Microwave versus radiofrequency ablation for the treatment of liver malignancies: a randomized controlled phase 2 trial.

Microwave (MWA) and radiofrequency ablation (RFA) are main ablative techniques for hepatocellular carcinoma (HCC) and colorectal liver metastasis (MT). This randomized phase 2 clinical trial compares the effectiveness of MWA and RFA as well as morphology of corresponding ablation zones. HCC and MT patients with 1.5-4 cm tumors, suitable for ablation, were randomized into MWA or RFA Groups. The primary endpoint was short-to-long diameter ratio of ablation zone (SLR). Primary technical success (TS) and a cumulative local tumor progression (LTP) after a median 2-year follow-up were compared. Between June 2015 and April 2020, 82 patients were randomly assigned (41 patients per group). For the per-protocol analysis, five patients were excluded. MWA created larger ablation zones than RFA (p = 0.036) although without differences in SLR (0.5 for both groups, p = 0.229). The TS was achieved in 98% (46/47) and 90% (45/50) (p = 0.108), and LTP was observed in 21% (10/47) vs. 12% (6/50) (OR 1.9 [95% CI 0.66-5.3], p = 0.238) of tumors in MWA vs. RFA Group, respectively. Major complications were found in 5 cases (11%) vs. 2 cases (4%), without statistical significance. MWA and RFA show similar SLR, effectiveness and safety in liver tumors between 1.5 and 4 cm.

Pancreatic duct ligation reduces premalignant pancreatic lesions in a Kras model of pancreatic adenocarcinoma in mice.

Pancreatic duct ligation (PDL) in the murine model has been described as an exocrine pancreatic atrophy-inducing procedure. However, its influence has scarcely been described on premalignant lesions. This study describes the histological changes of premalignant lesions and the gene expression in a well-defined model of pancreatic ductal adenocarcinoma by PDL. Selective ligation of the splenic lobe of the pancreas was performed in Ptf1a-Cre(+/ki); K-ras LSLG12Vgeo(+/ki) mice (PDL-Kras mice). Three experimental groups were evaluated: PDL group, controls and shams. The presence and number of premalignant lesions (PanIN 1-3 and Atypical Flat Lesions-AFL) in proximal (PP) and distal (DP) pancreas were studied for each group over time. Microarray analysis was performed to find differentially expressed genes (DEG) between PP and PD. Clinical human specimens after pancreaticoduodenectomy with ductal occlusion were also evaluated. PDL-Kras mice showed an intense pattern of atrophy in DP which was shrunk to a minimal portion of tissue. Mice in control and sham groups had a 7 and 10-time increase respectively of risk of high-grade PanIN 2 and 3 and AFL in their DP than PDL-Kras mice. Furthermore, PDL-Kras mice had significantly less PanIN 1 and 2 and AFL lesions in DP compared to PP. We identified 38 DEGs comparing PP and PD. Among them, several mapped to protein secretion and digestion while others such as Nupr1 have been previously associated with PanIN and PDAC. PDL in Ptf1a-Cre(+/ki); K-ras LSLG12Vgeo(+/ki) mice induces a decrease in the presence of premalignant lesions in the ligated DP. This could be a potential line of research of interest in some cancerous risk patients.

Morphological changes of the pancreas after pancreaticoduodenectomy.

The aim of this retrospective study was thus to evaluate postoperative morphological changes in the remnant pancreas after pancreaticoduodenectomy (PD) associated with postoperative pancreatic fistula (POPF). Fifty-one patients subjected to PD were enrolled in the study and allocated into 2 groups according to the presence (n = 16) or absence of POPF (n = 35). A morphological evaluation of the pancreas was conducted for up to a 20 months follow-up on CT scans and compared between groups. No significant differences were observed in morphology between the groups at the different preoperative and PO intervals, regardless of the clinical relevance of the POPF or POPF grade. However, in the overall patient analysis we observed a significant reduction of the entire pancreas over time. In fact, thickness decreased 0.4 mm/month, length 1.2 mm/month and volume 1.17 cm3/month over the PO. The impact of age, POPF, type of anastomosis, surgical technique and PO follow-up (time) was evaluated in a multivariate analysis using the general linear model, but only PO follow-up had a significant influence on the final model (p < 0.001). A significant reduction on pancreatic parenchyma (thickness, length and volume) occurs after PD with no significant differences between patients with or without POPF.

