Liver specification of human iPSC-derived endothelial cells transplanted into mouse liver.

Background & Aims: Liver sinusoidal endothelial cells (LSECs) are important in liver development, regeneration, and pathophysiology, but the differentiation process underlying their tissue-specific phenotype is poorly understood and difficult to study because primary human cells are scarce. The aim of this study was to use human induced pluripotent stem cell (hiPSC)-derived LSEC-like cells to investigate the differentiation process of LSECs. Methods: hiPSC-derived endothelial cells (iECs) were transplanted into the livers of Fah-/-/Rag2-/-/Il2rg-/- mice and assessed over a 12-week period. Lineage tracing, immunofluorescence, flow cytometry, plasma human factor VIII measurement, and bulk and single cell transcriptomic analysis were used to assess the molecular and functional changes that occurred following transplantation. Results: Progressive and long-term repopulation of the liver vasculature occurred as iECs expanded along the sinusoids between hepatocytes and increasingly produced human factor VIII, indicating differentiation into LSEC-like cells. To chart the developmental profile associated with LSEC specification, the bulk transcriptomes of transplanted cells between 1 and 12 weeks after transplantation were compared against primary human adult LSECs. This demonstrated a chronological increase in LSEC markers, LSEC differentiation pathways, and zonation. Bulk transcriptome analysis suggested that the transcription factors NOTCH1, GATA4, and FOS have a central role in LSEC specification, interacting with a network of 27 transcription factors. Novel markers associated with this process included EMCN and CLEC14A. Additionally, single cell transcriptomic analysis demonstrated that transplanted iECs at 4 weeks contained zonal subpopulations with a region-specific phenotype. Conclusions: Collectively, this study confirms that hiPSCs can adopt LSEC-like features and provides insight into LSEC specification. This humanised xenograft system can be applied to further interrogate LSEC developmental biology and pathophysiology, bypassing current logistical obstacles associated with primary human LSECs. Impact and implications: Liver sinusoidal endothelial cells (LSECs) are important cells for liver biology, but better model systems are required to study them. We present a pluripotent stem cell xenografting model that produces human LSEC-like cells. A detailed and longitudinal transcriptomic analysis of the development of LSEC-like cells is included, which will guide future studies to interrogate LSEC biology and produce LSEC-like cells that could be used for regenerative medicine.

Early onset pancreatic cancer-exploring contemporary treatment and outcomes using real-world data.

BACKGROUND: Pancreatic cancer incidence is increasing in younger populations. Differences between early onset pancreatic cancer (EOPC) and later onset pancreatic cancer (LOPC), and how these should inform management warrant exploration in the contemporary setting. METHODS: A prospectively collected multi-site dataset on consecutive pancreatic adenocarcinoma patients was interrogated. Patient, tumour, treatment, and outcome data were extracted for EOPC (≤50 years old) vs LOPC (>50 years old). RESULTS: Of 1683 patients diagnosed between 2016 and 2022, 112 (6.7%) were EOPC. EOPC more frequently had the tail of pancreas tumours, earlier stage disease, surgical resection, and trended towards increased receipt of chemotherapy in the curative setting compared to LOPC. EOPC more frequently received 1st line chemotherapy, 2nd line chemotherapy, and chemoradiotherapy than LOPC in the palliative setting. Recurrence-free survival was improved for the tail of pancreas EOPC vs LOPC in the resected setting; overall survival was superior for EOPC compared to LOPC across the resected, locally advanced unresectable and metastatic settings. CONCLUSIONS: EOPC remains a small proportion of pancreatic cancer diagnoses. The more favourable outcomes in EOPC suggest these younger patients are overall deriving benefits from increased treatment in the curative setting and increased therapy in the palliative setting.

Use and outcomes from neoadjuvant chemotherapy in borderline resectable pancreatic ductal adenocarcinoma in an Australasian population.

