Although biomedical engineering (BME) is a profession with ethical responsibilities comparable to those in medicine, it has, until now, lacked a counterpart to the Hippocratic Oath. While professional societies have established codes of ethics for biomedical engineers, these documents lack the symbolic and ceremonial significance of an oath or pledge. By contrast, the recitation of the Hippocratic Oath, or its modern version, the "Physician's Pledge," serves as a powerful rite of passage for medical students, fostering a strong sense of ethical duty at the start of their professional journey. However, the content of the Hippocratic Oath includes elements specific to clinical practice and is not directly applicable to biomedical engineering. To fill this gap, we have created a "Biomedical Engineer's Pledge," comprising a preamble, ten promises, and a concluding statement, to inspire ethical awareness and establish a meaningful graduation tradition.

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.

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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.

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 cm 3 /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.

Introduction: Irreversible Electroporation (IRE) is highly dependent on the electrical conductivity of the tissue and the high conductivity of tumor tissue, which leads to a lower field than in the surrounding healthy tissue. Hypersaline Infusion (HI) through the portal vein focuses IRE on scattered liver tumors, by creating a differential conductivity between the different types of tissue. The aim of this study is to determine the effects of the HI protocol on the hepatic and histological biochemical results. Methods: Ten male Sprague Dawley rats were used for HI protocol. Blood samples were collected at pre-, immediately post-, 24-hrs, 72-hrs, 1-week and 3-weeks post-HI. All the animals were sacrificed after one-month follow-up in order to collect histological samples. Results: The mortality rate in this procedure reached 30% (3/10). Only the pH and transaminases at 24-hrs were significantly and directly linked to mortality (p=0.036 and p=0.004, respectively). The three non-surviving animals had a four-time higher AST level at 24-hrs. Natremia normalized at 24-hrs post-HI. Statistically significant differences were found in hepatic necrosis between the non-surviving (n=3) and surviving rats (n=7) (30.67 ± 10.97 vs. 2.86 ± 7.56% respectively, p=0.01). Discussion: HI through the portal system involves a significant risk of possibly lethal cytolysis and acidosis. Therefore, compensatory measures and a reduced saline overload are warranted to improve the survival rates.

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.

Abstract 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.

Introduction: Pancreatic duct ligation (PDL) in murine model has been described as an exocrine pancreatic atrophy-inducing procedure. However, its influence has not been described on premalignant lesions. This study describes the histological changes of premalignant lesions in a transgenic murine PDL model. Methods: Selective ligation of the splenic lobe of the pancreas was performed, including its main pancreatic duct, in Ptf1a-Cre (+/ki); K-ras LSLG12Vgeo (+/ki) mice (PDL-Kras mice).Three experimental groups have been considered: PDL group, controls and shams. We analyzed the presence and number of premalignant lesions (PanIN 1, 2, 3 and Atypical Flat Lesions) in Proximal (PP) and distal (DP) pancreas for each group at different postoperative periods. Results: Controls and shams have a 7 and 9-time increase of risk of presenting PanIN 2, 3 and AFL in their distal pancreas (High Grade Pancreatic lesions -HGPL-), than PDL-Kras mice. Furthermore, PDL-Kras mice have significantly less PanIN 1, 2 and AFL lesions in DP compared to PP. Conclusions: Pancreatic duct ligation in Ptf1a-Cre (+/ki); K-ras LSLG12Vgeo (+/ki) mice induces a decrease in the presence of premalignant lesions in the ligatured distal pancreas.

Abstract Purpose: To improve the computer modelling of radiofrequency ablation (RFA) by internally cooled wet (ICW) electrodes with added clinically oriented features. Methods: An improved RFA computer model by ICW electrode included: (1) a realistic spatial distribution of the infused saline, and (2) different domains to distinguish between healthy tissue, saline-infused tumour, and non-infused tumour, under the assumption that infused saline is retained within the tumour boundary. A realistic saline spatial distribution was obtained from an in vivo pig liver study. The computer results were analysed in terms of impedance evolution and coagulation zone (CZ) size, and were compared to the results of clinical trials conducted on 17 patients with the same ICW electrode. Results: The new features added to the model provided computer results that matched well with the clinical results. No roll-offs occurred during the 4-min ablation. CZ transversal diameter (4.10 ± 0.19 cm) was similar to the computed diameter (4.16 cm). Including the tumour and saline infusion in the model involved (1) a reduction of the initial impedance by 10 − 20 Ω, (2) a delay in roll-off of 20 s and 70 − 100 s, respectively, and (3) 18 − 31% and 22 − 36% larger CZ size, respectively. The saline spatial distribution geometry was also seen to affect roll-off delay and CZ size. Conclusions: Using a three-compartment model and a realistic saline spatial distribution notably improves the match with the outcome of the clinical trials.

