Clinical audit of the image quality and customised contrast volume using P3T contrast injection software versus standard injection protocol in CT coronary angiography.

INTRODUCTION: The implications of shorter scan time and lower tube voltage in the dual-source CT coronary angiography (CTCA) scan protocol necessitate the adaptation of contrast media (CM) injection parameters. This audit evaluates the coronary arteries' vascular attenuation and image quality by comparing the personalised patient protocol technology (P3T) contrast injection software with standard injection protocol. The secondary aim is to determine the relationship between CM volume and the patient's weight. METHODOLOGY: A Siemens Somatom Definition Force CT Unit was used to scan 30 sets of patients between August 2020 and October 2020. Patients were selected retrospectively and separated into Standard Injection and P3T injection protocols. An experienced radiologist blinded to the groups reviewed the coronary vessels' contrast enhancement and image quality. RESULTS: Overall, the mean HU of all the main coronary artery vessels obtained from P3T injection software reached above 350 HU and was diagnostically sufficient. The mean attenuation at the proximal region of RCA in the 80-99 kg weight category was significantly higher in the P3T injection software than the standard injection protocol (p < 0.001). The CM volume proposed by P3T injection software for 40-59 kg was approximately 57 ± 5 mls, while 75 ml was used for the standard injection protocol. CONCLUSION: P3T injection software in CTCA resulted in an adequate diagnostic attenuation of coronary arteries (>350HU) in all weight groups, most effectively in the higher weight group, while maintaining diagnostic image quality. Further, the P3T software reduces CM volumes in lower-weight patients. IMPLICATIONS: P3T software enables reducing CM volume in lower-weight patients while improving vascular enhancement in CTCA scans in higher-weight patients.

Preventative strategies for low anterior resection syndrome.

BACKGROUND: A common and debilitating complication of low anterior resection for rectal cancer is low anterior resection syndrome (LARS). As a multifactorial entity, LARS is poorly understood and challenging to treat. Despite this, prevention strategies are commonly overlooked. Our aim was to review the pathophysiology of LARS and explore current evidence on the efficacy and feasibility of prophylactic techniques. METHODS: A literature review was performed between [1st January 2000 to 1st October 2023] for studies which investigated preventative interventions for LARS. Mechanisms by which LARS develop are described, followed by a review of prophylactic strategies to prevent LARS. Medline, Cochrane, and PubMed databases were searched, 189 articles screened, 8 duplicates removed and 18 studies reviewed. RESULTS: Colonic dysmotility, anal sphincter dysfunction and neorectal dysfunction all contribute to the development of LARS, with the complex mechanism of defecation interrupted by surgery. Transanal irrigation (TAI) and pelvic floor rehabilitation (PFR) have shown benefits in preventing LARS, but may be limited by patient compliance. Intraoperative nerve monitoring (IONM) and robotic-assisted surgery have shown some promise in surgically preventing LARS. Nerve stimulation and other novel strategies currently used in treatment of LARS have yet to be investigated in their roles prophylactically. CONCLUSIONS: To date, there is a limited evidence base for all preventative strategies including IONM, RAS, PFP and TAI. These strategies are limited by either access (IONM, RAS and PFP) or acceptability (PFP and TAI), which are both key to the success of any intervention. The results of ongoing trials will serve to assess acceptability, while technological advancement may improve access to some of the aforementioned strategies.

Genetically engineered human umbilical cord-derived mesenchymal stem cells expressing human interleukin-12 and in vitro growth inhibition against lung adenocarcinoma cells.

INTRODUCTION: Mesenchymal stromal cells (MSCs) are promising vehicles for cancer therapy due to their homing ability and potency to be genetically manipulated through either viral or non-viral methods. Interleukin-12 (IL-12) is one of the key immunomodulatory cytokines which has anti-tumour effect. However, systemic administration of the cytokine at therapeutic dosage can cause serious toxicity in the host system due to the high systemic level of interferon-γ (IFN-γ) induced. OBJECTIVES: This study aimed to investigate the in vitro growth inhibition of genetically engineered human umbilical cord-derived mesenchymal stromal cells (hUCMSC) expressing IL-12 on H1975 human lung adenocarcinoma cells. MATERIALS AND METHODS: Both adenoviral method and electroporation which used to generate hUCMSC-IL12 were compared. The method with better outcome was selected to generate hUCMSC-IL12 for the co-culture experiment with H1975 or MRC-5 cells. Characterisation of hUCMSC and hUCMSC-IL12 was performed. RESULTS: Adenoviral method showed superior results in transfection efficiency (63.6%), post-transfection cell viability (82.6%) and hIL-12 protein expression (1.2 x 107 pg/ml) and thus was selected for the downstream experiments. Subsequently, hUCMSC-IL12 showed significant inhibition effect on H1975 cells after 5 days of co-culture. No significant difference was observed for all other co-culture groups, indicating that the inhibition effect was because of hIL-12. Lastly, the integrity of hUCMSC-IL12 remained unaffected by the transduction through examination of their surface markers and differentiation properties. CONCLUSION: This study provided proof of concept that hUCMSC can be genetically engineered to express hIL-12 which exerts direct growth inhibition effect on human lung adenocarcinoma cells.

