Preexposition Prophylaxis With Truvada (Tenofovir/Emtricitabine) as Potential Cause of Celiac Disease-Like Enteropathy.

We present here a case of a 39-year-old patient who presented with celiac-disease-like symptoms and MARSH 3a histology in duodenal biopsies under normal diet. Interestingly, HLA genotyping and celiac-specific serology were negative, primarily leading to exclusion of celiac disease. However, biopsies from a second endoscopy a couple of months later (still under normal diet) showed histologic progression of the disease to MARSH 3b and led to the re-evaluation of the out-of-hospital-obtained histological samples by a pathologist experienced in celiac disease. The second biopsy described previously as MARSH 3b turned out to be non-specific and was therefore re-classified as MARSH 0. After all known causes of duodenal villous atrophy were excluded by a thorough evaluation, a correlation between the first biopsy (MARSH 3a) and Truvada intake could be established. After Truvada discontinuation and under normal diet, normalisation of duodenal mucosa was observed, leading to the assumption that Truvada could lead to celiac-like enteropathy.

Interactions of EGFR/PTEN/mTOR-Pathway Activation and Estrogen Receptor Expression in Cervical Cancer.

(1) Objective: Late-line chemotherapy rechallenge in recurrent cervical cancer is associated with modest therapy response but significant side effects. As mTOR pathways modulate cellular growth via estrogen receptor (ER) signaling and combined mTOR and ER inhibition previously demonstrated survival benefits in breast cancer, this exploratory study evaluates mTOR pathway and ER expression interactions in a preclinical cervical cancer model. (2) Methods: Immunostaining of a 126-tumor core tissue microarray was performed to assess phosphorylated-mTOR and ER expression. To identify tumor subsets with different clinical behavior, expression results were matched with clinicopathologic patient characteristics, and both univariate and multivariable survival statistics were performed. (3) Results: phosphorylated-mTOR correlates with ER (r = 0.309, p < 0.001) and loss of PTEN expression (r = -2.09, p = 0.022) in tumor samples across stages but not in matched negative controls. Positive ER expression is observed significantly more often in phosphorylated-mTOR positive samples (30.0% vs. 6.3%, p = 0.001). In the subgroup of phosphorylated-mTOR positive tumors (n = 60), ER expression is associated with improved survival (p = 0.040). (4) Conclusion: ER expression appears closely intertwined with EGFR/PTEN/mTOR-pathway activation and seems to define a subgroup with clinically distinct behavior. Considering limited therapeutic options in recurrent cervical cancer, further validation of combined mTOR and ER inhibition in selected patients could appear promising.