Sequential Irreversible Electroporation for Locally Advanced Pancreatic Cancer.

Pancreatic cancer is a lethal disease, with locally advanced pancreatic cancer (LAPC) having a dismal prognosis. For patients with LAPC, gemcitabine-based regimens, with or without radiation, have long been the standard of care. Irreversible electroporation (IRE), a non-thermal ablative technique, may potentially prolong the survival of patients with LAPC. In this article, the authors present a case of LAPC of the uncinate process (biopsy proven pancreatic neuroendocrine carcinoma) with duodenal invasion. The patient had a combination of chemotherapy and radiation therapy but was found to have stable disease. He then underwent intra-operative IRE with cholecystectomy, Roux-en-Y gastrojejunostomy and hepaticojejunostomy. He subsequently underwent percutaneous IRE 13 months post open IRE. The patient also completed peptide receptor radionuclide therapy and has been started on Lanreotide. Following combination therapy, the pancreatic tumor showed significant reduction in size, with patient survival at 53 months post-diagnosis at the time of writing.

Utility of BeBack crossing catheter in fistula creation during percutaneous deep vein arterialization.

For patients with "no-option" chronic limb-threatening ischemia, a final attempt can be made for limb salvage in the form of percutaneous deep vein arterialization (pDVA). In the present study, we describe five cases of pDVA using a BeBack crossing catheter (Bentley InnoMed GmbH; previously, the GoBack crossing catheter; Upstream Peripheral Technologies). From November 2021 to July 2022, five patients underwent pDVA using the BeBack crossing catheter. The demographic data, procedural details, and patient outcomes were recorded. Successful vascular crossing was achieved in all five cases using the BeBack device. No surgical complications were encountered. The limb salvage rate was 60%, and the wound closure rate was 40%. No mortalities occurred during the follow-up period. The findings from the present study demonstrate that the use of the BeBack crossing catheter for pDVA is safe and feasible.

The Utility of Ultrasound Guidance to Improve the Safety of Closure of Antegrade Common Femoral Artery Access after Lower Limb Revascularization.

This study aimed to investigate the feasibility of ultrasound (US)-guidance in reducing adverse event (AE) rates when using Angioseal device during antegrade lower limb angioplasty via common femoral artery access. From December 2016 to November 2022, 1,322 patients were identified, including 1,131 (85.6%) patients who underwent US-guided closure and 191 (14.4%) who underwent non-US-guided closure. Moderate AEs were encountered in 10 (5.2%) patients in the non-US-guided closure group compared to 38 (3.4%) patients in the US-guided closure group (P = .208). Severe AEs were encountered in 4 (2.1%) patients in the non-US-guided closure group compared to 3 (0.3%) patients in the US-guided closure group (P = .010). Overall AEs occurred in 14 (7.3%) patients in the non-US-guided closure group compared to 41 (3.6%) patients in the US-guided closure group (P = .029). Binary logistic regression showed that only non-US guidance was an independent risk factor for the occurrence of severe AEs (P = .008).

Irreversible electroporation of the pancreas - A decade on.

Irreversible electroporation (IRE) employs the use of an electric field to cause irreversible permeability of the cell membrane, inducing apoptosis. The use of IRE for locally advanced pancreatic cancer (LAPC) was first described in 2012. The crucial advantage of IRE compared with other devices employing thermal ablation is the safety around vital structures such as vessels and ducts. This makes it an attractive option for use in the pancreas due to the close proximity of multiple major vascular structures, biliary ducts, and adjacent gastrointestinal organs. Over the past decade, IRE has established itself as a useful treatment adjunct and may soon become the standard of care, particularly for LAPC. This article will explore the current evidence and provide a concise summary of pertinent issues, including patient selection, preoperative management, clinical outcomes, radiological response and future prospects of IRE in pancreatic cancer.

Elevated pentose phosphate pathway flux supports appendage regeneration.

