The value of Augmented Reality in surgery — A usability study on laparoscopic liver surgery

Augmented Reality (AR) is considered to be a promising technology for the guidance of laparoscopic liver surgery. By overlaying pre-operative 3D information of the liver and internal blood vessels on the laparoscopic view, surgeons can better understand the location of critical structures. In an effort to enable AR, several authors have focused on the development of methods to obtain an accurate alignment between the laparoscopic video image and the pre-operative 3D data of the liver, without assessing the benefit that the resulting overlay can provide during surgery. In this paper, we present a study that aims to assess quantitatively and qualitatively the value of an AR overlay in laparoscopic surgery during a simulated surgical task on a phantom setup. We design a study where participants are asked to physically localise pre-operative tumours in a liver phantom using three image guidance conditions — a baseline condition without any image guidance, a condition where the 3D surfaces of the liver are aligned to the video and displayed on a black background, and a condition where video see-through AR is displayed on the laparoscopic video. Using data collected from a cohort of 24 participants which include 12 surgeons, we observe that compared to the baseline, AR decreases the median localisation error of surgeons on non-peripheral targets from 25.8 mm to 9.2 mm. Using subjective feedback, we also identify that AR introduces usability improvements in the surgical task and increases the perceived confidence of the users. Between the two tested displays, the majority of participants preferred to use the AR overlay instead of navigated view of the 3D surfaces on a separate screen. We conclude that AR has the potential to improve performance and decision making in laparoscopic surgery, and that improvements in overlay alignment accuracy and depth perception should be pursued in the future

Intestinal tissue engineering

Tissue engineering (TE) principles have been successfully clinically applied to treat disease affecting specific organs (e.g. trachea) but developments in some organs has lagged behind. The inability to repair or replace significantly damaged intestinal tissue remains a barrier to improving patient outcomes and the promise of Tissue Engineered Intestine (TEI) that was first made more than 20 years ago, is yet to be realised. This work explored the potential of TEI and literature review formed a basis for developing a clinically transferrable experimental model. It was hypothesised that, porcine large intestine could be retrieved from pigs and decellularized to create a biological scaffold that demonstrated favourable properties for TE, including potential for vascular perfusion and cell engraftment. Novel experiments were performed in intestinal retrieval and decellularization, resulting in scaffolds characterised by a number of methods (e.g. histology, immunohistochemistry). Assessment of the scaffoldâs ability to support cell engraftment required development of protocols for isolation and culture of appropriate progenitors, including adipose/ bone marrow derived mesenchymal stromal cells and intestinal organoid units. Finally, in-vitro cultures combining scaffolds and cells were used to assess the ability of scaffolds to promote tissue regeneration. Perfusion decellularization methods proved effective in creating biological scaffolds that retained radiologically demonstrated vascular perfusion networks, permitting a future route for recellularization and/or transplantation. Scaffolds demonstrated retention of essential extracellular matrix components (e.g. glycosaminoglycans, collagen) and an absence of cell nuclei. Mesenchymal stem cells were isolated, cultured and combined in-vitro with scaffolds in an attempted scaled-down seeding model. Control of culture conditions was challenging and results inconclusive with respect to the scaffoldâs regenerative potential. The work demonstrates an exciting prospect for biological scaffold development for a clinically transferrable, semi-xenogeneic transplant or drug delivery model but further experiments in scaffold seeding are required to assess the full potential.</p

