Chemosaturation with percutaneous hepatic perfusion is effective in patients with ocular melanoma and cholangiocarcinoma.

BACKGROUND: Chemosaturation with percutaneous hepatic perfusion (CS-PHP; Hepatic CHEMOSAT® Delivery System; Delcath Systems Inc, USA) is a novel interventional procedure, which delivers high doses of melphalan directly to the liver in patients with liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. We have previously shown promising efficacy for patients with ocular melanoma (OM) and cholangiocarcinoma (CCA) within our single-center and multi-center experiences. The aim of this study was to analyze the safety and efficacy of CS-PHP after 141 treatments at Hannover Medical School, Germany. METHODS: Overall response rates (ORR) were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST1.1). Median Overall survival (mOS), median progression-free survival (mPFS), and median hepatic PFS (mhPFS) were analyzed using the Kaplan-Meier estimation. RESULTS: Overall, 60 patients were treated with CS-PHP in the salvage setting from October 2014 until January 2019 at Hannover Medical School with a total of 141 procedures. Half of the patients were patients with hepatic metastases of ocular melanoma (OM) (n = 30), 14 patients had CCA (23.3%), 6 patients had hepatocellular carcinoma (10%), and 10 patients were treated for other secondary liver malignancies (16.7%). In total, ORR and disease stabilization rate were 33.3% and 70.3% (n = 25), respectively. ORR was highest for patients with OM (42.3%), followed by patients with CCA (30.8%). Independent response-associated factors were normal levels of lactate dehydrogenase (odds ratio (OR) 13.7; p = 0.015) and diagnosis with OM (OR 9.3; p = 0.028). Overall, mOS was 9 months, mPFS was 4 months, and mhPFS was 5 months. Patients with OM had the longest mOS, mPFS, and mhPFS with 12, 6, and 6 months, respectively. Adverse events included most frequently significant, but transient, hematologic toxicities (80% of grade 3/4 thrombopenia), less frequently hepatic injury up to liver failure (3.3%) and cardiovascular events including two cases of ischemic insults (5%). CONCLUSION: Salvage treatment with CS-PHP is safe and effective particularly in patients OM and CCA. Careful attention should be paid to possible, serious hepatic, and cardiovascular complications.

Shear wave elastography prior to transjugular intrahepatic portosystemic shunt may predict the decrease in hepatic vein pressure gradient.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure used to treat portal hypertension complications. Our aim was to evaluate liver and spleen stiffness measurement (LSM and SSM, respectively) changes using acoustic radiation force impulse imaging (ARFI) in comparison to Child-Pugh scores for predicting hepatic venous pressure gradient (HVPG) decreases after TIPS implantation. METHODS: This prospective study included 31 consecutive clinically significant portal hypertension patients with TIPS indication. All patients received LSM and SSM before TIPS, at baseline, 2 days (follow-up 1) and 6 weeks (follow-up 2) post-implantation. HVPG was performed during the TIPS procedure. RESULTS: The mean decrease in HVPG after TIPS was 63%. LSM and SSM decreased significantly between baseline and follow-up 2 (p < 0.001 and p < 0.001, respectively). At baseline, follow-up 1 and follow-up 2, significant correlations were detected between mean SSM and mean HVPG (p = 0.026; p = 0.018; p = 0.002, respectively). HVPG decreased to ≤ 10 mmHg in 61% of patients for which LSM, SSM, and Child-Pugh score were predictors (p = 0.033, p = 0.002 and p = 0.030, respectively). The area under the curve (AUC) for LSM, SSM, and Child-Pugh was 0.88, 0.90, and 0.84, respectively, with close sensitivity and specificity. SSM had the highest diagnostic accuracy for predicting an HVPG decrease to ≤ 10 mmHg in comparison to LSM and Child-Pugh score. CONCLUSION: Spleen stiffness is superior to liver stiffness and Child-Pugh score as a non-invasive surveillance tool for evaluating patients with clinically significant portal hypertension (HVPG ≥ 10 mmHg) prior to TIPS.

