Dosimetric advantages for cardiac substructures in radiotherapy of esophageal cancer in deep-inspiration breath hold.

BACKGROUND: Radiotherapy is one of the main treatment options for patients with esophageal cancer; however, it has been linked with an increased risk of cardiac toxicities. In the current study, we evaluated the effect of planning the radiation in deep-inspiration breath hold (DIBH) on the dose sparing of cardiac substructures and lung. MATERIALS AND METHODS: In this study, we analyzed 30 radiation therapy plans from 15 patients diagnosed with esophageal cancer planned for neoadjuvant radiotherapy. Radiation plans were generated for 41.4 Gy and delivered in 1.8 Gy per fraction for free-breathing (FB) and DIBH techniques. We then conducted a comparative dosimetric analysis, evaluating target volume coverage, the impact on cardiac substructures, and lung doses across the two planning techniques for each patient. RESULTS: There was no significant disparity in target volume dose coverage between DIBH and FB plans. However, the Dmean, D2%, and V30% of the heart experienced substantial reductions in DIBH relative to FB, with values of 6.21 versus 7.02 Gy (p = 0.011), 35.28 versus 35.84 Gy (p = 0.047), and 5% versus 5.8% (p = 0.048), respectively. The Dmean of the left ventricle was notably lower in DIBH compared to FB (4.27 vs. 5.12 Gy, p = 0.0018), accompanied by significant improvements in V10. Additionally, the Dmean and D2% of the left coronary artery, as well as the D2% of the right coronary artery, were significantly lower in DIBH. The dosimetric impact of DIBH on cardiac substructures proved more advantageous for middle esophageal (ME) than distal esophageal (DE) tumors. CONCLUSION: Radiotherapy in DIBH could provide a method to reduce the radiation dose to the left ventricle and coronaries, which could reduce the cardiac toxicity of the modality.

Managing hepatocellular carcinoma across the stages: efficacy and outcomes of stereotactic body radiotherapy : A retrospective study.

PURPOSE: Hepatocellular carcinoma (HCC) poses a unique challenge due to its predilection for developing on compromised livers, often limiting surgical options. Stereotactic body radiotherapy (SBRT) has emerged as a promising local treatment modality for HCC. This study aims to assess the effectiveness of SBRT in HCC patients not suitable for surgery, focusing on local control, optimal radiation dosing, and prognostic factors. METHODS: In this retrospective analysis, 52 HCC patients treated with SBRT were examined. The study assessed local control, progression-free survival (PFS), and overall survival (OS) while conducting dosimetric analyses. The relationship between mean liver dose and Child-Pugh score (CPS) progression was also explored. RESULTS: SBRT demonstrated 93.4% freedom from local progression (FFLP) at 12 months. Notably, a near minimum dose (D98%) below 61 Gy as an equivalent dose in 2­Gy fractions with α/ß 10 Gy (EQD2α/ß10) was associated with reduced FFLP (p-value 0.034). Logistic regression analysis revealed a dose-response relationship for FFLP and D98% with 95% and 98% probability of FFLP at a dose of 56.9 and 73.1 Gy, respectively. The study observed OS rates of 63.7% at 1 year and 34.3% at 3 years. Patients with portal vein tumor thrombus (PVTT) and larger tumors (≥ 37 cm3) experienced decreased PFS and OS. Multivariate analysis identified PVTT, larger tumor volume, and performance status as independent predictors of reduced OS. Notably, classical radiation-induced disease (cRILD) was absent, but nonclassical (nc) RILD occurred in 7.7% of patients. Regression analysis linked a mean EQD2α/ß3-8 dose to the liver (12.8-12.6) with a 10% likelihood of ncRILD. CONCLUSION: SBRT offers a compelling option for achieving high local control and promising survival outcomes in HCC. The study supports a radiation dose range of 61-73.1 Gy, coupled with a mean liver dose under 12.6-12.8 Gy as EQD2, to achieve favorable FFLP rates, with acceptable toxicity rates.

Preoperative predictors for non-resectability in perihilar cholangiocarcinoma.

