS: Transient elastography (TE) has routinely been implemented in the diagnosis and assessment of chronic liver disease. Little data are available in the post liver transplant (LTx) setting. METHODS: Three months after LTx, we performed TE in 137 liver transplant recipients and investigated its predictive value upon further clinical outcome. The mean follow-up time for clinical outcome was 24 months. RESULTS: Mean TE value was 10.6 kPa (± 6.3 kPa; range 2.8 - 29.9 kPa). There was a significant correlation between TE and aspartate aminotransferase (AST) (p=0.004), gamma-glutamyl transferase (GGT) (p=0.031) and bilirubin (p<0.001) serum levels. In Cox univariate analysis, TE served as a predictor of actuarial survival free of liver transplantation (OR=1.111, 95%CI: 1.051-1.174; p<0.001). In multivariate analysis, TE remained an independent risk factor associated with reduced actuarial survival free of liver transplantation (OR=1.080, 95%CI: 1.001-1.166; p=0.047), along with thrombocytes (OR=0.992, 95%CI: 0.986-0.999; p=0.020) and metabolic co-disease (OR = 0.250, 95%CI: 0.070-0.895; p=0.033). CONCLUSION: Transient elastography measurement at three months after LTx seems a robust predictor of survival in liver transplant recipients.

Multidrug-Resistant Bacteria and Disease Progression in Patients with End-Stage Liver Disease and after Liver Transplantation.

BACKGROUND: Multidrug-resistant (MDR) pathogens represent an emerging challenge in end-stage liver disease and in liver transplant recipients. METHODS: We evaluated the impact of MDR bacteria upon clinical outcomes in patients with end-stage liver disease (n = 777) at the time of enrollment on the liver transplant (LTx) waiting list, after first LTx (n = 645), and after second LTx (n = 128). RESULTS: Colonization/infection with MDR bacteria was present in 72/777 patients on the waiting list, in 98/645 patients at first LTx, and in 46/128 patients at second LTx. While on the LTx waiting list, the time until first hydropic decompensation (p = 0.021), hepatic encephalopathy (p < 0.001) and hepatorenal syndrome (p < 0.001) was reduced in the presence of MDR bacteria, which remained an independent risk factor of poor survival in multivariate analysis (p < 0.001). Following first and second liver transplant, MDR bacteria were associated with an increased risk of infection-related deaths (first LTx: p < 0.001; second LTx: p = 0.037) and reduced actuarial survival (first LTx: p < 0.001; second LTx: p = 0.046). CONCLUSIONS: We showed that MDR pathogens are associated with poor outcomes before, after first and after recurrent LTx.

The impact of major extended donor criteria on graft failure and patient mortality after liver transplantation.

INTRODUCTION: Numerous extended donor criteria (EDC) have been identified in liver transplantation (LT), but different EDC have different impacts on graft and patient survival. This study aimed to identify major EDC (maEDC) that were best able to predict the outcome after LT and to examine the plausibility of an allocation algorithm based on these criteria. METHODS: All consecutive LTs between 12/2006 and 03/2014 were included (n = 611). We analyzed the following EDC: donor age > 65 years, body mass index > 30, malignancy and drug abuse history, intensive care unit stay/ventilation > 7 days, aminotransferases > 3 times normal, serum bilirubin > 3 mg/dL, serum Na+ > 165 mmol/L, positive hepatitis serology, biopsy-proven macrovesicular steatosis (BPS) > 40%, and cold ischemia time (CIT) > 14 h. We analyzed hazard risk ratios of graft failure for each EDC and evaluated primary non-function (PNF). In addition, we analyzed 30-day, 90-day, 1-year, and 3-year graft survival. We established low- and high-risk graft (maEDC 0 vs. ≥ 1) and recipient (labMELD < 20 vs. ≥ 20) groups and compared the post-LT outcomes between these groups. RESULTS: BPS > 40%, donor age > 65 years, and CIT > 14 h (all p < 0.05) were independent predictors of graft failure and patient mortality and increased PNF, 30-day, 90-day, 1-year, and 3-year graft failure rates. Three-year graft and patient survival decreased in recipients of ≥ 1 maEDC grafts (all p < 0.05) and LT of high-risk grafts into high-risk recipients yielded worse outcomes compared with other groups. CONCLUSION: Donor age > 65 years, BPS > 40%, and CIT > 14 h are major EDC that decrease short and 3-year graft survival, and 3-year patient survival. An allocation algorithm based on maEDC and labMELD is therefore plausible.

Cognitive and Behavioral Consequences of Pediatric Delirium: A Pilot Study.