Percutaneous hepatic perfusion (chemosaturation) with melphalan in patients with intrahepatic cholangiocarcinoma: European multicentre study on safety, short-term effects and survival.

OBJECTIVES: Cholangiocarcinoma is the second most common primary liver tumour with a poor overall prognosis. Percutaneous hepatic perfusion (PHP) is a directed therapy for primary and secondary liver malignancies, and its efficacy and safety have been shown in different entities. The purpose of this study was to prove the safety and efficacy of PHP in patients with unresectable intrahepatic cholangiocarcinoma (iCCA). PATIENTS AND METHODS: We retrospectively reviewed data from 15 patients with unresectable iCCA treated with PHP in nine different hospitals throughout Europe. Overall response rates (ORR) were assessed according to response evaluation criteria in solid tumours (RECIST1.1). Overall survival (OS), progression-free survival (PFS) and hepatic PFS (hPFS) were analysed using the Kaplan-Meier estimation. Adverse events (AEs) and toxicity were evaluated. RESULTS: Fifteen patients were treated with 26 PHPs. ORR was 20%, disease control was achieved in 53% after the first PHP. Median OS was 26.9 months from initial diagnosis and 7.6 months from first PHP. Median PFS and hPFS were 122 and 131 days, respectively. Patients with liver-only disease had a significantly longer median OS compared to patients with locoregional lymph node metastases (12.9 vs. 4.8 months, respectively; p < 0.01). Haematological toxicity was common, but manageable. No AEs of grade 3 or 4 occurred during the procedures. DISCUSSION: PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with iCCA, especially in non-metastatic disease. KEY POINTS: • Percutaneous hepatic perfusion (PHP) offers an additional locoregional therapy strategy for the treatment of unresectable primary or secondary intrahepatic malignancies. • PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with intrahepatic cholangiocarcinoma (iCCA), especially in non-metastatic disease. • Side effects seem to be tolerable and comparable to other systemic or local treatment strategies.

Transjugular intrahepatic portosystemic shunt (TIPS) dysfunction: quantitative assessment of flow and perfusion changes using 2D-perfusion angiography following shunt revision.

PURPOSE: To analyze the feasibility of 2D-perfusion angiography (2D-PA) to quantify flow and perfusion changes pre- and post-transjugular intrahepatic portosystemic shunt (TIPS) revision. MATERIALS AND METHODS: Fifteen consecutive patients (54 ± 14 years, seven men and eight women) scheduled for TIPS revision were included in this study. To quantify flow and perfusion changes caused by TIPS revision, digital subtraction angiography (DSA) series acquired during the revision were post-processed using a dedicated software. Reference region-of-interest (ROI) in the main portal vein (input function) and target ROIs in the TIPS lumen, the liver parenchyma and in the right atrium were placed in corresponding areas on DSA pre- and post-TIPS revision. 2D-PA evaluation included time to peak (TTP), peak density (PD), and the area under the curve (AUC) assessment. The ratios of reference ROI to target ROIs pre- and post-TIPS revision were calculated (TTPparenchyma/TTPinflow, PDparenchyma/PDinflow, AUCparenchyma/AUCinflow, TTPTIPS/TTPinflow, PDTIPS/PDinflow, AUCTIPS/AUCinflow, TTPatrium/TTPinflow, PDatrium/PDinflow, and AUCatrium/AUCinflow). Pressure measurements pre- and post-TIPS revision were performed and correlated to the 2D-PA parameters. Reproducibility of 2D-PA was assessed by the intra-class correlation coefficient (ICC). RESULTS: The portosystemic pressure gradient was significantly reduced following TIPS revision (17.1 ± 6.3 vs. 8.9 ± 4.3 mmHg; p < 0.0001). PDTIPS/PDinflow (0.22 vs. 0.35; p = 0.0014) and AUCTIPS/AUCinflow (0.24 vs. 0.39; p = 0.0012) increased significantly. Likewise, PDatrium/PDinflow (0.32 vs. 0.78; p = 0.0004) and AUCatrium/AUCinflow (0.3 vs. 0.79; p < 0.0001) increased, whereas PDparenchyma/PDinflow decreased significantly (0.14 vs. 0.1; p = 0.0084). Pressure gradient changes correlated significantly with the increase in PDatrium/PDinflow (r = - 0.77, p = 0.0012) and AUCatrium/AUCinflow (r = - 0.76, p = 0.0018). ICC of the 2D-PA parameters was in the range of 0.88-0.99. CONCLUSION: 2D-PA offers a feasible approach to quantify flow and perfusion changes during TIPS revision. Therefore, 2D-PA may be a valuable amendment to mere pressure measurements.