BACKGROUND: Use of neoadjuvant (NA) chemotherapy is recommended when pancreatic ductal adenocarcinoma (PDAC) is borderline resectable METHOD: A retrospective analysis of consecutive patients with localized PDAC between January 2016 and March 2019 within the Australasian Pancreatic Cancer Registry (PURPLE, Pancreatic cancer: Understanding Routine Practice and Lifting End results) was performed. Clinicopathological characteristics, treatment, and outcome were analyzed. Overall survival (OS) comparison was performed using log-rank model and Kaplan-Meier analysis. RESULTS: The PURPLE database included 754 cases with localised PDAC, including 148 (20%) cases with borderline resectable pancreatic cancer (BRPC). Of the 148 BRPC patients, 44 (30%) underwent immediate surgery, 80 (54%) received NA chemotherapy, and 24 (16%) were inoperable. The median age of NA therapy patients was 63 years and FOLFIRINOX (53%) was more often used as NA therapy than gemcitabine/nab-paclitaxel (31%). Patients who received FOLFIRINOX were younger than those who received gemcitabine/nab-paclitaxel (60 years vs. 67 years, p = .01). Surgery was performed in 54% (43 of 80) of BRPC patients receiving NA chemotherapy, with 53% (16 of 30) achieving R0 resections. BRPC patients undergoing surgery had a median OS of 30 months, and 38% (9 of 24) achieved R0 resection. NA chemotherapy patients had a median OS of 20 months, improving to 24 months versus 10 months for patients receiving FOLFIRINOX compared to gemcitabine/nab-paclitaxel (Hazard Ratio (HR) .3, p < .0001). CONCLUSIONS: NA chemotherapy use in BRPC is increasing in Australia. One half of patients receiving NA chemotherapy proceed to curative resection, with 53% achieving R0 resections. Patients receiving Infusional 5-flurouracil, Irinotecan and Oxaliplatin (FOLIRINOX) had increased survival than gemcitabine/nab-paclitaxel. Treatment strategies are being explored in the MASTERPLAN and DYNAMIC-Pancreas trials.

An algorithm for the management of traumatic abdominal wall hernia based on a 9-year review.

BACKGROUND: Traumatic abdominal wall hernia (TAWH) is a rare consequence of blunt abdominal trauma, usually in the setting of multitrauma, with little consensus or guidelines for management. We present a case series of patients with traumatic herniae over a 9-year period and a suggested management algorithm. METHOD: Retrospective review of all patients with TAWH from 1st January 2011 to 31st December 2019 at a Level 1 adult Major Trauma Centre. Clinical presentation, surgical intervention and complications and recurrence were analysed. RESULTS: Forty-seven patients were found to have TAWH, 0.5% of all major trauma admissions. Thirty (63.8%) were repaired, 12 acutely, 11 semi-acute and 7 delayed. All but 1 (fall>3 m) were transport associated, with a median Injury Severity Score (ISS) of 29. Follow-up data for operative cases were available for all but one (97%). Seven (23.3%) cases had a recurrence, more common in the acute repair group (33.3%) compared to semi-acute (18.2%), and elective group (14.3%). CONCLUSION: TAWH is a rare but potentially serious consequence of blunt abdominal trauma. This series has favoured earlier repair for anterior TAWH, or all those undergoing a laparotomy for other reasons, and elective repair for lumbar or lateral TAWH that do not require a laparotomy for other conditions. We present our preferred algorithm for management, accepting that there are many available strategies in this heterogeneous group of injuries. Loss of follow up and recurrence are a concern, and clinicians are encouraged to develop processes to ensure that TAWH are not a 'forgotten hernia'.

Telemedicine versus face-to-face follow up in general surgery: a randomized controlled trial.

