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  • br Discussion br This study on men

    2020-03-24


    Discussion
    This study on 104 men treated for rectal cancer demonstrates that the risk of severe postoperative adverse events is related to radiation-induced primary testicular failure, displayed by preop-erative decrease in T levels and increase in LH/T-ratio.
    We have previously demonstrated that RT in men treated for rectal cancer leads to a dose-dependent primary testicular failure, attributed to radiation-induced Leydig cell dysfunction [20]. Interestingly, this study clearly indicates that the decline in T due to primary testicular failure after RT is associated with severe post-operative AE. Other predictors/signs of primary testicular failure, the testicular exposure to radiation and the consecutive increase in LH, were not found to be associated with severe postoperative AE by themselves. Collectively, these data suggest that the periopera-tive T level is an important factor regarding susceptibility for severe postoperative AE. The parent study data includes different types of RT and varying time to surgery. Therefore, it is not possible to distinguish if impaired T production is due to immediate radiation-induced Leydig cell damage or due to pathological response to hypothalamic-pituitary-gonadal axis stimulation. The radiation dose was similar between groups, which may point towards an individual vulnerability to radiation and is reinforced by the
    Please cite this article as: Tapper J et al., Acute primary testicular failure due to radiotherapy increases risk of severe postoperative adverse events in rectal cancer patients, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2019.07.023
    4 J. Tapper et al. / European Journal of Surgical Oncology xxx (xxxx) xxx
    Table 1
    Clinical characteristics.
    Clavien 0-2 Clavien 3þ p
    Number of participants 78
    ASA-score
    No. of comorbidities
    Current smoker
    Radiological tumor stage
    Radiological RGX-104 node status
    Neoadjuvant treatment
    Type of resection
    Notes: Continuous variable reported as median (range), Categorical data reported as frequency (percentage), * ¼ Fisher's exact test, y ¼ Wilcoxon rank-sum test, ASA ¼ American Society of Anesthesiologists, Gy ¼ Gray.
    Table 2
    Hormones and laboratory markers.
    Clavien 3þ
    Baseline hormones
    p
    Testosterone (nmol/L)
    Free testosterone (pmol/L)
    Luteinizing Hormone (IU/L)
    LH/T-ratio
    Preoperative hormones
    Testosterone (nmol/L)
    Free testosterone (nmol/L)
    Luteinizing Hormone (IU/L)
    LH/T-ratio
    Laboratory markers
    Preoperative
    C-reactive protein
    White cell blood count
    Albumin
    Postoperative, day 1 after surgery
    White cell blood count, Units x 10 /L
    Albumin, g/L
    Notes: Continuous variable reported as median (range), Categorical data reported as frequency (percentage) y ¼ Wilcoxon rank-sum test, * ¼ Fischer's exact test.
    Please cite this article as: Tapper J et al., Acute primary testicular failure due to radiotherapy increases risk of severe postoperative adverse events in rectal cancer patients, European Journal of Surgical Oncology, https://doi.org/10.1016/j.ejso.2019.07.023
    J. RGX-104 Tapper et al. / European Journal of Surgical Oncology xxx (xxxx) xxx 5
    Table 3
    Longitudinal regression analysis of primary testicular failure after preoperative radiotherapy for rectal cancer on severe postoperative adverse events. All models are adjusted for elapsed time between start of RT and surgery.
    Markers or predictors or for testicular damage.
    Surgical complications, Clavien-Dindo grade 3þ
    Mean change in preoperative hormones and TD Odds Ratio for Severe AE 95% Confidence interval p
    Mean change in preoperative hormones and TD (additionally adjusted for age, ASA & BMI)
    Notes: TD ¼ Cumulative mean testicular radiation dose. AE ¼ postoperative adverse events graded Clavien-Dindo 3 or more. ASA ¼ The American Society of Anesthesiologists physical status classification. BMI ¼ Body Mass Index.