INTRODUCTION: Explorative laparotomy without subsequent curative-intent liver resection remains a major clinical problem in the treatment of perihilar cholangiocarcinoma (pCCA). Thus, we aimed to identify preoperative risk factors for non-resectability of pCCA patients. MATERIAL AND METHODS: Patients undergoing surgical exploration between 2010 and 2022 were eligible for the analysis. Separate binary logistic regressions analyses were used to determine risk factors for non-resectability after explorative laparotomy due to technical (tumor extent, vessel infiltration) and oncological (peritoneal carcinomatosis, distant nodal or liver metastases)/liver function reasons. RESULTS: This monocentric cohort comprised 318 patients with 209 (65.7%) being surgically resected and 109 (34.3%) being surgically explored [explorative laparotomy: 87 (27.4%), laparoscopic exploration: 22 (6.9%)]. The median age in the cohort was 69 years (range 60-75) and a majority had significant comorbidities with ASA-Score ≥ 3 (202/318, 63.5%). Statistically significant (p < 0.05) risk factors for non-resectability were age above 70 years (HR = 3.76, p = 0.003), portal vein embolization (PVE, HR = 5.73, p = 0.007), and arterial infiltration > 180° (HR = 8.05 p < 0.001) for technical non-resectability and PVE (HR = 4.67, p = 0.018), arterial infiltration > 180° (HR = 3.24, p = 0.015), and elevated CA 19-9 (HR = 3.2, p = 0.009) for oncological/liver-functional non-resectability. CONCLUSION: Advanced age, PVE, arterial infiltration, and elevated CA19-9 are major risk factors for non-resectability in pCCA. Preoperative assessment of those factors is crucial for better therapeutical pathways. Diagnostic laparoscopy, especially in high-risk situations, should be used to reduce the amount of explorative laparotomies without subsequent liver resection.

Artificial Intelligence for Clinical Interpretation of Bedside Chest Radiographs.

Background Supine chest radiography for bedridden patients in intensive care units (ICUs) is one of the most frequently ordered imaging studies worldwide. Purpose To evaluate the diagnostic performance of a neural network-based model that is trained on structured semiquantitative radiologic reports of bedside chest radiographs. Materials and Methods For this retrospective single-center study, children and adults in the ICU of a university hospital who had been imaged using bedside chest radiography from January 2009 to December 2020 were reported by using a structured and itemized template. Ninety-eight radiologists rated the radiographs semiquantitatively for the severity of disease patterns. These data were used to train a neural network to identify cardiomegaly, pulmonary congestion, pleural effusion, pulmonary opacities, and atelectasis. A held-out internal test set (100 radiographs from 100 patients) that was assessed independently by an expert panel of six radiologists provided the ground truth. Individual assessments by each of these six radiologists, by two nonradiologist physicians in the ICU, and by the neural network were compared with the ground truth. Separately, the nonradiologist physicians assessed the images without and with preliminary readings provided by the neural network. The weighted Cohen κ coefficient was used to measure agreement between the readers and the ground truth. Results A total of 193 566 radiographs in 45 016 patients (mean age, 66 years ± 16 [SD]; 61% men) were included and divided into training (n = 122 294; 64%), validation (n = 31 243; 16%), and test (n = 40 029; 20%) sets. The neural network exhibited higher agreement with a majority vote of the expert panel (κ = 0.86) than each individual radiologist compared with the majority vote of the expert panel (κ = 0.81 to ≤0.84). When the neural network provided preliminary readings, the reports of the nonradiologist physicians improved considerably (aided vs unaided, κ = 0.87 vs 0.79, respectively; P < .001). Conclusion A neural network trained with structured semiquantitative bedside chest radiography reports allowed nonradiologist physicians improved interpretations compared with the consensus reading of expert radiologists. © RSNA, 2022 Supplemental material is available for this article. See also the editorial by Wielpütz in this issue.

Survival after combined resection and ablation is not inferior to that after resection alone, in patients with four or more colorectal liver metastases.