BACKGROUND: Telemedicine provides healthcare to patients at a distance from their treating clinician. There is a lack of high-quality evidence to support the safety and acceptability of telemedicine for postoperative outpatient follow-up. This randomized controlled trial-conducted before the COVID-19 pandemic-aimed to assess patient satisfaction and safety (as determined by readmission, reoperation and complication rates) by telephone compared to face-to-face follow-up after uncomplicated general surgical procedures. METHODS: Patients following laparoscopic appendicectomy or cholecystectomy and laparoscopic or open umbilical or inguinal hernia repairs were randomized to a telephone or face-to-face outpatient clinic. Patient demographics, perioperative details and postoperative outcomes were compared. Patient satisfaction was assessed via a standardized Likert-style scale. RESULTS: One hundred and twenty-three patients were randomized over 12 months. Mean consultation times were significantly shorter for telemedicine than face-to-face clinics (telemedicine 10.52 ± 7.2 min, face-to-face 15.95 ± 9.96 min, P = 0.0021). There was no difference between groups in the attendance rates, nor the incidence or detection of postoperative complications. Of the 58 patients randomized to the telemedicine arm, 40% reported high, and 60% reported very high satisfaction with the method of clinic follow-up. CONCLUSION: Telemedicine postoperative follow-up is safe and acceptable to patients and could be considered in patients undergoing uncomplicated benign general surgery.

Comparison of risk adjusted excess post-operative pancreatic fistula rates after pancreaticoduodenectomy using cumulative sum analysis.

BACKGROUND: Post-operative pancreatic fistula (POPF) is a key outcome post pancreaticoduodenectomy. There are numerous POPF risk calculators but no agreed benchmark, a key component of meaningful audit. We compared observed versus predicted POPF for six risk adjusted POPF calculators, to ascertain how they differ and thus contribute to discussion around benchmarking. METHODS: This was a retrospective single-arm cohort study at the Royal Melbourne Hospital of patients who underwent pancreaticoduodenectomy 1 November 2015 to 31 December 2021 with a primary outcome of a clinically relevant POPF. Cumulative sum (CUSUM) plots of observed versus predicted rate of POPF for sequential patients were constructed for six risk adjusted POPF calculators - Birmingham, updated Birmingham, fistula risk score (FRS), modified FRS (m-FRS), alternative FRS (a-FRS), and updated alternative FRS (ua-FRS). RESULTS: The study included 77 patients. The actual rate of clinically relevant POPF was 14.3%. FRS calculated an excess of 1.3 POPF per 100 cases. All other calculators demonstrated prevention of POPF per 100 cases: Birmingham 3.4, updated Birmingham 14.0, m-FRS 0.3, a-FRS 1.2, ua-FRS 19.7. CONCLUSION: The observed versus predicted rate of POPF was near zero for all risk calculators except ua-FRS and updated Birmingham, which predicted a higher POPF than observed (19.7, 14.0, respectively). These results indicate that, excepting ua-FRS and updated Birmingham, these calculators yield comparable results. Benchmarks for POPF should prescribe which risk calculators are used, and ideally a unified standard between centres should be the goal to provide consistency in outcome reporting and robust audit processes.

The association between quality care and outcomes for a real-world population of Australian patients diagnosed with pancreatic cancer.

BACKGROUND: This study: (i) assessed compliance with a consensus set of quality indicators (QIs) in pancreatic cancer (PC); and (ii) evaluated the association between compliance with these QIs and survival. METHODS: Four years of data were collected for patients diagnosed with PC. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A multivariable analysis tested the relationship between significant patient and hospital characteristics, patient cluster effects within hospitals and survival. RESULTS: 1061 patients were eligible for this study. Significant association with improved survival were: (i) in the potentially resectable group having adjuvant chemotherapy administered following surgery or a reason documented (HR, 0.29; 95 CI, 0.19-0.46); (ii) in the locally advanced group included having chemotherapy ± chemoradiation, or a reason documented for not undergoing treatment (HR, 0.38; 95 CI, 0.25-0.58); and (iii) in the metastatic disease group included having documented performance status at presentation (HR, 0.65; 95 CI, 0.47-0.89), being seen by an oncologist in the absence of treatment (HR, 0.48; 95 CI, 0.31-0.77), and disease management discussed at a multidisciplinary team meeting (HR, 0.79; 95 CI, 0.64-0.96). CONCLUSION: Capture of a concise data set has enabled quality of care to be assessed.

