Delta-6 desaturase FADS2 is a tumor-promoting factor in cholangiocarcinoma.

Cholangiocarcinoma is a fatal disease with limited therapeutic options. We screened genes required for cholangiocarcinoma tumorigenicity and identified FADS2, a delta-6 desaturase. FADS2 depletion reduced in vivo tumorigenicity and cell proliferation. In clinical samples, FADS2 was expressed in cancer cells but not in stromal cells. FADS2 inhibition also reduced the migration and sphere-forming ability of cells and increased apoptotic cell death and ferroptosis markers. Lipidome assay revealed that triglyceride and cholesterol ester levels were decreased in FADS2-knockdown cells. The oxygen consumption ratio was also decreased in FADS2-depleted cells. These data indicate that FADS2 depletion causes a reduction in lipid levels, resulting in decrease of energy production and attenuation of cancer cell malignancy.

Efficacy of an enhanced recovery after surgery pathway to manage pain, nausea and vomiting after head and neck surgeries with free tissue transfer reconstruction.

BACKGROUND: Pain and post-operative nausea and vomiting are the main factors that impair the quality of recovery after surgery. Very few reports have analyzed patient-reported outcomes to investigate the efficacy of an enhanced recovery after surgery protocol to alleviate these symptoms after head and neck surgeries with free tissue transfer reconstruction. METHODS: We investigated post-operative pain and post-operative nausea and vomiting in 47 patients who underwent head and neck surgeries with free tissue transfer reconstruction with enhanced recovery after surgery support between February 2021 and August 2022. Patient-reported outcomes were assessed using the visual analog scale and Japanese version of the Quality of Recovery-40. RESULTS: Significant increases in the mean visual analog scale scores for pain and post-operative nausea and vomiting were observed only on post-operative Day 1 compared with preoperative values (pain: 3.19 ± 2.78 vs. 1.96 ± 2.42, P = 0.0408; post-operative nausea and vomiting: 1.52 ± 2.09 vs. 0.54 ± 1.37, P = 0.0194). From post-operative Day 2, there were no significant differences between the pre- and post-operative visual analog scale scores, and no significant increases in the incidences of moderate or severe pain and post-operative nausea and vomiting compared with preoperatively. The Japanese version of the Quality of Recovery-40 score for post-operative pain showed no significant deterioration compared with preoperatively, while the Japanese version of the Quality of Recovery-40 score for post-operative nausea and vomiting showed significant deterioration compared with the preoperative value on post-operative Days 2, 4 and 7. CONCLUSIONS: The visual analog scale and Japanese version of the Quality of Recovery-40 scores for post-operative pain and visual analog scale score for post-operative nausea and vomiting suggested that the enhanced recovery after surgery strategy favorably controlled pain and post-operative nausea and vomiting after head and neck surgeries with free tissue transfer reconstruction. However, as the post-operative Japanese version of the Quality of Recovery-40 score for post-operative nausea and vomiting was lower than the preoperative value, there is still a need for further improvement of the enhanced recovery after surgery pathway.

Postoperative serum interleukin-6 level as a risk factor for development of hyperactive delirium with agitation after head and neck surgery with free tissue transfer reconstruction.

OBJECTIVE: Occurrence of hyperactive postoperative delirium (POD) with agitation after head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) is associated with the risk of life-threatening complications. The relationships between occurrence of hyperactive POD after HNS-FTTR and inflammatory markers reflecting the surgical stress response, represented by postoperative interleukin-6 levels, are not fully understood. METHODS: A retrospective study was conducted on 221 consecutive patients who underwent HNS-FTTR at our department between September 2016 and December 2021. Potential risk factors for POD were examined, including age, operation time, intraoperative blood loss, and postoperative serum levels of blood parameters such as interleukin-6, C-reactive protein, and neutrophil-to-lymphocyte ratio. RESULTS: Hyperactive POD with agitation was observed in 54 subjects (24.4%). The postoperative hospital stay in the POD group was significantly longer than that in the non-POD group (median: 32.5 days vs. 28 days; p=0.0129). Multivariate logistic regression analysis identified age (in years) (odds ratio: 1.102; p<0.0001), operation time (min) (odds ratio: 1.004; p=0.0359), and postoperative serum interleukin-6 level (pg/mL) (odds ratio: 1.005; p=0.0384) as significant risk factors for development of POD. In a receiver operating characteristic curve and area under the curve analysis, the cut-off value for postoperative serum interleukin-6 level to predict POD development was 82.5 pg/mL. The postoperative serum interleukin-6 ≥82.5 pg/mL group developed hyperactive POD with agitation significantly more often than the postoperative serum IL-6 <82.5 pg/mL group (odds ratio: 4.400; p<0.0001). The postoperative serum IL-6 ≥82.5 pg/mL group also had significantly longer postoperative hospital stay (41.58 ± 33.42 days vs. 31.73 ± 22.89 days; p=0.0151), older age (68.60 ± 9.99 years vs. 64.30 ± 12.58 years; p=0.0054), and longer operation time (625.4 ± 114.05 min vs. 575.5 ± 98.73 min; p=0.0009) than the postoperative serum IL-6 <82.5 pg/mL group. CONCLUSION: Postoperative serum interleukin-6 level, as well as age and operation time, were identified as significant independent risk factors for development of hyperactive POD with agitation after HNS-FTTR. Inflammation is a potential target for the prevention and treatment of POD after HNS-FTTR.

Preoperative serum interleukin-6 level in head and neck cancer reflects systemic inflammatory response and is a predictor of postoperative prognosis.

BACKGROUND: The outcome of head and neck cancer has improved in recent years but survival is not yet satisfactory. Interleukin (IL)-6 is a representative inflammatory cytokine and inducer of systemic inflammatory response. It is not known whether preoperative serum level of IL-6 is a prognostic factor in head and neck cancer surgery. METHODS: We studied 181 consecutive patients who underwent head and neck surgery with free tissue transfer reconstruction (HNS-FTTR) between September 2016 and December 2020. Whether preoperative serum IL-6 level was a prognostic risk factor was retrospectively investigated by univariate and multivariate analyses. We also investigated the association between preoperative IL-6 level and representative systemic inflammatory response markers. RESULTS: The preoperative IL-6 ≥ 8 pg/mL group had a significantly worse prognosis than the preoperative IL-6 < 8 pg/mL group (overall survival [OS]: hazard ratio [HR] 3.098, P = 0.0006; disease-specific survival [DSS]: HR 3.335, P = 0.0008). In multivariate analysis, IL-6 ≥ 8 pg/mL and age ≥ 70 years were independent poor prognostic factors for OS (HR 1.860, P = 0.0435 and HR 1.883, P = 0.0233, respectively). The only independent poor prognostic factor for DSS was IL-6 ≥ 8 pg/mL (HR 2.052, P = 0.0329). Serum albumin was significantly lower and serum C-reactive protein and neutrophil-to-lymphocyte ratio were significantly higher in the IL-6 ≥ 8 pg/mL group than in the IL-6 < 8 pg/mL group (all P < 0.0001). CONCLUSIONS: Preoperative serum IL-6 level is an independent poor prognostic factor for both OS and DSS after HNS-FTTR, reflecting the degree of preoperative systemic inflammatory response.