Dataset Information

Surgical Therapy for Perihilar Cholangiocarcinoma: State of the Art.

ABSTRACT:

Background

Surgical therapy still offers the only chance of long-term survival for patients with perihilar cholangiocarcinoma (pCCA). The aim of this narrative review is to summarize the current standards and challenges in the surgical treatment of pCCA.

Summary

After imaging and defining resectability, the first step towards optimal surgical treatment is optimizing biliary drainage and preventing cholangitis, followed by securing adequate future liver remnant volume and/or function. The main goal of resection for pCCA is achieving radical resection and ultimately long-term survival. In order to achieve radical resection, several points will be addressed (e.g., vascular resection and reconstruction, intraoperative frozen sections, right versus left hemihepatectomy, and the usefulness of preoperative [chemo]therapy).

Key messages

In order to optimize long-term outcomes for patients with pCCA, collaboration between leading centers should be increased. In addition, this collaboration is necessary to design large prospective randomized controlled trials, as the incidence of pCCA is low and the number of resectable patients is even lower. Currently, most results are based on small retrospective cohort studies resulting in low evidence. In order to properly investigate how to improve long-term survival, we need to set up trials to confirm the results of small series suggesting the positive effect of preoperative chemotherapy and extended lymph node resection.

SUBMITTER: Nooijen LE

PROVIDER: S-EPMC7923954 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Surgical Therapy for Perihilar Cholangiocarcinoma: State of the Art.

Nooijen Lynn E LE Swijnenburg Rutger-Jan RJ Klümpen Heinz-Josef HJ Verheij Joanne J Kazemier Geert G van Gulik Thomas M TM Erdmann Joris I JI

Visceral medicine 20210107 1

<h4>Background</h4>Surgical therapy still offers the only chance of long-term survival for patients with perihilar cholangiocarcinoma (pCCA). The aim of this narrative review is to summarize the current standards and challenges in the surgical treatment of pCCA.<h4>Summary</h4>After imaging and defining resectability, the first step towards optimal surgical treatment is optimizing biliary drainage and preventing cholangitis, followed by securing adequate future liver remnant volume and/or functi ...[more]

PMID: 33708815

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Project description:BackgroundPhotodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)-, hypoxia-inducible factor 1-alpha (HIF-1α)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-, and unfolded protein response-mediated pathways).MethodsTo assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm(2)). Cells were harvested 90 min post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. The data were interpreted in the context of the survival pathways. In addition, the safety of ZnPC-encapsulating liposomes was tested both in vitro and in vivo.ResultsPDT-treated SK-ChA-1 cells exhibited activation of the hypoxia-induced stress response via HIF-1α and initiation of the pro-inflammatory response via NF-кB. PDT at low laser power in particular caused extensive survival signaling, as evidenced by the significant upregulation of HIF-1- (P < 0.001) and NF-кB-related (P < 0.001) genes. Low-power PDT was less lethal to SK-ChA-1 cells 90 min post-PDT, confirmed by annexin V/propidium iodide staining. In vitro toxicogenomics and toxicological testing in chicken embryos and mice revealed that the ZnPC-encapsulating liposomes are non-toxic.ConclusionsPDT-treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling that may translate to a suboptimal therapeutic response and possibly tumor recurrence. These findings encourage the development of photosensitizer delivery systems with co-encapsulated inhibitors of survival pathways.

Project description:IntroductionAlthough the consequences of testicular torsion (TT) have been recognized for centuries, little progress has been made to improve outcomes beyond those seen with timely scrotal exploration. Even with testicular salvage, ischemia/reperfusion injury cause significant atrophy and functional impairment. Recent efforts have sought to identify adjuvant pharmacological or surgical interventions that may attenuate these consequences. In this review, we assess the evidence supporting clinical use of these nascent interventions.MethodsWe conducted a review of the literature published from 2000 to 2020, using the search terms "torsion", "testicular", "reperfusion", "ischemia", and "injury". Clinical and laboratory research focused on adjuvant pharmacological and surgical techniques mitigating torsion-associated injury in animal models and humans were identified. We recorded intervention timing/dose/route, and outcome timing/category through biomarkers of reperfusion injury, histology, and hormonal/reproductive function.ResultsFifty-four FDA-approved agents, plus 52 herbal/investigational drugs, were reported in animal TT models. In every study, the investigated agents showed beneficial effects on measured endpoints compared to controls. Despite these universally promising animal findings, no pharmacological trials in humans were reported. Surgical techniques studied in animal models included decompression (tunica albuginea incision, TAI), "ischemic conditioning", and hypothermia. Only three human studies on surgical adjuvant maneuvers have been reported, all involving TAI; these showed potential benefit, but the level of evidence is low.ConclusionThere is preliminary evidence that adjuvant treatments may mitigate the effects of ischemia/reperfusion injury. However, the pool of investigated pharmacological agents is wide, yet remarkably shallow; most compounds have been reported in a single animal study. To advance this field, a mechanism-based approach should be used to select promising agents that can be tested systematically. This will determine treatment parameters that maximize safety, efficacy, and tolerability. Only then is it possible to move toward human trials. Adjuvant surgical methods such as TAI show promise in humans but require more robust clinical evaluation.

Dataset Information

Surgical Therapy for Perihilar Cholangiocarcinoma: State of the Art.

Background

Summary

Key messages

Publications

Surgical Therapy for Perihilar Cholangiocarcinoma: State of the Art.

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