Role of routine lymph node dissection alongside resection of intrahepatic cholangiocarcinoma: Systematic review and meta-analysis.

BACKGROUND: The global incidence of intrahepatic cholangiocarcinoma (ICCA) is soaring. Due to often delayed presentation, only a narrow spectrum of the disease is usually surgically resectable. To more accurately stage the disease, reduce recurrence, and improve overall survival, surgical teams are increasingly performing intraoperative lymph node dissection (LND) as well. This procedure has its associated morbidity, while there is no consensus or formal guidelines on its role in this setting. Hence, there is a need to better delineate the evidence for performing LND alongside surgical resection of the ICCA. AIM: To perform a systematic review and meta-analysis on the role of LND in improving prognostication and survival post-resection of ICCA. METHODS: We performed a systematic literature search using Pubmed, Medline, Embase, and the Cochrane Library, for all studies involving LND, ICCA, and surgical resection using several keywords, Medical Subject Headings (MeSH) tags, and appropriate synonyms. All clinical studies comparing curative intent resection of ICCA with LND vs resection without LND were included, while single-arm case series, studies with insufficient data, and duplicates were excluded. We included all English-language studies from the different academic databases up till early December 2022. The primary outcome measures were set for overall survival (OS) and disease-free survival (DFS). RESULTS: This systematic review and meta-analysis included 15 studies that fulfilled the selection criteria comprising 11413 patients with surgically-resectable ICCA, of whom 6424 (56.3%) underwent hepatectomy with LND while the remainder underwent hepatectomy only. In patients who underwent LND, on average, 27.7% of the resected lymph nodes were positive for metastatic disease. Overall, the results showed that performing LND did not significantly improve OS or DFS. However, the effect of LND on OS showed a degree of variability by geographical region, in Eastern and Western countries. As LND is increasingly being performed, further time-based analysis was undertaken to identify time-dependent changes in the role of LND. An increasing adoption of LND was not associated with improved OS. Furthermore, no roles were identified for neoadjuvant/adjuvant chemotherapy or increasing lymph node retrieval in improving OS either. CONCLUSION: LND might aid in staging, prognosticating, and deciding further management of resected ICCA, but does not improve OS and DFS and is unsuitable for high-risk patients unlikely to benefit from further treatments.

Phenotypic and Functional Studies of Human Treg Cell Subpopulations.

CD4+ regulatory T (Treg) cells play an important role in maintaining immune homeostasis. Although these cells were initially studied as a homogenous cohort, we now know that they have unprecedented underlying heterogeneity. This heterogeneity is reflected in their phenotype and functions. As human Treg subpopulations are very small in numbers, it is necessary to develop novel ways of isolating and manipulating these cell populations. In this chapter, we discuss immunoassays established to this effect.

Pre-COVID-19 Immunity to Common Cold Human Coronaviruses Induces a Recall-Type IgG Response to SARS-CoV-2 Antigens Without Cross-Neutralisation.

The capacity of pre-existing immunity to human common coronaviruses (HCoV) to cross-protect against de novo COVID-19is yet unknown. In this work, we studied the sera of 175 COVID-19 patients, 76 healthy donors and 3 intravenous immunoglobulins (IVIG) batches. We found that most COVID-19 patients developed anti-SARS-CoV-2 IgG antibodies before IgM. Moreover, the capacity of their IgGs to react to beta-HCoV, was present in the early sera of most patients before the appearance of anti-SARS-CoV-2 IgG. This implied that a recall-type antibody response was generated. In comparison, the patients that mounted an anti-SARS-COV2 IgM response, prior to IgG responses had lower titres of anti-beta-HCoV IgG antibodies. This indicated that pre-existing immunity to beta-HCoV was conducive to the generation of memory type responses to SARS-COV-2. Finally, we also found that pre-COVID-19-era sera and IVIG cross-reacted with SARS-CoV-2 antigens without neutralising SARS-CoV-2 infectivity in vitro. Put together, these results indicate that whilst pre-existing immunity to HCoV is responsible for recall-type IgG responses to SARS-CoV-2, it does not lead to cross-protection against COVID-19.

Metabolic Optimisation of Regulatory T Cells in Transplantation.

Regulatory T (Treg) cells expressing the FOXP3 transcription factor are presently under investigation by many teams globally as a cellular therapy to induce tolerance in transplantation. This is primarily due to their immunosuppressive and homeostatic functions. Depending on the type of allograft, Treg cells will need to infiltrate and function in metabolically diverse microenvironments. This means that any resident and circulating Treg cells need to differentially adapt to counter acute or chronic allograft rejection. However, the links between Treg cell metabolism and function are still not entirely delineated. Current data suggest that Treg cells and their effector counterparts have different metabolite dependencies and metabolic programs. These properties could be exploited to optimize intragraft Treg cell function. In this review, we discuss the current paradigms regarding Treg cell metabolism and outline critical intracellular axes that link metabolism and function. Finally, we discuss how this knowledge could be clinically translated for the benefit of transplant patients.