PURPOSE: Colorectal liver metastases (CRLM) are the predominant factor limiting survival in patients with colorectal cancer. Multimodal treatment strategies are frequently necessary to achieve total tumor elimination. This study examines the efficacy of liver resection combined with local ablative therapy in comparison to liver resection only, in the treatment of patients with ≥ 4 CRLM. METHODS: This retrospective cohort study was conducted at the University Hospital RWTH Aachen, Germany. Patients with ≥ 4 CRLM in preoperative imaging, who underwent curative resection between 2010-2021, were included. Recurrent resections and deaths in the early postoperative phase were excluded. Ablation modalities included radiofrequency or microwave ablation, and irreversible electroporation. Differences in overall- (OS) and recurrence-free-survival (RFS) between patients undergoing combined resection-ablation vs. resection only, were examined. RESULTS: Of 178 included patients, 46 (27%) underwent combined resection-ablation and 132 (73%) resection only. Apart from increased rates of adjuvant chemotherapy in the first group (44% vs. 25%, p = 0.014), there were no differences in perioperative systemic therapy. Kaplan-Meier and log-rank test analyses showed no statistically significant differences in median OS (36 months for both, p = 0.638) or RFS (9 months for combined resection-ablation vs. 8 months, p = 0.921). Cox regression analysis showed a hazard ratio of 0.891 (p = 0.642) for OS and 0.981 (p = 0.924) for RFS, for patients undergoing resection only. CONCLUSION: For patients with ≥ 4 CRLM, combined resection-ablation is a viable option in terms of OS and RFS. Therefore, combined resection-ablation should be considered for complete tumor clearance, in patients with multifocal disease.

Time to surgery is not an oncological risk factor in HCC patients undergoing liver resection.

PURPOSE: Given limitations of the health care systems in case of unforeseeable events, e.g., the COVID pandemic as well as trends in prehabilitation, time from diagnosis to surgery (time to surgery, (TTS)) has become a research issue in malignancies. Thus, we investigated whether TTS is associated with oncological outcome in HCC patients undergoing surgery. METHODS: A monocentric cohort of 217 patients undergoing liver resection for HCC between 2009 and 2021 was analyzed. Individuals were grouped according to TTS and compared regarding clinical characteristics. Overall survival (OS) and recurrence-free survival (RFS) was compared using Kaplan-Meier analysis and investigated by univariate and multivariable Cox regressions. RESULTS: TTS was not associated with OS (p=0.126) or RFS (p=0.761) of the study cohort in univariate analysis. In multivariable analysis age (p=0.028), ASA (p=0.027), INR (0.016), number of HCC nodules (p=0.026), microvascular invasion (MVI; p<0.001), and postoperative complications (p<0.001) were associated with OS and INR (p=0.005), and number of HCC nodules (p<0.001) and MVI (p<0.001) were associated with RFS. A comparative analysis of TTS subgroups was conducted (group 1, ≤30 days, n=55; group 2, 31-60 days, n=79; group 3, 61-90 days, n=45; group 4, >90 days, n=38). Here, the median OS were 62, 41, 38, and 40 months (p=0.602 log rank) and median RFS were 21, 26, 26, and 25 months (p=0.994 log rank). No statistical difference regarding oncological risk factors were observed between these groups. CONCLUSION: TTS is not associated with earlier tumor recurrence or reduced overall survival in surgically treated HCC patients.

Value of prognostic scoring systems in the era of multimodal therapy for recurrent colorectal liver metastases.

BACKGROUND: Various predictive scoring systems have been developed to estimate outcomes of patients undergoing surgery for colorectal liver metastases (CRLM). However, data regarding their effectiveness in recurrent CRLM (recCRLM) are very limited. METHODS: Patients who underwent repeat hepatectomy for recCRLM at the University Hospital RWTH Aachen, Germany from 2010 to 2021 were included. Nine predictive scoring systems (Fong's, Nordlinger, Nagashima, RAS mutation, Tumor Burden, GAME, CERR, and Glasgow Prognostic score, Basingstoke Index) were evaluated by likelihood ratio (LR) χ2, linear trend (LT) χ2 and Akaike Information Criterion (AIC) for their predictive value regarding overall survival (OS) and recurrence free survival (RFS). RESULTS: Among 150 patients, median RFS was 9 (2-124) months with a 5-year RFS rate of 10%. Median OS was 39 (4-131) months with a 5-year OS rate of 32%. For RFS and OS, the Nagashima score showed the best prognostic ability (LT χ2 3.00, LR χ2 9.39, AIC 266.66 and LT χ2 2.91, LR χ2 20.91, 290.36). DISCUSSION: The Nagashima score showed the best prognostic stratification to predict recurrence as well as survival, and therefore might be considered when evaluating patients with recCRLM for repeat hepatectomy.

Safety and efficacy of right portal vein embolization in patients with prior left lateral liver resection.