Surgical treatment of coronary artery aneurysms.

INTRODUCTION: Coronary artery aneurysms (CAA) are rare. We present our experience with the surgical treatment of patients with CAAs. METHODS: Between March 2000 and October 2016, 15 patients with CAA underwent surgery. RESULTS: Mean age of patients was 60 ± 16 years and 47% (n = 7) were male. Kawasaki syndrome was present in two (13%) patients and 7% (n = 1) patients had Marfan syndrome. Isolated CAAs were found in 73% (n = 11) and involvement of multiple vessels was present in 27% (n = 4) of patients. Coronary arteries (CA) affected by aneurysms were: 19% (n = 4) left main stem, 33% (n = 7) left anterior descending, 14% (n = 3) left circumflex, and 33% (n = 7) right coronary artery. The majority of patients (93%, n = 14) were operated on pump with a mean cross-clamp time of 51 ± 23 min. 53% (n = 8) of patients received total arterial CA bypass grafting, while the remaining patients (47%, n = 7) received venous ± internal thoracic artery grafts. Resection/ligation of CAA was performed in 27% (n = 4) of patients. In-hospital mortality was 0% (n = 0). Follow-up was complete for 100% of patients and comprised a total of 80 patient-years. During follow-up, only one patient (7%) required re-intervention. CONCLUSION: Surgical treatment of CAA has good short- and long-term results.

Coil embolization of reversed-curve hepatointestinal collaterals in radioembolization: potential solutions for a challenging task.

Depending on the planned catheter position for selective internal radioembolization, coil embolization of hepatic artery branches can be necessary to enable a selective and safe procedure. The anatomy of the hepatic arterial bed has been demonstrated to have a substantial number of anatomic variations, which turns coil embolization into a challenge if the feeder shows a reversed, "hairpin-like" turn immediately after its origin. Hepatointestinal collateral vessels originating from the periphery of the right hepatic artery often present with such a reversed course and can preclude patients from uncomplicated radioembolization if catheterization fails. The purpose of this report is to describe 2 potential solutions for successful coil embolization of reversed-curve hepatointestinal collateral vessels using either a regular 4 French RIM catheter or a novel steerable tip-deflecting microcatheter.

Safety and efficacy of chemosaturation in patients with primary and secondary liver tumors.

BACKGROUND: Chemosaturation with percutaneous hepatic perfusion (CS-PHP; hepatic CHEMOSAT® delivery system; Delcath Systems Inc, USA) is a novel medical device, which delivers high doses of melphalan directly to the liver in patients with primary and secondary liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. The aim of this study was to analyze the safety and efficacy of the second-generation CS-PHP after 54 treatments at Hannover Medical School, Germany. METHODS: Overall response rates (ORR) were assessed according to response evaluation criteria in solid tumors (RECIST1.1). Overall survival (OS), progression-free survival (PFS), and hepatic PFS (hPFS) were analyzed using the Kaplan-Meier estimation. RESULTS: 29 patients were treated with CS-PHP as last-line therapy up to five sessions. 19 patients had unresectable hepatic metastases from solid tumors [ocular melanoma (OM) n = 11; colorectal carcinoma n = 2; pancreatic adenocarcinoma n = 2; periampular carcinoma n = 2; breast and endometrial cancer each n = 1] and 10 patients were diagnosed with hepatocellular or cholangiocarcinoma (HCC/CCA). ORR was 19.2%. Patients with OM had the highest ORR (33.3%). Similar to patients with OM, patients with hepatobiliary tumors had durable disease stabilization (40%). Median OS, PFS, and hPFS were 261, 117, and 135 days, respectively. Tumor volume negatively correlated with OS. Complications and toxicities included thrombocytopenia, cardiovascular events, ulcerous bleeding, and edema. CONCLUSION: Second-generation CS-PHP seems to be effective and tolerable. Patient selection based on tumor volume and entity is of importance. Particularly, patients with OM and hepatobiliary tumors represent promising candidates for CS-PHP.