Survival benefit of neoadjuvant chemotherapy and surgery versus surgery first for resectable colorectal liver metastases: a cohort study.

BACKGROUND: There is continued debate about the survival benefit of neoadjuvant chemotherapy (neoCT) in patients with resectable colorectal liver metastases (CRLM). METHODS: In this retrospective cohort study, we included 201 patients with metastatic colorectal cancer who underwent their first CRLM resection and achieved resection of all sites of disease. We compared the overall survival (OS) and progression-free survival (PFS) between patients who received neoCT prior to CRLM resection with those who underwent CRLM upfront. A multivariable Cox proportional hazard regression analysis was performed to adjust for potential confounders. RESULTS: A total of 101 of 201 (51.2%) patients received chemotherapy prior to CRLM resection and 100 of 201 had surgery upfront. Multivariable Cox proportional hazard regression showed no statistically significant difference in the hazard of death for those given neoCT prior to resection of CRLM compared with surgery first for both OS and PFS (OS: hazard ratio 1.74, 95% confidence interval 0.85-3.55, P = 0.127, PFS: hazard ratio 1.42, 95% confidence interval 0.93-2.19, P = 0.107). CONCLUSION: In our series of patients with metastatic colorectal cancer who achieved surgical resection of all sites of disease, neoCT prior to CRLM resection was not associated with any survival benefit.

The incidence of symptomatic remnant gall bladder: a population study.

BACKGROUND: Subtotal cholecystectomy is utilized in conditions of high risk to critical structures, like the common bile duct. However, the remnant gall bladder may become symptomatic and require a completion cholecystectomy for treatment. This second procedure can itself be a risk to critical structures. To establish the incidence of redo-cholecystectomy and identify risk factors that lead to subtotal cholecystectomy and repeat operation in a review of state-based practices for cholecystectomy. METHODS: A search of state coding records relating to cholecystectomy from 1998 to 2016. Patients who were coded for cholecystectomy-related procedures on different dates were identified. Patients who underwent the procedures within 6 months were excluded to avoid acute post-operative complications and gall bladder malignancy. RESULTS: 210 719 cholecystectomies were performed. 1133 required repeat procedure. 616 were excluded, leaving 516 (0.25%) cholecystectomy patients requiring a second cholecystectomy. The subsequent operation was more likely to be an emergency procedure; involve transcystic bile duct exploration, adhesiolysis and require intensive care unit admission post-operatively. A repeat cholecystectomy was more likely to occur after having the primary procedure at a public hospital and when an intra-operative cholangiogram was not performed. Over the study period, the rate of repeat cholecystectomy increased from 0.02% to 0.6%. Incidentally, the rate of intra-operative cholangiogram during a primary cholecystectomy increased from 43% to 73%. CONCLUSIONS: Repeat cholecystectomy is an uncommon procedure. A second cholecystectomy is a more complex and likely to require intensive care unit support. Referral to a tertiary hepatobiliary unit is recommended.

Coagulation in liver surgery: an observational haemostatic profile and thromboelastography study.

BACKGROUND: International normalized ratio (INR) is used as a marker of the haemostatic status following liver resection. However, the impact of liver resection on haemostasis is complex and beyond what can be measured by INR. This study aimed to prospectively assess haemostatic profile following liver resection and determine if INR measurement can safely guide post-operative thromboprophylaxis. METHODS: In this prospective cohort study, patients undergoing liver resection had coagulation parameters (International normalised ratio (INR), prothrombin time (PT), activated partial thromboplastin time, fibrinogen, d-dimer, von Willebrand factor antigen, procoagulant activity of phospholipids and clotting factors II, VII, VIIIc, IX and X) and thromboelastogram parameters assessed perioperatively. Clinical follow-up assessed for thromboembolism and haemorrhage. RESULTS: In the 41 patients included, INR was significantly (P < 0.0001) elevated post-operatively, and INR >1.5 was observed in seven of 41 (17.1%) on post-operative day 1 and one of 41 (2.4%) patients on post-operative day 3, respectively. Factor VII levels showed transient reduction but other factors, especially factors II and X, remained within normal range following liver resection. Thromboelastogram parameters remained normal or supranormal for all patients at all time points. One incident of post-hepatectomy haemorrhage occurred, despite a normal coagulation profile. Two patients suffered late pulmonary embolic episodes. CONCLUSION: Post liver resection haemostasis is complex and poorly reflected by INR, which should not guide initiation of chemical thromboprophylaxis in the immediate post-operative period.