BACKGROUND: In patients with bilobar metastatic liver disease, surgical clearance of both liver lobes may be achieved through multiple-stage liver resections. For patients with extensive disease, a major two-staged hepatectomy consisting of resection of liver segments II and III before right-sided portal vein embolization (PVE) and resection of segments V-VIII may be performed, leaving only segments IV ± I as the liver remnant. PURPOSE: To describe the outcome following right-sided PVE after prior complete resection of liver segments II and III. MATERIAL AND METHODS: In this retrospective study, 15 patients (mean age = 60.4 ± 9.3 years) with liver metastases from colorectal cancer (n = 14) and uveal melanoma (n = 1) who were scheduled to undergo a major two-stage hepatectomy, were included. Total liver volume (TLV) and volume of the future liver remnant (FLR) were measured on pre- and postinterventional computed tomography (CT) scans, and standardized FLR volumes (ratio FLR/TLV) were calculated. Patient data were retrospectively analyzed regarding peri- and postinterventional complications, with special emphasis on liver function tests. RESULTS: The mean standardized post-PVE FLR volume was 26.9% ± 6.4% and no patient developed hepatic insufficiency after the PVE. Based on FLR hypertrophy and liver function tests, all but one patient were considered eligible for the subsequent right-sided hepatectomy. However, due to local tumor progression, only 9/15 patients eventually proceeded to the second stage of surgery.  . CONCLUSION: Right-sided PVE was safe and efficacious in this cohort of patients who had previously undergone a complete resection of liver segments II and III as part of a major staged hepatectomy pathway leaving only segments IV(±I) as the FLR. .

An accelerometer-based guidance device for CT-guided procedures: an improved wireless prototype.

INTRODUCTION: The aim of the study was to demonstrate the feasibility of a prototype for accelerometer-based guidance for percutaneous CT-guided punctures and compare it with free-hand punctures. MATERIAL AND METHODS: The prototype enabled alignment with the CT coordinate system and a wireless connectivity. Its feasibility was tested in a swine cadaver model: 20 out-of-plane device-assisted punctures performed without intermittent control scans (one-step punctures) were evaluated regarding deviation to target and difference between planned and obtained angle. Thereafter, 22 device-assisted punctures were compared with 20 free-hand punctures regarding distance to target, deviation from the planned angle, number of control scans and procedure time. Differences were compared with the Mann-Whitney U-test (p < .05). RESULTS: The one-step punctures revealed a deviation to target of 0.26 ± 0.37 cm (axial plane) and 0.21 ± 0.19 cm (sagittal plane) and differences between planned and performed puncture angles of 0.9 ± 1.09° (axial plane) and 1.15 ± 0.91° (sagittal planes). In the comparative study, device-assisted punctures showed a significantly higher accuracy, 0.20 ± 0.17 cm vs. 0.30 ± 0.21 cm (p < .05) and lower number of required control scans, 1.3 ± 1.1 vs. 3.7 ± 0.9 (p < .05) compared with free-hand punctures. CONCLUSION: The accelerometer-based device proved to be feasible and demonstrated significantly higher accuracy and required significantly less control scans compared to free-hand puncture.

Percutaneous transhepatic biliary drainage (PTBD) in patients with dilated vs. nondilated bile ducts: technical considerations and complications.

OBJECTIVES: The aim of this study was to compare success, technical complexity, and complication rates of percutaneous transhepatic biliary drainage (PTBD) in patients with dilated vs. nondilated bile ducts. METHODS: In a retrospective analysis, we evaluated all consecutive PTBD performed in our department over a period of 5 years. Technical success, technical data (side, fluoroscopy time, radiation dose, amount of contrast media, use of disposable equipment), procedure-related complications and peri-interventional mortality were compared for patients with dilated vs. non-dilated bile ducts. Independent t test and χ2 test were used to evaluate the statistical significance. RESULTS: A total of 253 procedures were performed on 187 patients, of whom 101/253 had dilated bile ducts and 152/253 not. In total, 243/253 procedures were successful. PTBD was significantly more often successful in patients with dilated vs. nondilated bile ducts (150/153 vs. 93/101; p 0.02). Overall complication rate (13%) did not differ significantly between patients with dilated vs. nondilated bile ducts. Procedures in patients with normal, nondilated bile ducts were associated with a significantly higher rate of post-interventional bleeding (5/101 vs. 0/152). Mean fluoroscopy time (42:36 ± 35:39 h vs. 30:28 ± 25:10 h; p 0.002) and amount of contrast media (66 ± 40 ml vs. 52 ± 24 ml; p 0.07) or use of disposables were significantly higher in patients with nondilated ducts. A significantly lower fluoroscopy time and amount of contrast medium were used in left hepatic PTBD. CONCLUSION: Despite the higher technical complexity, PTBD with nondilated bile ducts was associated with similar overall complication rates but higher bleeding complications compared with PTBD with dilated bile ducts. KEY POINTS: • PTBD was associated with similar overall complication rates in patients with dilated vs. nondilated bile ducts. • Although overall complication rates were low, PTBD in patients with nondilated bile ducts was associated with a higher incidence of post-interventional bleeding. • PTBD in patients with nondilated bile ducts is technically more complex.