Health-Related Quality of Life in Patients with Hepatocellular Carcinoma Treated with Initial Transarterial Chemoembolization.

PURPOSE: To investigate the impact of the first transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) on health-related quality of life (HRQoL) and identify predictors for low HRQoL following TACE. MATERIALS AND METHODS: HRQoL was prospectively evaluated in 79 patients with standardized questionnaires (QlQ-C30 and HCC18) pre- and 2 weeks post-TACE. Treatment response was evaluated using common tumour response criteria. Clinical parameters [e.g. Eastern Cooperative Oncology Group (ECOG) performance status, Model of End Stage Liver Disease (MELD) score], tumour load and pre-TACE HRQoL scores were tested for predicting HRQoL after TACE. RESULTS: Patients showed a 12.1% decrease in global health score (GHS). Major decreases were observed for physical (-21.4%), role (-23.4%), and social (-21.5%) functioning and increases in symptom severity for fatigue (+30.1%), loss of appetite (+25.3%), pain (+19.4%) after TACE. ECOG performance status >1 was associated with increased nausea/vomiting (p = 0.002) and decreased GHS (p = 0.01). MELD score >10 was associated with increased fatigue (p = 0.021) and abdominal swelling (p < 0.001). Our study showed an increase in symptom severity in patients with no symptoms before TACE for pain (p = 0.005) and abdominal swelling (p < 0.001). CONCLUSION: The first TACE for treatment of HCC does not result in a major loss of HRQoL in general. For TACE as a palliative therapy maintaining HRQoL is of critical importance and standardized HRQoL assessment can help to detect HRQoL problems.

A Close Call: An Impacted Knife Injury to the Thorax.

A 21-year-old woman with a history of psychiatric treatment was admitted to the emergency department with self-inflicted stab wounds to the neck, chest, and abdomen as the result of a suicide attempt. Inspection showed a seemingly superficial cut at the jugular fossa. The patient's mother stated that one long ceramic kitchen bread knife was totally embedded in the right thorax. Further diagnostic measures showed the missing kitchen bread knife penetrating the right chest, with the path of insertion starting 2 cm above the right clavicle and the blade in contact with the right hilum and ending next to the seventh thoracic vertebra. Retrieval the object was a challenging problem.

Comparison of C-arm Computed Tomography and Digital Subtraction Angiography in Patients with Chronic Thromboembolic Pulmonary Hypertension.

PURPOSE: To assess the feasibility and diagnostic performance of contrast-enhanced, C-arm computed tomography (CACT) of the pulmonary arteries compared to digital subtraction angiography (DSA) in patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH). MATERIALS: Fifty-two patients with CTEPH underwent ECG-gated DSA and contrast-enhanced CACT. Two readers (R1, R2) independently evaluated pulmonary artery segments and their sub-segmental branching using DSA and CACT for optimal image quality. Afterwards, the diagnostic findings, i.e., intraluminal filling defects, stenosis, and occlusion, were compared. Inter-modality and inter-observer agreement was calculated, and subsequently consensus reading was done and correlated to a reference standard representing the overall consensus of both modalities. Fisher's exact test and Cohen's Kappa were applied. RESULTS: A total of 1352 pulmonary segments were evaluated, of which 1255 (92.8 %) on DSA and 1256 (92.9 %) on CACT were rated to be fully diagnostic. The main causes of the non-diagnostic image quality were motion artifacts on CACT (R1:37, R2:78) and insufficient contrast enhancement on DSA (R1:59, R2:38). Inter-observer agreement was good for DSA (κ = 0.74) and CACT (κ = 0.75), while inter-modality agreement was moderate (R1: κ = 0.46, R2: κ = 0.47). Compared to the reference standard, the inter-modality agreement for CACT was excellent (κ = 0.96), whereas it was inferior for DSA (κ = 0.61) due to the higher number of abnormal consensus findings read as normal on DSA. CONCLUSION: CACT of the pulmonary arteries is feasible and provides additional information to DSA. CACT has the potential to improve the diagnostic work-up of patients with CTEPH and may be particularly useful prior to surgical or interventional treatment.