A fundamental step in regeneration is rapid growth to replace lost tissue. Cells must generate sufficient lipids, nucleotides, and proteins to fuel rapid cell division. To define metabolic pathways underlying regenerative growth, we undertake a multimodal investigation of metabolic reprogramming in Xenopus tropicalis appendage regeneration. Regenerating tissues have increased glucose uptake; however, inhibition of glycolysis does not decrease regeneration. Instead, glucose is funneled to the pentose phosphate pathway (PPP), which is essential for full tail regeneration. Liquid chromatography-mass spectrometry (LC-MS) metabolite profiling reveals increased nucleotide and nicotinamide intermediates required for cell division. Using single-cell RNA sequencing (scRNA-seq), we find that highly proliferative cells have increased transcription of PPP enzymes and not glycolytic enzymes. Further, PPP inhibition results in decreased cell division specifically in regenerating tissue. Our results inform a model wherein regenerating tissues direct glucose toward the PPP, yielding nucleotide precursors to drive regenerative cell proliferation.

Impact of waiting time on hepatocellular carcinoma progression in patients undergoing curative tumour ablation.

BACKGROUND: A feared consequence to delay in oncological treatment includes disease progression. This study aims to evaluate the relationship between waiting time for ablative therapy in patients with hepatocellular carcinoma (HCC), and the outcomes of local tumour progression, or new HCC foci. METHODS: Between January 2011 to July 2017, 215 patients with HCC underwent ablative (microwave and radiofrequency) procedures. Demographic information, and duration between diagnosis on imaging and ablative procedure were recorded. Follow-up imaging data were analysed to assess for development of either new HCC, or local tumour progression. The median waiting time to ablative therapy was 42 days, hence, patients were separated into two groups: wait time <42 days versus wait time ≥42 days. Simple cox regression was conducted to explore the association between wait time and the clinical outcomes of new HCC or local tumour progression. Survival analyses for outcomes of new HCC or local tumour progression were also compared between the two groups using log-rank test. All the statistical analyses were two sided and P value of less than 0.05 was considered as statistically significant. RESULTS: Hazard ratio for local tumour progression was 1.002 (0.996, 1.007) P=0.579, while hazard ratio for new HCC foci was 1.002 (0.998, 1.005) P=0.373. There was no statistically significant difference when comparing the two groups (wait time <42 versus ≥42 days) for survival estimates for local tumour progression P=0.346, and for new HCC P=0.680. CONCLUSIONS: This study demonstrates that delay in HCC ablative therapy is not associated with significant risk of local tumour progression, or new HCC foci.

Single-Setting Superior Vena Cava Biopsy and Stenting Utilizing Cone Beam Computed Tomography as an Additional Tool.

BACKGROUND Malignant disease is a common etiology of superior vena cava syndrome (SVCS). Being a medical emergency, it often requires rapid diagnostic evaluation and therapy. Transcaval biopsy and endovascular stenting in a single-setting has been described, but only in a handful of cases. These cases utilized intra-operative venograms. In this study, we also used intra-operative cone beam computed tomography (CBCT) to increase the safety and efficacy of such single-setting procedures. CASE REPORT From January 2017 to July 2019, there were 5 patients with malignant SVCS who underwent single-setting superior vena cava biopsy and endovascular stenting utilizing intra-operative CBCT as an adjunct. Demographic data, clinical presentation, investigation results, procedural details, and patient outcomes were recorded. CBCT was utilized in all cases to optimize sampling of biopsies, visualize subsequent stent positioning, and for early detection of procedure-related complications. Transcaval biopsy was diagnostic in 4 of the 5 patients. Endovascular stents were deployed successfully in all cases, with post-stenting venogram demonstrating relief of prior obstructed segments. One patient had a complication of an apical pneumothorax, with no associated long-term pneumothorax-related morbidity or mortality. CONCLUSIONS This study demonstrates that single-setting transcaval biopsy and stenting in the context of malignant SVCS is a cost-efficient, safe, and feasible approach. In addition, the additional use of intra-operative CBCT is a useful tool to increase procedure efficacy and safety.

Coil Embolization of Arc of Buhler Aneurysm Rupture.

