Altered expression of cytokines, chemokines, growth factors, and soluble receptors in patients with colorectal cancer, and correlation with treatment outcome.

Insofar as they play an important role in the pathogenesis of colorectal cancer (CRC), this study analyzes the serum profile of cytokines, chemokines, growth factors, and soluble receptors in patients with CRC and cancer-free controls as possible CRC signatures. Serum levels of 65 analytes were measured in patients with CRC and age- and sex-matched cancer-free controls using the ProcartaPlex Human Immune Monitoring 65-Plex Panel. Of the 65 tested analytes, 8 cytokines (CSF-3, IFN-γ, IL-12p70, IL-18, IL-20, MIF, TNF-α and TSLP), 8 chemokines (fractalkine, MIP-1ß, BLC, Eotaxin-1, Eotaxin-2, IP-10, MIP-1a, MIP-3a), 2 growth factors (FGF-2, MMP-1), and 4 soluble receptors (APRIL, CD30, TNFRII, and TWEAK), were differentially expressed in CRC. ROC analysis confirmed the high association of TNF-α, BLC, Eotaxin-1, APRIL, and Tweak with AUC > 0.70, suggesting theranostic application. The expression of IFN-γ, IL-18, MIF, BLC, Eotaxin-1, Eotaxin-2, IP-10, and MMP1 was lower in metastatic compared to non-metastatic CRC; only AUC of MIF and MIP-1ß were > 0.7. Moreover, MDC, IL-7, MIF, IL-21, and TNF-α are positively associated with tolerance to CRC chemotherapy (CT) (AUC > 0.7), whereas IL-31, Fractalkine, Eotaxin-1, and Eotaxin-2 were positively associated with resistance to CT. TNF-α, BLC, Eotaxin-1, APRIL, and Tweak may be used as first-line early detection of CRC. The variable levels of MIF and MIP-1ß between metastatic and non-metastatic cases assign prognostic nature to these factors in CRC progression. Regarding tolerance to CT, MDC, IL-7, MIF, IL-21, and TNF-α are key when down-regulated or resistant to treatment is observed.

A multi-organ map of the human immune system across age, sex and ethnicity.

Understanding tissue biology's heterogeneity is crucial for advancing precision medicine. Despite the centrality of the immune system in tissue homeostasis, a detailed and comprehensive map of immune cell distribution and interactions across human tissues and demographics remains elusive. To fill this gap, we harmonised data from 12,981 single-cell RNA sequencing samples and curated 29 million cells from 45 anatomical sites to create a comprehensive compositional and transcriptional healthy map of the healthy immune system. We used this resource and a novel multilevel modelling approach to track immune ageing and test differences across sex and ethnicity. We uncovered conserved and tissue-specific immune-ageing programs, resolved sex-dependent differential ageing and identified ethnic diversity in clinically critical immune checkpoints. This study provides a quantitative baseline of the immune system, facilitating advances in precision medicine. By sharing our immune map, we hope to catalyse further breakthroughs in cancer, infectious disease, immunology and precision medicine.

Complication-related removal of totally implantable venous access port systems: Does the interval between placement and first use and the neutropenia-inducing potential of chemotherapy regimens influence their incidence? A four-year prospective study of 4045 patients.

BACKGROUND: Totally implantable venous access port systems are widely used in oncology, with frequent complications that sometimes necessitate device removal. The aim of this study is to investigate the impact of the time interval between port placement and initiation of chemotherapy and the neutropenia-inducing potential of the chemotherapy administered upon complication-related port removal. PATIENTS AND METHODS: Between January 2010 and December 2013, 4045 consecutive patients were included in this observational, single-center prospective study. The chemotherapy regimens were classified as having a low (<10%), intermediate (10-20%), or high (>20%) risk for inducing neutropenia. RESULTS: The overall removal rate due to complications was 7.2%. Among them, port-related infection (2.5%) and port expulsion (1%) were the most frequent. The interval between port insertion and its first use was shown to be a predictive factor for complication-related removal rates. A cut-off of 6 days was statistically significant (p = 0.008), as the removal rate for complications was 9.4% when this interval was 0-5 days and 5.7% when it was ≥6 days. Another factor associated with port complication rate was the neutropenia-inducing potential of the chemotherapy regimens used, with removal for complications involved in 5.5% of low-risk regimens versus 9.4% for the intermediate- and high-risk regimens (p = 0.003). CONCLUSION: An interval of 6 days between placement and first use of the port reduces the removal rate from complications. The intermediate- and high-risk for neutropenia chemotherapy regimens are related to higher port removal rates from complications than low-risk regimens.

Morphologic assessment of mandibular reconstruction by free fibula flap and donor-site functional impairment in a series of 23 patients.

