To stitch or not to stitch: the skin closure of laparoscopic port sites, a meta-analysis.

BACKGROUND: Previous meta-analyses examining skin closure methods for all surgical wounds have found suture to have significantly decreased rates of wound dehiscence compared to tissue adhesive; however, this was not specific to laparoscopic wounds alone. This study aims to determine the best method of skin closure in patients undergoing laparoscopic abdominopelvic surgery in order to minimize wound complications and pain, while maximize cosmesis, time and cost efficiency. METHODS: A comprehensive search of EMBASE, Medline, Pubmed, and CENTRAL was conducted from inception to 1st May 2020 for randomized controlled trials (RCTs). Two independent reviewers extracted data and assessed risk of bias. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to describe the quality of evidence. Meta-analysis was performed using a random-effects model. A summary relative risk (RR) was calculated for dichotomous outcomes where data could be pooled. (Prospero registration number: CRD42019122639). RESULTS: The literature search identified 11,628 potentially eligible studies. Twelve RCTs met inclusion criteria. There was no difference in wound complications (infection, dehiscence, and drainage) between sutures, tissue adhesives nor adhesive papertape. Low-quality evidence found transcutaneous suture had lower rates of wound complications compared with subcuticular sutures (RR 0.22, 95%: CI 0.05-0.98). There was no evidence of a difference in patient-evaluated cosmesis, prolonged pain, or patient satisfaction between the three groups. Closure with tissue adhesive and adhesive papertape was faster and cheaper than suture. CONCLUSION: Tissue adhesive and adhesive papertape offer safe, cost and time-saving alternatives to closure of laparoscopic port sites compared to suture.

Liver resection as a component of en-bloc multivisceral resection for upper abdominal tumors is associated with increased morbidity.

BACKGROUND AND METHODS: Complex en-bloc multivisceral and oncovascular resections for upper abdominal tumors remain rare, but there is increasing interest in their role. We analyze complications and survival for these operations. We performed a retrospective cohort study of patients who underwent en-bloc upper abdominal resections for tumors involving multiple organs. Primary outcomes were complications as per the Clavien-Dindo Classification and Comprehensive Complication Index (CCI). Secondary outcome was overall survival (OS). RESULTS: We identified 60 consecutive patients who underwent resection from 2011 to 2018. Histopathology was heterogeneous, the most common being renal cell carcinoma. Eighteen patients had major complications. Mean (interquartile range) CCI was 29.6 (9.6-43.9). Liver resection was significantly associated with an increased CCI and increased the odds of a major complication (odds ratio: 4.67, 95% confidence interval [CI]: 1.31-16.59; P = .017). Charlson Comorbidity Score was significantly associated with the presence of at least one major complication. Mean OS was 47.1 months (95% CI: 37.6-56.6). CONCLUSION: In appropriately selected patients, and when undertaken in centers with appropriate subspecialist surgical teams and intensive care services, en-bloc multivisceral resection of upper abdominal tumors is safe, but liver resection is associated with an increase in major complications.

Functional Imaging with Nucleic-Acid-Based Sensors: Technology, Application and Future Healthcare Prospects.

Timely monitoring and assessment of human health plays a crucial role in maintaining the wellbeing of our advancing society. In addition to medical tools and devices, suitable probe agents are crucial to assist such monitoring, either in passive or active ways (i.e., sensors) through inducible signals. In this review we highlight recent developments in activatable optical sensors based on nucleic acids. Sensing mechanisms and bio-applications of these nucleic acid sensors in ex vivo assays, intracellular or in vivo settings are described. In addition, we discuss the limitations of these sensors and how nanotechnology can complement/enhance sensor properties to promote translation into clinical applications.

Real-Time Imaging of Dynamic Cell Reprogramming with Nanosensors.