Patient-reported outcome measures (PROMs) in pancreatic cancer: a systematic review.

BACKGROUND: The aim of this systematic review is to examine patient-reported outcome measures (PROMs), their attributes and application in patients with pancreatic cancer (PC). METHOD: A systematic literature search was undertaken of articles published to June 2018 to identify PROMs applied in primary studies in PC. Characteristics of the included studies and PROMs were described with identified scales grouped into five domains. The psychometric properties of the identified PROMs were further assessed for reliability and validity among patients with PC. RESULTS: From 1688 studies screened, 170 were included. Almost half (48%) were conducted in patients with unresectable PC; the majority of these (68%) were evaluated in randomized controlled trials. Median questionnaire completion rates fell below 10% of the original cohort within 12 months in patients with unresectable PC compared to 75% in patients with resectable PC. Seventy PROMs were identified, 32 measuring unidimensional parameters (e.g. pain) and 35 measuring multidimensional (e.g. quality of life) constructs. Only five (7%) PROMs were disease-specific and 13 (19%) were validated in patients with PC. Fifty scales were grouped into 19 physical, 9 psychological, 6 psychiatric, 9 social and 7 other domains. CONCLUSION: Three multidimensional PROMs, the: (i) FACT-HEP in unresectable PC; (ii) QLQ-PAN26 (in conjunction with its core QLQ-C30 PROM) in resectable PC; and (iii) MDASI-GI are recommended as instruments to capture quality of life in patients with PC. Summarised scales and psychometric evaluation provide a framework to choose PROMs for scales not captured by the recommended PROMs.

Systematic review of liver directed therapy for uveal melanoma hepatic metastases.

BACKGROUND: Uveal melanoma (UM) is a rare malignancy with a propensity for metastasis to the liver. Systemic chemotherapy is typically ineffective in these patients with liver metastases and overall survival is poor. There are no evidence-based guidelines for management of UM liver metastases. The aim of this study was to review the evidence for management of UM liver metastases. METHODS: A systematic review of English literature publications was conducted across Ovid Medline, Ovid MEDLINE and Cochrane CENTRAL databases until April 2019. The primary outcome was overall survival, with disease free survival as a secondary outcome. RESULTS: 55 studies were included in the study, with 2446 patients treated overall. The majority of these studies were retrospective, with 17 of 55 including comparative data. Treatment modalities included surgery, isolated hepatic perfusion (IHP), hepatic artery infusion (HAI), transarterial chemoembolization (TACE), selective internal radiotherapy (SIRT) and Immunoembolization (IE). Survival varied greatly between treatments and between studies using the same treatments. Both surgery and liver-directed treatments were shown to have benefit in selected patients. CONCLUSION: Predominantly retrospective and uncontrolled studies suggest that surgery and locoregional techniques may prolong survival. Substantial variability in patient selection and study design makes comparison of data and formulation of recommendations challenging.

The Upper Gastrointestinal Cancer Registry (UGICR): a clinical quality registry to monitor and improve care in upper gastrointestinal cancers.

