Safety and feasibility of robotic liver resection after previous abdominal surgeries.

BACKGROUND: While minimally invasive liver surgery has been increasingly adopted at least for minor resections, experience with robotic liver surgery is still limited to a few highly specialized centers. Due to the fear of abdominal adhesions, a history of prior surgeries is still used as an argument for open approaches. METHODS: Clinical data of all consecutive robotic resections at our center, using the da Vinci Xi surgical system, between April, 2018 and December, 2020, were collected and analyzed as part of a prospective, post-marketing observational study (DRKS00017229). Prior abdominal surgeries were specified according to the surgical approach and localization. Baseline and perioperative outcome criteria were compared between patients with prior surgeries (PS) and patients with no prior surgeries (NPS) in univariate and multivariate analyses. RESULTS: Out of the 126 patients undergoing robotic liver resections, 59% had a history of abdominal surgeries, which were most often colorectal resections (28%) followed by liver resections (20%). Patients with NPS were more likely to undergo robotic liver resection for hepatocellular carcinoma or benign tumors, and to have underlying liver cirrhosis when compared to patients with PS. Other baseline characteristics as well as the extent of resections were similar. Duration of surgery (258 min), conversion rates (6%), and postoperative complications rates (21% Clavien-Dindo ≥ 3) showed no differences between NPS and PS. A subgroup of patients with a history of prior liver surgery showed a longer duration of surgery in univariate analysis. However, this was not confirmed in multivariate analysis which instead revealed tumor entity and liver cirrhosis as independently correlated with duration of surgery. CONCLUSIONS: We propose robotic liver resection to be safe and feasible, including in patients with prior abdominal surgeries. Each patient should be evaluated for a minimally invasive procedure regardless of a history of previous operations.

Safety of intermittent Pringle maneuver during minimally invasive liver resection in patients with hepatocellular carcinoma with and without cirrhosis.

PURPOSE: The aim of this study was to analyze the impact of minimally invasive intermittent Pringle maneuver (IPM) on postoperative outcomes in patients with hepatocellular carcinoma (HCC) and liver cirrhosis. METHODS: In this retrospective cohort study, we evaluated the safety of IPM in patients with HCC who underwent minimally invasive liver resection during five years at our center. Factors influencing the use of IPM were examined in univariate and multivariate regression analysis. Cases with use of IPM (IPM) and those without use of IPM (no IPM) were then compared regarding intraoperative and postoperative outcomes after propensity score matching (PSM) for surgical difficulty. RESULTS: One hundred fifty-one patients underwent liver resection for HCC at our center and met inclusion criteria. Of these, 73 patients (48%) received IPM with a median duration of 18 min (5-78). One hundred patients (66%) had confirmed liver cirrhosis. In multivariate analysis, patients with large tumors (≥ 3 cm) and difficult tumor locations (segments VII or VIII) were more likely to undergo IPM (OR 1.176, p = 0.043, and OR 3.243, p = 0.001, respectively). After PSM, there were no differences in intraoperative blood transfusion or postoperative complication rates between the IPM and no IPM groups. Neither did we observe any differences in the subgroup analysis for cirrhotic patients. Postoperative serum liver function tests were not affected by the use of IPM. CONCLUSIONS: Based on our findings, we conclude that the use of IPM in minimally invasive liver resection is safe and feasible for patients with HCC, including those with compensated liver cirrhosis.

Irradiation Delays Tissue Growth but Enhances Osteogenic Differentiation in Vascularized Constructs.

BACKGROUND: Regenerative medicine is still deficient in the reconstruction after cancer due to impaired vascularization after radiotherapy and due to the need to substitute larger defects after tumor excision. Aiming at introducing regenerative medicine for reconstruction after cancer, we tested an axially vascularized bone construct in an experimental setting that mimics the clinical situation after tumor resection and adjuvant radiotherapy. METHODS: Twenty bone constructs were axially vascularized using microsurgically created arteriovenous loops and were implanted subcutaneously in Lewis rats. After 2 weeks, the animals were randomly allocated either to receive a clinically relevant single dose of external beam irradiation or not (n = 10 for each group). The animals were sacrificed either after 1 week or 10 weeks after irradiation (n = 5 for each time point). The constructs were tested for vascularization, tissue growth, cellular proliferation, cellular apoptosis, and osteogenic differentiation via histomorphometric, immunohistochemical, and polymerase chain reaction (PCR) analysis. One construct per group was subjected at 10 weeks to qualitative micro-computed tomography (CT) imaging. RESULTS: Tissue generation and cellular proliferation were significantly reduced at 1 week after irradiation, but no longer significantly different after 10 weeks.No significant differences in vascularization were detected at any time point. Apoptosis did not show any statistically significant differences between both groups at both time points. At the late time point, mature bone was considerably more in the irradiated group, but the results were not statistically significant. PCR analysis showed a significantly enhanced expression of osteocalcin in the irradiated group at 1 week. Micro-CT imaging showed that both constructs were adequately vascularized with no evident morphologic differences regarding vascular density or vascular distribution. CONCLUSIONS: Axially vascularized bone constructs can withstand clinically relevant doses of irradiation and retain their angiogenic and osteogenic potential in the long term. Irradiation led to a delayed tissue generation with a comparatively enhanced osteogenic differentiation within the constructs.