Cellular reprogramming, the process by which somatic cells regain pluripotency, is relevant in many disease modeling, therapeutic, and drug discovery applications. Molecular evaluation of reprogramming (e.g., polymerase chain reaction, immunostaining) is typically disruptive, and only provides snapshots of phenotypic traits. Gene reporter constructs facilitate live-cell evaluation but is labor intensive and may risk insertional mutagenesis during viral transfection. Herein, the utilization of a non-integrative nanosensor is demonstrated to visualize key reprogramming events in situ within live cells. Principally based on sustained intracellular release of encapsulated molecular probes, nanosensors successfully monitored mesenchymal-epithelial transition, pluripotency acquisition, and transdifferentiation events. Tracking the dynamic expression of four pivotal biomarkers (i.e., THY1, E-CADHERIN, OCT4, and GATA4 mRNA), nanosensor signal showed great agreement with polymerase chain reaction and gene reporter imaging (R2 > 0.9). Overall, such facile, versatile nanosensor enables real-time monitoring of low-frequency reprogramming events, thereby useful for high-throughput assessment, optimization, and biomarker-specific cell enrichment.

Oligonucleotide Molecular Sprinkler for Intracellular Detection and Spontaneous Regulation of mRNA for Theranostics of Scar Fibroblasts.

Early diagnosis and timely intervention are key for the successful treatment of skin diseases like abnormal scars. This study introduces a nucleic-acid-based probe (i.e., molecular sprinkler) for the diagnosis and spontaneous regulation of the abnormal expression of fibrosis-related mRNA in scar-derived skin fibroblasts. Using mRNA encoding connective tissue growth factor (CTGF) as the model gene, a probe with three oligonucleotides is constructed, including a recognition sequence complementary to the CTGF mRNA, a siRNA against transforming growth factor receptor I (TGFßRI) as the CTGF mRNA suppressor, and a connecting sequence. The probe can detect CTGF mRNA with a limit of 10 × 10-9 m and distinguishes scar fibroblasts from normal ones in both 2D and 3D environments. Two days after transfection, the siRNA released from the probe reduces the expression of TGFßRI and, consequently, decreases the cellular expression of CTGF mRNA (up to 70%). This dual-role probe presents opportunities to monitor the TGF- ß signaling pathway, screen for drugs that target the CTGF pathway, and determine the role of inhibition of the CTGF pathway in therapeutic efficacy.

Near-Infrared Fluorescent Molecular Probe for Sensitive Imaging of Keloid.

Early detection of skin diseases is imperative for their effective treatment. However, fluorescence molecular probes that allow this are rare. The first activatable near-infrared (NIR) fluorescent molecular probe is reported for sensitive imaging of keloid cells, skin cells from abnormal scar fibrous lesions. As keloid cells have high expression levels of fibroblast activation protein-alpha (FAPα), the probe (FNP1) is designed to have a caged NIR dye and a FAPα-cleavable peptide substrate linked by a self-immolative segment. FNP1 can quickly and specifically turn on its fluorescence at 710 nm by 45-fold in the presence of FAPα, allowing it to effectively recognize keloid cells from normal skin cells. Integration of FNP1 with a simple microneedle-assisted topical application enables sensitive detection of keloid cells in metabolically-active human skin tissue with a theoretical limit of detection down to 20 000 cells.

Can response to locoregional therapy help predict longterm survival after liver transplantation for hepatocellular carcinoma? A systematic review.

For a selected group of patients with hepatocellular carcinoma (HCC), liver transplantation (LT) represents the best chance of a cure. Organ shortages necessitate an efficient allocation of resources and careful prioritization on the transplantation waiting list. In this review, we aim to collate and evaluate the published evidence for using response to locoregional therapies (LRTs), measured by modified Response Evaluation Criteria in Solid Tumors (mRECIST), as a predictor of longterm survival after LT. Our aim was to assess whether response to LRTs before LT for HCC, as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) or mRECIST criteria, can help predict recurrence-free and/or longterm survival outcomes. We searched MEDLINE, Embase, and the Cochrane database. We included randomized controlled trials (RCTs), cohort, case control, and case series studies. Poster and conference abstracts were included. Studies were required to use RECIST or mRECIST criteria when assessing tumor response and were limited to LT for HCC only. A total of 15 records were included in the final systematic review: 7 published manuscripts and 8 conference abstracts. No RCTs were identified. Several included articles were conference abstracts with limited data available. No RCTs were found, and no meta-analysis was undertaken. Several retrospective cohort studies were identified that demonstrated statistically significant differences in survival and recurrence between different RECIST criteria after LT. Liver Transplantation 23 375-385 2017 AASLD.

