Treatment of Postoperative Lymphatic Leakage Applying Transpedal Lymphangiography - Experience in 355 Consecutive Patients.

PURPOSE: Report of experience from a single institution in treating postoperative lymphatic leakage (PLL) applying conventional transpedal lymphangiography (TL). MATERIALS AND METHODS: 453 patients with the initial diagnosis of PLL receiving TL between 03/1993 and 09/2018 were identified in the database. Only patients with confirmed PLL were included in the study. The technical success, safety, and treatment success of TL were evaluated. Independent predictors of TL treatment failure were examined using univariate and multivariate logistic regression analysis. RESULTS: 355 consecutive patients (218 men, 137 women; median age of 62 years) who underwent TL for PLL (e. g., chylothorax) after ineffective conservative treatment were included. The median time between causal surgery and TL was 27 days. The median technical success rate of TL was 88.5 %, with a median volume of Lipiodol of 10.0 ml. No complication of TL was recorded. Three groups were defined according to the different clinical courses: group A (41/355, 11.5 %) - TL with technical failure; group B (258/355, 72.7 %) - "therapeutic" TL alone with technical success; and group C (56/355, 15.8 %) - "diagnostic" TL with simultaneously invasive treatment (incl. surgical revision and percutaneous sclerotherapy). Treatment success rate and median time to treatment success were higher in group C than in group B, but without significant differences (64.3 % vs. 61.6 %, p = 0.710; six vs. five days, p = 0.065). Univariate and multivariate logistic regression analyses for group B confirmed drainage volume (> 500 ml/d) and Lipiodol extravasation as independent predictors of TL clinical failure (odds ratios [ORs] of 2.128 and 2.372 [p = 0.005 and p = 0.003, respectively]). CONCLUSION: TL is technically reliable, safe, and effective in treating PLL. When conservative treatment fails, TL can be regarded as the next treatment option. KEY POINTS: · TL is technically reliable, safe, and effective for treating PLL.. · When conservative treatment fails, TL can be regarded as the next treatment option.. · Drainage volume > 500 ml/day is an independent predictor of clinical failure after TL.. · Lipiodol extravasation is an independent predictor of clinical failure after TL.. CITATION FORMAT: · Pan F, Richter GM, Do TD et al. Treatment of Postoperative Lymphatic Leakage Applying Transpedal Lymphangiography - Experience in 355 Consecutive Patients. Fortschr Röntgenstr 2022; 194: 634 - 643.

Conventional Lymphangiography (CL) in the Management of Postoperative Lymphatic Leakage (PLL): A Systematic Review.

BACKGROUND: Postoperative lymphatic leakage (PLL) is usually managed by conservative and/or surgical treatments but these procedures can be challenging to perform and potentially clinically ineffective. Therefore, conventional lymphangiography (CL) has emerged as an important alternative. The aim of this review is to present the available outcome data on CL in the management of PLL. METHOD: A systematic literature search (PubMed) using the MeSH term "lymphangiography" was performed and the search was restricted to literature published between January 2007 and August 2019. Identification, screening, and assessment for eligibility and inclusion were conducted in accordance with PRISMA. RESULTS: From the initially obtained 1006 articles (identification), 28 articles with a total of 201 patients were finally included (inclusion). The methodological quality of all included articles corresponds to level 4 (Oxford Centre for Evidence-based Medicine - Levels of Evidence, March 2009). PLL occurs after oncological and non-oncological surgery in the form of chylothorax, chylous ascites, and cervical, thoracic, abdominal and peripheral lymph fistula and/or lymphocele. The technical success rate of CL is 75-100 %. Access for CL is transpedal (176 patients) or intranodal (25 patients). Lipiodol is used as the contrast material in all articles, with a maximum amount of 20 ml for transpedal CL and 30 ml for intranodal CL. The X-ray imaging modalities used for CL are fluoroscopy, radiography and/or CT. Two articles report CL-associated major complications and CL-associated morbidity and mortality. The PLL cure rate is 51-70 % for transpedal CL (time to PLL cure: 2-29 days) and 33-100 % for intranodal CL (time to PLL cure: 2-< 30 days). Bailout procedures in the case of clinically ineffective CL include a range of treatments. CONCLUSION: CL is feasible, safe, and effective in the management of PLL. Lipiodol as the contrast material is essential in CL because the highly viscous iodinated poppy-seed oil has not only diagnostic but therapeutic effects. Guidelines and randomized controlled trials are further steps towards defining the ultimate value of CL. KEY POINTS: · PLL is a difficult-to-treat and potentially life-threatening surgical complication.. · CL has emerged as an alternative to conservative/surgical treatment of PLL.. · CL is feasible, safe, and effective in the management of PLL. · Lipiodol-based CL can be regarded as a therapeutic procedure.. · Guidelines and randomized controlled trials are further important steps.. CITATION FORMAT: · Sommer CM, Pieper CC, Itkin M et al. Conventional Lymphangiography (CL) in the Management of Postoperative Lymphatic Leakage (PLL): A Systematic Review. Fortschr Röntgenstr 2020; 192: 1025 - 1035.