The arc of Buhler (AOB) is a rare anatomical variant. Rupture of an AOB aneurysm is exceedingly rare. In this study, we report a case of AOB aneurysm rupture, which was successfully treated by transcatheter coil embolization. A 74-year-old man presented with symptomatic AOB aneurysm rupture. A computed tomography scan and subsequent angiography revealed the aberrant connection between the common hepatic artery and the superior mesenteric artery. A fusiform AOB aneurysm with focus of active bleeding was detected. This was successfully treated through embolization and sacrifice of the AOB. This suggests that conventional embolization with sacrifice of AOB is a feasible and safe approach.

Ten tips for foundation doctors when making inpatient referrals to surgical specialties.

Making referrals to another specialty is an underemphasised skill in the undergraduate medical curriculum. As a result, many new foundation doctors find themselves ill-equipped to make effective referrals to other specialties as part of their day-to-day responsibilities. This can often be frustrating to the foundation doctor, the specialist and contribute to critical delays in patient care. Surgical registrars are required to triage patients (for urgent review or even to take to theatre) often under time and high patient volume pressures. As such, it is imperative for foundation doctors to make referrals as efficiently as possible to facilitate surgical specialty decision making and, ultimately, to expedite medical care to patients. In this article, we describe 10 tips for the foundation doctor in making inpatient referrals to surgical specialties.

Determination of the Excitation and Coupling Rates Between Light Emitters and Surface Plasmon Polaritons.

We have developed a unique method to measure the excitation and coupling rates between the light emitters and surface plasmon polaritons (SPPs) arising from metallic periodic arrays without involving time-resolved techniques. We have formulated the rates by quantities that can be measured by simple optical measurements. The instrumentation based on angle- and polarization-resolved reflectivity and photoluminescence spectroscopy will be described in detail here. Our approach is intriguing due to its simplicity, which requires routine optics and several mechanical stages, and thus is highly affordable to most of the research laboratories.

Common Femoral Artery Caliber Changes after Percutaneous versus Surgical Access in Endovascular Aneurysm Repair in the Asian Population.

BACKGROUND: Western studies showed vascular caliber changes post-endovascular aneurysm repair (EVAR). This study aims to evaluate for postoperative changes of the common femoral artery inner diameter (CFA ID) in the Asian population. METHODS: From January 2011 to June 2016, 202 patients who underwent EVAR were reviewed. CFA IDs were evaluated at 3 fixed levels on computed tomography (CT) aortograms. Preoperative and postoperative measurements were compared. Per-groin analysis was carried out after division into percutaneous access endovascular aneurysm repair (PEVAR) and surgical access endovascular aneurysm repair (SEVAR) groups. Independent sample t-test compared for differences in overall CFA ID changes between PEVAR and SEVAR groups. Paired sample t-test evaluated CFA ID changes in each group. P value < 0.05 was considered significant. RESULTS: One hundred and twenty patients were included, with 200 groins subsequently analyzed. The PEVAR and SEVAR groups have no significant demographic differences, except in sheath size and duration of CT aortogram follow-up. No significant differences in overall CFA ID changes comparing PEVAR and SEVAR groups (-0.12 ± 1.05 mm, -0.10 ± 0.81 mm, P = 0.36). No significant overall CFA ID changes in both PEVAR (7.92 ± 1.23 mm, 7.80 ± 1.38 mm, P = 0.34) and SEVAR groups (7.47 ± 1.44 mm, 7.36 ± 1.64 mm, P = 0.15). CONCLUSIONS: No significant differences in CFA caliber changes comparing PEVAR and SEVAR. No significant CFA caliber changes in either group.

Computed tomography of the head for adult patients with minor head injury: are clinical decision rules a necessary evil?