Axially vascularized tissue-engineered bone constructs retain their in vivo angiogenic and osteogenic capacity after high-dose irradiation.

In order to introduce bone tissue engineering to the field of oncological reconstruction, we are investigating for the first time the effect of various doses of ionizing irradiation on axially vascularized bone constructs. Synthetic bone constructs were created and implanted in 32 Lewis rats. Each construct was axially vascularized through an arteriovenous loop made by direct anastomosis of the saphenous vessels. After 2 weeks, the animals received ionizing irradiation of 9 Gy, 12 Gy and 15 Gy, and were accordingly classified to groups I, II and III, respectively. Group IV was not irradiated and acted as a control. Tissue generation, vascularity, cellular proliferation and apoptosis were investigated either 2 or 5 weeks after irradiation through micro-computed tomography, histomorphometry and real-time polymerase chain reaction (PCR). At 2 weeks after irradiation, tissue generation and central vascularity were significantly lower and apoptosis was significantly higher in groups II and III than group IV, but without signs of necrosis. Cellular proliferation was significantly lower in groups I and II. After 5 weeks, the irradiated groups showed improvement in all parameters in relation to the control group, indicating a retained capacity for angiogenesis after irradiation. PCR results confirmed the expression of osteogenesis-related genes in all irradiated groups. Dense collagen was detected 5 weeks after irradiation, and one construct showed discrete islands of bone indicating a retained osteogenic capacity after irradiation. This demonstrates for the first time that axial vascularization was capable of supporting a synthetic bone construct after a high dose of irradiation that is comparable to adjuvant radiotherapy. Copyright © 2016 John Wiley & Sons, Ltd.

The impact of various scaffold components on vascularized bone constructs.

Bone tissue engineering is gaining more interest in the field of craniofacial surgery where continuous efforts are being made to improve the outcomes via modulation of the scaffold components. In an in vitro three dimensional (3D) culture, the effect of bone morphogenic protein 2 (BMP2, 60 µg/ml) and the effect of different cell seeding densities (0.25, 0.5, and 1 × 104) of rat mesenchymal stem cells seeded on nanocrystalline hydroxyapatite in silica gel matrix (Nanobone®) on the cell viability and differentiation were studied. Alkaline phosphatase and viability assays were performed at day 7, day 14, and day 21 to assess the differentiation and the relative fraction of viable cells in the 3D cell cultures. In a subsequent in vivo study, we examined the effect of axial vascularization, the scaffold's particle size and the nature of the matrix (collagen type I vs. diluted fibrin) on vascularization and tissue generation in vascularized bone construct in rats. Regarding vascularization, we compared constructs vascularized randomly by extrinsic vascularization from the periphery of the implanted construct with others vascularized axially via an implanted arteriovenous loop (AVL). Regarding the particle size, we compared constructs having a scaffold particle size of 0.2 mm (powder) with other constructs having a particle size of 2 × 0.6 mm (granules). Regarding the matrix we compared constructs having a collagen matrix with others having a fibrin matrix. Various groups were compared regarding the amount of tissue generation, vascularization, and cellular proliferation. The initial seeding density had a temporary and minimal effect on the overall osteogenic differentiation of the cells. On the contrary, adding BMP2 in a concentration of 60 µg/ml over one week led to an overall enhanced osteogenic differentiation despite depressed cell viability. Axial vascularization was mandatory for efficient tissue formation and vascularization of the bone construct. Collagen matrix and a smaller particle size provided more favorable results in terms of vascularization and tissue formation than diluted fibrin and larger Nanobone particles.