Back to the Future: Lipiodol in Lymphography-From Diagnostics to Theranostics.

Lipiodol is an iodinated poppy seed oil first synthesized in 1901. Originally developed for therapeutic purposes, it has mainly become a diagnostic contrast medium since the 1920s. At the end of the 20th century, Lipiodol underwent a transition back to a therapeutic agent, as exemplified by its increasing use in lymphangiography and lymphatic interventions. Nowadays, indications for lymphangiography include chylothorax, chylous ascites, chyluria, and peripheral lymphatic fistula or lymphoceles. In these indications, Lipiodol alone has a therapeutic effect with clinical success in 51% to 100% of cases. The 2 main access sites to the lymphatic system for lymphangiography are cannulation of lymphatic vessels in the foot (transpedal) and direct puncture of (mainly inguinal) lymph nodes (transnodal). In case of failure of lymphangiography alone to occlude the leaking lymphatic vessel as well as in indications such as protein-losing enteropathy, postoperative hepatic lymphorrhea, or plastic bronchitis, lymphatic vessels can also be embolized directly by injecting a mixture of Lipiodol and surgical glues (most commonly in thoracic duct embolization). The aim of this article is to review the historical role of Lipiodol and the evolution of its clinical application in lymphangiography over time until the current state-of-the-art lymphatic imaging techniques and interventions.

The Novel X-Ray Visible Zein-Based Non-adhesive Precipitating Liquid Embolic HEIE1_2017: An Exploratory Study.

PURPOSE: To investigate the novel zein-based non-adhesive precipitating liquid embolic HEIE1_2017. MATERIALS AND METHODS: Zein-based liquid embolics are an own class of embolization material. In this study, HEIE1_2017, a novel zein-based liquid embolic, was investigated. Visibility was assessed in vitro in CT and MRI phantoms, embolization characteristics were assessed in vivo in the kidneys of 12 pigs. Components of HEIE1_2017 were zein as occlusion material, ethanol as solvent, and iodized oil as radiopaque material. HEIE1_2017 was used in pure (HEI-PURE) and manually modified (HEI-MOD) form and compared with 6% ethylene vinyl alcohol copolymer (EVOH). Different radiological methods (CT, MRI, DSA, cone-beam CT, and micro-CT) and histopathologic analyses were applied to compare visibility and vascular occlusion patterns. RESULTS: In CT phantoms, all embolics were definitely visible as hyperdense materials. In MRI phantoms, signal-to-noise ratio was highest for HEI-PURE, followed by HEI-MOD and EVOH. In all kidneys, embolization procedures were technically successful and without complications. In DSA, all embolics were definitely visible during and after embolization. Only EVOH caused substantial artifacts in cone-beam CT and CT. In micro-CT and histopathology, HEI-PURE showed a homogeneous occlusion from segmental arteries to glomerular capillaries. HEI-MOD demonstrated the deepest vascular penetration (up to the level of peritubular capillaries), but with an inhomogeneous distribution. For EVOH, there was inhomogeneous vascular occlusion from segmental arteries to glomerular capillaries. CONCLUSION: HEIE1_2017 is a promising novel zein-based liquid embolic. Further preclinical and clinical studies with higher case numbers and long-term follow-up are needed to further assess the value of this embolic material.