PURPOSE: The Upper Gastrointestinal Cancer Registry (UGICR) was developed to monitor and improve the quality of care provided to patients with upper gastrointestinal cancers in Australia. PARTICIPANTS: It supports four cancer modules: pancreatic, oesophagogastric, biliary and primary liver cancer. The pancreatic cancer (PC) module was the first module to be implemented, with others being established in a staged approach. Individuals are recruited to the registry if they are aged 18 years or older, have received care for their cancer at a participating public/private hospital or private clinic in Australia and do not opt out of participation. FINDINGS TO DATE: The UGICR is governed by a multidisciplinary steering committee that provides clinical governance and oversees clinical working parties. The role of the working parties is to develop quality indicators based on best practice for each registry module, develop the minimum datasets and provide guidance in analysing and reporting of results. Data are captured from existing data sources (population-based cancer incidence registries, pathology databases and hospital-coded data) and manually from clinical records. Data collectors directly enter information into a secure web-based Research Electronic Data Capture (REDCap) data collection platform. The PC module began with a pilot phase, and subsequently, we used a formal modified Delphi consensus process to establish a core set of quality indicators for PC. The second module developed was the oesophagogastric cancer (OGC) module. Results of the 1 year pilot phases for PC and OGC modules are included in this cohort profile. FUTURE PLANS: The UGICR will provide regular reports of risk-adjusted, benchmarked performance on a range of quality indicators that will highlight variations in care and clinical outcomes at a health service level. The registry has also been developed with the view to collect patient-reported outcomes (PROs), which will further add to our understanding of the care of patients with these cancers.

Safety, efficacy and compliance of extended thromboprophylaxis in hepatobiliary and upper gastrointestinal surgery.

BACKGROUND: Extended venothromboprophylaxis (eVTP) after abdominal surgery for hepatobiliary (HPB) and upper gastrointestinal (UGI) malignancies is recommended. Safety, efficacy and compliance within this group of surgical patients are not well described. The primary aim was to assess safety and compliance of post-operative administration of eVTP with low molecular weight heparin. Secondary aim was to assess barriers to treatment and monitor the rate of post-operative venous thromboembolism. METHODS: A prospective observational cohort study of patients undergoing abdominal surgery for HPB or UGI malignancies was undertaken from January 2014 to June 2016. All patients were assessed for eVTP. Demographics, clinical outcomes and clinical questionnaires on discharge and at follow-up 6 weeks post their initial surgery were used to assess the safety, compliance and efficacy of eVTP. RESULTS: A total of 100 patients were assessed for post-operative eVTP. Of these, 80 patients were prescribed 28 days of low molecular weight heparin. Of 80 patients, 65 (85%) patients completed the full eVTP, 11 (13%) missed 1-5 injections and only four (6%) missed 6-15 injections. In the 80 eVTP patients, there were no episodes of significant bleeding or venous thromboembolism. A total of nine (11%) patients would be unwilling to undertake eVTP again for a variety of reasons, including ease of disposal of syringes and needle phobias. CONCLUSION: The administration of eVTP in patients undergoing major HPB and UGI surgery is safe, with minimal morbidity and high compliance. The greatest barrier to administration is doctor prescription.

Formation of silver nanoparticles by human gut microbiota.

Metal nanoparticles have received global attention and one of the most promising nanotechnologies is the use of microorganisms for synthesizing nanoparticles. The oral exposure study has demonstrated the formation of silver (Ag) nanoparticles with in vivo animal models. However, there is limitation in the effect of in vitro cultured human gut microbiota on silver. Here, the phenomenon of biosynthesis of Ag nanoparticles by human gut microbiota has been reported. The size, shape, and morphology of the nanoparticles were characterized using transmission electron microscopy (TEM). Exposure to aqueous AgNO3 solution resulted in the intracellular reduction of Ag+ ions and the formation of approximately spherical Ag nanoparticles with dimensions of 34 ±â€¯10 nm. Electron microscopy analysis of the gut microbial cells by TEM images of thin sections and scanning electron microscopy (SEM), indicated that most of Ag nanoparticles were located on the cytoplasmic membrane and within the cytoplasm, where abundant silver reductases were present. In addition, some nanoparticles were bound to the cell wall, likely via exocytosis. The oral exposure to Ag+ led to in vivo formation of nanoparticles by gut microbiota, and their biological effects and potential applications in human body warrant further investigation.