INTRODUCTION: This study aimed to evaluate compliance with and performance of the Canadian Computed Tomography Head Rule (CCHR), and its applicability to the Singapore adult population with minor head injury. METHODS: We conducted a retrospective study over six months of consecutive patients who presented to the adult emergency department (ED) with minor head injury. Data on predictor variables indicated in the CCHR was collected and compliance with the CCHR was assessed by comparing the recommendations for head computed tomography (CT) to its actual usage. RESULTS: In total, 349 patients satisfied the inclusion criteria. Common mechanisms of injury were falls (59.3%), motor vehicle crashes (16.9%) and assault (12.0%). 249 (71.3%) patients underwent head CT, yielding 42 (12.0%) clinically significant findings. 1 (0.3%) patient required neurosurgical intervention. According to the CCHR, head CT was recommended for 209 (59.9%) patients. Compliance with the CCHR was 71.3%. Among the noncompliant group, head CT was overperformed for 20.1% and underperformed for 8.6% of patients. Multivariate logistic regression analysis revealed that absence of retrograde amnesia (odds ratio [OR] 4.1, 95% confidence interval [CI] 1.8-9.7) was associated with noncompliance to the CCHR. Factors associated with underperformance were absence of motor vehicle crashes as a mechanism of injury (OR 6.6, 95% CI 1.2-36.3) and absence of headache (OR 10.8, 95% CI 1.3-87.4). CONCLUSION: Compliance with the CCHR for adult patients with minor head injury remains low in the ED. A qualitative review of physicians' practices and patients' preferences may be carried out to evaluate reasons for noncompliance.

Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study.

BACKGROUND: Previous studies have demonstrated that statin therapy improves cardiac outcomes, probably by stabilizing thin-cap fibroatheroma in patients with coronary artery disease. However, major adverse cardiac events still occur in some patients, despite statin therapy. The aim of this study is to identify clinical predictors for the lack of a favorable vascular response to statin therapy in patients with coronary artery disease. METHODS AND RESULTS: A total of 140 nonculprit plaques from 84 patients with coronary artery disease who were treated with a statin and had serial optical coherence tomography imaging (median interval, 6.3 months) were included. Thin-cap area (fibrous cap thickness, <200 µm) was measured using a novel 3-dimensional computer-aided algorithm. Overall, the thin-cap area significantly decreased from baseline (median, 2.852 mm2; 25th-75th percentile, 1.023-6.157 mm2) to follow-up (median, 1.210 mm2; 25th-75th percentile, 0.250-3.192 mm2; P<0.001), and low-density lipoprotein cholesterol significantly decreased from baseline (mean±SD, 92.9±30.1 mg/dL) to follow-up (mean±SD, 76.3±23.3 mg/dL; P<0.001). The general linear model with multiple predictor variables revealed that the thin-cap area was significantly higher in patients with chronic kidney disease than in those without it (regression coefficient b, 1.691 mm2; 95% confidence interval, 0.350-3.033 mm2; P=0.013) and lower in patients with acute coronary syndrome (regression coefficient b, -1.535 mm2; 95% confidence interval, -2.561 to -0.509 mm2; P=0.003). CONCLUSIONS: Chronic kidney disease is an independent predictor for the lack of a favorable vascular response to statin therapy, whereas acute coronary syndrome is an independent predictor for favorable vascular response to statin therapy. These findings should be further warranted in future prospective studies. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538.

Is age an important factor for vascular response to statin therapy? A serial optical coherence tomography and intravascular ultrasound study.

OBJECTIVE: Age-related structural and functional changes in vessel wall may affect the time course of vascular response to statin therapy. In this study, we sought to compare the response of lipid-rich plaque to statin therapy in elderly versus younger patients using optical coherence tomography and intravascular ultrasound. PATIENTS AND METHODS: Sixty-nine patients who underwent serial optical coherence tomography and intravascular ultrasound at the time point of baseline, 6, and 12 months were divided into two groups according to median age: group A (age<57 years, n=35) and group B (age≥57 years, n=34). Patients were treated with intensive (atorvastatin 60 mg/day) or moderate (atorvastatin 20 mg/day or rosuvastatin 10 mg/day) statin therapy. RESULTS: A continuous increase in fibrous-cap thickness (FCT) from baseline to 12 months was observed in both groups (P<0.001, <0.001, respectively). Intensive statin induced greater percent change in FCT at 12 months than moderate statin in group B (P=0.020), but not in group A (P=0.251). Mean lipid arc decreased significantly at 12 months in two groups (P<0.001, <0.001, respectively), and this response was delayed for 6 months (P=0.403) and began to decrease during the second 6 months (P<0.001) in group B. Normalized total atheroma volume decreased significantly in group A (P<0.001), but not in group B (P=0.349). CONCLUSION: Statin therapy could stabilize lipid-rich plaque irrespective of age, and intensive statin therapy was more effective than a moderate dose of statin in increasing FCT, particularly in older patients. A delayed response of lipid content and unfavorable change in normalized total atheroma volume to statin were observed in elderly patients.