Development of a catheter-based technique for endoluminal radiofrequency sealing of pancreatic duct.

Introduction: Endoluminal sealing of the pancreatic duct by glue or sutures facilitates the management of the pancreatic stump. Our objective was to develop a catheter-based alternative for endoluminal radiofrequency (RF) sealing of the pancreatic duct. Materials and methods: We devised a novel RF ablation technique based on impedance-guided catheter pullback. First, bench tests were performed on ex vivo models to tune up the technique before the in vivo study, after which endoluminal RF sealing of a ∼10 cm non-transected pancreatic duct was conducted on porcine models using a 3 Fr catheter. After 30 days, sealing effectiveness was assessed by a permeability test and a histological analysis. Results: The RF technique was feasible in all cases and delivered ∼5 W of power on an initial impedance of 308 ± 60 Ω. Electrical impedance evolution was similar in all cases and provided guidance for modulating the pullback speed to avoid tissue sticking and achieve a continuous lesion. During the follow-up the animals rate of weight gain was significantly reduced (p < 0.05). Apart from signs of exocrine atrophy, no other postoperative complications were found. At necropsy, the permeability test failed and the catheter could not be reintroduced endoluminally, confirming that sealing had been successful. The histological analysis revealed a homogeneous exocrine atrophy along the ablated segment in all the animals. Conclusions: Catheter-based RF ablation could be used effectively and safely for endoluminal sealing of the pancreatic duct. The findings suggest that a fully continuous lesion may not be required to obtain complete exocrine atrophy.

Endoluminal radiofrequency ablation of the main pancreatic duct is a secure and effective method to produce pancreatic atrophy and to achieve stump closure.

Radiofrequency energy has been used both experimentally and clinically to manage the pancreatic remnant after distal pancreatectomies. Our goal was to determine whether endoluminal radiofrequency (RF) ablation of the main pancreatic duct in large animals would be more efficient than glue occlusion as an exocrine pancreatic atrophy-inducing procedure. Thirty-four Landrace pigs were assigned to either the transpapilar (n = 16) or transection (n = 18) groups. The transection implied the pancreas neck was severed. In each of these groups the remaining distal pancreatic duct was occluded either by RF or by glue. In the transpapilar group complete atrophy was observed in all the RF cases, while atrophy was incomplete in all the members of the glue subgroup. The failure rate of the main pancreatic duct (usually expressed by a pseudocyst) in the transection groups was dramatically higher in the glue subgroup than the RF subgroups (9 out of 9 and 1 out of 9, respectively) and postoperative mortality occurred only in the glue subgroup (3 out of 9). These results show the superiority of endoluminal RF ablation over glue for main pancreatic duct occlusion, as seen by the degree of atrophy and fewer postoperative pancreatic fistulas.

Impact of monopolar radiofrequency coagulation on intraoperative blood loss during liver resection: a prospective randomised controlled trial.

PURPOSE: To evaluate the impact of using monopolar thermal coagulation based on radiofrequency (RF) currents on intraoperative blood loss during liver resection. MATERIALS AND METHODS: A prospective randomised controlled trial was planned. Patients undergoing hepatectomy were randomised into two groups. In the control group (n = 10), hemostasis was obtained with a combination of stitches, vessel-sealing bipolar RF systems, sutures or clips. In the monopolar radiofrequency coagulation (MRFC) group (n = 18), hemostasis was mainly obtained using an internally cooled monopolar RF electrode. RESULTS: No differences in demographic or clinical characteristics were found between groups. Mean blood loss during liver resection in the control group was more than twice that of the MRFC group (556 ± 471 ml vs. 225 ± 313 ml, p = .02). The adjusted mean bleeding/transection area was also significantly higher in the control group (7.0 ± 3.3 ml/cm2 vs. 2.8 ± 4.0 ml/cm2, p = .006). No significant differences were observed in the rate of complications between the groups. CONCLUSIONS: The findings suggest that the monopolar electrocoagulation created with an internally cooled RF electrode considerably reduces intraoperative blood loss during liver resection.

Focused Transhepatic Electroporation Mediated by Hypersaline Infusion through the Portal Vein in Rat Model. Preliminary Results on Differential Conductivity.