Radiographic analysis of critical anatomical structures for pterygoid implant placement in Chinese patients with a severely atrophied maxilla.

The pterygoid implant is a feasible alternative for posterior dental rehabilitation without grafting; however, the ideal pterygoid implant placement continues to be debated. The aim of this study was to identify effective landmarks and establish valid guidelines to determine the ideal pterygoid implant placement. Cone beam computed tomography (CBCT) data of 100 severely atrophied maxillae requiring implant rehabilitation, obtained between January 2015 and December 2018, were included. The CBCT data were obtained in DICOM format from the radiographic database and imported into Nobel Clinician software (Nobel Biocare) for radiographic analysis. Virtual pterygoid implant placement was successful in 67 maxillae: a 13-mm virtual implant in four maxillae (6.0%), 15-mm in 52 maxillae (77.6%), and 18-mm in 11 maxillae (16.4%). For the virtual pterygoid implant, the mean implant angulation± standard deviation in the anteroposterior axis (sagittal view) was 45.08 ± 2.56° relative to the Frankfort plane. In the buccopalatal axis (coronal view), the mean implant angulation was 64.30 ± 4.99° relative to the Frankfort plane and the mean value for the shortest linear distance between the palatine canal and apical tip of the virtual implant was 3.91 ± 0.62 mm. A 15-mm pterygoid implant placed at 45° in the anteroposterior axis and 60° in the buccopalatal axis (relative to the Frankfort plane), is generally recommended in this Chinese patient population.

Delayed manipulation of regeneration within injured peripheral axons.

While several new translational strategies to enhance regrowth of peripheral axons have been identified, combined approaches with different targets are rare. Moreover, few have been studied after a significant delay when growth programs are already well established and regeneration-related protein expression has waned. Here we study two approaches, Rb1 (Retinoblastoma 1) knockdown that targets overall neuron plasticity, and near nerve insulin acting as a growth factor. Both are validated to boost regrowth only at the outset of regeneration. We show that local delivery of Rb1 siRNA alone, with electroporation to an area of prior sciatic nerve injury generated knockdown of Rb1 mRNA in ipsilateral lumbar dorsal root ganglia. While mice treated with Rb1-targeted siRNA, compared with scrambled control siRNA, starting 2 weeks after the onset of regeneration, had only limited behavioural or electrophysiological benefits, they had enhanced reinnervation of epidermal axons. We next confirmed that intrinsic Rb1 knockdown combined with exogenous insulin had dramatic synergistic impacts on the growth patterns of adult sensory neurons studied in vitro, prompting analysis of a combined approach in vivo. Using an identical delayed post-injury protocol, we noted that added insulin not only augmented epidermal reinnervation rendered by Rb1 knockdown alone but also improved indices of mechanical sensation and motor axon recovery. The findings illustrate that peripheral neurons that are well into attempted regrowth retain their responsiveness to both intrinsic and exogenous approaches that improve their recovery. We also identify a novel local approach to manipulate gene expression and outcome in regrowing axons.

Myosin IIA and formin dependent mechanosensitivity of filopodia adhesion.

Filopodia, dynamic membrane protrusions driven by polymerization of an actin filament core, can adhere to the extracellular matrix and experience both external and cell-generated pulling forces. The role of such forces in filopodia adhesion is however insufficiently understood. Here, we study filopodia induced by overexpression of myosin X, typical for cancer cells. The lifetime of such filopodia positively correlates with the presence of myosin IIA filaments at the filopodia bases. Application of pulling forces to the filopodia tips through attached fibronectin-coated laser-trapped beads results in sustained growth of the filopodia. Pharmacological inhibition or knockdown of myosin IIA abolishes the filopodia adhesion to the beads. Formin inhibitor SMIFH2, which causes detachment of actin filaments from formin molecules, produces similar effect. Thus, centripetal force generated by myosin IIA filaments at the base of filopodium and transmitted to the tip through actin core in a formin-dependent fashion is required for filopodia adhesion.