Nanosensors for Continuous and Noninvasive Monitoring of Mesenchymal Stem Cell Osteogenic Differentiation.

Assessing mesenchymal stem cell (MSC) differentiation status is crucial to verify therapeutic efficacy and optimize treatment procedures. Currently, this involves destructive methods including antibody-based protein detection and polymerase chain reaction gene analysis, or laborious and technically challenging genetic reporters. Development of noninvasive methods for real-time differentiation status assessment can greatly benefit MSC-based therapies. This report introduces a nanoparticle-based sensing platform that encapsulates two molecular beacon (MB) probes within the same biodegradable polymeric nanoparticles. One MB targets housekeeping gene glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal reference, while another detects alkaline phosphatase (ALP), a functional biomarker. Following internalization, MBs are gradually released as the nanoparticle degrades. GAPDH MBs provide a stable reference signal throughout the monitoring period (18 days) regardless of differentiation induction. Meanwhile, ALP mRNA undergoes well-defined dynamics with peak expression observed during early stages of osteogenic differentiation. By normalizing ALP-MB signal with GAPDH-MB, changes in ALP expression can be monitored, to noninvasively validate osteogenic differentiation. As proof-of-concept, a dual-colored nanosensor is applied to validate MSC osteogenesis on 2D culture and polycaprolactone films containing osteo-inductive tricalcium phospate.

Cation-Controlled Enantioselective and Diastereoselective Synthesis of Indolines: An Autoinductive Phase-Transfer Initiated 5-endo-trig Process.

A catalytic enantioselective approach to the synthesis of indolines bearing two asymmetric centers, one of which is all-carbon and quaternary, is described. This reaction proceeds with high levels of diastereoselectivity (>20:1) and high levels of enantioselectivity (up to 99.5:0.5 er) in the presence of CsOH·H2O and a quinine-derived ammonium salt. The reaction most likely proceeds via a delocalized 2-aza-pentadienyl anion that cyclizes either by a suprafacial electrocyclic mechanism, or through a kinetically controlled 5-endo-trig Mannich process. Density functional theory calculations are used to probe these two mechanistic pathways and lead to the conclusion that a nonpericyclic mechanism is most probable. The base-catalyzed interconversion of diastereoisomeric indolines in the presence of certain quaternary ammonium catalysts is observed; this may be rationalized as a cycloreversion-cyclization process. Mechanistic investigations have demonstrated that the reaction is initiated via a Makosza-like interfacial process, and kinetic analysis has shown that the reaction possesses a significant induction period consistent with autoinduction. A zwitterionic quinine-derived entity generated by deprotonation of an ammonium salt with the anionic reaction product is identified as a key catalytic species and the role that protonation plays in the enantioselective process outlined. We also propose that the reaction subsequently occurs entirely within the organic phase. Consequently, the reaction may be better described as a phase-transfer-initiated rather than a phase-transfer-catalyzed process; this observation may have implications for mechanistic pathways followed by other phase-transfer-mediated reactions.

Orthogonal functionalisation of α-helix mimetics.

α-Helix mediated protein-protein interactions are of major therapeutic importance. As such, the design of inhibitors of this class of interaction is of significant interest. We present methodology to modify N-alkylated aromatic oligoamide α-helix mimetics using 'click' chemistry. The effect is shown to modulate the binding properties of a series of selective p53/hDM2 inhibitors.

