Tri-mode optical biopsy probe with fluorescence endomicroscopy, Raman spectroscopy, and time-resolved fluorescence spectroscopy.

We present an endoscopic probe that combines three distinct optical fibre technologies including: A high-resolution imaging fibre for optical endomicroscopy, a multimode fibre for time-resolved fluorescence spectroscopy, and a hollow-core fibre with multimode signal collection cores for Raman spectroscopy. The three fibers are all enclosed within a 1.2 mm diameter clinical grade catheter with a 1.4 mm end cap. To demonstrate the probe's flexibility we provide data acquired with it in loops of radii down to 2 cm. We then use the probe in an anatomically accurate model of adult human airways, showing that it can be navigated to any part of the distal lung using a commercial bronchoscope. Finally, we present data acquired from fresh ex vivo human lung tissue. Our experiments show that this minimally invasive probe can deliver real-time optical biopsies from within the distal lung - simultaneously acquiring co-located high-resolution endomicroscopy and biochemical spectra.

T cells drive negative feedback mechanisms in cancer associated fibroblasts, promoting expression of co-inhibitory ligands, CD73 and IL-27 in non-small cell lung cancer.

The success of immune checkpoint therapy shows tumor-reactive T cells can eliminate cancer cells but are restrained by immunosuppression within the tumor micro-environment (TME). Cancer associated fibroblasts (CAFs) are the dominant stromal cell in the TME and co-localize with T cells in non-small cell lung cancer. We demonstrate the bidirectional nature of CAF/T cell interactions; T cells promote expression of co-inhibitory ligands, MHC molecules and CD73 on CAFs, increasing their production of IL-6 and eliciting production of IL-27. In turn CAFs upregulate co-inhibitory receptors on T cells including the ectonucleotidase CD39 promoting development of an exhausted but highly cytotoxic phenotype. Our results highlight the bidirectional interaction between T cells and CAFs in promoting components of the immunosuppressive CD39, CD73 adenosine pathway and demonstrate IL-27 production can be induced in CAF by activated T cells.

Testicular Volume Changes in Laparoscopic Staged Fowler-Stephens Orchiopexy: Studying the Impact of Testicular Vessel Division.

OBJECTIVE: To study the effect of testicular vessel division on testicular volume during laparoscopic staged Fowler Stephens orchiopexy (LSFSO). METHODS: Testicular dimensions were prospectively measured intraoperatively at both first (S1) and second stages (S2) of LSFSO, and with scrotal ultrasound 3-12 months postoperatively. Testicular volumes were compared to reference ranges. Volume changes were tracked with a change of >20% considered clinically significant. RESULTS: A total of 52 nonpalpable testes treated with LSFSO between 2008 and 2018 were included in the study. After a median follow-up of 6.8 (3-91.3) months, 46 (88.5%) testes were palpable in a scrotal location without adjunctive procedures and 39 (75%) maintained vascular flow on duplex ultrasound. One testis retracted to an inguinal position and was successfully treated with inguinal orchiopexy for an overall success of 90.4% (47/52). Of 36 testes with intra- and postoperative testicular volume documentation, only 2 (5.6%) had significant volume loss after S1. Both testes had catch-up growth after S2. Eight (22.2%) testes had significant volume loss after S2. At follow-up, 24 (66.7%) testes were smaller than the mean for age, of which 20 (83.3%) were small at baseline. Only 41.7% of testes larger than mean for age at follow-up, were small at baseline (P = .02). CONCLUSION: Significant testicular volume loss does not occur after testicular vessel division at S1, but expected in approximately 1 quarter of testes after S2. We propose that testicular atrophy after LSFSO is primarily due to defective testicular development and rarely due to vascular compromise during S2.