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.

Single-Center Retrospective Comparative Study Evaluating the Benefit of Computed Tomography Angiography Prior to Prostatic Artery Embolization.

PURPOSE: To explore whether a computed tomography angiography (CTA) of the pelvis prior to prostatic artery embolization (PAE) is a beneficial preprocedural planning tool regarding the technical success. MATERIALS AND METHODS: Eighty patients with lower urinary tract symptoms treated with PAE were analyzed retrospectively. Forty of these patients received a CTA of the pelvis prior to the procedure (Group A) and were compared to 40 patients who were treated with PAE without prior CT imaging (Group B). Technical success rate, rate of complications, fluoroscopy time (FT), and mean dose area product (DAP) were assessed and compared. All operators performed at least 50 PAE prior to this study. When needed, cone-beam CT (CBCT) was available during intervention. RESULTS: Mean age was 68.43 ± 8.30 years in Group A and 70.42 ± 7.11 years in Group B (p = 0.252). Mean body mass index was 26.78 ± 3.73 in Group A and 26.85 ± 3.5 in Group B (p = 0.319). Overall technical success was 96.3%. Bilateral PAE was achieved in 60 patients (75.0%) while unilateral PAE was performed in 17 patients (21.3%). Technical failure (no embolization) occurred in two patients of Group A and one patient of Group B. No statistical significance was seen between groups for technical success rate (p = 1.0). Mean DAP was 10,164 × cm2 ± 3944 cGy × cm2 in Group A and 10,039 × cm2 ± 3761 cGy × cm2 in Group B (p = 0.885). Mean FT was 49.27 ± 22.97 min in Group A and 44.32 ± 17.82 min in Group B (p = 0.285). No intervention-related complications during PAE were reported. CONCLUSION: With experienced interventionalists and CBCT available during PAE, preprocedural CTA has no additional benefit for technical outcome.

Intraoperative (Contrast-Enhanced) Ultrasound Has the Highest Diagnostic Accuracy of Any Imaging Modality in Resection of Colorectal Liver Metastases.

AIM: Defining sensitivity, specificity, diagnostic accuracy for detection of colorectal liver metastases in imaging compared to intraoperative assessment. Defining a cutoff, where accuracy of detection is impaired. METHODS: Prospective single-institution clinical trial (clinicaltrials.gov: NCT01522209). Patients underwent CEUS, MDCT, and 3 Tesla EOB-MRI within 2 weeks preoperatively. Intraoperative palpation, IOUS, and CEIOUS were performed. A patient and lesion-based database was analyzed for accuracy of detection of CEUS, CT, MRI, and Palp/IOUS/CEIOUS combined read. Histology was standard of reference. RESULTS: Forty-seven high tumor load (mean 5, 4 lesions) patients were analyzed. Histopathology confirmed 264 lesions (245 malignant: 19 benign). Accuracy for detection of all lesions: CEUS 63%, CT 71%, MRI 92%, and PALP/IOUS/CEIOUS 98%. ROC analysis for lesion size showed severe impairment of accuracy in lesion detection smaller than 5mm. Intraoperative imaging was not impaired by lesion size. Patient-based analysis revealed a change of resection plan after IOUS/CEIOUS in 35% of patients. CONCLUSION: At 5-mm lesion size, preoperative imaging shows a drop in accuracy of detection. In patients with multiple lesions, addition of MRI to MDCT seems useful. Accuracy of intraoperative ultrasound is not impacted by lesion size and should be mandatory. CEIOUS can improve intraoperative decision-making. TRIAL REGISTRATION: Study registered with clinicaltrials.gov : NCT01522209.

Early prediction of anticancer effects with diffusion-weighted MR imaging in patients with colorectal liver metastases following selective internal radiotherapy.