Background: After resection of colorectal liver metastasis, the incidence of local hepatic recurrence (LHER) ranges from 7 to 17% or even higher in some laparoscopic non-anatomical laparoscopic resections in some series. The aim of this study is to determinate if a RF-assisted transection device (RFAT) has any effect on (LHER) compared to conventional technologies. Methods: A study population of 103 patients who had undergone a hepatic surgical resection was analysed. Two groups were considered: RFAT group (n=45) and conventional technique group (n=58). LHER was defined as any growing or enhancing tumour in the margin of hepatic resection during follow-up. Cox proportional models were constructed and variables were eliminated only if p>0.20 to protect against residual confounding. To assess the stability of Cox's regression model and its internal validity, a bootstrap investigation was also performed. Results: Baseline and operative characteristics were similar in both groups. In patients with positive margins, we demonstrated 0% of LHER in RFAT vs 27% in control group (p=0.03). In the multivariate analysis, factors with significant influence on LHER were: RFAT group, size of the largest metastases, number of resected metastases, positive margin and usage of Pringle-manoeuvre. Conclusion: Parenchymal transection using a RFAT able to create deep thermal lesions may reduce LHER especially in case of margin invasion during transection. This could be especially relevant in some difficult laparoscopic non-anatomical resections.

Irreversible electroporation (IRE) has recently gained in popularity as an ablative technique, however little is known about its oncological long-term outcomes. To determine the long-time survival of animals treated with a high dose of IRE and which histological changes it induces in tumoral tissue, IRE ablation was performed in forty-six athymic-nude mice with KM12C tumors implanted in the liver by applying electric current with different voltages (2000 V/cm, 1000 V/cm). The tumors were allowed to continue to grow until the animals reached the end-point criteria. Histology was harvested and the extent of tumor necrosis was semi-quantitatively assessed. IRE treatment with the 2000 V/cm protocol significantly prolonged median mouse survival from 74.3 ± 6.9 days in the sham group to 112.5 ± 15.2 days in the 2000 V/cm group. No differences were observed between the mean survival of the 1000 V/cm and the sham group (83.2 ± 16.4 days, p = 0.62). Histology revealed 63.05% ± 23.12 of tumor necrosis in animals of the 2000 V/cm group as compared to 17.50% ± 2.50 in the 1000 V/cm group and 25.6% ± 22.1 in the Sham group (p = 0.001). IRE prolonged the survival of animals treated with the highest electric field (2000 V/cm). The animals in this group showed significantly higher rate of tumoral necrosis.

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.

Although radiofrequency-assisted devices have sometimes been used in partial splenectomy, this is not a common technique. This report describes the first case of laparoscopic partial splenectomy using an RF-assisted device (Coolinside) which allows both coagulation and transection of the parenchyma and eventually the protective coagulation of the remnant side.

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 (556471ml vs. 225 +/- 313ml, p=.02). The adjusted mean bleeding/transection area was also significantly higher in the control group (7.0 +/- 3.3ml/cm(2) vs. 2.8 +/- 4.0ml/cm(2), 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.

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.

Irreversible electroporation is a fast-growing liver ablation technique. Although safety has been well documented in small ablations, our aim is to assess its safety and feasibility when a large portion of liver is ablated. Eighty-seven mice were subjected to high voltage pulses directly delivered across parallel plate electrodes comprising around 40% of mouse liver. One group consisted in 55 athymic-nude, in which a tumor from the KM12C cell line was grown and the other thirty-two C57-Bl6 non-tumoral mice. Both groups were subsequently divided into subsets according to the delivered field strength (1000 V/cm, 2000 V/cm) and whether or not they received anti-hyperkalemia therapy. Early mortality (less than 24 hours post-IRE) in the 2000 V/cm group was observed and revealed considerably higher mean potassium levels. In contrast, the animals subjected to a 2000 V/cm field treated with the anti-hyperkalemia therapy had higher survival rates (OR = 0.1, 95%CI = 0.02–0.32, p < 0.001). Early mortality also depended on the electric field magnitude of the IRE protocol, as mice given 1000 V/cm survived longer than those given 2000 V/cm (OR = 4.7, 95%CI = 1.8–11.8, p = 0.001). Our findings suggest that ionic disturbances, mainly due to potassium alterations, should be warned and envisioned when large volume ablations are performed by IRE.

Background: Pancreatic duct ligation (PDL) has been used as a model of chronic pancreatitis and as a model to increase beta-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 I (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. Copyright (C) 2015, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved.