Radioablation by Image-Guided (HDR) Brachytherapy and Transarterial Chemoembolization in Hepatocellular Carcinoma: A Randomized Phase II Trial.

BACKGROUND AND AIMS: The aim of this single-center, open-label phase II study was to assess the efficacy of image-guided high-dose-rate (HDR) brachytherapy (iBT) compared with conventional transarterial embolization (cTACE) in unresectable hepatocellular carcinoma. METHODS: Seventy-seven patients were treated after randomization to iBT or cTACE, as single or repeated interventions. Crossover was allowed if clinically indicated. The primary endpoint was time to untreatable progression (TTUP). Eligibility criteria included a Child-Pugh score of ≤ 8 points, absence of portal vein thrombosis (PVT) at the affected liver lobe, and ≤ 4 lesions. Survival was analyzed by using the Cox proportional hazard model with stratification for Barcelona Clinic Liver Cancer (BCLC) stages. RESULTS: Twenty patients were classified as BCLC-A (iBT/cTACE 8/12), 35 as BCLC-B (16/19), and 22 as BCLC-C (13/9). The 1-, 2-, and 3-year TTUP probabilities for iBT compared with cTACE were 67.5% versus 55.2%, 56.0% versus 27.4%, and 29.5% versus 11.0%, respectively, with an adjusted hazard ratio (HR) of 0.49 (95% confidence interval 0.27-0.89; p = 0.019). The 1-, 2-, and 3-year TTPs for iBT versus cTACE were 56.0% versus 28.2%, 23.9% versus 6.3%, and 15.9% versus 6.3%, respectively, with an adjusted HR of 0.49 (0.29-0.85; p = 0.011). The 1-, 2-, and 3-year OS rates were 78.4% versus 67.7%, 62.0% versus 47.3%, and 36.7% versus 27.0%, respectively, with an adjusted HR of 0.62 (0.33-1.16; p = 0.136). CONCLUSIONS: This explorative phase II trial showed a superior outcome of iBT compared with cTACE in hepatocellular carcinoma and supports proceeding to a phase III trial.

Risk factors for delayed gastric emptying after esophagectomy.

PURPOSE: Delayed gastric emptying (DGE) is a common functional disorder after esophagectomy with gastric tube reconstruction. Little is known about risk factors that can predict this debilitating complication. METHODS: Patients who underwent elective esophagectomy from 2008 to 2016 in a single center were retrospectively reviewed. Diagnosis of DGE was based on clinical, radiological, and endoscopic findings. Uni- and multivariate analyses were performed to identify patient-, tumor-, and procedure-related factors that increase the risk of DGE. RESULTS: One hundred eighty-two patients were included. Incidence of DGE was 39.0%. Overall, 27 (14.8%) needed an endoscopic intervention. Patients in the DGE group had a longer hospital stay (p < 0.01). No differences were found for the 30-day (p = 1.0) and hospital mortality (p = 1.0). On univariate analyses, a significant influence on DGE was demonstrated for pre-existing pulmonary comorbidity (p = 0.04), an anastomotic leak (p < 0.01), and postoperative pulmonary complications (pneumonia: p = 0.02, pleural empyema: p < 0.01, and adult respiratory distress syndrome: p = 0.03). Furthermore, there was a non-significant trend toward an increased risk for DGE for the following variable: female gender (p = 0.09) and longer operative time (p = 0.09). On multivariate analysis, only female gender (p = 0.03) and anastomotic leak (p = 0.01) were significantly associated with an increased risk for DGE. CONCLUSIONS: DGE is a frequent complication following esophagectomy that can successfully be managed with conservative or endoscopic measures. DGE did not increase mortality but was associated with increased morbidity and prolonged hospitalization. We identified risk factors that increase the incidence of DGE. However, this has to be confirmed in future studies with standardized definition of DGE.

Extensive Use of Interventional Therapies Improves Survival in Unresectable or Recurrent Intrahepatic Cholangiocarcinoma.

Aim. To assess the outcomes of patients with unresectable intrahepatic cholangiocellular carcinoma (ICC) treated by a tailored therapeutic approach, combining systemic with advanced image-guided local or locoregional therapies. Materials and Methods. Treatment followed an algorithm established by a multidisciplinary GI-tumor team. Treatment options comprised ablation (RFA, CT-guided brachytherapy) or locoregional techniques (TACE, radioembolization, i.a. chemotherapy). Results. Median survival was 33.1 months from time of diagnosis and 16.0 months from first therapy. UICC stage analysis showed a median survival of 15.9 months for stage I, 9 months for IIIa, 18.4 months for IIIc, and 13 months for IV. Only the number of lesions, baseline serum CEA and serum CA19-9, and objective response (RECIST) were independently associated with survival. Extrahepatic metastases had no influence. Conclusion. Patients with unresectable ICC may benefit from hepatic tumor control provided by local or locoregional therapies. Future prospective study formats should focus on supplementing systemic therapy by classes of interventions ("toolbox") rather than specific techniques, that is, local ablation leading to complete tumor destruction (such as RFA) or locoregional treatment leading to partial remission (such as radioembolization). This trial is registered with German Clinical Trials Registry (Deutsche Register Klinischer Studien), DRKS-ID: DRKS00006237.

Upfront FOLFOXIRI+bevacizumab followed by fluoropyrimidin and bevacizumab maintenance in patients with molecularly unselected metastatic colorectal cancer.

BACKGROUND: The addition of bevacizumab (BEV) to standard doublet chemotherapy improves outcomes compared with chemotherapy alone in patients with metastatic colorectal cancer (mCRC). The OPAL study examined the effect of BEV+FOLFOXIRI followed by 5FU/LV and BEV maintenance on progression-free survival (PFS) in patients with previously untreated unresectable mCRC. METHODS: Eligible patients had histologically confirmed mCRC, ECOG performance status ⩽1 and were 18-70 years old. Patients received up to 12 cycles of FOLFOXIRI+BEV q2w (induction phase) followed by up to ⩽40 cycles of 5FU/LV+BEV q2w (maintenance phase). Median PFS was the primary end point; secondary end points included response, OS, secondary resection rate, safety and prognostic value of pharmacogenetic profiling. RESULTS: Ninety-seven patients were enrolled. Of these, 90 received study medication and formed the safety population: 64 males; median age 58 (range 28-71) years; ECOG performance status 0/1 in 54%/46% patients; and liver only disease in 35 patients. Relative dose intensities were 79-85% for all four drugs. The incidence of adverse events (AEs) was as previously reported and there were no new safety signals. In total, 87 serious AEs occurred in 39 patients (43%). Median PFS was 11.1 months (95% CI 9.4-12.0) and did thus not meet the primary objective of 12 months. Median OS was 32.2 months (95% CI 22.6-36.9). Fifty-two patients were pharmacogenetically profiled. CONCLUSIONS: FOLFOXIRI+BEV was feasible in this molecularly unselected mCRC patient population, showing a high efficacy in terms of survival, overall response and secondary resection rate. Pharmacogenomic profiling revealed no clinically relevant marker.

Locally ablative treatment of breast cancer liver metastases: identification of factors influencing survival (the Mammary Cancer Microtherapy and Interventional Approaches (MAMMA MIA) study).

BACKGROUND: Liver metastases from breast cancer (LMBC) are typically considered to indicate systemic disease spread and patients are most often offered systemic palliative treatment only. However, retrospective studies suggest that some patients may have improved survival with local treatment of their liver metastases compared to systemic therapy alone. In the absence of randomized trials, it is important to identify patient characteristics indicating that benefit from local treatment can be expected. METHODS: 59 patients undergoing radiofrequency ablation (RFA), interstitial brachytherapy (BT), or radioembolization (RE) of LMBC as a salvage treatment were studied. Potential factors influencing survival were analyzed in a multivariate Cox model. For factors identified to have an independent survival impact, Kaplan-Meier analysis and comparison of overall survival (OS) using the log-rank test was performed. RESULTS: Median OS following local interventional treatment was 21.9 months. Considering only factors evaluable at treatment initiation, maximum diameter of liver metastases (≥3.9 cm; HR: 3.1), liver volume (≥ 1376 mL; HR: 2.3), and history of prior chemotherapy (≥ 3 lines of treatment; HR: 2.5-2.6) showed an independent survival impact. When follow-up data were included in the analysis, significant factors were maximum diameter of liver metastases (≥ 3.9 cm; HR: 3.1), control of LMBC during follow-up (HR: 0.29), and objective response as best overall response (HR: 0.21). Neither the presence of any extrahepatic metastases nor presence of bone metastases only had a significant survival impact. Median OS was 38.7 vs. 16.1 months in patients with metastases < vs. ≥ 3.9 cm, 36.6 vs. 10.2 months for patients having objective response vs. stable/progressive disease, and 38.5 vs. 14.2 months for patients having controlled vs. non-controlled disease at follow-up. CONCLUSION: Local control of LMBC confers a survival benefit and local interventional treatment for LMBC should be studied in a randomized trial. Patients with small metastases and limited history of systemic LMBC treatment are most likely to benefit from local approaches. Limited extrahepatic disease should not lead to exclusion from a randomized study and should not be a contraindication for local LMBC treatment as long as no randomized data are available.

Involving Medical Students in Informed Consent: A Pilot Study.