OBJECTIVE: To prospectively evaluate diffusion-weighted imaging (DWI) for early prediction of tumour response in patients with colorectal liver metastases following selective internal radiotherapy (SIRT). METHODS: We evaluated 41 metastases in 21 patients, age 62.9 ± 9.9 years. All patients underwent magnetic resonance imaging (MRI) including breath-hold echoplanar DWI sequences. Imaging was performed before therapy (baseline MRI), 2 days after SIRT (early MRI) as well as 6 weeks later (follow-up MRI). Tumour volume (TV) and intratumoural apparent diffusion coefficient (ADC) were measured independently by two radiologists at all time points. RESULTS: Metastases were categorised as responding lesions (RL; n = 33) or non-responding lesions (NRL; n = 8) according to changes in TV after 6 weeks. We found an inverse correlation of changes in TV and ADC at follow-up MRI with a Pearson's correlation coefficient of r = -0.66 (p < 0.0001). On early MRI, no significant changes in TV were found for either RL or NRL. Conversely, ADC decreased significantly in RL by 10.7 ± 8.4% (p < 0.0001). ADC increased in NRL by 9.6 ± 20.8%, which was not statistically significant (p = 0.40). CONCLUSION: DWI was capable of predicting therapy effects of SIRT in patients with colorectal hepatic metastases as early as 2 days following treatment.

Correlation between SACE (Subjective Angiographic Chemoembolization Endpoint) score and tumor response and its impact on survival after DEB-TACE in patients with hepatocellular carcinoma.

PURPOSE: To asses angiographic and computed tomographic success criteria during and after transcatheter arterial drug-eluting bead chemoembolization (DEB-TACE) in patients with hepatocellular carcinoma (HCC) and its impact on progression-free survival (PFS) and overall survival (OS). METHODS: In this retrospective single-center study, 50 patients with unresectable HCC having undergone DEB-TACE from January 2010 to July 2015 were assessed. The angiographic endpoint was classified by Subjective Angiographic Chemoembolization Endpoint (SACE) scale. Relative tumor density in arterial (DArt) and portal venous phase (DPV) computed tomography post- versus pre-DEB-TACE were calculated, respectively. Tumor response according to modified Response Criteria in Solid Tumors (mRECIST) was assessed. Univariate Kaplan-Meier and Cox regression analysis were carried out. RESULTS: SACE scores I, II, III, and IV were found in 1 (2%), 20 (40%), 15 (30%), and 14 (28%) patients, respectively. Median OS and PFS were 14.2 and 5.5 months, respectively. Death rates at 6 months, 1 year and 2 years were 24%, 38%, and 52%, respectively. SACE score during DEB-TACE significantly correlated with local and overall mRECIST results (local: p < 0.001, r = 0.49, overall: p = 0.042, r = 0.29) and inversely correlated with DPV (p = 0.005, r = - 0.40). In univariate analysis, progressive disease (PD) according to mRECIST and increase of DArt and DPV were associated with significantly shorter PFS. Modified RECIST independently predicted OS (hazard ratio for complete remission vs. PD = 0.15, 95% confidence interval 0.03-0.68, p = 0.014). CONCLUSIONS: A direct impact of SACE on PFS or OS could not be shown. However, SACE significantly correlated with local and overall mRECIST tumor response that again significantly predicted OS. We therefore postulate an indirect impact of SACE on OS. Consequently, complete embolization should be attempted.

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.

Percutaneous Isolated Hepatic Perfusion as a Treatment for Isolated Hepatic Metastases of Uveal Melanoma: Patient Outcome and Safety in a Multi-centre Study.

PURPOSE: Percutaneous isolated hepatic perfusion (PIHP) with Melphalan has been developed as a treatment for patients with isolated hepatic metastases of uveal melanoma. We discuss patient outcome and safety in a retrospective multi-centre study. MATERIALS AND METHODS: Between 2012 and 2016 18 patients with un-resectable isolated hepatic metastases of uveal melanoma received single or repeated PIHP with Melphalan (n = 35) at seven sites. Progression-free time, overall survival time (OS) and tumour response by means of RECIST 1.1 criteria were evaluated. Peri- and post-procedural adverse events (AE) were registered. Patients' life quality was assessed using four-point scale questionnaires. RESULTS: Of 18 patients, initial PIHP treatment resulted in partial response (PR) in eight, stable disease (SD) in seven and progressive disease (PD) in three cases. Nine patients underwent second PIHP with PR in eight cases and PD in one case. Six patients were evaluated after third PIHP with PR in five patients and SD in one patient. Two patients received fourth PIHP with PD in both cases. Median OS was 9.6 months (range 1.6-41.0 months). Median progression-free survival time was 12.4 months (range 0.9-41.0 months) with 1-year survival of 44%. Most common post-procedural AE grade 3 and 4 were temporary leukopenia (n = 11) and thrombocytopenia (n = 8). Patients' self-assessments showed good ratings for overall health and quality of life with only slight changes after PIHP, and a high degree of satisfaction with PIHP treatment. CONCLUSION: PIHP with Melphalan proved to be a relatively safe, minimal-invasive and repeatable treatment for patients with non-resectable hepatic metastases of uveal melanoma.