INTRODUCTION: Micro-anastomosed free fibula flap is an attitude of choice in mandibular defect repair in oncology, enabling effective functional rehabilitation. The present study assessed donor and recipient site morphology and donor-site sequelae. PATIENTS AND METHODS: The study consecutively recruited patients undergoing mandibular resection with free fibula flap reconstruction in our centre between December 2003 and September 2008. Assessment on adapted scales was performed by two independent expert physicians and patient self-assessment. RESULTS: Out of 49 mandibular reconstructions performed in the centre over the 5-year study period, 23 patients free of recurrence were included. Satisfaction rates were 73% for the recipient site and 70% for the donor-site, with patient/expert agreement of 47% and 49.5% respectively. Donor-site impact was mainly in terms of reduced ankle range of motion (43% of cases) and flexion strength (39%) and discomfort in running (35%) and walking (26%). Risk factors for dissatisfaction were more than 5% weight loss at admission for recipient site dissatisfaction (patient, P=0.012; expert, P=0.046), and skin graft for donor-site dissatisfaction (patient, P=0.04; expert, P=0.035). CONCLUSION: Free fibula flap was associated with high satisfaction rates, but non-negligible donor-site impact.

Totally implantable venous access port systems and risk factors for complications: a one-year prospective study in a cancer centre.

BACKGROUND: Totally Implantable Venous Access Port Systems (TIVAPS) are widely used in oncology, but complications are frequent, sometimes necessitating device removal and consequently delays in chemotherapy. The aim of this study was to investigate possible risk factors for morbidity. METHODS: A total of 815 consecutive cancer patients (median age: 56.2 years [0.8-85.2]; 522 female) were enrolled in this observational, single-centre study between May 2nd 2006 and April 30th 2007. TIVAPS implantation involved principally cephalic or external jugular vein access. Patients were followed up for one year unless the device was removed earlier. RESULTS: The overall morbidity rate was 16.1% (131/815). Complications necessitated device removal in 55 patients a mean of 3.7 months [0.2-12.0] after implantation. These comprised TIVAPS-related infection (19), port expulsion (14), catheter migration (6), venous thrombosis (5), mechanical problems (3), skin disorders (2), pain (2), drug extravasation (2) infection unrelated to TIVAPS (1) and inflammation (1). No patient died during the study. The factor most strongly predictive of complications was the interval between insertion and first use of the TIVAPS, ranging from 0 to 135 days (median: 8.0 days). The morbidity rate was 24.4% when this interval was 0-3 days, 17.1% when it was 4-7 days and 12.1% when it exceeded 7 days (p < 0.01; Chi(2) test). The median interval was 6 days (0-53) and 8 days (0-135), respectively, in patients with and without complications (p < 0.001). CONCLUSION: To reduce complications, an interval of at least 8 days between placement of the TIVAPS and its first use may be advisable.

Cancer-associated hypercalcaemia in squamous-cell malignancies: a survival and prognostic factor analysis.

The aim of this study is to analyse survival and prognostic factors in patients diagnosed with squamous cell carcinoma (SCC) presenting a first episode of cancer-associated hypercalcaemia (CAH). Retrospectively, the authors reviewed data from 220 patients with biopsy proven SCC who presented a first episode of CAH. They were treated in a single centre between 1995 and 2007. The survival analyses were done using the Kaplan-Meier method and Cox analysis. The primary endpoint was the overall survival from the date of hypercalcaemia episode. Median age was 55 years. Median survival was 64 days (1-197). Three independent prognostic factors were identified: brain metastasis (hazard ratio (HR)=2.58 CI (1.03-6.45)), corrected calcaemia>3 mmol/l (HR=1.45 CI (1.05-2.01)) and hypoalbuminaemia (HR=1.48 CI (1.07-2.04)). Using these factors, the authors performed a bedside prognostic score. In conclusion, median survival in patients diagnosed with SCC and CAH is extremely poor. The bedside prognostic score that the authors developed can help to anticipate patients' prognosis and adapt the treatment. This score needs to be validated on an independent cohort.

[New challenge in head and neck oncology surgery: the transoral robotic surgery]. / Nouveaux aspects télérobotiques en cancérologie tête et cou.

Robotic assisted surgery is a new field of developing program for many specialties. As to head and neck oncology, the new procedure potentially offers alternatives to conventional surgery with decreased morbidity. The aim of this article is a description of the state of the art via a review of the literature. We emphasize limits and future prospects on this topic with a special focus on dependability. Transoral robotic surgery (TORS) is a promising surgical procedure contingent on the development of new associated functions like an image guidance system or a force feedback control. The good developing of this new tool will also depend on the quality of clinical works and research programs.

The free vascularized flap and the pectoralis major pedicled flap options: comparative results of reconstruction of the tongue.