Retrospective review of image quality of CT in polytrauma patients: comparison of patients scanned using a scoop stretcher and without a scoop stretcher.

Increasingly pre-hospital trauma management involves transfer of patients using a scoop stretcher; a number of computed tomography (CT) compatible scoops have recently appeared on the market. We sought to evaluate any differences in image quality in polytrauma patients scanned in a scoop stretcher. CT studies of 234 consecutive patients presenting between December 2011 and August 2012 at our regional level 1 tertiary trauma centre were retrospectively reviewed. Patients were allocated into two groups: those scanned with a scoop stretcher and without. CTs were reviewed by a consultant radiologist and two senior radiology trainees and graded separately for quality/artefact. A scale of 1-5 was employed: 1-uninterpretable, 2-borderline image quality, 3-acceptable, 4-good, 5-excellent. A total of 128 (54.7 %) patients were scanned in a scoop stretcher and 106 (45.3 %) were scanned without, 183 males and 51 females (average age, 46 (16-94) years; SD, 20). The average quality grading for the patients scanned in the scoop was 4.64 compared to 4.68 in those without the scoop. There was no significant grading difference between the groups, consultant (p = 0.096) and trainees (p = 0.782). No artefacts were attributable to the scoop stretcher 0/128 (0 %). Following our experience, the use of scoop stretchers is recommended for efficient, safe and practical management of trauma patients and in terms of imaging, with no detrimental effect on image quality.

A rare case of benign pneumatosis intestinalis in Sjogren's syndrome.

Pneumatosis intestinalis (PI)-the presence of intramural bowel gas-is an uncommon radiological finding, the severity of which depends on the underlying pathological process, ranging from benign disease to life-threatening ischaemia and intra-abdominal sepsis. PI has been described in systemic sclerosis and mixed connective tissue disease; however, few cases have been reported in Sjogren's syndrome (SjS). The exact pathogenesis of PI in systemic connective tissue disorders is not fully understood and likely multifactorial. We have described a unique case of PI without evidence of peritonitis in a stable patient with long-standing SjS managed non-operatively. An awareness of such benign PI, particularly amongst patients with systemic connective tissue disease, is crucial for diagnostic accuracy and safe patient care, particularly in preventing unnecessary surgical intervention.

Single-incision laparoscopic cholecystectomy with routine intraoperative cholangiography and common bile duct exploration via the umbilical port.

BACKGROUND: Laparoscopic cholecystectomy currently is the gold standard technique for gallbladder removal. The use of routine intraoperative cholangiography (IOC) is widely practiced during conventional four-port laparoscopic cholecystectomy (4PLC) to confirm biliary anatomy and allow for immediate management of unexpected choledocholithiasis. Single-incision laparoscopic surgery (SILS) offers a more aesthetic technique for gallbladder removal and has been reported by several groups. However, no series to date have included routine IOC without a separate incision. This study aimed to demonstrate the feasibility of the SILS technique for cholecystectomy with routine IOC (LCIOC) and common bile duct (CBD) exploration as needed via the umbilical port. METHODS: A database was prospectively completed for a series of 60 consecutive patients undergoing single-incision LCIOC via the umbilical port. Details of the patients, operations, indications, outcomes, and follow-up evaluation were included. RESULTS: Of the 60 patients included in the database, 55 (91.7%) successfully underwent single-incision laparoscopic cholecystectomy (SILC), whereas the remaining five patients required conversion to 4PLC. No patient required conversion to open cholecystectomy (OC). Of the 55 successful SILC patients, 53 (88.3%) successfully received IOCs, 48 of which were normal. The remaining five IOCs demonstrated choledocholithiasis, four of which could be managed laparoscopically without the need for conversion to either 4PLC or OC. One patient required postoperative endoscopic retrograde cholangiopancreatography (ERCP). Complications included four wound infections (7.8%), one incisional hernia (2.0%), and one bile leak (3.2%). The operating time ranged from 35 to 180 min and decreased with experience. CONCLUSIONS: This study represents the largest series to date of single-incision laparoscopic cholecystectomies with routine IOC via the umbilical port and is the first study to demonstrate that the laparoscopic management of choledocholithiasis during SILC is feasible.