Did the International ALPPS Meeting 2015 Have an Impact on Daily Practice? The Hamburg Barmbek Experience of 58 Cases.

BACKGROUND: ALPPS (associating liver partition and portal vein ligation for staged hepatectomy) was introduced only 10 years ago and has gained wide acceptance as a variation of staged procedures in liver surgery. It has been criticized for its high morbidity and mortality, which all centers reported in their initial series. METHODS: After a world expert meeting in Hamburg in 2015 where all experts in the field met to discuss this method, caveats were extracted and formulated. We researched our complete prospective ALPPS database to see if the recommendations had any impact on outcome. RESULTS: In total, we performed 58 ALPPS procedures in our center. 33 patients were operated on before, 25 after the meeting. Results in terms of morbidity and mortality were significantly better after the meeting, as were patient selection and strategy. CONCLUSION: In our own center's experience, the implementation of the meetings' recommendations and the information gathered through this valuable exchange had a dramatic impact on results. Having performed 58 ALPPS procedures in total, we can now conclude that ALPPS has become much safer in our hands since the 2015 meeting and that morbidity and mortality are no longer the issue to be discussed. Future research must focus on oncologic outcomes in these patients.

Identification of cofactors influencing hypertrophy of the future liver remnant after portal vein embolization-the effect of collaterals on embolized liver volume.

OBJECTIVE: The purpose of this retrospective study was to monitor hypertrophy of future liver remnant following portal vein embolization (PVE) before planned extended right hepatectomy. However, because individual responses to PVE are highly variable, our focus was to identify cofactors of successful hypertrophy. METHODS: 28 patients with primary or secondary liver tumours, mean age 64.1 ± 12.9 years, underwent PVE. Volumetric analysis of hypertrophy before and after PVE (median 39.0 ± 15.7 days) was performed. The embolized liver segments were investigated for occurrence of reperfusion of their portal branches. Blood parameters before PVE were additionally investigated. RESULTS: Patients were divided into responders (21/28) and non-responders (7/28) by post-PVE standardized future liver remnant being above or below 25%, respectively. No significant differences between the groups were found regarding biometric and volumetric parameters before PVE. In the entire group after PVE, the mean absolute increase of Segments 2 and 3 was 196.0 ± 84.7 cm3 and the median relative increase was 46.6 ± 98.8%. The formation of left to right hepatic portoportal collaterals exhibited a negative correlation to successful hypertrophy (p = 0.004) as well as low plasma total protein (p = 0.019). Successful embolization of Segment IV showed only a trend to significance (p = 0.098). CONCLUSION: Cofactors associated with a favourable outcome regarding hypertrophy were the absence of collaterals in the control CT scans and high plasma total protein. Advances in knowledge: Portoportal collaterals negatively influence hypertrophy after PVE. On the other hand, plasma total protein is a positive prognostic indicator on hypertrophy of the liver in our cohort.

Rupture of renal angiomyolipoma during childbirth.

Renal angiomyolipoma is a benign tumor of the kidney, originating from perivascular epithelioid cells. Normally asymptomatic, symptoms that can occur are flank pain due to strong growth or spontaneous rupture with retroperitoneal hemorrhage and hypovolemic shock. The risk of rupture is higher during pregnancy and also growth can be enhanced, probably hormone mediated. We report a case of a ruptured renal angiomyolipoma during childbirth in a woman who presented with hypovolemic shock as a result of retroperitoneal hemorrhage. Emergency endovascular treatment was successful with sparing most of the affected kidney as demonstrated by angiography imaging and follow-up computed tomographic scan.