BACKGROUND: Spread hepatic tumours are not suitable for treatment either by surgery or conventional ablation methods. The aim of this study was to evaluate feasibility and safety of selectively increasing the healthy hepatic conductivity by the hypersaline infusion (HI) through the portal vein. We hypothesize this will allow simultaneous safe treatment of all nodules by irreversible electroporation (IRE) when applied in a transhepatic fashion. MATERIAL AND METHODS: Sprague Dawley (Group A, n = 10) and Athymic rats with implanted hepatic tumour (Group B, n = 8) were employed. HI was performed (NaCl 20%, 3.8 mL/Kg) by trans-splenic puncture. Deionized serum (40 mL/Kg) and furosemide (2 mL/Kg) were simultaneously infused through the jugular vein to compensate hypernatremia. Changes in conductivity were monitored in the hepatic and tumour tissue. The period in which hepatic conductivity was higher than tumour conductivity was defined as the therapeutic window (TW). Animals were monitored during 1-month follow-up. The animals were sacrificed and selective samples were used for histological analysis. RESULTS: The overall survival rate was 82.4% after the HI protocol. The mean maximum hepatic conductivity after HI was 2.7 and 3.5 times higher than the baseline value, in group A and B, respectively. The mean maximum hepatic conductivity after HI was 1.4 times higher than tumour tissue in group B creating a TW to implement selective IRE. CONCLUSIONS: HI through the portal vein is safe when the hypersaline overload is compensated with deionized serum and it may provide a TW for focused IRE treatment on tumour nodules.

Radiofrequency-induced heating versus mechanical stapler for pancreatic stump closure: in vivo comparative study.

PURPOSE: The aim of this study was to assess the capacity of two methods of surgical pancreatic stump closure in terms of reducing the risk of pancreatic fistula formation (POPF): radiofrequency-induced heating versus mechanical stapler. MATERIALS AND METHODS: Sixteen pigs underwent a laparoscopic transection of the neck of the pancreas. Pancreatic anastomosis was always avoided in order to work with an experimental model prone to POPF. Pancreatic stump closure was conducted either by stapler (ST group, n = 8) or radiofrequency energy (RF group, n = 8). Both groups were compared for incidence of POPF and histopathological alterations of the pancreatic remnant. RESULTS: Six animals (75%) in the ST group and one (14%) in the RF group were diagnosed with POPF (p = 0.019). One animal in the RF group and three animals in the ST group had a pseudocyst in close contact with both pancreas stumps. On day 30 post-operation (PO), almost complete atrophy of the exocrine distal pancreas was observed when the main pancreatic duct was efficiently sealed. CONCLUSIONS: Our findings suggest that RF-induced heating is more effective at closing the pancreatic stump than mechanical stapler and leads to the complete atrophy of the distal remnant pancreas.

Long-term evolution of acinar-to-ductal metaplasia and ß-cell mass after radiofrequency-assisted transection of the pancreas in a controlled large animal model.

BACKGROUND: Pancreatic duct ligation (PDL) has been used as a model of chronic pancreatitis and as a model to increase ß-cell mass. However, studies in mice have demonstrated acinar regeneration after PDL, questioning the long-term validity of the model. We aim to elucidate whether RF-assisted transection (RFAT) of the main pancreatic duct is a reliable PDL model, both in short (ST, 1-month) and long-term (LT, 6-months) follow-ups. METHODS: Eleven pigs were subjected to RFAT. Biochemical (serum/peripancreatic amylase and glucose) and histological changes (including a semiautomatic morphometric study of over 1000 images/pancreas and IHC analysis) were evaluated after ST or LT follow-up and also in fresh pancreas specimens that were used as controls for 1 (n = 4) and 6 months (n = 6). RESULTS: The distal pancreas in the ST was characterized by areas of acinar-to-ductal metaplasia (56%) which were significantly reduced at LT (21%) by fibrotic replacement and adipose tissue. The endocrine mass showed a normal increase. CONCLUSION: RFAT in the pig seems to be an appropriate PDL model without restoration of pancreatic drainage or reduction of endocrine mass.

Radiofrequency pancreatic ablation and section of the main pancreatic duct does not lead to necrotizing pancreatitis.