INTRODUCTION: Studies have reported that patients often sign consent documents without understanding the content. Written paperwork, audio-visual materials, and decision aids have shown to consistently improve patients' knowledge. How informed consent should be taken is not properly taught at most universities in Germany. MATERIALS AND METHODS: In this cross-sectional study, we investigated how much information about their procedure our patients retain. In particular, it should be elucidated whether an additional conversation between patients and properly prepared medical students shortly before surgery as an adjunct to informed consent can be introduced as a new teaching unit aimed to increase the understanding of surgery by patients and students. Informed consent of all patients had been previously obtained by three surgical residents 1-3 days in advance. All patients had received a copy of their consent form. The same residents developed assessment forms for thyroidectomy, laparoscopic cholecystectomy, umbilical hernia repair, and Lichtenstein procedure for inguinal hernia, respectively, containing 3-4 major common complications (e.g., bile duct injury, hepatic artery injury, stone spillage, and retained stones for laparoscopic cholecystectomy) and briefed the medical students before seeing the patients. Structured one-to-one interviews between students (n = 9) and patients (n = 55) based on four different assessment forms were performed and recorded by students. Both patients and students were asked to assess the new teaching unit using a short structured questionnaire. RESULTS: Although 100% of patients said at the beginning of their interview to have understood and memorized the risks of their imminent procedure, 5.8% (3/55) were not even able to indicate the correct part of the body where the incision would take place. Only 18.2% (10/55) of the patients were able to mention 2 or more complications, and 45.3% (25/55) could not even recall a single one. 96.4% (53/55) of the patients and 100% (9/9) of the students taking part in this teaching unit found that this exercise represents a significant improvement of clinical teaching and recommended to introduce this teaching unit as a standard on the normal wards. CONCLUSION AND OUTLOOK: Students teaching patients (SteP) appears to be an easy and cost-efficient tool to improve patients' education and students' learning. Students become aware of how difficult it is to explain surgical procedures and complications to patients and patients are better informed about their treatment. We plan to (i) introduce the STeP protocol as a standard teaching project in daily clinical routine and (ii) continue the pilot study to reach representative student and patient numbers for a possible final statement and derived recommendation.

Left-liver hypertrophy after therapeutic right-liver radioembolization is substantial but less than after portal vein embolization.

UNLABELLED: In patients with liver malignancies potentially amenable to curative extended right hepatectomy but insufficient size of the future liver remnant (FLR), portal vein embolization (PVE) of the tumor-bearing liver is used to induce contralateral liver hypertrophy but leaves the tumor untreated. Radioembolization (RE) treats the tumor in the embolized lobe along with contralateral hypertrophy induction. We performed a matched-pair analysis to compare the capacity for hypertrophy induction of these two modalities. Patients with right-hepatic secondary liver malignancies with no or negligible left-hepatic tumor involvement who were treated by right-lobar PVE (n = 141) or RE (n = 35) at two centers were matched for criteria known to influence liver regeneration following PVE: 1) baseline FLR/Total liver volume ratio (<25 versus ≥ 25%); 2) prior platinum-containing systemic chemotherapy; 3) embolization of segments 5-8 versus 4-8; and 4) baseline platelet count (<200 versus ≥ 200 Gpt/L).The primary endpoint was relative change in FLR volume from baseline to follow-up. Twenty-six matched pairs were identified. FLR volume increase from baseline to follow-up (median 33 [24-56] days after PVE or 46 [27-79] days after RE) was significant in both groups but PVE produced significantly more FLR hypertrophy than RE (61.5 versus 29%, P < 0.001). Time between treatment and follow-up was not correlated with the degree of contralateral hypertrophy achieved in both groups. Although group differences in patient history and treatment setting were present and some bias cannot be excluded, this was minimized by the matched-pair design, as remaining group differences after matching were found to have no significant influence on contralateral hypertrophy development. CONCLUSION: PVE induces significantly more contralateral hypertrophy than RE with therapeutic (nonlobectomy) doses. However, contralateral hypertrophy induced by RE is substantial and RE minimizes the risk of tumor progression in the treated lobe, possibly making it a suitable modality for selected patients.

Prevention of intraprocedural puncture site bleeding during arterial port implantation by use of a suture-mediated arterial closure system: a prospective randomized trial.

PURPOSE: To investigate a modified technique for arterial port placement that uses a suture-mediated closure system with the aim to reduce delays caused by intraprocedural oozing around the catheter. MATERIALS AND METHODS: Forty consecutive patients (age, 63.9 y ± 11.8) stratified for regional arterial infusion chemotherapy were prospectively randomized to undergo conventional or modified port implantation. Time for device placement, total procedure time, number of catheters, size of largest and final catheters placed, duration of bleeding from puncture site, procedural delays, and time until hemostasis was achieved were recorded. RESULTS: Time for device placement was 3.7 minutes ± 1.1, with no complications encountered. Total procedure times were 133.0 minutes ± 62.8 for conventional port implantation and 100.0 minutes ± 49.5 for modified implantation (P = .13). No differences were found in the number of catheters or size of largest or final catheter used. Duration of groin bleeding necessitating manual compression was 21.8 minutes ± 24.4 for conventional port implantation, resulting in a mean procedural delay of 6.2 minutes ± 7.0. Hemostasis was achieved after a mean of 17.1 minutes ± 20.9. Groin hematoma was observed in three patients. In contrast, with the modified technique, mean duration of oozing and intraprocedural delays were only 0.2 minutes ± 0.6 and 0.1 minutes ± 0.5, respectively (both P < .0001 vs conventional technique). Hemostasis was achieved within 3.2 minutes ± 4.1 (P < .0001), with no cases of hematoma found. CONCLUSIONS: Use of a suture-mediated closure system facilitated arterial port implantation by effective prevention of groin bleeding while allowing the use of a sheath.