Consensus report on the radiological management of patients with gastrointestinal stromal tumours (GIST): recommendations of the German GIST Imaging Working Group.

The aim was to reach consensus in imaging for staging and follow-up as well as for therapy response assessment in patients with gastrointestinal stromal tumours (GIST). The German GIST Imaging Working Group was formed by 9 radiologists engaged in assessing patients with GIST treated with targeted therapy. The following topics were discussed: indication and optimal acquisition techniques of computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT; tumour response assessment considering response criteria and measurement techniques on CT, MRI and PET/CT; result interpretation; staging interval and pitfalls. Contrast-enhanced CT is the standard method for GIST imaging. MRI is the method of choice in case of liver-specific questions or contraindications to CT. PET/CT should be used for early response assessment or inconclusive results on morphologic imaging. All imaging techniques should be standardized allowing a reliable response assessment. Response has to be assessed with respect to lesion size, lesion density and appearance of new lesions. A critical issue is pseudoprogression due to myxoid degeneration or intratumoural haemorrhage. The management of patients with GIST receiving a targeted therapy requires a standardized algorithm for imaging and an appropriate response assessment with respect to changes in lesion size and density.

Value of diffusion weighted MR imaging as an early surrogate parameter for evaluation of tumor response to high-dose-rate brachytherapy of colorectal liver metastases.

BACKGROUND: To assess the value of diffusion weighted imaging (DWI) as an early surrogate parameter for treatment response of colorectal liver metastases to image-guided single-fraction ¹9²Ir-high-dose-rate brachytherapy (HDR-BT). METHODS: Thirty patients with a total of 43 metastases underwent CT- or MRI-guided HDR-BT. In 13 of these patients a total of 15 additional lesions were identified, which were not treated at the initial session and served for comparison. Magnetic resonance imaging (MRI) including breathhold echoplanar DWI sequences was performed prior to therapy (baseline MRI), 2 days after HDR-BT (early MRI) as well as after 3 months (follow-up MRI). Tumor volume (TV) and intratumoral apparent diffusion coefficient (ADC) were measured independently by two radiologists. Statistical analysis was performed using univariate comparison, ANOVA and paired t test as well as Pearson's correlation. RESULTS: At early MRI no changes of TV and ADC were found for non-treated colorectal liver metastases. In contrast, mean TV of liver lesions treated with HDR-BT increased by 8.8% (p = 0.054) while mean tumor ADC decreased significantly by 11.4% (p < 0.001). At follow-up MRI mean TV of non-treated metastases increased by 50.8% (p = 0.027) without significant change of mean ADC values. In contrast, mean TV of treated lesions decreased by 47.0% (p = 0.026) while the mean ADC increased inversely by 28.6% compared to baseline values (p < 0.001; Pearson's correlation coefficient of r = -0.257; p < 0.001). CONCLUSIONS: DWI is a promising imaging biomarker for early prediction of tumor response in patients with colorectal liver metastases treated with HDR-BT, yet the optimal interval between therapy and early follow-up needs to be elucidated.

Diffusion-weighted echo-planar magnetic resonance imaging for the assessment of tumor cellularity in patients with soft-tissue sarcomas.

PURPOSE: To investigate the eligibility of diffusion-weighted imaging (DWI) for the evaluation of tumor cellularity in patients with soft-tissue sarcomas. MATERIALS AND METHODS: Thirty consecutive patients with a total of 31 histologically-proven soft-tissue sarcomas prospectively underwent magnetic resonance imaging (MRI) including DWI with echo-planar imaging (EPI) technique immediately before open biopsy (N = 1) or tumor resection (N = 30). Fourteen patients had no previous anticancer treatment, 16 had received neoadjuvant therapy. Tumor cellularity as determined from histological sections was compared with minimum apparent diffusion coefficient (ADC). RESULTS: Tumor cellularity correlated well with minimum ADC in a linear fashion, with a Pearson correlation coefficient of -0.88 (95% confidence interval [CI]: -0.75 to -0.96). This relationship was not influenced by prior anticancer treatment. There was only a tendency toward lower ADC in tumor with higher grading but no significant dependency (P = 0.08). CONCLUSION: DWI has proven useful for the assessment of tumor cellularity in soft-tissue sarcomas. In result, DWI may be used as a powerful noninvasive tool to monitor responses of cytotoxic treatment as reflected by changes in tumor cellularity.