Role of IL-13Rα2 in modulating IL-13-induced MUC5AC and ciliary changes in healthy and CRSwNP mucosa.

BACKGROUND: The IL-13 receptor α2 (IL-13Rα2) is a receptor for IL-13 which has conflicting roles in mediating IL-13 responses in the lower airway, with little known about its impact on upper airway diseases. We sought to investigate the expression of IL-13 receptors, IL-13Rα1 and IL-13Rα2, in chronically inflamed nasal epithelium, and explore IL-13-induced signaling pathways in an in vitro model of human nasal epithelial cells (hNECs). METHODS: The protein and mRNA expression levels of IL-13 and its receptors in nasal biopsies of patients with nasal polyps (NP) and healthy controls were evaluated. We investigated goblet cell stimulation with mucus hypersecretion induced by IL-13 (10 ng/mL, 72 hours) treatment in hNECs using a pseudostratified epithelium in air-liquid interface (ALI) culture. RESULTS: There were significant increases in IL-13, IL-13Rα1, and IL-13Rα2 mRNA and protein levels in NP epithelium with healthy controls as baseline. MUC5AC mRNA positively correlated with IL-13Rα2 (r = .5886, P = .002) but not with IL-13Rα1 in primary hNECs. IL-13 treatment resulted in a significant increase in mRNA and protein levels of IL-13Rα2 only in hNECs. IL-13 treatment induced an activation of extracellular signal-regulated kinases (ERK)1/2 and an upregulation of C-JUN, where the IL-13-induced effects on hNECs could be attenuated by ERK1/2 inhibitor (50 µmol/L) or dexamethasone (10-4 -10-7  mol/L) treatment. CONCLUSIONS: IL-13Rα2 has a potential role in IL-13-induced MUC5AC and ciliary changes through ERK1/2 signal pathway in the nasal epithelium. IL-13Rα2 may contribute to airway inflammation and aberrant remodeling which are the main pathological features of CRSwNP.

Does a mandibular access osteotomy improve survival in pT2 oral tongue cancers? Retrospective study at a single institution.

The surgical approach to the resection of oral tongue cancers can involve transoral resection (TOR) or a temporary mandibulotomy access (TMA). There are no relevant guidelines, and the oncological safety of TOR needs consideration. The objective of this study was to investigate TMA and TOR in pT2 oral tongue cancer surgery with regard to cancer outcomes. Demographic, surgical, and histology data from primary pT2 tongue cancers were recorded and evaluated through multivariate Cox regression for local recurrence (LR), disease-free survival (DFS), and overall survival (OS). A total of 166 patients with pT2 primary oral tongue cancer fulfilled the inclusion criteria; TOR was used in 95 patients and TMA in 71 patients. The minimum follow-up was 29 months. Group comparisons showed a significantly higher frequency of perineural spread (P=0.013) in the TMA group; a higher frequency of involved margins on initial resection was seen in TOR patients (P=0.010). Adjuvant postoperative radiotherapy was preferred in the TMA group, in line with the high pN positive status. Multivariate Cox regression showed significantly higher LR and lower DFS in the TOR group despite stratification of the major prognostic factors. The 5-year survival rate was reduced to 82.2% in the TOR group, while it remained constant at 93.0% in the TMA group. TMA provided superior local control and DFS compared to TOR in pT2 tongue cancers.

A seven-year retrospective analysis of the clinicopathological and mycological manifestations of fungal rhinosinusitis in a single-centre tropical climate hospital.

OBJECTIVE: To evaluate the clinicopathological and mycological manifestations of fungal rhinosinusitis occurring in the Tengku Ampuan Rahimah Hospital, in Klang, Malaysia, which has a tropical climate. METHODS: Records of patients treated from 2009 to 2016 were analysed retrospectively. Data from the records were indexed based on age, gender, clinical presentations, symptom duration, clinical signs and mycological growth. RESULTS: Of 80 samples, 27 (33.75 per cent) had fungal growth. Sixteen patients were classified as having non-invasive fungal rhinosinusitis and 11 as having invasive fungal rhinosinusitis. The commonest clinical presentation was nasal polyposis in non-invasive fungal rhinosinusitis patients (p < 0.05) and ocular symptoms in invasive fungal rhinosinusitis patients (p < 0.05). The commonest organism was aspergillus sp. (p < 0.05) in non-invasive fungal rhinosinusitis and mucorales in invasive fungal rhinosinusitis. CONCLUSION: There is an almost equal distribution of both invasive and non-invasive fungal rhinosinusitis, as seen in some Asian countries. Invasive fungal rhinosinusitis, while slightly uncommon when compared to non-invasive fungal rhinosinusitis, is potentially life threatening, and may require early and extensive surgical debridement. The clinical presentation of nasal polyposis was often associated with non-invasive fungal rhinosinusitis, whereas ocular symptoms were more likely to be associated with invasive fungal rhinosinusitis.