Induction of Contralateral Hepatic Hypertrophy by Unilobar Yttrium-90 Transarterial Radioembolization versus Portal Vein Embolization: An Animal Study.

PURPOSE: To compare hepatic hypertrophy in the contralateral lobe achieved by unilobar transarterial radioembolization (TARE) versus portal vein embolization (PVE) in a swine model. METHODS: After an escalation study to determine the optimum dose to achieve hypertrophy after unilobar TARE in 4 animals, 16 pigs were treated by TARE (yttrium-90 resin microspheres) or PVE (lipiodol/n-butyl cyanoacrylate). Liver volume was calculated based on CT before treatment and during 6 months of follow-up. Independent t-test (P < .05) was used to compare hypertrophy. The relationship between hypertrophy after TARE and absorbed dose was calculated using the Pearson correlation. RESULTS: At 2 and 4 weeks after treatment, a significantly higher degree of future liver remnant hypertrophy was observed in the PVE group versus the TARE group, with a median volume gain of 31% (interquartile range [IQR]: 16%-66%) for PVE versus 23% (IQR: 6%-36%) for TARE after 2 weeks and 51% (IQR: 47%-69%) for PVE versus 29% (IQR: 20%-50%) for TARE after 4 weeks. After 3 and 6 months, hypertrophy converged without a statistically significant difference, with a volume gain of 103% (IQR: 86%-119%) for PVE versus 82% (IQR: 70%-96%) for TARE after 3 months and 115% (IQR: 70%-46%) for PVE versus 86% (IQR: 58%-111%) for TARE after 6 months. A strong correlation was observed between radiation dose (median 162 Gy, IQR: 139-175) and hypertrophy. CONCLUSIONS: PVE resulted in rapid hypertrophy within 1 month of the procedure, followed by a plateau, whereas TARE resulted in comparable hypertrophy by 3-6 months. TARE-induced hypertrophy correlated with radiation absorbed dose.

Clinical value and limitations of the preoperative C-reactive-protein-to-albumin ratio in predicting post-operative morbidity and mortality after deceased-donor liver transplantation: a retrospective single-centre study.

Liver transplantation is still associated with a high risk of severe complications and post-operative mortality. This study examines the predictive value of the preoperative C-reactive-protein-to-albumin ratio (CAR) regarding perioperative morbidity and mortality in deceased-donor liver transplantation (DDLT) recipients. In total, 390 DDLT recipients between 05/2010 and 03/2020 were eligible. Predictive abilities of CAR were examined through receiver operating characteristic curve (ROC) analyses. Groups were compared using parametric and non-parametric tests as appropriate. Independent risk factors for morbidity and mortality were identified using uni- and multivariable logistic regression analyses. A good predictive ability for CAR was shown regarding perioperative morbidity (comprehensive complication index ≥75, Clavien-Dindo score ≥4a) and 12-month mortality, with an ideal cut-off of CAR = 26%. Patients with CAR>26% had significantly higher median CCI scores (60 vs. 43, P < 0.001), longer intensive care unit (ICU, 5 vs. 4 days, P < 0.001) and hospital (28 vs. 21 days, P < 0.001) stays and higher 12-month mortality rates (20% vs 6%, P < 0.001). Multivariable analyses identified CAR>26%, pre-OLT inpatient hospitalization (including ICU) and post-operative red blood cell transfusions as independent predictors of severe cumulative morbidity (CCI≥75). Preoperative CAR might be a reliable additional tool to predict perioperative morbidity and mortality in DDLT recipients.

Prognostic evaluation of HCC patients undergoing surgical resection: an analysis of 8 different staging systems.

PURPOSE: No consensus exists regarding the most appropriate staging system to predict overall survival (OS) for hepatocellular carcinoma (HCC) in surgical candidates. Thus, we aimed to determine the prognostic ability of eight different staging systems in a European cohort of patients undergoing liver resection for HCC. METHODS: Patients resected for HCC between 2010 and 2019 at our institution were analyzed with Kaplan-Meier and Cox regression analyses. Likelihood ratio (LR) χ2 (homogeneity), linear trend (LT) χ2 (discriminatory ability), and Akaike Information Criterion (AIC, explanatory ability) were used to determine the staging system with the best overall prognostic performance. RESULTS: Liver resection for HCC was performed in 160 patients. Median OS was 39 months (95% confidence interval (CI): 32-46 months) and median RFS was 26 months (95% CI: 16-34 months). All staging systems (BCLC, HKLC, Okuda, CLIP, ITA.LI.CA staging and score, MESH, and GRETCH) showed significant discriminatory ability regarding OS, with ITA.LI.CA score (LR χ2 30.08, LT χ2 13.90, AIC 455.27) and CLIP (LR χ2 28.65, LT χ2 18.95, AIC 460.07) being the best performing staging systems. CONCLUSIONS: ITA.LI.CA and CLIP are the most suitable staging system to predict OS in European HCC patients scheduled for curative-intent surgery.

Insufficient future liver remnant and preoperative cholangitis predict perioperative outcome in perihilar cholangiocarcinoma.

BACKGROUND: Major liver resection has evolved as the mainstay of treatment for patients with perihilar cholangiocarcinoma (pCCA). Here we assessed the suitability of preoperative future liver remnant (FLR) measurement to predict perioperative complications, since surgical morbidity and mortality are high compared to other malignancies. METHODS: Between 2011 and 2016, 91 patients with pCCA underwent surgery in curative intent at our institution. The associations of surgical complications with FLR and clinico-pathological characteristics were assessed using logistic regression analyses. Different methods of FLR assessment, the calculated-FLR (cFLR; ratio of FLR to total liver volume), standardized FLR (sFLR; ratio of FLR to liver volume estimated by body surface area) and FLR to bodyweight ratio (FLR/BW) were tested for validity. RESULTS: Multivariable analysis identified preoperative cholangitis (Exp(B) = 0.236; p = 0.030) as the single significant predictor of postoperative mortality and cFLR (Exp(B) = 0.009, p = 0.004) as the single significant predictor of major postoperative morbidity (Clavien-Dindo ≥ 3b). Based on these findings we designed a futility criterion (cFLR<40% OR preoperative cholangitis) predicting in-house mortality. CONCLUSIONS: In patients with pCCA, the preoperative FLR<40% as well as preoperative cholangitis are two risk factors to independently predict perioperative morbidity and mortality. The cFLR should be the preferred method of liver volumetry.

The prognostic role of tumor-associated unilateral portal vein occlusion in perihilar cholangiocarcinoma.

BACKGROUND: While a certain degree of tumor infiltration of the portal vein is common in patients with perihilar cholangiocarcinoma (pCCA) scheduled for surgery, complete tumor-associated portal vein occlusion (PVO) is less frequently observed. Here, we analyzed the impact of PVO on perioperative and oncological outcomes in pCCA patients. METHODS: Between 2010 and 2019, 127 patients with pCCA underwent surgery in curative intent at our department of which 17.3% (22/127) presented with PVO. Extensive group comparisons were conducted and the association of cancer-specific (CSS) and disease-free survival (DFS) with PVO and other clinico-pathological characteristics were assessed using Cox regression models. RESULTS: Patients without PVO showed a median CSS of 65 months (3-year-CSS = 64%, 5-year-CSS = 53%) compared to 31 months (3-year-CSS = 43%, 5-year-CSS = 17%) in patients with PVO (p = 0.025 log rank). Patients with PVO did also display significant perioperative mortality (22.7%, 5/22) compared to patients without PVO (14.3%, 15/105, p = 0.323). Further, PVO (CSS: HR = 5.25, p = 0.001; DFS: HR = 5.53, p = 0.001) was identified as independent predictors of oncological outcome. CONCLUSIONS: PVO has been identified as an important prognostic marker playing a role in inferior oncological outcome in patients with pCCA. As PVO is also associated with notable perioperative mortality, surgical therapy should be considered carefully in pCCA patients.

Salvage RFA in patients with intrahepatic recurrence after major hepatic surgery for colorectal cancer liver metastases: mid-term outcome.