Intestinal tissue engineering

Tissue engineering (TE) principles have been successfully clinically applied to treat disease affecting specific organs (e.g. trachea) but developments in some organs has lagged behind. The inability to repair or replace significantly damaged intestinal tissue remains a barrier to improving patient outcomes and the promise of Tissue Engineered Intestine (TEI) that was first made more than 20 years ago, is yet to be realised. This work explored the potential of TEI and literature review formed a basis for developing a clinically transferrable experimental model. It was hypothesised that, porcine large intestine could be retrieved from pigs and decellularized to create a biological scaffold that demonstrated favourable properties for TE, including potential for vascular perfusion and cell engraftment. Novel experiments were performed in intestinal retrieval and decellularization, resulting in scaffolds characterised by a number of methods (e.g. histology, immunohistochemistry). Assessment of the scaffold’s ability to support cell engraftment required development of protocols for isolation and culture of appropriate progenitors, including adipose/ bone marrow derived mesenchymal stromal cells and intestinal organoid units. Finally, in-vitro cultures combining scaffolds and cells were used to assess the ability of scaffolds to promote tissue regeneration. Perfusion decellularization methods proved effective in creating biological scaffolds that retained radiologically demonstrated vascular perfusion networks, permitting a future route for recellularization and/or transplantation. Scaffolds demonstrated retention of essential extracellular matrix components (e.g. glycosaminoglycans, collagen) and an absence of cell nuclei. Mesenchymal stem cells were isolated, cultured and combined in-vitro with scaffolds in an attempted scaled-down seeding model. Control of culture conditions was challenging and results inconclusive with respect to the scaffold’s regenerative potential. The work demonstrates an exciting prospect for biological scaffold development for a clinically transferrable, semi-xenogeneic transplant or drug delivery model but further experiments in scaffold seeding are required to assess the full potential.</p

Mixed ligand ruthenium(II) complexes of bis(pyrid-2-yl)-/bis(benzimidazol-2-yl)-dithioether and diimines: study of non-covalent DNA binding and cytotoxicity

A series of mixed ligand ruthenium(II) complexes [Ru(pdto)(diimine)](ClO4)2/(PF6)21-3 and [Ru(bbdo)(diimine)](ClO4)24-6, where pdto is 1,8-bis(pyrid-2-yl)-3,6-dithiooctane, bbdo is 1,8-bis(benzimidazol-2-yl)-3,6-dithiooctane and diimine is 1,10-phenanthroline (phen), dipyrido-[3,2-d:2',3'-f]-quinoxaline (dpq) and dipyrido[3,2-a:2',3'-c]phenazine (dppz), have been isolated and characterised by analytical and spectral methods. The complexes [Ru(pdto)(phen)](PF6)21a, [Ru(pdto)(dpq)(Cl)](PF6) 2a, [Ru(bbdo)(phen)](PF6)24a and [Ru(bbdo)(dpq)](ClO4)25 have been structurally characterized and their coordination geometries around ruthenium(II) are described as distorted octahedral. In 1a, 4a and 5 the two thioether sulfur and two py/bzim nitrogen atoms of the tetradentate pdto/bbdo ligand are folded around Ru(II) to give predominantly a "cis-&#945;" configuration. IH NMR spectral data of the complexes support this configuration in solution. In [Ru(pdto)(dpq)Cl](PF6) 2a with a distorted octahedral coordination geometry, one of the two py nitrogens of pdto is not coordinated. The DNA binding constants (Kb: 2, 2.00 &#177; 0.02 &#215; 104 M-1, s = 1.0; 3, 3.00 &#177; 0.01 &#215; 106 M-1, s = 1.3) determined by absorption spectral titrations of the complexes with CT DNA reveal that 3 interacts with DNA more tightly than 2 through partial intercalation of the extended planar ring of coordinated dppz with the DNA base stack. The DNA binding affinities of the complexes increase with increase in the number of planar aromatic rings in the co-ligand, and on replacing both the py moieties in pdto complexes (1-3) by bzim moieties to give bbdo complexes (4-6). Upon interaction with CT DNA the complexes 1, 2, 5 and 6 show a decrease in anodic current in the cyclic voltammograms. On the other hand, interestingly, 3 and 4 show an increase in anodic current suggesting their involvement in electrocatalytic guanine oxidation. Interestingly, of all the complexes, only 6 alters the superhelicity of DNA upon binding with supercoiled pBR322 DNA. The cytotoxicities of the dppz complexes 3 and 6, which avidly bind to DNA, have been examined by screening them against cell lines of different cancer origins. It is noteworthy that 6 exhibits selectivity with higher cytotoxicity against the melanoma cancer cell line (A375) than other cell lines, potency approximately twice that of cisplatin and toxicity to normal cells 3 and 90 times less than cisplatin and adriamycin respectively

Mixed ligand ruthenium(II) complexes of bis(pyrid-2-yl)-/bis(benzimidazol-2-yl)-dithioether and diimines: Study of non-covalent DNA binding and cytotoxicity