Cytoplasmic neuropilin 2 is associated with metastasis and a poor prognosis in early tongue cancer patients.

Neuropilin 2 (Nrp2) plays an important role in regulating lymphangiogenesis. Nrp2 expression in early tongue cancer was investigated to predict lymph node metastasis and the long-term prognosis. The relationships between clinicopathological variables of cT1-T2N0 tongue squamous cell carcinoma (SCC) and overexpression of Nrp2, vascular endothelial growth factor C (VEGFC), vascular endothelial growth factor receptor 3 (VEGFR3), and semaphorin 3F (Sema3F) were analyzed. Expression levels were compared using oral SCC cell lines. The Nrp2 gene was silenced to determine the impact of Nrp2. Cytoplasmic Nrp2 overexpression predicted regional metastasis with sensitivity and specificity of 90.3% and 42.1%, respectively. Cytoplasmic Nrp2 overexpression (P<0.001) and VEGFC overexpression (P=0.006) were significantly related to regional metastasis (Student t-test). However, only cytoplasmic Nrp2 overexpression was an independent prognostic factor for both disease-free survival (DFS; P=0.008) and overall survival (OS; P=0.016) (Cox regression); the risk of recurrence was 12-times higher (P=0.015) and risk of mortality was 8-times higher (P=0.016). Co-localization of Nrp2 and VEGFC was greater within the cytoplasm of aggressive cell lines (HN12 and RCa-T). Nrp2 plays a role in tumourigenesis; VEGFC supplementation cannot rescue the biological function of Nrp2 in Nrp2-depleted cell lines. Cytoplasmic Nrp2 overexpression is associated with decreased OS and DFS. Cytoplasmic Nrp2 overexpression may be a reliable diagnostic and prognostic marker for early tongue SCC.

The oral microbiome community variations associated with normal, potentially malignant disorders and malignant lesions of the oral cavity.

The human oral microbiome has been known to show strong association with various oral diseases including oral cancer. This study attempts to characterize the community variations between normal, oral potentially malignant disorders (OPMD) and cancer associated microbiota using 16S rDNA sequencing. Swab samples were collected from three groups (normal, OPMD and oral cancer) with nine subjects from each group. Bacteria genomic DNA was isolated in which full length 16S rDNA were amplified and used for cloned library sequencing. 16S rDNA sequences were processed and analysed with MOTHUR. A core oral microbiome was identified consisting of Firmicutes, Proteobacteria, Fusobacteria, Bacteroidetes and Actinobacteria at the phylum level while Streptococcus, Veillonella, Gemella, Granulicatella, Neisseria, Haemophilus, Selenomonas, Fusobacterium, Leptotrichia, Prevotella, Porphyromonas and Lachnoanaerobaculum were detected at the genus level. Firmicutes and Streptococcus were the predominant phylum and genus respectively. Potential oral microbiome memberships unique to normal, OPMD and oral cancer oral cavities were also identified. Analysis of Molecular Variance (AMOVA) showed a significant difference between the normal and the cancer associated oral microbiota but not between the OPMD and the other two groups. However, 2D NMDS showed an overlapping of the OPMD associated oral microbiome between the normal and cancer groups. These findings indicated that oral microbes could be potential biomarkers to distinguish between normal, OPMD and cancer subjects.

Outcome after laparoscopic versus open wedge resection for suspected gastric gastrointestinal stromal tumors: A matched-pair case-control study.