OBJECTIVES: To evaluate the mid-term outcome of salvage radiofrequency ablation (RFA) treatment in patients who exhibited intrahepatic recurrence after major hepatectomy for colorectal liver metastases (CRCLM). METHODS: Observational study on 23 consecutive patients (mean age 59 ± 9 years; 14/9 male/female) who, after a single (11/23) or multiple rounds (12/23) of major hepatic surgery, developed recurrent CRCLM in the liver remnant. Patients with a maximum of three metastases measuring up to 3 cm, and without relevant extrahepatic disease, underwent CT-guided RFA. Using the Kaplan-Meier-method, median intrahepatic progression-free-survival (ihPFS) and overall survival (OS) times after salvage RFA were compared with the same patients' time between the respective last round of surgery and diagnosis of intrahepatic recurrence leading to RFA. RESULTS: Median follow-up was 26 months (range 12-103 months). Median ihPFS time after RFA was 8 months (range 1-81 months). Median ihPFS time after the respective last round of surgery and RFA in the same patients had been 5 months (range 1-23 months), thus yielding similar ihPFS times after surgery vs. after salvage RFA (p = 0.238; Mood's median test). After RFA, 15/23 (65%) of patients developed new hepatic metastases within the first year post-RFA. Median OS was 37 months, with a 1-year OS rate of 100%, 3-year OS rate of 57%, and 5-year OS rate of 24%. No major complications were observed. CONCLUSIONS: Patients who exhibit intrahepatic recurrence of CRCLM after major hepatectomy will experience intrahepatic recurrence after salvage RFA as well, and after similar time intervals. However, long-term ihPFS may still be achieved in some patients. KEY POINTS: • Patients who exhibit intrahepatic recurrence of colorectal liver metastases after major hepatectomy will experience intrahepatic recurrence after salvage RFA as well, and after similar time intervals. • About two-thirds of all patients develop new metastases elsewhere in the liver within 1 year after RFA. • However, long-term intrahepatic progression-free survival may still be achieved in some patients.

Predictors of Occlusion of Hepatic Blood Vessels after Irreversible Electroporation of Liver Tumors.

PURPOSE: To examine predictors of midterm occlusion in portal and hepatic veins within or adjacent to the ablation zone after irreversible electroporation (IRE) of liver tumors. MATERIALS AND METHODS: This retrospective cohort analysis included 39 patients who underwent CT-guided IRE of liver tumors. Vessels within or adjacent to the ablation zone were identified on CT images acquired immediately after the procedure, and the positional relationships with the ablation zone (within/adjacent), locations (proximal/distal), and diameters (< 4 mm or ≥ 4 mm) were evaluated. Using contrast-enhanced follow-up scans, each vessel was classified as patent, stenosed, or occluded. Associations between vessel occlusion and each variable were investigated. RESULTS: Overall, 33 portal veins and 64 hepatic veins were analyzed. Follow-up scans showed occlusion in 12/33 (36.7%) portal veins and 17/64 (26.6%) hepatic veins. Vessels within the ablation zone were occluded significantly more frequently than vessels adjacent to the ablation zone (portal: 55.6% [10/18] vs 13.3% [2/15], P = .04; hepatic: 45.4% [15/33] vs 6.4% [2/31], P = .011). Vessels with a diameter < 4 mm were also occluded significantly more frequently than vessels with a diameter ≥ 4 mm (portal: 72.7% [8/11] vs 18.1% [4/22], P = .011; hepatic: 54.8% [17/31] vs 0% [0/33], P < .001). The respective positive and negative predictive values for occlusion of vessels categorized as both within and < 4 mm were 88% (7/8) and 82% (20/25) for portal veins and 79% (15/19) and 96% (43/45) for hepatic veins. CONCLUSIONS: Midterm vessel occlusion after liver IRE could be predicted with relatively high accuracy by assessing ablation location and vessel diameter.

ALPPS versus two-stage hepatectomy for colorectal liver metastases--a comparative retrospective cohort study.