Focal intrahepatic strictures: a review of diagnosis and management.

INTRODUCTION: Focal intrahepatic strictures are becoming more common owing to more prevalent and accurate cross-sectional imaging. However, data relating to their management are lacking. The purpose of the present review was to synthesize the current evidence regarding these lesions and to formulate a strategy for diagnosis and management. METHODS: A literature search of relevant terms was performed using Medline. References of papers were subsequently searched to obtain older literature. RESULTS: Focal intrahepatic strictures involve segmental hepatic ducts and/or left and right main hepatic ducts during their intrahepatic course. Most patients are asymptomatic while the minority present with vague abdominal pain or recurrent sepsis and only rarely with jaundice. Investigations used to distinguish benign from malignant aetiologies include blood tests (CEA, Ca19.9), imaging studies [ultrasonography (US), computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP) and fluorodeoxyglucose-positron emission tomography (FDG-PET)], endoscopic modalities [endoscopic retrograde cholangiopancreatography (ERCP)/endoscopic ultrasound (EUS)/cholangioscopy] and tissue sampling (brush cytology/biopsy). CONCLUSIONS: A focal intrahepatic stricture requires thorough investigation to exclude malignancy even in patients with a history of biliary surgery, hepatolithiasis or parasitic infection. If during the investigative process a diagnosis or suspicion of malignancy is demonstrated then surgical resection should be performed. If all diagnostic modalities suggest a benign aetiology, then cholangioscopy with targeted biopsies should be performed.

Metastatic osteosarcoma bowel perforation secondary to chemotherapy-induced tumour necrosis.

Osteosarcoma is the most common paediatric and adolescent primary bone malignancy and is highly chemosensitive. Gastrointestinal metastases from osteosarcomas are rare. Bowel perforation secondary to chemotherapy is a potential serious complication reported in ovarian, colorectal and haematological malignancies. We report the first documented case of chemotherapy-mediated bowel perforation in an osteosarcoma patient with gastrointestinal metastases. A man in his 20s, with a history of resected osteosarcoma in remission, presented with abdominal pain. A computed tomography (CT) scan demonstrated a large calcified intrabdominal mass (15×13×9 cm) consistent with new peritoneal disease. After one cycle of palliative ifosfamide and etoposide chemotherapy, he developed a large bowel perforation and neutropenic sepsis consequently requiring resection of the perforated mass. Chemotherapy-induced bowel perforation is a rare but serious complication that should be considered in patients with osteosarcoma, and other chemosensitive malignancies, with intra-abdominal metastases. Recommencement of systemic therapies after bowel complications must be assessed cautiously on a case-by-case basis.

The rare case of oesophago-pericardial fistula secondary to pulmonary tuberculosis.

We report the case of a healthy 35-year-old male with two rare pathologies: pneumopericardium and oesophago-pericardial fistula (OPF) secondary to tuberculosis. Purulent pericarditis and cardiac tamponade are known complications with potential for significant morbidity and mortality. Unfortunately, the symptoms of OPF are non-specific often delaying diagnosis. There is no gold standard for treatment or determinant of when nonsurgical versus surgical approach should be considered. Anti-tuberculous therapy alone is often adequate however an oesophageal stent was utilized in this case to rapidly gain control of the fistula and prevent ongoing contamination from mediastinitis.

Individualised, targeted step count intervention following gastrointestinal cancer surgery: The Fit-4-Home randomised clinical trial.