Morphological predictors for no reflow phenomenon after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction caused by plaque rupture.

AIMS: Myocardial no reflow after percutaneous coronary intervention (PCI) is associated with poor outcome. Patients with ST-segment elevation myocardial infarction (STEMI) caused by plaque rupture are at high risk for no reflow. However, specific morphologic characteristics associated with no reflow are unknown in this population. The aim of this study is to identify the morphological characteristics of culprit plaques associated with no reflow in patients with STEMI caused by plaque rupture using both optical coherence tomography (OCT) and intravascular ultrasound (IVUS). METHODS AND RESULTS: We enrolled 145 patients with STEMI who underwent both OCT and IVUS within 12 h of symptom onset. Among these patients, we excluded those with plaque erosion and calcified nodule and included 72 patients who had plaque rupture as an underlying mechanism for STEMI. Myocardial no reflow, defined as Thrombolysis in Myocardial Infarction flow grade 0-2 and/or myocardial blush grade 0-1 after PCI, was observed in 28 patients (38.9%). Onset to recanalization time was similar between the groups with and without no reflow. Receiver-operating curve analysis revealed OCT-derived lipid index > 3500 [area under curve (AUC) 0.77, P < 0.001] and IVUS-derived plaque burden > 81.5% (AUC 0.70, P = 0.002) were the best discriminators for myocardial no reflow. CONCLUSION: No reflow occurred in nearly 40% of patients with STEMI caused by plaque rupture. Large lipid index and plaque burden were critical morphological discriminators between no reflow and normal flow.

Prospective, Randomized Clinical Trial of Povidone-Iodine 1.25% Solution Versus Topical Antibiotics for Treatment of Bacterial Keratitis.

PURPOSE: To compare povidone-iodine 1.25% ophthalmic solution with topical antibiotics for treatment of bacterial keratitis in areas of the world where use of effective topical antibiotics may not be an option. STUDY DESIGN: Randomized, controlled, investigator-masked clinical trial. METHODS: We randomized 172 individuals with bacterial keratitis to topical treatment with povidone-iodine or antibiotics (neomycin-polymyxin B-gramicidin in the Philippines; ciprofloxacin 0.3% in India). Using survival analysis, we compared intervals from start of treatment to "presumed cure" (primary outcome measure, defined as a closed epithelial defect without associated inflammatory signs) and to "recovering" (residual epithelial defect <1 mm2 with only minimal inflammation). RESULTS: Median interval to presumed cure in the Philippines was 7 days for povidone-iodine and 7 days for neomycin-polymyxin B-gramicidin (95% confidence interval [CI] for difference in median interval, -9.5 to 0.7 days) and in India was 12 days for povidone-iodine and 17 days for ciprofloxacin (95% CI, -35.2 to 3.2 days). Hazard ratio (HR) for presumed cure among those treated with povidone-iodine (vs antibiotics) was 1.46 in the Philippines (95% CI, 0.90-2.36; P = .13) and 1.70 in India (95% CI, 0.73-3.94; P = .22). Comparisons of intervals to recovering and HR for recovering also revealed no significant differences between treatment groups in either country. CONCLUSIONS: There is no significant difference between the effect of topical povidone-iodine 1.25% and topical antibiotics commonly available in the developing world for treatment of bacterial keratitis. Povidone-iodine 1.25%, which is widely available and inexpensive, can be considered for treatment of bacterial keratitis when antibiotic treatment is not practical.