Single-cell Profiling of Tumor Immune Microenvironment Reveals Immune Irresponsiveness in Gastric Signet-ring Cell Carcinoma

Gastric cancer (GC) is a major cancer type characterized by high heterogeneity in both tumor cells and the tumor immune microenvironment (TIME). One intractable GC subtype is gastric signet-ring cell carcinoma (GSRCC), which is associated with poor prognosis. However, it remains unclear what the GSRCC TIME characteristics are and how these characteristics may contribute to clinical outcomes.

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Rates of malignancies among patients with moderate to severe atopic dermatitis: a retrospective cohort study

Objectives
Patients with atopic dermatitis (AD), also known as eczema, may be at an increased risk for malignancies compared with patients without AD; however, incidence rates (IRs) of malignancies in patients with moderate to severe AD are largely unknown. The objective of this study was to evaluate and compare IRs of malignancies in adults with moderate to severe AD (aged ≥18 years).

Design
Retrospective cohort study using data from a Kaiser Permanente Northern California (KPNC) cohort. AD severity classification was adjudicated with medical chart review. Covariates and stratification variables included age, sex and smoking status.

Setting
Data were obtained from the KPNC healthcare delivery system in northern California, USA. Cases of AD were defined by outpatient dermatologist-rendered codes and prescriptions of topical therapy or phototherapy (moderate) or systemic treatment (severe).

Participants
KPNC health plan members with moderate or severe AD (2007–2018).

Primary and secondary outcome measures
Malignancy IRs and 95% CIs per 1000 person-years were calculated.

Results
7050 KPNC health plan members with moderate and severe AD met eligibility criteria for inclusion. IRs (95% CI) were highest for non-melanoma skin cancer (NMSC) in patients with moderate and severe AD (4.6 (95% CI 3.9 to 5.5) and 5.9 (95% CI 3.8 to 9.2), respectively) and breast cancer (2.2 (95% CI 1.6 to 3.0) and 0.5 (95% CI 0.1 to 3.9), respectively). Except for breast cancer, which was only evaluated in women, malignancies were higher (with non-overlapping CIs) in patients with moderate and moderate to severe AD in men versus women for basal cell carcinoma and NMSC and in former versus never smokers for NMSC and squamous cell carcinoma.

Conclusions
This study estimated IRs of malignancies in patients with moderate and severe AD and provides valuable information for dermatology clinicians and ongoing clinical trials in these populations.

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Refining genetic and molecular classifications to facilitate breakthrough treatments in intrahepatic cholangiocarcinoma: are we there yet?

Intrahepatic cholangiocarcinoma (ICC) is a type of biliary tract cancer and the second most common primary hepatic malignancy after hepatocellular carcinoma (HCC). ICC incidence and mortality have been continuously increasing worldwide over the past decades.1 ICCs are rarely diagnosed early, and there is a high risk of distant recurrence even after complete surgical resection. Most ICC patients present with unresectable, advanced disease, for which the first-line treatment is systemic gemcitabine/cisplatin treatment. This combination chemotherapy is used for all biliary tract cancers and can delay tumour progression in many patients but is invariably followed by the development of treatment resistance. Genomic characterisation over the last decade had led to successful clinical development of molecularly targeted drugs in ICC, such as fibroblast growth factor receptor (FGFR) and isocitrate dehydrogenase (IDH) inhibitors for the treatment of FGFR-driven and IDH-driven ICCs, respectively.2 However, these drugs have also shown generally…

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