Computed tomography and histopathological findings after embolization with inherently radiopaque 40µm-microspheres, standard 40µm-microspheres and iodized oil in a porcine liver model.

PURPOSE: The present study compared standard computed tomography (CT) and histopathological findings after endovascular embolization using a prototype of inherently radiopaque 40µm-microspheres with both standard 40µm-microspheres and iodized oil in a porcine liver model. MATERIALS AND METHODS: Twelve pigs were divided into six study groups, of two pigs each. Four pigs were embolized with iodized oil alone and four with radiopaque microspheres; two animals in each group were sacrificed at 2 hours and two at 7 days. Two pigs were embolized with radiopaque microspheres and heparin and sacrificed at 7 days. Two pigs were embolized with standard microspheres and sacrificed at 2 hours. CT was performed before and after segmental embolization and before sacrifice at 7 days. The distribution of embolic agent, inflammatory response and tissue necrosis were assessed histopathologically. RESULTS: Radiopaque microspheres and iodized oil were visible on standard CT 2 hours and 7 days after embolization, showing qualitatively comparable arterial and parenchymal enhancement. Quantitatively, the enhancement was more intense for iodized oil. Standard microspheres, delivered without contrast, were not visible by imaging. Radiopaque and standard microspheres similarly occluded subsegmental and interlobular arteries and, to a lesser extent, sinusoids. Iodized oil resulted in the deepest penetration into sinusoids. Necrosis was always observed after embolization with microspheres, but never after embolization with iodized oil. The inflammatory response was mild to moderate for microspheres and moderate to severe for iodized oil. CONCLUSION: Radiopaque 40µm-microspheres are visible on standard CT with qualitatively similar but quantitatively less intense enhancement compared to iodized oil, and with a tendency towards less of an inflammatory reaction than iodized oil. These microspheres also result in tissue necrosis, which was not observed after embolization with iodized oil. Both radiopaque and standard 40µm-microspheres are found within subsegmental and interlobar arteries, as well as in hepatic sinusoids.

In vivo characterization of a new type of biodegradable starch microsphere for transarterial embolization.

Transarterial embolization is an established minimally invasive treatment for solid tumors. Unintended inflammation, foreign body reactions and ischemia-triggered neoangiogenesis are clinical drawbacks of permanent embolic materials. The aim of the current study was to characterize a new type of biodegradable starch microsphere with regard to angiographic and histopathological features such as patterns of acute arterial occlusion as well as induction of tissue necrosis, microsphere biodegradation, and inflammation and foreign body reactions during follow-up. Key characteristics of both biodegradable prototypes (L1 and L2; prototype groups) were as follows: microspheres are biodegradable by serum α-amylase, produced from chemically crosslinked potato starch to different extents, in a diameter range of ∼300-800 µm, differing in size distribution and featuring a microsphere deformation of ∼1%. In vivo transarterial embolization with L1 and L2, while applying clinical standard techniques, was performed and compared with clinically established permanent microspheres (Embosphere®500-700 and Embosphere®700-900; control groups). Twenty-four pig kidneys were embolized with the different embolic materials by following the study protocol, and there were no technical failures or complications. Parenchymal necrosis with interstitial calcification was observed in all kidneys independent of the type of embolic material used. Compared with the permanent embolic materials, biodegradable microspheres showed complete (L1) or partial (L2) biodegradation within one week after transarterial embolization, and induced a comparable (L1) or a lower (L2) degree of arterial wall necrosis and a lower degree of inflammation and foreign body reactions. In conclusion, the presented new type of biodegradable microsphere is promising, and could be further evaluated in terms of clinical translation.