BACKGROUND: To determine the effectiveness of an individualised, daily targeted step count intervention and usual care compared with usual care alone on improving surgical and patient reported outcomes. METHODS: The Fit-4-Home trial was a pragmatic, randomised controlled trial conducted from April 2019 to February 2021. Patients undergoing elective surgery for liver, stomach or pancreatic cancer in two Australian hospitals were recruited. Participants were randomly allocated to receive an individualised, targeted step count intervention and usual care (intervention) or usual care alone (control). A wearable activity tracker was provided to the intervention group to monitor their daily step count target. Primary outcome was the length of stay in the gastrointestinal ward. Secondary outcomes included postoperative complication rates, discharge destination, quality of life, physical activity, pain, fatigue, distress and hospital re-admission within 30 days. Outcome measures were compared between groups using non-parametric statistics. RESULTS: Of the 96 patients recruited, 47 were randomised to the intervention group and 49 were randomised to the control group. The median (interquartile) length of stay in the ward was 7 days (5.0-13.0) in the intervention group and 7 days (5.0- 12.0) in the control group (p = 0.330). Fatigue scores were worse in the intervention group when compared to control (p = 0.018). No other differences between groups were observed. CONCLUSIONS: An individualised, daily targeted step count intervention and usual care did not confer additional benefits in reducing the length of stay in the ward compared to usual care alone for patients undergoing gastrointestinal cancer surgery. TRIAL REGISTRATION: Registered with the Australia and New Zealand Clinical Trials Registry (ACTRN12619000194167).

Use of Lhasa Limited Products for the In Silico Prediction of Drug Toxicity.

Lhasa Limited have had a role in the in silico prediction of drug and other chemical toxicity for over 30 years. This role has always been multifaceted, both as a provider of predictive software such as Derek Nexus, and as an honest broker for the sharing of proprietary chemical and toxicity data. A changing regulatory environment and the drive for the Replacement, Reduction and Refinement (the 3Rs) of animal testing have led both to increased acceptance of in silico predictions and a desire for the sharing of data to reduce duplicate testing. The combination of these factors has led to Lhasa Limited providing a suite of products and coordinating numerous data-sharing consortia that do indeed facilitate a significant reduction in the testing burden that companies would otherwise be laboring under. Many of these products and consortia can be organized into workflows for specific regulatory use cases, and it is these that will be used to frame the narrative in this chapter.

The long haul: Lived experiences of survivors following different treatments for advanced colorectal cancer: A qualitative study.

PURPOSE: Modern treatments, including surgery and palliative chemotherapy without surgery, enable longer survival for people with advanced/recurrent colorectal cancer (CRC). Qualitative research comparing the physical and psychosocial outcomes of these different treatments is lacking. This study therefore aimed to explore and compare the physical and psychosocial challenges and survivorship experiences of people who receive different treatments for advanced CRC, through a qualitative study. METHOD: Adults with CRC who have undergone treatment for advanced/recurrent CRC were recruited 0.5-2 years post-surgery or, for palliative chemotherapy participants, 0.5-2 years post-diagnosis of advanced CRC. Qualitative semi-structured telephone interviews, analysed via framework analysis, explored quality of life (QoL) experiences. Demographic, clinical, and QoL data (Functional Assessment of Cancer Therapy - Colorectal (FACT-C), Distress Thermometer) were collected to characterise the sample and inform the framework analysis. RESULTS: A diverse sample of 38 participants (22 female) participated, with ages ranging 27-84 (Median = 59), FACT-C 56-132 (Median = 102), and distress 0-10 (median = 3). Analysis of interviews revealed three overarching themes: 1) the overwhelming impact of protracted, complex illness; 2) compounding and interacting effects of multiple treatments, impacts, and multimorbidity; and 3) the long haul is unpredictable, bumpy, and wearing. These themes reveal that people with advanced CRC experience many challenges due to the complex nature of the illness, its treatment, and side effects. CONCLUSIONS: Survivors require continued multi-disciplinary supportive care throughout follow-up to manage survivorship challenges. Guideline-led survivorship care and routine monitoring of physical and psychosocial wellbeing throughout follow up is imperative to manage patient expectations and support advanced CRC survivors.