Patterns and resectability of colorectal cancer recurrences: outcome study within the COLOFOL trial.

BACKGROUND: Improvements in surgery, imaging, adjuvant treatment, and management of metastatic disease have led to modification of previous approaches regarding the risk of recurrence and prognosis in colorectal cancer. The aims of this study were to map patterns, risk factors, and the possibility of curative treatment of recurrent colorectal cancer in a multimodal setting. METHODS: This was a cohort study based on the COLOFOL trial population of patients who underwent radical resection of stage II or III colorectal cancer. The medical files of all patients with recurrence within 5 years after resection of the primary tumour were scrutinized. Follow-up time was 5 years after the first recurrence. Primary endpoints were cumulative incidence, site, timing, and risk factors for recurrence, and rate of potentially curative treatment. A secondary endpoint was survival. RESULTS: Of 2442 patients, 471 developed recurrences. The 5-year cumulative incidence was 21.4 (95 per cent c.i. 19.5 to 23.3) per cent. The median time to detection was 1.1 years after surgery and 87.3 per cent were detected within 3 years. Some 98.2 per cent of patients who had potentially curative treatment were assessed by a multidisciplinary tumour board. A total of 47.8 per cent of the recurrences were potentially curatively treated. The 5-year overall survival rate after detection was 32.0 (95 per cent c.i. 27.9 to 36.3) per cent for all patients with recurrence, 58.6 (51.9 to 64.7) per cent in the potentially curatively treated group and 7.7 (4.8 to 11.5) per cent in the palliatively treated group. CONCLUSION: Time to recurrence was similar to previous results, whereas the 21.4 per cent risk of recurrence was somewhat lower. The high proportion of patients who received potentially curative treatment, linked to a 5-year overall survival rate of 58.6 per cent, indicates that it is possible to achieve good results in recurrent colorectal cancer following multidisciplinary assessment.

Chemoradiation induces upregulation of immunogenic cell death-related molecules together with increased expression of PD-L1 and galectin-9 in gastric cancer.

Surgery alone or combined with chemo- and/or radiation therapy remains the primary treatment for gastric cancer (GC) to date and immunotherapeutic tools such as monoclonal antibodies are only slowly being implemented. This is partly due to the fact that the immune microenvironment in GC during chemoradiation and other treatment modalities is still poorly understood. 7 gastric cancer (GC) cell lines were tested for their response to chemoradiation using 5-FU in combination with X-ray irradiation. We conducted flow cytometric analysis to determine the cells' ability to undergo immunogenic cell death (ICD) and their expression of the two immunosuppressive proteins programmed death-ligand 1 (PD-L1) and galectin-9 (Gal-9). We evaluated the overall immunogenicity of two cell lines (MKN7, MKN74) in co-culture experiments with human monocyte-derived dendritic cells (Mo-DCs). Chemoradiation induces distinct responses in different GC cell lines. We observe ICD in vitro in all tested GC cell lines in the form of calreticulin (CRT) translocation to the plasma membrane. As a resistance mechanism, these cells also upregulated Gal-9 and PD-L1. Mo-DC maturation experiments showed that GCs provoked the maturation of Mo-DCs after chemoradiation in vitro. The addition of α-PD-L1 blocking antibody further enhanced the immunogenicity of these cells while improving DC viability. Blocking Tim-3, as the main receptor for Gal-9, had no such effect. Our findings suggest that the benefits of chemoradiation can substantially depend on tumor subtype and these benefits can be offset by induced immune evasion in GC. Combination treatment using checkpoint inhibitors could potentially lead to enhanced immune responses and yield better patient outcomes.

Effects of intranasal ZnSO4 irrigation on olfactory and trigeminal cues.

Intranasal irrigation with ZnSO4 solutions is used for experimental induction of anosmia. It is, however, unknown whether the trigeminal nerve is affected by the treatment. One day after irrigation (concentrations investigated were between 0.05-1%) the ability of food finding, an olfactory cue, was decreased in a concentration-dependent manner. The trigeminal effect was investigated from a reflexively induced decrease in respiratory rate due to n-propanol exposure. No impairment occurred at 1% ZnSO4. Anosmia was also seen 2-3 h after an irrigation with solutions of 0.05-1% ZnSO4. At the same time, 0.2 and 1% solutions in themselves decreased the respiratory rate due to reflexes from the upper and lower respiratory tract. A conspicuous systemic effect can be ruled out as the Zn++ antidote, CaNa2EDTA, had no effect on the decrease. A direct activation of the trigeminal nerve due to a reaction with a thiol group may explain the effect from the upper airways.

Ventilation, CO2 production, and CO2 exposure effects in conscious, restrained CF-1 mice.

Respiratory rate (f), tidal volume (VT) and carbon dioxide production (VECO2) were measured in restrained, conscious CF-1 mice. Mean f +/- S.D. and mean VT +/- S.D. were 270 +/- 8 breaths/min. and 0.123 +/- 0.024 ml (STPD) for male, and 274 +/- 15 breaths/min. and 0.115 +/- 0.023 ml (STPD) for female mice, respectively. VECO2 was obtained from a rebreathing (closed loop) system. The maximum VECO2 (STPD) amounted to 95.5 +/- 15.4 ml/(kg min.) in males and to 72.7 +/- 4.2 ml/(kg min.) in females. The CO2 concentration in the closed loop system increased slowly during a 30 min. rebreathing period and reached a concentration of about 2.7%. No effect was seen on f and on VT. Dynamic (abrupt) exposure up to 10.3% CO2 had no effect on f in male mice, whereas VT increased from 112% (2.3% CO2) to 181% (10.3% CO2). The estimated O2 concentrations decreased from 20.5% to 18.7% with increasing CO2 exposure. The equivalent CO2 experiments with O2 kept at 16% by N2 administration showed that the lower O2 concentration added an additional drive on the respiratory centre.

Mucosolvan in the treatment of patients with primary Sjögren's syndrome. Results from a double-blind cross-over investigation.

Thirty-six patients with primary Sjögren's syndrome were randomized to Mucosolvan (60 mg X 2 daily) or placebo, in a double-blind cross-over study. Each period of treatment was 3 weeks with 1 week wash-out in between. None of the objective ophthalmological tests (Schirmer-1-test, break-up time, van Bijsterveld score, cornea sensitivity, appearance of nuclear chromatin in conjunctival epithelial cells, tear lysozyme) improved during the investigation period.

Contact sensitization to benzoyl peroxide following topical treatment of chronic leg ulcers.

Sixteen patients with chronic leg ulcers were treated with 10% benzoyl peroxide gel for 6 weeks. At the end of the treatment, patch tests with 2% benzoyl peroxide in petrolatum and 10% in a gel showed that nine patients (56%) had become sensitized. This high sensitization rate is in good accord with the results obtained by experimental investigations using human maximization tests and repeated insult patch tests. A strong sensitizer such as benzoyl peroxide should not be used in the routine treatment of chronic leg ulcers, despite its good healing effect.