OBJECTIVES: To investigate the long-term impact of postoperative delirium in children. DESIGN: Single-center point prevalence study. SETTING: Twenty-two bed PICU. PATIENTS: Forty-seven patients 1-16 years old. INTERVENTIONS: Standardized neuropsychologic follow-up investigation after a mean time of 17.7 ± 2.9 months after PICU discharge. MEASUREMENTS AND MAIN RESULTS: Pediatric delirium did not have significant long-term impact on global cognition, executive functions, or behavior. Severity of delirium did not influence the outcome. Different predictors were identified for later cognitive functioning, executive functions, and behavioral problems. Younger age was confirmed to be a relevant risk factor for delirium as well as for the cognitive and behavioral outcome. CONCLUSIONS: Contrary to the findings in adults, there was no clear association between pediatric delirium and long-term cognition or behavior in this cohort. However, this is a first pilot study with several limitations that should promote more comprehensive prospective trials.

Risk Factors for the Development of Postoperative Delirium in Pediatric Intensive Care Patients.

OBJECTIVES: To determine and quantify risk factors for postoperative pediatric delirium. DESIGN: Single-center prospective cohort study. SETTING: Twenty-two bed PICU in a tertiary care academic medical center in Germany. PATIENTS: All children admitted after major elective surgery (n = 93; 0-17 yr). INTERVENTIONS: After awakening, children were screened for delirium using the Cornell Assessment of Pediatric Delirium bid over a period of 5 days. Demographic and clinical data were collected from the initiation of general anesthesia. MEASUREMENTS AND MAIN RESULTS: A total of 61 patients (66%) were delirious. Younger children developed delirium more frequently, and the symptoms were more pronounced. The number of preceding operations did not influence the risk of delirium. Total IV anesthesia had a lower risk than inhalational anesthesia (p < 0.05). Duration of anesthesia was similar in all groups. Patients with delirium had a longer duration of mechanical ventilation in the PICU (p < 0.001). Significant differences in cumulative doses of various medications (e.g., sedatives, analgesics, and anticholinergics) were noted between groups; these differences were independent of disease severity. Invasive catheters and respiratory devices (p < 0.01) as well as infections (p < 0.001) increased risk of delirium. CONCLUSIONS: A high prevalence of delirium was noted in the PICU, and several perioperative risk factors were identified. Our data may be a base for development of strategies to prevent and treat postoperative delirium in children.

Combination of Modified Bentall Procedure and Orthotopic Liver Transplantation.

Indication for combined cardiac surgery and orthotopic liver transplantation is rare and patients are at high risks. Individual surgical strategy must be developed since a general standard of such procedure does not exist. We report the case of a 45-year-old woman who underwent simultaneously modified Bentall procedure and orthotopic liver transplantation. Underlying diseases were end-stage polycystic liver, aneurysm of the ascending aorta, and severe aortic regurgitation. To avoid prolonged bypass times, both teams worked simultaneously. During cardiac reperfusion, time inferior vena cava stayed ligated while the cyst liver was explanted.

Survey among critical care nurses and physicians about delirium management.

BACKGROUND: Delirium is a serious complication in patients in intensive care units. Previous surveys on delirium management in daily practice showed low adherence to published guidelines. AIM: To evaluate delirium management in nurses and physicians working in intensive care units in German-speaking countries and to identify related differences between nurses and physicians. DESIGN: The study used an open online survey with multiple-choice responses. METHODS: An invitation for participation was spread via journals and electronic resources using a snowball system. Apart from recording socio-demographical characteristics, the survey collected data on delirium assessment, delirium-related processes, non-pharmacological prevention and treatment and barriers for implementation. Differences between nurses and physicians were tested by Fisher's exact test with sequential Bonferroni correction. RESULTS: The survey was conducted in autumn 2016, and 559 clinicians participated. More nurses than physicians reported screening for delirium. The majority of clinicians reported screening for delirium when this was suspected; more than 50% used validated instruments. Half of the clinicians had delirium-related structures implemented, such as two thirds reporting delirium-related processes. Most cited barriers were lack of time and missing knowledge about delirium and its assessment. With significant difference, physicians recommended more than nurses early removal of catheters and daily interprofessional goals for patients. CONCLUSION: In German-speaking countries, assessment of delirium needs further improvement, leading to accurate assessment. Delirium-related structures and processes appear to be implemented widely, with only a few differences between nurses and physicians. RELEVANCE TO CLINICAL PRACTICE: Nurses and physicians in this survey reported similar perceptions and attitudes towards management of delirium. Both professions need more knowledge and inter-professional training on when and how to use validated assessment instruments.

Chemosaturation Percutaneous Hepatic Perfusion: A Systematic Review.