Changes in the management of liver trauma leading to reduced mortality: 15-year experience in a major trauma centre.

BACKGROUND: Worldwide, the evolution of management of liver injury has resulted in improved outcomes. The aim of this study was to examine the trend in the management and outcomes of patients with liver injury. Primary outcomes were defined as mortality and hospital length of stay. The secondary aim was to identify independent predictors of mortality. METHODS: This study utilized hospital trauma registry data of all trauma patients with liver injuries admitted from 1999 to 2013. Patients in this 15-year period were divided into three periods of 5 years each and compared in terms of demographics, management and outcomes. RESULTS: A total of 725 patients with hepatic trauma were included. Patient demographics were similar, except for an increase in patient transfers from rural locations. Non-operative management increased significantly. There was a significant increase in the use of damage control surgery with perihepatic packing in high-grade liver injuries managed operatively. Hepatic angioembolization commenced midway through the study period. The overall mortality decreased by approximately threefold (P < 0.001) and mortality within 24 h of arrival to hospital by approximately fivefold (P < 0.001). Controlling for independent predictive factors of mortality, the mortality within 24 h reduced from 18.8% in period 1 to 3.6% in period 3 (P = 0.001). CONCLUSIONS: At this institution, an integrated trauma service has led to an evolution in the management of hepatic trauma, favouring non-operative management, damage control surgery and the use of hepatic angioembolization. We experienced a significantly improved mortality within 24 h of arrival to hospital in patients with liver trauma.

Synthesis and characterisation of nickel Schiff base complexes containing the meso-1,2-diphenylethylenediamine moiety: selective interactions with a tetramolecular DNA quadruplex.

As part of a program of preparing metal complexes which exhibit unique affinities towards different DNA structures, we have synthesised the novel Schiff base complex N,N'-bis-4-(hydroxysalicylidine)meso-diphenylethylenediaminenickel(ii) (), via the reaction of meso-1,2-diphenylethylenediamine and 2,4-dihydroxybenzaldehyde. This compound was subsequently reacted with 1-(2-chloroethyl)piperidine or 1-(2-chloropropyl)piperidine, to afford the alkylated complexes N,N'-bis-(4-((1-(2-ethyl)piperidine)oxy)salicylidine)meso-1,2-diphenylethylenediaminenickel(ii) () and N,N'-bis-(4-((1-(3-propyl)piperidine)oxy)-salicylidine)meso-1,2-diphenylethylenediaminenickel(ii) (), respectively. These complexes were characterised by microanalysis and X-ray crystallography in the solid state, and in solution by (1)H and (13)C NMR spectroscopy. Electrospray ionisation mass spectrometry (ESI-MS) was used to confirm the identity of () and (). The affinities of () and () towards a discrete 16 mer duplex DNA molecule, and examples of both tetramolecular and unimolecular DNA quadruplexes, was explored using a variety of techniques. In addition, the affinity of two other complexes () and (), towards the same DNA molecules was examined. Complexes () and () were prepared by methods analogous to those which afforded () and (), however 1,2-phenylenediamine was used instead of meso-1,2-diphenylethylenediamine in the initial step of the synthetic procedure. The results of ESI-MS and DNA melting temperature measurements suggest that () and () exhibit a lower affinity than () and () towards the 16 mer duplex DNA molecule, while circular dichroism (CD) spectroscopy suggested that none of the four complexes had a major effect on the conformation of the nucleic acid. In contrast, ESI-MS and CD spectroscopy suggested that both () and () show significant binding to a tetramolecular DNA quadruplex. The results of ESI-MS and Fluorescence Resonance Energy Transfer (FRET) assays indicated that () and () did not bind as tightly to a unimolecular DNA quadruplex, although both complexes had a major effect on the CD spectrum of the latter. These results highlight that the presence of the meso-1,2-diphenylethylenediamine moiety in metal complexes of this type may provide a general method for instilling selectivity for some DNA quadruplexes over dsDNA.