OBJECTIVE: The aim of this study was to determine whether radiofrequency ablation (RFA) of the pancreas and subsequent transection of the main pancreatic duct may avoid the risk of both necrotizing pancreatitis and postoperative pancreatic fistula (POPF) formation. METHODS: Thirty-two rats were subjected to RFA and section of the pancreas over their portal vein. Animals were killed at 3, 7, 15, and 21 days (groups 0-3, respectively). Two additional control groups (sham operation and user manipulation only, respectively) of 15 days of postoperative period were considered. Postoperative complications, histological changes (including morphometric and immunohistochemical analysis), and incidence of POPF were evaluated. RESULTS: A significant increase in serum amylase levels (P < 0.05) on the third postoperative day, which return to baseline levels in the following weeks, was noted in groups 0 to 3. Those groups showed a rapid atrophy of the distal pancreas by apoptosis with no signs of necrotizing pancreatitis or POPF. The distal pancreas in groups 1 to 3 compared with group 0 and control groups showed a significant increase of small islets (<1000 µm). CONCLUSIONS: The rapid acinar atrophy of the distal pancreas after RFA and section of the pancreatic ducts in this model does not lead to necrotizing pancreatitis.

Radiofrequency is a secure and effective method for pancreatic transection in laparoscopic distal pancreatectomy: results of a randomized, controlled trial in an experimental model.

BACKGROUND: Postoperative pancreatic fistula (PPF) is the most frequent and serious complication after laparoscopic distal pancreatectomy (LDP). Our goal was to compare the performance, in terms of PPF prevention, and safety of a radiofrequency (RF)-assisted transection device versus a stapler device in a porcine LDP model. METHODS: Thirty-two animals were randomly divided into two groups to perform LDP using a RF-assisted device (RF group; n = 16) and stapler device (ST group; n = 16) and necropsied 4 weeks after surgery. The primary endpoint was the incidence of PPF. Secondary endpoints were surgery/transection time, intra/postoperative complications/deaths, postoperative plasmatic amylase and glucose concentration, peritoneal liquid amylase and interleukin 6 (IL-6) concentrations, weight variations, and histopathological changes. RESULTS: Two clinical and one biochemical PPF were observed in the ST and RF groups respectively. Peritoneal amylase concentration was significantly higher in the RF group 4 days after surgery, but this difference was no longer present at necropsy. Both groups presented a significant decrease in peritoneal IL-6 concentration during the postoperative follow-up, with no differences between the groups. RF group animals showed a higher postoperative weight gain. In the histopathological exam, all RF group animals showed a common pattern of central coagulative necrosis of the parenchymal surface, surrounded by a thick fibrosis, which sealed main and secondary pancreatic ducts and was not found in ST group. CONCLUSIONS: The fibrosis caused by an RF-assisted device can be at least as safe and effective as stapler compression to achieve pancreatic parenchyma sealing in a porcine LDP model.

Laparoscopic distal pancreatectomy: feasibility study of radiofrequency-assisted transection in a porcine model.

BACKGROUND AND AIM: Despite technological improvements in pancreatic surgery, the incidence and morbidity of pancreatic leak after resection of distal pancreas are persistently high in most series. Laparoscopic distal pancreatectomy (LDP) is today the gold standard procedure for benign and certain malignant neoplasms of the pancreatic body and tail in specialized centers. This study evaluated safety and feasibility of a radiofrequency (RF)-assisted transection device in a porcine model of LDP. MATERIALS AND METHODS: LDP was performed on 10 pigs (median weight, 39.6 kg) using a new device based on an internally cooled RF-assisted electrode (Coolinside(®), Apeiron Medical, Valencia, Spain). The animals were subjected to daily observation and then sacrificed and necropsied at 4 weeks postoperatively. Primary end points were the development of postoperative pancreatic fistula using the Pancreatic Anastomotic Leak Study Group definition and/or the presence of abdominal amylase-rich fluid collections or abscesses during necropsy and pathological study and/or dye extravasation from the pancreatic remnant duct. Secondary end points were intra- or postoperative complications, surgery, and transection duration. RESULTS: No clinically relevant postoperative pancreatic fistulas were observed. In one case a grade A postoperative fistula was diagnosed due to amylase drain concentration of more than 6200 IU/mL on postoperative day 4. Median peritoneal liquid amylase concentration on postoperative day 4 was 2399.0 IU/L (range, 819.2-7122.0 IU/L), similar to the median plasma amylase level of 1520.8 IU/L (range, 1015.3-4056.6 IU/L). Median surgery time was 93.5 minutes (range, 46.0-140.0 minutes), and median transection time was 4.5 minutes (range, 2.0-26.0 minutes). There was one postoperative wound infection. There were no postoperative deaths or major complications. During the histopathological study, the surgical margin of the remaining pancreas showed a common pattern with a central area of necrosis surrounded by granulomatous infiltrate and fibrosis. Ductal obliteration was observed. No purulent inflammatory infiltrate or abscesses were present. CONCLUSION: Experimental findings suggest that performing pancreatic transection with Coolinside in a animal model of LDP is feasible and safe.

