The use of neoadjuvant lobar radioembolization prior to major hepatic resection for malignancy results in a low rate of post hepatectomy liver failure

BackgroundNeoadjuvant yttrium-90 transarterial radioembolization (TARE) is increasingly being used as a strategy to facilitate resection of otherwise unresectable tumors due to its ability to generate both tumor response and remnant liver hypertrophy. Perioperative outcomes after the use of neoadjuvant lobar TARE remain underinvestigated.MethodsA single center retrospective review of patients who underwent lobar TARE prior to major hepatectomy for primary or metastatic liver cancer between 2007 and 2018 was conducted. Baseline demographics, radioembolization parameters, pre- and post-radioembolization volumetrics, intra-operative surgical data, adverse events, and post-operative outcomes were analyzed.ResultsTwenty-six patients underwent major hepatectomy after neoadjuvant lobar TARE. The mean age was 58.3 years (17–88 years). 62% of patients (n=16) had primary liver malignancies while the remainder had metastatic disease. Liver resection included right hepatectomy or trisegmentectomy, left or extended left hepatectomy, and sectorectomy/segmentectomy in 77% (n=20), 8% (n=2), and 15% (n=4) of patients, respectively. The mean length of stay was 8.3 days (range, 3–33 days) and there were no grade IV morbidities or 90-day mortalities. The incidence of post hepatectomy liver failure (PHLF) was 3.8% (n=1). The median time to progression after resection was 4.5 months (range, 3.3–10 months). Twenty-three percent (n=6) of patients had no recurrence. The median survival was 28.9 months (range, 16.9–46.8 months) from major hepatectomy and 37.6 months (range, 25.2–53.1 months) from TARE.ConclusionsMajor hepatectomy after neoadjuvant lobar radioembolization is safe with a low incidence of PHLF.     

Damage-associated molecular pattern (DAMP) activation in melanoma: investigation of the immunogenic activity of 15-deoxy, Δ12,14 prostamide J2

Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ^12,14 prostamide J₂ (15dPMJ₂). As such, the current study investigates whether 15dPMJ₂ induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ₂ caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ₂ also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ₂ to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ₂-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ₂-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ₂ and the ER stress pathway. These results demonstrate that 15dPMJ₂ is a tumor-selective inducer of DAMP signaling in melanoma.     

Hospital Episode Statistics and trends in ophthalmic surgery 1998 – 2004

Background  

Hospital episode statistics (HES) is a UK national database for the National Health Service (NHS), now available online. The purpose of this study was to observe trends in ophthalmic operations performed during the period from 1998 to 2004, using this data.     

Long-term surgical results for congenital aural atresia

Thirty-nine primary surgical cases for correction of congenital aural atresia were reviewed for complications and long-term hearing results. Hearing averages of 25 dB for mild atresia, 40 dB for moderate atresia, and 46 dB for severe atresia were obtained. Serviceable hearing was achieved in 64% of the cases. The two most frequent complications were stenosis and recurrent infections of the cavity and canal skin, with an incidence of 33% and 31%, respectively. Use of split-thickness instead of full-thickness skin graft was associated with fewer complications. The goal of this review is also to share the experience of the senior author in the management of this complex problem.     

Human interleukin 4 regulates the phenotype of lymphocytes generated during mixed lymphocyte culture and inhibits the IL-2-induced development of LAK function in normal and leukaemic cells

This study examined the immunoregulatory role of recombinant interleukin 4 (IL-4), also known as B-cell stimulating factor 1, on the generation of cytotoxic effector cells from normal and leukaemic human blood mononuclear cells. When tested on cells from normal individuals, the addition of IL-4 to mixed lymphocyte cultures led to a dose-dependent proliferation of T-helper cells (CD3, 4 positive) with a concomitant decrease in phenotypic and functional cytotoxic T cells and natural killer (NK) cells. IL-4 also inhibited the interleukin-2 (IL-2)-induced generation of lymphokine-activated killer (LAK) activity when added at the beginning of mixed lymphocyte culture. When tested on mature leukaemic NK cells, IL-4 also inhibited the ability of IL-2 to induce LAK function using a short-term culture system. These results show that IL-4 acts on both normal and leukaemic cells and suggests that it acts at more than one level during the development of LAK function.     

Conditionally replicating luciferase reporter phages: improved sensitivity for rapid detection and assessment of drug susceptibility of Mycobacterium tuberculosis.

TM4 is a lytic mycobacteriophage which infects mycobacteria of clinical importance. A luciferase reporter phage, phAE40, has been constructed from TM4 and was previously shown to be useful for the rapid detection and drug susceptibility testing of Mycobacterium tuberculosis. However, the lytic nature of the phage results in a loss of detectable light output and limits the sensitivity of detection. We describe several strategies aimed at improving the luciferase activity generated by TM4 luciferase phages, including (i) varying the position of the luciferase gene in the phage genome, (ii) isolating host-range mutants of the phage, and (iii) introducing temperature-sensitive mutations in the phage such that it will not replicate at the infecting temperature. Several new phages generated by these methods show increased intensity of luciferase production compared to the first-generation reporter phage phAE40, and one phage, phAE88, also demonstrates an enhanced duration of luciferase activity. This has allowed the detection of as few as 120 BCG cells and the determination of drug susceptibilities of M. tuberculosis in as little as 1 day.