Diffusion-weighted magnetic resonance imaging allows monitoring of anticancer treatment effects in patients with soft-tissue sarcomas.

PURPOSE: To determine if diffusion-weighted imaging (DWI) can be used as a surrogate marker of tumor response to anticancer therapy in patients with soft-tissue sarcomas. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) including echo-planar DWI sequences was performed prospectively in 23 consecutive patients with soft-tissue sarcomas before and after initiation of regional or systemic chemotherapy. The mean interval between initial and follow-up MRI was 56.9 +/- 23.2 days. Tumor volumes were determined by manual segmentation of tumor borders on contrast-enhanced T1-weighted images. The apparent diffusion coefficient (ADC) was calculated from corresponding sections of ADC maps on initial and follow-up DWI. Subsequently, changes in tumor volumes and ADC were correlated using the Pearson correlation coefficient. RESULTS: A high degree of correlation was found when changes in tumor volumes and ADC values were compared (r = -0.925, P < 0.0001), regardless of the effectiveness of anticancer therapy expressed as changes of tumor volume. CONCLUSION: DWI can be used as a supplement to morphologic imaging for the evaluation of tumor response to anticancer therapy in patients with soft-tissue sarcomas. As cellular changes are expected to precede morphologic changes in treated tumors, DWI performed at an early stage of fractionated therapy may provide unique prognostic information of its effectiveness.

Significance of sagittal reformations in routine thoracic and abdominal multislice CT studies for detecting osteoporotic fractures and other spine abnormalities.

The purpose was to assess osteoporotic vertebral fractures and other spinal lesions in sagittal reformations obtained from routine multidetector computed tomography (MDCT) studies of the thorax and abdomen, to compare sagittal reformations with axial images in detecting these lesions and to investigate how frequently they were missed in the official radiology report. Routine abdominal or thoracoabdominal MDCT using a standard protocol was performed in 112 postmenopausal women. Axial images and sagittal reformations were analyzed separately by two radiologists in consensus and were compared in order to evaluate how often spinal lesions could be detected. In addition the official radiology reports were assessed to determine how many of those abnormalities were identified. Spine abnormalities were visualized in 101/112 postmenopausal women. In 27 patients osteoporotic vertebral deformities were found; 6 of these were shown in the axial images, but none of these were diagnosed in the official radiology report. Additional abnormalities included degenerative disc disease, osteoarthritis of the facet joints, scoliosis, hemangiomas and bone metastases. In only 9/101 patients spine abnormalities were mentioned in the radiology report. Sagittal reformations of standard MDCT images provide important additional information on spinal abnormalities; in particular, osteoporotic vertebral deformities are substantially better detected.

Epidural venous enlargements presenting with intractable lower back pain and sciatica in a patient with absence of the infrarenal inferior vena cava and bilateral deep venous thrombosis.

STUDY DESIGN: Case report. OBJECTIVE: To present a rare anomaly of the inferior vena cava associated with radicular pain and to illustrate its imaging characteristics. SUMMARY OF BACKGROUND DATA: Irritation of the trigeminal nerve by vascular anomalies, resulting in neuralgia is a well-recognized entity. Recently, compression of peripheral nerve roots due to enlarged epidural venous plexus has been described as a possible cause of back and radicular pain, too. METHODS: A 26-year-old man presented with acute exacerbation of lower back pain associated with radiculopathy down his left thigh. On radiologic workup, a prolapse of a lumbar intervertebral disc was ruled out, but agenesis of the infrarenal segment of the inferior vena cava was found, which has caused bilateral deep venous thrombosis. Venous flow was redirected mainly via enlarged lumbar epidural, ascending lumbar, and paravertebral veins. RESULTS: No associated congenital heart or abdominal organ defects were found and screening for thrombophilia was negative. The patient was successfully treated with anticoagulation under which symptoms gradually resolved. CONCLUSION: The authors believe that epidural venous enlargements should be considered as a cause of radicular and/or back pain in patients with anomalies of the inferior vena cava, because pathologic processes compressing nervous structures can cause pain.