Reconstruction after extensive resection of the tongue remains a surgical challenge. Free soft-tissue transfer is now favored for head and neck reconstruction following cancer resection. However, the choice of either free tissue transfer (FTT) or of the pedicled Pectoralis Major Musculocutaneous Flap (PMMF), the workhorse in head and neck reconstruction, remains controversial. The purpose of this study is to assess the post-operative outcomes after radical ablative surgery and reconstruction for patients with a tongue cancer. We conducted a retrospective comparison of two different reconstruction techniques. From January 2000 to December 2006, 70 consecutive patients with tongue cancer had been treated with curative intent by extensive ablative surgery and soft-tissue reconstruction. Sixty percent of tumors were T3 or T4. We compared the post-operative outcomes of both populations: 25 patients underwent FTT and 45 underwent pedicled PMMF. Fifty-seven men and 13 women with a mean age of 55 years constitute the study population. The two groups were comparable in terms of age, gender, and addiction. The choice of flap technique was independent of the ASA scale (p=1.00), the weight of comorbidities (p=0.13), previous radiation therapy (p=0.09), the T-stage (p=0.44) or N-stage (p=0.21). Apart from the rate of flap necrosis, which occurred significantly more often in the PMMF group (p=0.02), post-operative complication rates did not differ between the two groups. The success rate of FTT was 96% (24/25). The duration of the post-operative stay was longer after use of the pedicled flap technique, but the difference did not reach statistical significance (mean duration in days: 23.2 vs. 18.1; p=0.10). Both groups did not differ as regards duration of use of a feeding tube (p=0.84) or of tracheostomy (p=0.54). Local disease-free survival was also similar (p=0.65). The two groups were similar in terms of patients' characteristics. The reliability of free flaps was higher than that of PMMF. The assessment of our practice in the case of extensive tongue defect suggests that reconstruction with free soft-tissue transfer, whenever feasible, should be the first-choice treatment option.

[Echinococcosis of the rib with epidural extension]. / Kyste hydatique costovertébral : pathologie bénigne ou maligne ?

Osseous hydatidosis, especially when located in the rib, is a very rare disease. Less than 50 cases of costal echinococcosis have been reported in the literature to date. The authors report a case of echinococcosis of the rib with epidural extension in a 76-year-old patient presenting paraparesis. In addition, the patient presented a large posterior and thoracic soft tissue mass measuring about 30 centimetres in diameter. A chest x-ray, a CT thoracic scan and an MRI of the dorsal spine were performed. The imaging suggested echinococcosis of the rib with epidural extension. The cyst was completely resected. Histopathology of the resected specimen confirmed the diagnosis of echinococcosis. The patient died due to postoperative complications. Accurate presurgical diagnosis allows for appropriate management and helps eradicate the disease. This also prevents the dissemination of parasites and further complications.

CD26 (dipeptidyl-peptidase IV)-dependent recruitment of T cells in a rat asthma model.

CD26 truncates several chemokines as well as neuropeptides and influences immune responses via modulation of cell adhesion and T cell activation, suggesting an involvement of CD26 in asthmatic and airway inflammation. Therefore, Fischer 344 (F344), Brown Norway (BN) and Lewis (LEW) rat strains, which differ in their CD26-like enzymatic activity, were compared using an asthma model. Additionally, two CD26-deficient mutant F344 rat substrains were included and compared to the wild-type F344 substrain. Immunization was performed twice with ovalbumin (OVA), and 2 weeks later the rats were challenged with OVA intratracheally Flow cytometry (FACS) analysis of different leucocyte subsets as well as enzyme-linked immunosorbent assay (ELISA) for IgE levels in the blood and bronchoalveolar lavage (BAL) were performed 24 h after challenge. LEW rats with the lowest CD26 activity among the rat strains investigated here displayed significantly reduced CD4+ T cell numbers in the BAL compared to wild-type F344 and BN rats. Moreover, in asthma, the ratio of CD26+ to CD26- T cell receptor (TCR)-positive cells increased significantly in F344 and LEW but not BN rats. Most intriguingly, in both CD26-deficient F344 rat substrains the number of CD4+ T lymphocytes was markedly reduced compared to wild-type F344. The decrease in T cell recruitment observed in the CD26-deficient rats was associated with significantly reduced OVA-specific IgE-titres. This is the first report to show a remarkably reduced T cell recruitment in rat strains that either lack or exhibit reduced CD26-like enzymatic activity, suggesting a role for CD26 in the pathogenesis of asthma via T cell-dependent processes such as antibody production.

Differential effects of neuropeptide Y (NPY) on leukocyte subsets in the blood: mobilization of B-1-like B-lymphocytes and activated monocytes.

Sympathetic nervous system activation mobilizes leukocytes but it is unknown whether the concomitant neuropeptide Y (NPY)-release also alters blood leukocyte counts. Using chronic intravenous (i.v.) cannulation of freely moving rats and flow cytometry, time-, dose- and subset-specific effects of NPY on blood leukocytes were investigated 1-15 min after injection: High-dose NPY increases leukocytes numbers by preferentially mobilizing CD4(+) T-cells, activated NKR-P1A(+) monocytes and NK-cells. Low-dose NPY significantly decreases B-lymphocyte and NK-cell numbers. Furthermore, NPY dose-dependently mobilizes a previously undetected IgM(low)CD5(+)CD11b(+) B-cell subpopulation in rats ("B1-like" B-lymphocytes). These data suggest a role for the sympathetic neurotransmitter NPY in neuroimmune alterations in vivo.