BACKGROUND: Laparoscopic resection of gastric gastrointestinal stromal tumors (GISTs) has been shown by several retrospective studies to be technically feasible and associated with favorable outcomes when compared to the open approach. This study aims to mitigate potential selection bias by performing a case control study of laparoscopic (LWR) versus open wedge resection (OWR) matched by resection type, location and tumor size. METHODS: We retrospectively identified 50 consecutive patients who underwent LWR for a suspected gastric GIST from a prospective database and matched this cohort with 50 patients who underwent OWR. RESULTS: There was no statistical difference between the key baseline clinicopathological features of patients' who underwent LWR versus OWR. Patients who underwent LWR had longer operating times [150 (range, 65-270) minutes vs 92.5 (25-200) minutes, P < .001] but decreased median blood loss [0 (0-300) ml vs 0 (0-1200) ml, P = .015], decreased frequency of intraoperative or postoperative blood transfusion [1 (2%) vs 8 (16%), P = .031], decreased median time to liquid diet [2 (0-5) vs 3 (1-7) days, P < .001], decreased median time to solid diet [3 (1-6) vs 5 (2-11) days, P < .001] and decreased postoperative stay [4 (2-10) vs 4.5 (3-17), P < .001] compared to OWR. There was no difference in oncological outcomes such as frequency of close margins (≤ 1 mm) and recurrence-free survival. CONCLUSION: This matched case-control study provides supporting evidence that LWR results in superior perioperative outcomes compared to OWR without compromising on oncological outcomes.

Establishment of functional acinar-like cultures from human salivary glands.

Disorders of human salivary glands resulting from therapeutic radiation treatment for head and neck cancers or from the autoimmune disease Sjögren syndrome (SS) frequently result in the reduction or complete loss of saliva secretion. Such irreversible dysfunction of the salivary glands is due to the impairment of acinar cells, the major glandular cells of protein, salt secretion, and fluid movement. Availability of primary epithelial cells from human salivary gland tissue is critical for studying the underlying mechanisms of these irreversible disorders. We applied 2 culture system techniques on human minor salivary gland epithelial cells (phmSG) and optimized the growth conditions to achieve the maintenance of phmSG in an acinar-like phenotype. These phmSG cells exhibited progenitor cell markers (keratin 5 and nanog) as well as acinar-specific markers-namely, α-amylase, cystatin C, TMEM16A, and NKCC1. Importantly, with an increase of the calcium concentration in the growth medium, these phmSG cells were further promoted to acinar-like cells in vitro, as indicated by an increase in AQP5 expression. In addition, these phmSG cells also demonstrated functional calcium mobilization, formation of epithelial monolayer with high transepithelial electrical resistance (TER), and polarized secretion of α-amylase secretion after ß-adrenergic receptor stimulation. Taken together, suitable growth conditions have been established to isolate and support culture of acinar-like cells from the human salivary gland. These primary epithelial cells can be useful for study of molecular mechanisms involved in regulating the function of acinar cells and in the loss of salivary gland function in patients.

Radical resection of a Shamblin type III carotid body tumour without cerebro-neurological deficit: Improved technique with preoperative embolization and carotid stenting.

The surgical resection of a large unfavourable Shamblin type III carotid body tumour (CBT) can be very challenging technically, with many potential significant complications. Preoperative embolization aids in shrinking the lesion, reducing intraoperative blood loss, and improving visualization of the surgical field. Preoperative internal carotid artery (ICA) stenting aids in reinforcing the arterial wall, thereby providing a better dissection plane. A woman presented to our institution with a large right-sided CBT. Failure of the preoperative temporary balloon occlusion (TBO) test emphasized the importance of intraoperative preservation of the ipsilateral ICA. A combination of both preoperative embolization and carotid stenting allowed a less hazardous radical resection of the CBT. An almost bloodless surgical field permitted meticulous dissection, hence reducing the risk of intraoperative vascular and nerve injury. Embolization and carotid stenting prior to surgical resection should be considered in cases with bilateral CBT or a skull base orientated high CBT, and for those with intracranial extension and patients who have failed the TBO test.

Dermatofibrosarcoma protuberans on the right neck with superior vena cava syndrome: case report and literature review.

Dermatofibrosarcoma protuberans (DFSP) is an uncommon dermal soft tissue tumour of intermediate malignancy. A 44-year-old man presented to the hospital with a large lesion on the right upper chest and neck. Despite eight previous surgical excisions, the tumour had continued to recur. Contrast-enhanced computed tomography showed recurrence of the tumour, associated with superior vena cava (SVC) syndrome. He declined radical surgical resection of the recurrent tumour, which may have required right upper limb amputation. Targeted therapy with sunitinib malate was therefore introduced. This case demonstrates the recurrent nature of DFSP and the association of this lesion on the upper chest/neck with SVC syndrome. Primary wide radical resection is essential for better local control and to avoid the development of SVC syndrome.