A series of mixed ligand ruthenium(II) complexes [Ru(pdto)(diimine)]$(ClO_4)_2/(PF_6)_2$ 1–3 and [Ru(bbdo)(diimine)]$(ClO_4)_2$ 4–6, where pdto is 1,8-bis(pyrid-2-yl)-3,6-dithiooctane, bbdo is 1,8-bis(benzimidazol-2-yl)-3,6-dithiooctane and diimine is 1,10-phenanthroline (phen), dipyrido-[3,2-d:2,3-f]-quinoxaline (dpq) and dipyrido[3,2-a:2,3-c]phenazine (dppz), have been isolated and characterised by analytical and spectral methods. The complexes [Ru(pdto)(phen)]$(PF_6)_2$ 1a, [Ru(pdto)(dpq)(Cl)]$(PF_6)$ 2a, [Ru(bbdo)(phen)]$(PF_6)_2$ 4a and [Ru(bbdo)(dpq)]$(ClO_4)_2$ 5 have been structurally characterized and their coordination geometries around ruthenium(II) are described as distorted octahedral. In 1a, 4a and 5 the two thioether sulfur and two py/bzim nitrogen atoms of the tetradentate pdto/bbdo ligand are folded around Ru(II) to give predominantly a cis- configuration. IH NMR spectral data of the complexes support this configuration in solution. In [Ru(pdto)(dpq)Cl]$(PF_6)$ 2a with a distorted octahedral coordination geometry, one of the two py nitrogens of pdto is not coordinated. The DNA binding constants $(Kb: 2, 2.00 \pm 0.02 X 104 M^{-1}, s = 1.0; 3, 3.00 \pm 0.01 X 106 M^{-1}, s = 1.3)$ determined by absorption spectral titrations of the complexes with CT DNA reveal that 3 interacts with DNA more tightly than 2 through partial intercalation of the extended planar ring of coordinated dppz with the DNA base stack. The DNA binding affinities of the complexes increase with increase in the number of planar aromatic rings in the co-ligand, and on replacing both the py moieties in pdto complexes (1–3) by bzim moieties to give bbdo complexes (4–6). Upon interaction with CT DNA the complexes 1, 2, 5 and 6 show a decrease in anodic current in the cyclic voltammograms. On the other hand, interestingly, 3 and 4 show an increase in anodic current suggesting their involvement in electrocatalytic guanine oxidation. Interestingly, of all the complexes, only 6 alters the superhelicity of DNA upon binding with supercoiled pBR322 DNA. The cytotoxicities of the dppz complexes 3 and 6, which avidly bind to DNA, have been examined by screening them against cell lines of different cancer origins. It is noteworthy that 6 exhibits selectivity with higher cytotoxicity against the melanoma cancer cell line (A375) than other cell lines, potency approximately twice that of cisplatin and toxicity to normal cells 3 and 90 times less than cisplatin and adriamycin respectively

lnterleukin-2 mediated regulation of mitogen-activated T cell reactivity from different lymphoid sources in patients with squamous cell carcinoma of the oral cavity

Peripheral blood lymphocytes (PBL) from patients with oral cancer (treated and untreated), oral leukoplakia and healthy donors; lymphocytes from metastatic and non-metastatic lymph nodes (met LNL and non-met LNL); and tumor infiltrating lymphocytes (TIL) were tested for proliferative response to mitogen PHA (phytohemagglutinin) and its augmentation by recombinant Interleukin-2 (rIL-2), for expression of Tac antigen (CD25) and for production of IL-2. Depressed PHA responses were found in PEL of treated and untreated patients, and in TIL. Addition of IL-2 could bring about 16% to 31% augmentation in lymphocyte response to PHA from all the three sources. PEL from 50% of healthy donors, 45% of patients with leukoplakia, 25% untreated oral cancer patients and 35% treated oral cancer patients showed IL-2 mediated augmentation of PHA response. While, 40% non-met LNL samples, 70% met LNL samples and only 23% TIL samples showed increased mitogen induced proliferation by IL-2. The augmented levels of PHA response of PEL from treated and untreated patients, and of TIL, were still below those of normal PEL. PEL from patients with leukoplakia, treated oral cancer patients and TIL showed depressed CD25 antigen expression. Depressed IL-2 production was observed only in PEL of leukoplakia patients. Thus the IL-2 mediated events of T cell activation from different lymphoid sources in patients with oral cancer did not correlate with their proliferative responses