Evaluation of a novel liquid embolic agent (precipitating hydrophobic injectable liquid (PHIL)) in an animal endovascular embolization model.

BACKGROUND: The choice of the embolic agent and the embolization technique can have a significant impact on the success of endovascular embolization. OBJECTIVE: To evaluate a novel iodinated copolymer-based liquid embolic agent (precipitating hydrophobic injectable liquid (PHIL)) in the porcine rete mirabile (RM), serving as an endovascular embolization model. Onyx, as an established liquid embolic agent, served as comparator. MATERIALS AND METHODS: Sixteen embolization procedures were performed using PHIL (n=8) or Onyx (n=8) as liquid embolic agent. Waiting time between injections was set to 30 or 60 s (n=4 per study group). Survival time after intervention was 2 hours or 7 days. Embolization characteristics (eg, procedure times, number of injections and volume of embolic agent) and embolization extent (percentage of embolized RM in post-interventional x-ray) were assessed. Post-interventional CT and histopathological analyses were performed. RESULTS: Embolization characteristics and embolization extent were not significantly different for PHIL and Onyx, including subgroups (eg, embolization extent 44% vs 69% (medians); p=0.101). For PHIL, extension of the waiting time from 30 to 60 s led to a significantly higher embolization extent (24% vs 72% (medians); p=0.035). Moderate disintegration and mild inflammation of the embolized blood vessels were present for both embolic agents. CONCLUSION: PHIL is feasible for transarterial embolization in an acute and subacute endovascular embolization model. In this preliminary experimental in vivo study, embolization characteristics, embolization extent, and biocompatibility seem to be similar to those of Onyx.

Electrochemical Effects after Transarterial Chemoembolization in Combination with Percutaneous Irreversible Electroporation: Observations in an Acute Porcine Liver Model.

PURPOSE: To evaluate the effects of combined use of transarterial chemoembolization and irreversible electroporation (IRE) for focal tissue ablation in an acute porcine liver model. MATERIALS AND METHODS: Two established interventional techniques were combined: IRE with zones of irreversible and reversible electroporation and chemoembolization with microspheres, iodized oil, and doxorubicin. IRE was performed before chemoembolization in two pigs (pigs 1 and 2; IRE/chemoembolization group), chemoembolization was performed before IRE in two pigs (pigs 3 and 4; chemoembolization/IRE group), and only IRE was performed in two pigs (pigs 5 and 6). Five study groups were defined: IRE/chemoembolization (pigs 1 and 2), chemoembolization/IRE (pigs 3 and 4), IRE only (pigs 5 and 6), chemoembolization only (tissue outside the IRE zones in pigs 1-4), and control (untreated liver tissue outside the IRE zones in pigs 5 and 6). Animals were euthanized 2 hours after intervention. Size and shape of IRE zones on contrast-enhanced computed tomography, cell death on light microscopy, and doxorubicin tissue concentrations on chromatography and fluorescence microscopy were analyzed. RESULTS: Size and shape of IRE zones were not significantly different (eg, P = .067 for volume). A histologic marker for irreversible cell death was positive in IRE/chemoembolization, chemoembolization/IRE, and IRE groups only in the macroscopically visible IRE zones. Doxorubicin tissue concentrations were not significantly different (P = .873). However, in the reversible electroporation (RE) zones, broad areas with intense intranuclear doxorubicin accumulation were observed in IRE/chemoembolization but not in chemoembolization/IRE and chemoembolization groups. CONCLUSIONS: IRE before chemoembolization enhances the intranuclear accumulation of doxorubicin in the RE zone.

Efficacy and nontarget effects of transarterial chemoembolization in bridging of hepatocellular carcinoma patients to liver transplantation: a histopathologic study.

PURPOSE: To histologically evaluate the efficacy and nontarget effects induced by transarterial chemoembolization as a "bridge" treatment of hepatocellular carcinoma (HCC) before liver transplantation (LT) and its relation to patient survival. MATERIALS AND METHODS: Between October 2003 and January 2011, 51 patients with HCC underwent LT after chemoembolization with iodized oil, small spherical particles, and carboplatin. The decision for LT was made according to national guidelines. The efficacy and nontarget effects of chemoembolization were determined histologically in explanted livers, and their impact on patients' survival after LT was analyzed. RESULTS: A total of 126 chemoembolization procedures were performed in 51 patients; the median number of procedures per patient was three (range, one to six). The extent of HCC necrosis was less than or equal to 50% in 32% of treated HCCs, more than 50% and less than or equal to 90% in 17%, and more than 90%-99% in 14%; 38% showed complete necrosis of the lesion. The most common nontarget effects were focal necrosis of the liver parenchyma adjacent to the embolized HCC nodule (28%), intralesional (micro)abscess (26%), intralesional hemorrhage (22%), and peritumoral bile duct necrosis (12%). Based on histopathologic examination, 35% of patients had HCC that did not meet Milan criteria. None of these findings was significantly associated with patient survival after LT. CONCLUSIONS: Transarterial chemoembolization induces histopathologically confirmed HCC necrosis with a high degree of efficacy, but histologically proven complete HCC necrosis was not predictive of survival in this cohort of patients. Although histopathologic examination revealed (clinically relevant) nontarget effects in a subset of patients, they did not impair survival.

Therapeutic lymphangiography and CT-guided sclerotherapy for the treatment of refractory lymphatic leakage.

PURPOSE: To evaluate therapeutic lymphangiography and computed tomography (CT)-guided sclerotherapy for the treatment of refractory inguinal, pelvic, abdominal, and thoracic lymphatic leakage. MATERIALS AND METHODS: Between January 2008 and April 2011, 18 patients with refractory lymphatic leakage were treated with therapeutic lymphangiography. Additionally, 10 of these 18 patients underwent CT-guided sclerotherapy with injection of ethanol at the site of the leakage. In the delayed sclerotherapy group (n = 5), the sclerotherapy procedure was performed when the leak persisted after therapeutic lymphangiography. In the immediate sclerotherapy group (n = 5), sclerotherapy was performed on the same day as lymphangiography. The sites of the lymphatic leakage were as follows: inguinal leakage in 8 patients, pelvic leakage in 4 patients, abdominal leakage in 2 patients, and thoracic leakage in 4 patients. Data collected included technical success, clinical success, and procedural complications. RESULTS: Lymphangiography was technically successful in all patients. In eight patients undergoing therapeutic lymphangiography alone, the clinical success rate was 75%, and the drainage catheter could be removed in six patients after the treatment. Lymphangiography followed by immediate sclerotherapy was clinically successful in four of five patients. Lymphangiography combined with delayed sclerotherapy was clinically successful in three of five patients. Overall, the clinical success rate was 72% (13 of 18 patients). One minor complication occurred. CONCLUSIONS: Therapeutic lymphangiography alone or in combination with CT-guided sclerotherapy is a promising treatment option for the management of refractory lymphatic leakage.

Optimisation of the coagulation zone for thermal ablation procedures: a theoretical approach with considerations for practical use.

PURPOSE: This paper outlines a theoretical approach for optimisation of the coagulation zone for thermal ablation procedures and considerations for its practical application. METHODS: The theoretical approach is outlined in the Cartesian coordinate system. Considerations for practical application are implemented. The optimised coagulation zone is defined as the bare coverage of tumour mass plus a safety margin. The eccentricity of coagulation centre (ECC) is defined as the distance between the coagulation centre and the tumour centre. The direction of the applicator shaft is determined based on the x-axis direction. The tumour centre and coagulation centre are defined within the x/y-plane. The distance between coagulation margin (applicator tip) and tumour margin is called parallel offset (PAO). RESULTS: For spherical coagulation shapes, a linear relationship exists between optimised coagulation diameter and ECC. An exponential relationship exists between optimised coagulation volume and ECC. A complex relationship was found between PAO and determinants of ECC, which are ex and ey. PAO is an extremely important parameter, which allows for determination of the optimal applicator tip position in relation to the tumour margin. It can be calculated in such a manner that the optimised coagulation zone is minimised by neutralising dislocation of the coagulation centre in applicator shaft direction. The latter can be realised by withdrawing or further inserting the applicator shaft. CONCLUSIONS: The presented concept can be used to optimise the extent of the coagulation zone for thermal ablation procedures after positioning of the applicator. Its inherent advantage is the simple adjustment of the applicator shaft, which obviates the need for a repuncture.

Portal vein embolization using a Histoacryl/Lipiodol mixture before right liver resection.

PURPOSE: The purpose of this retrospective study was to evaluate the efficacy and safety of percutaneous transhepatic portal vein embolization (PVE) of the right liver lobe using Histoacryl/Lipiodol mixture to induce contralateral liver hypertrophy before right-sided (or extended right-sided) hepatectomy in patients with primarily unresectable liver tumors. METHODS: Twenty-one patients (9 females and 12 males) underwent PVE due to an insufficient future liver remnant; 17 showed liver metastases and 4 suffered from biliary cancer. Imaging was performed prior to and 4 weeks after PVE. Surgery was scheduled for 1 week after a CT or MRI control. The primary study end point was technical success, defined as complete angiographical occlusion of the portal vein. The secondary study end point was evaluation of liver hypertrophy by CT and MRI volumetry and transfer to operability. RESULTS: In all the patients, PVE could be performed with a Histoacryl/Lipiodol mixture (n = 20) or a Histoacryl/Lipiodol mixture with microcoils (n = 1). No procedure-related complications occurred. The volume of the left liver lobe increased significantly (p < 0.0001) by 28% from a mean of 549 ml to 709 ml. Eighteen of twenty-one patients (85.7%) could be transferred to surgery, and the intended resection could be performed as planned in 13/18 (72.3%) patients. CONCLUSION: Preoperative right-sided PVE using a Histoacryl/Lipiodol mixture is a safe technique and achieves a sufficient hypertrophy of the future liver remnant in the left liver lobe.

Paclitaxel-induced arterial wall toxicity and inflammation: tissue uptake in various dose densities in a minipig model.

PURPOSE: Paclitaxel is an antiproliferative agent in drug-eluting stents with largely unknown tissue interaction. Toxicity might result from overdosage and/or accumulation. Part 1 of this two-step study investigated how paclitaxel uptake depends on dose density, coronary drug transfer kinetics, and elution efficacy. MATERIALS AND METHODS: With cobalt chromium stents and Polyzene-F nanoscale coating, low, intermediate, and high paclitaxel dose densities (25 microg, 50 microg, and 150 microg per stent) were investigated in porcine right coronary arteries (RCAs). Coronary and myocardial tissue concentration measurements and determination of on-stent paclitaxel and plasma concentrations were performed at 2, 8, 24, and 72 hours. RESULTS: For all stents, uptake was similar at all time intervals (paclitaxel RCA concentration range, 1,610-33,300 ng). Low- and intermediate-dose stents showed similar RCA concentrations, but those for high-dose stents were three times greater. Residual on-stent paclitaxel concentration was not time-dependent, at 33.3% on low-, 30.6% on intermediate-, and 17.4% on high-dose stents. Paclitaxel was measurable in only the plasma immediately after stent placement, with a linear dose relationship and a timely regression: measurements in high-dose stents were 0.0454-0.656 ng/mL at 1 minute and 0.0329-0.0879 ng/mL at 5 minutes. Untreated control samples of the left coronary artery showed a linear dose-dependent concentration (12.6 ng/g, 21.2 ng/g, and 85.2 ng/g). CONCLUSIONS: Overall coronary paclitaxel uptake is fairly independent from the baseline overall dose density and, hence, depends on immediate binding mechanisms of the arterial wall. This is supported by the fact that, regardless of the applied dose density, the kinetics of paclitaxel uptake did not follow an exposure time pattern.