The Hepatic CHEMOSAT® Delivery System is an innovative medical device for the treatment of patients with unresectable primary liver tumors or unresectable hepatic metastases from solid organ malignancies. This system is used to perform chemosaturation percutaneous hepatic perfusion (CS-PHP), a procedure in which a high dose of the chemotherapeutic agent melphalan is delivered directly to the liver while limiting systemic exposure. In a clinical trial program, CS-PHP with melphalan significantly improved hepatic progression-free survival in patients with unresectable hepatic metastases from ocular or cutaneous melanoma. Clinically meaningful hepatic responses were also observed in patients with hepatocellular carcinoma or neuroendocrine tumors. Furthermore, the results of published studies and case reports demonstrated that CS-PHP with melphalan resulted in favorable tumor response rates in a range of tumor histologies (ocular or cutaneous melanoma, colorectal cancer, and hepatobiliary tumors). Analyses of the safety profile of CS-PHP revealed that the most common adverse effects were hematologic events (thrombocytopenia, anemia, and neutropenia), which were clinically manageable. Taken together, these findings indicate that CS-PHP is a promising locoregional therapy for patients with primary and secondary liver tumors and has a acceptable safety profile. FUNDING: Delcath Systems Inc., New York, NY, USA.

Patterns of Postoperative Delirium in Children.

OBJECTIVE: Intensive care delirium is a substantial problem in adults. Intensive care delirium is increasingly recognized in pediatrics in parallel with the development of specific scoring systems for children. However, little is known about the fluctuating course of intensive care delirium in children after surgery and possible implications on diagnostic and therapeutic strategies. DESIGN: Patients that needed treatment in the PICU following elective surgery were screened for intensive care delirium with the Cornell Assessment of Pediatric Delirium. When the patients were awake (Richmond Agitation and Sedation Score > -3), two trained investigators conducted the Cornell Assessment of Pediatric Delirium twice daily for five consecutive days. PATIENTS: Ninety-three patients aged 0 to 17 years. INTERVENTIONS: Eight hundred forty-five assessments completed. MEASUREMENTS AND MAIN RESULTS: Of the 845 scores, 230 were consistent with delirium (27.2%). Sixty-one patients (65.5%) were diagnosed with intensive care delirium. Half of these patients (n = 30; 32.2%) had a short-lasting delirium that resolved within 24 hours, and half (n = 31; 33.3%) had delirium of longer duration. Delirium could be clearly distinguished from sedation by analysis of individual test items of the Cornell Assessment of Pediatric Delirium. Time spent delirious had a measurable effect on outcome variables, including hospital length of stay. CONCLUSION: Most postoperative PICU patients develop intensive care delirium. Some have a short-lasting course, which underlines the need for early screening. Our findings support the view of delirium as a continuum of acute neurocognitive disorder. Further research is needed to investigate prophylactic and treatment approaches for intensive care delirium.

Muscarinic M1 receptors modulate endotoxemia-induced loss of synaptic plasticity.

Septic encephalopathy is associated with rapid deterioration of cortical functions. Using magnetic resonance imaging (MRI) we detected functional abnormalities in the hippocampal formation of patients with septic delirium. Hippocampal dysfunction was further investigated in an animal model for sepsis using lipopolysaccharide (LPS) injections to induce endotoxemia in rats, followed by electrophysiological recordings in brain slices. Endotoxemia induced a deficit in long term potentiation which was completely reversed by apamin, a blocker of small conductance calcium-activated potassium (SK) channels, and partly restored by treatment with physostigmine (eserine), an acetylcholinesterase inhibitor, or TBPB, a selective M1 muscarinic acetylcholine receptor agonist. These results suggest a novel role for SK channels in the etiology of endotoxemia and explain why boosting cholinergic function restores deficits in synaptic plasticity. Drugs which enhance cholinergic or M1 activity in the brain may prove beneficial in treatment of septic delirium in the intensive care unit.

Unresectable isolated hepatic metastases from solid pseudopapillary neoplasm of the pancreas: a case report of chemosaturation with high-dose melphalan.

BACKGROUND/OBJECTIVES: Solid pseudopapillary neoplasms of the pancreas (SPN) are rare tumors. For patients with unresectable liver metastases of SPN, no standard treatment has been defined so far. Here we report a case of a 40-year-old woman with SPN and metastases confirmed to the liver, and disease progression in the liver after primary tumor resection and chemotherapy with gemcitabine and cisplatin. METHODS: Chemosaturation with percutaneous hepatic perfusions is a minimally invasive, repeatable regional therapy which delivers chemotherapy directly to the liver while limiting systemic toxicity. As an individual treatment approach, the patient was treated with chemosaturation with percutaneous hepatic perfusions of melphalan. RESULTS: The procedure was performed twice within 8 weeks after which the liver metastases showed a marked reduction in size and vascularization (partial response). Grade 3 leukopenia after the second procedure was managed effectively with granulocyte colony-stimulating factor. No other toxicities were observed. Ten months after initiating treatment, the patient had a good performance status and remained stable. CONCLUSIONS: For SPN with unresectable liver metastases and progression despite systemic treatment, repeat chemosaturation with high-dose melphalan may also offer an effective regional treatment option.