BACKGROUND: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and two stage hepatectomy with inter-stage portal vein embolization (TSH/PVE) are surgical maneuvers applied in patients with advanced malignancies considered unresectable by means of conventional liver surgery. The aim of this report is to compare the oncologic outcome and technical feasibility of ALPPS and TSH/PVE in the scenario of colorectal liver metastases (CRLM). METHODS: All consecutive patients who underwent either ALPPS or TSH/PVE for CRLM between 2011 and 2017 in one hepatobiliary center were analyzed and compared regarding perioperative and long-term oncologic outcome. RESULTS: A cohort of 58 patients who underwent ALPPS (n = 21) or TSH/PVE (n = 37) was analyzed. The median overall survival (OS) was 28 months and 34 months after ALPPS and TSH/PVE (p = 0.963), respectively. The median recurrence-free survival (RFS) was higher following ALPPS with 19 months than following TSH/PVE with 10 months, but marginally failed to achieve statistical significance (p = 0.05). There were no differences in morbidity and mortality after stages 1 and 2. Patients undergoing ALPPS due to insufficient hypertrophy after TSH/PVE (rescue-ALPPS) displayed similar oncologic outcome as patients treated by conventional ALPPS or TSH/PVE (p = 0.971). CONCLUSIONS: ALPPS and TSH/PVE show excellent technical feasibility and comparable long-term oncologic outcome in CRLM. Rescue ALPPS appears to be a viable option for patients displaying insufficient hypertrophy after a TSH/PVE approach.

Left- versus right-sided hepatectomy with hilar en-bloc resection in perihilar cholangiocarcinoma.

BACKGROUND: Major liver resections with portal vein resection (PVR) have emerged as the preferred treatment for patients with perihilar cholangiocarcinoma (pCCA). Whether the resection of the liver should be preferably performed as left- (LH) or right-sided hepatectomy (RH) with or without hilar en-bloc technique is still subject of ongoing debate. METHODS: Between 2011 and 2016, 91 patients with pCCA underwent surgery in curative intent at our institution. Perioperative, pathological and survival data from all consecutive patients undergoing hilar en-bloc resection for pCCA were analyzed retrospectively. Patients undergoing hepatoduodenectomy (n = 8) or ALPPS (Associating liver partition and portal vein ligation for staged hepatectomy) (n = 2) were excluded from the analysis. RESULTS: Tumor grading, microvascular invasion, lymphovascular invasion, N-category, T-category, R-status and UICC-tumor staging were similar in the RH (n = 45) and LH (n = 36) groups. Perioperative morbidity and mortality were higher after RH compared to LH (mortality: 15.6% (7/45) vs. 8.3% (3/36) p = 0.003). Three-year (62% vs. 51%) and the 5-year OS (30% vs. 46%) were comparable between LH and RH groups respectively (p = 0.519, log rank). CONCLUSIONS: The present study supports the concept of surgically aggressive therapy in pCCA. LH and RH hilar en-bloc resection demonstrate a comparable long-term survival, suggesting that LH hilar en-bloc resections are feasible and safe in high-volume centers.

Single-needle electroporation and interstitial electrochemotherapy: in vivo safety and efficacy evaluation of a new system.

OBJECTIVES: We conducted an in vivo trial to investigate the safety and efficacy of a newly developed system for the application of a combined therapy consisting of irreversible electroporation (IRE) and electrochemotherapy (IRECT) in the liver. The system is conceived as a single-needle multitined applicator with expandable electrodes that allow interstitial injection of fluids, e.g., chemotherapy. METHODS: Experiments were conducted in ten domestic pigs. The applicator was placed in different liver lobes under CT guidance. In one lobe, the applicator was used for conventional IRE (1500 V, 120 pulses, pulse length 100 µs). In the other lobe, the same procedure was performed preceded by the injection of a doxorubicin mixture through the expandable electrodes (IRECT). Contrast-enhanced CT and MRI were performed on days 1, 3, and 7 after the procedure. Accordingly, three animals were sacrificed on days 1, 3, and 7 after the imaging and ablation volumes were evaluated histopathologically. Related t test was used to compare the groups. RESULTS: Technical success was achieved in 9/10 experiments. One animal deceased during the intervention because of ventricular fibrillation. Follow-up CT 1 and 3 days after intervention showed a significant (p < 0.05) difference in the ablation volumes of IRECT vs IRE, respectively, of 4.47 ± 1.78 ml vs 2.51 ± 0.93 ml and of 3.39 ± 1.05 vs 1.53 ± 0.78 ml. CONCLUSIONS: IRECT using the newly developed system proved to be effective and provided significantly larger ablation volumes compared with IRE alone. However, ECG triggering is a necessary prerequisite to allow a safe application of the system. KEY POINTS: • Working on the geometry of the IRE applicator in terms of expandable electrodes may overcome the current limitations of IRE resulting from the placement of multiple electrodes. • Efficacy of IRE ablations can be enhanced by the interstitial application of chemotherapy in the periphery of ablation areas.