Applicator for RF thermokeratoplasty: feasibility study using theoretical modeling and ex vivo experiments.

Radiofrequency (RF) thermokeratoplasty uses RF currents to alter the curvature of the cornea by means of thermal lesions. An RF applicator which combined a microkeratome suction ring and a circular electrode was designed with the aim of creating circular thermal lesions in a predictable, uniform and safe way. An experimental study was conducted on ex vivo porcine eyes. A theoretical model was also designed. The experimental results showed a lesion depth of 34.2 ± 11.0% of corneal thickness at a constant voltage of 50 V up to roll-off (1000 Ω of impedance). With a voltage of 30 V for 30 s the mean depth was 36.8 ± 8.1%. The progress of electrical impedance throughout heating and lesion dimensions were used to compare the experimental and theoretical results. Both the impedance evolution and lesion dimensions obtained from the theoretical model showed good agreement with the experimental findings. The findings suggest that the new applicator could be a suitable option for creating uniform circular thermal lesions.

Transección hepática sin suturas mediante un nuevo instrumento asistido por radiofrecuencia. Modelado teórico, estudio experimental y ensayo clínico / Sutureless hepatic transection using a new radiofrequency assisted device. Theoretical model, experimental study and clinic trial

El instrumento ideal para realizar la transección hepática debería aunar en una sola herramienta hemostasia segura y rápida. Presentamos nuestra investigación multidisciplinar encaminada al desarrollo de un dispositivo de transección hepática asistido por radiofrecuencia (RF); la investigación incluye: modelado teórico por computador, estudio experimental y ensayo clínico de este dispositivo. El modelado teórico se realizó por computador basado en el Método de Elementos Finitos (MEF) con objeto de estudiar la distribución de energía eléctrica y temperatura en el tejido y valorar el efecto de las características del instrumento. El estudio experimental basado en un modelo in vivo porcino sugiere que el nuevo instrumento permitiría aumentar la velocidad de transección del parénquima hepático con una menor hemorragia por área de transección al compararlo con otras técnicas ampliamente extendidas en la cirugía hepática. Estos datos permitieron afrontar la realización de la primera fase de un ensayo clínico, cuyos resultados preliminares sugieren que el nuevo instrumento es seguro y eficaz (AU)

The ideal instrument for performing hepatic transection should combine safe and rapid haemostasis in a single tool. We present a new multidisciplinary investigation designed to develop a hepatic transection device assisted by radiofrequency (RF); the investigation included: a computerised theoretical model, and experimental study and a clinical trial of this device. The theoretic modelling was performed by computer, based on the Finite Elements Method (FEM), with the objective of studying the distribution of electrical energy and temperature in the tissue, and to assess the effect of the characteristics of the instrument. The experimental study, based on an in vivo porcine model, suggested that the new instrument would allow the transection velocity of the hepatic parenchyma to be increased with lower bleeding per transection area compared with other techniques extensively used in liver surgery. These data should enable the first phase of clinical trial to be conducted, with preliminary results that suggest that the new device is safe and effective (AU)

[Sutureless hepatic transection using a new radiofrequency assisted device. Theoretical model, experimental study and clinic trial]. / Transección hepática sin suturas mediante un nuevo instrumento asistido por radiofrecuencia. Modelado teórico, estudio experimental y ensayo clínico.

The ideal instrument for performing hepatic transection should combine safe and rapid haemostasis in a single tool. We present a new multidisciplinary investigation designed to develop a hepatic transection device assisted by radiofrequency (RF); the investigation included: a computerised theoretical model, and experimental study and a clinical trial of this device. The theoretic modelling was performed by computer, based on the Finite Elements Method (FEM), with the objective of studying the distribution of electrical energy and temperature in the tissue, and to assess the effect of the characteristics of the instrument. The experimental study, based on an in vivo porcine model, suggested that the new instrument would allow the transection velocity of the hepatic parenchyma to be increased with lower bleeding per transection area compared with other techniques extensively used in liver surgery. These data should enable the first phase of clinical trial to be conducted, with preliminary results that suggest that the new device is safe and effective.