Transarterial chemoembolization (TACE) for colorectal liver metastases--current status and critical review.

BACKGROUND: Transarterial liver-directed therapies are currently not recommended as a standard treatment for colorectal liver metastases. Transarterial chemoembolization (TACE), however, is increasingly used for patients with liver-dominant colorectal metastases after failure of surgery or systemic chemotherapy. The limited available data potentially reveals TACE as a valuable option for pre- and post-operative downsizing, minimizing time-to-surgery, and prolongation of overall survival after surgery in patients with colorectal liver only metastases. PURPOSE: In this overview, the current status of TACE for the treatment of liver-dominant colorectal liver metastases is presented. Critical comments on its rationale, technical success, complications, toxicity, and side effects as well as oncologic outcomes are discussed. The role of TACE as a valuable adjunct to surgery is addressed regarding pre- and post-operative downsizing, conversion to resectability as well as improvement of the recurrence rate after potentially curative liver resection. Additionally, the concept of TACE for liver-dominant metastatic disease with a focus on new embolization technologies is outlined. CONCLUSIONS: There is encouraging data with regard to technical success, safety, and oncologic efficacy of TACE for colorectal liver metastases. The majority of studies are non-randomized single-center series mostly after failure of systemic therapies in the 2nd line and beyond. Emerging techniques including embolization with calibrated microspheres, with or without additional cytotoxic drugs, degradable starch microspheres, and technical innovations, e.g., cone-beam computed tomography (CT) allow a new highly standardized TACE procedure. The real efficacy of TACE for colorectal liver metastases in a neoadjuvant, adjuvant, and palliative setting has now to be evaluated in prospective randomized controlled trials.

Impact of Anatomical, Procedural, and Operator Skill Factors on the Success and Duration of Fluoroscopy-Guided Transjugular Intrahepatic Portosystemic Shunt.

PURPOSE: To assess the impact of anatomical, procedural, and operator skill factors on the success and duration of fluoroscopy-guided transjugular intrahepatic portoystemic shunt following standard operating procedure (SOP). MATERIAL AND METHODS: During a 32-month period, 102 patients underwent transjugular intrahepatic portosystemic shunt creation (TIPS) by two interventional radiologists (IR) following our institutional SOP based on fluoroscopy guidance. Both demographic and procedural data were assessed. The duration of the intervention (D(Int)) and of the portal vein puncture (D(Punct)) was analyzed depending on the skill level of the IR as well as the anatomic or procedural factors. RESULTS: In 99 of the 102 patients, successful TIPS without peri-procedural complications was performed. The mean D(Int) (IR1: 77 min; IR2: 51 min, P < 0.005) and the mean D(Punct) (IR1: 19 min; IR2: 13 min, P < 0.005) were significantly higher in TIPS performed by IR1 (with 2 years of clinical experience performing TIPS, n = 38) than by IR2 (>10 years of clinical experience performing TIPS, n = 61), (P < 0.005 both, Mann-Whitney U test). D Int showed a higher correlation with D(Punct) for IR2 (R(2) = 0.63) than for IR1 (R(2) = 0.13). There was no significant difference in the D(Punct )for both IRs with regard to the success of the wedged portography (P = 0.90), diameter of the portal vein (P = 0.60), central right portal vein length (P = 0.49), or liver function (MELD-Score before the TIPS procedure; P = 0.14). CONCLUSION: TIPS following SOP is safe, fast, and reliable. The only significant factor for shorter D(Punct) and D(Int) was the clinical experience of the IR. Anatomic variability, successful portography, or liver function did not alter the duration or technical success of TIPS.