Boris Galjart

Does lower gastrointestinal endoscopy during pregnancy pose a risk for mother and child? - a systematic review.

BackgroundGastrointestinal endoscopy plays a crucial role in the diagnosis and management of gastrointestinal disorders. When endoscopy is indicated during pregnancy, concerns about the effects on pregnancy outcome often arise. The aim of this study was to assess whether lower gastrointestinal endoscopies (LGEs) across all three trimesters of pregnancy affects pregnancy outcomes.MethodsA systematic literature search was performed using Embase (including MEDLINE), Medline OvidSP, Cochrane Central Register of Controlled Trials, Web-of-Science, Google scholar and Pubmed. All original research articles from 1990 until May 2014 involving pregnant women who underwent LGE for any indication were included. Adverse pregnancy events like spontaneous abortion, preterm birth and fetal demise were assessed for a temporal and etiological relation with the LGE.ResultsIn total, 5514 references were screened by two independent reviewers. Eighty-two references met the inclusion criteria and were selected. Two retrospective, controlled studies, one uncontrolled study and 79 case reports were identified. In the three studies, birth outcomes did not differ between women undergoing LGE during pregnancy, compared to women that had an indication for LGE but in whom LGE was not performed because of pregnancy. In 79 case reports, 92 patients are described who underwent 100 LGE’s during pregnancy. LGEs performed in all trimesters (n = 32, 39 and 29) were both temporally and etiologically related to 1, 3 and 2 adverse events, respectively.ConclusionBased on the available literature, this review concludes that lower gastrointestinal endoscopy during pregnancy is of low risk for mother and child in all three trimesters of pregnancy.

International consensus guidelines for scoring the histopathological growth patterns of liver metastasis

Background:Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs.Methods:Guidelines for defining the HGPs were established by a large international team. To assess the validity of these guidelines, 12 independent observers scored a set of 159 liver metastases and interobserver variability was measured. In an independent cohort of 374 patients with colorectal liver metastases (CRCLM), the impact of HGPs on overall survival after hepatectomy was determined.Results:Good-to-excellent correlations (intraclass correlation coefficient >0.5) with the gold standard were obtained for the assessment of the replacement HGP and desmoplastic HGP. Overall survival was significantly superior in the desmoplastic HGP subgroup compared with the replacement or pushing HGP subgroup (P=0.006).Conclusions:The current guidelines allow for reproducible determination of liver metastasis HGPs. As HGPs impact overall survival after surgery for CRCLM, they may serve as a novel biomarker for individualised therapies.

Performance of prognostic scores and staging systems in predicting long-term survival outcomes after surgery for intrahepatic cholangiocarcinoma

We sought to validate the commonly used prognostic models and staging systems for intrahepatic cholangiocarcinoma (ICC) in a large multi‐center patient cohort.

Blockade of LAG3 enhances responses of tumor-infiltrating T cells in mismatch repair-proficient liver metastases of colorectal cancer

ABSTRACT Purpose: Liver metastasis develops in >50% of patients with colorectal cancer (CRC), and is a leading cause of CRC-related mortality. We aimed to identify which inhibitory immune checkpoint pathways can be targeted to enhance functionality of intra-tumoral T-cells in mismatch repair-proficient liver metastases of colorectal cancer (LM-CRC). Methodology: Intra-tumoral expression of multiple inhibitory molecules was compared among mismatch repair-proficient LM-CRC, peritoneal metastases of colorectal cancer (PM-CRC) and primary CRC. Expression of inhibitory molecules was also analyzed on leukocytes isolated from paired resected metastatic liver tumors, tumor-free liver tissues, and blood of patients with mismatch repair-proficient LM-CRC. The effects of blocking inhibitory pathways on tumor-infiltrating T-cell responses were studied in ex vivo functional assays. Results: Mismatch repair-proficient LM-CRC showed higher expression of inhibitory receptors on intra-tumoral T-cells and contained higher proportions of CD8+ T-cells, dendritic cells and monocytes than mismatch repair-proficient primary CRC and/or PM-CRC. Inhibitory receptors LAG3, PD-1, TIM3 and CTLA4 were higher expressed on CD8+ T-cells, CD4+ T-helper and/or regulatory T-cells in LM-CRC tumors compared with tumor-free liver and blood. Antibody blockade of LAG3 or PD-L1 increased proliferation and effector cytokine production of intra-tumoral T-cells isolated from LM-CRC in response to both polyclonal and autologous tumor-specific stimulations. Higher LAG3 expression on intra-tumoral CD8+ T-cells associated with longer progression-free survival of LM-CRC patients. Conclusion: Mismatch repair-proficient LM-CRC may be more sensitive to immune checkpoint inhibitors than mismatch repair-proficient primary CRC. Blocking LAG3 enhances tumor-infiltrating T-cell responses of mismatch repair-proficient LM-CRC, and therefore may be a new promising immunotherapeutic target for LM-CRC.

Prognostic value of intra-tumoral CD8+/FoxP3+ lymphocyte ratio in patients with resected colorectal cancer liver metastasis

Patients with isolated colorectal‐cancer‐liver‐metastases (CRCLM) frequently undergo metastatectomy. Tumor‐infiltrating‐lymphocytes (TILs) have prognostic potential in the setting of primary colorectal cancer, however, their role in CRCLM is less studied. We aimed to study the spatial distribution and prognostic role of tumor‐infiltrating CD8+ cytotoxic T‐cells and FoxP3+ regulatory T‐cells at the metastatic site of CRCLM patients.

The prognosis of colorectal cancer liver metastases associated with inflammatory bowel disease: An exploratory analysis: MARGONIS et al.

In contrast with sporadic colorectal cancer liver metastases (CRLM), inflammatory bowel disease (IBD)‐related CRLM have not been studied to date.