The recurrence rate of colorectal liver metastases (CRLM) patients treated with curative intent is above 50%. Standard of care surveillance includes intensive computed tomographic (CT) imaging as well as carcinoembryonic antigen (CEA) measurements. Nonetheless, relapse detection often happens too late to resume curative treatment. This longitudinal cohort study enrolled 115 patients with plasma samples (N = 439) prospectively collected before surgery, postoperatively at day 30 and every third month for up to 3 years. Droplet digital PCR (ddPCR) was used to monitor serial plasma samples for somatic mutations. Assessment of ctDNA status either immediately after surgery, or serially during surveillance, stratified the patients into groups of high and low recurrence risk (hazard ratio [HR], 7.6; 95% CI, 3.0‐19.7; P < .0001; and HR, 4.3; 95% CI, 2.3‐8.1; P < .0001, respectively). The positive predictive value (PPV) of ctDNA was 100% in all postoperative analyses. In multivariable analyses, postoperative ctDNA status was the only consistently significant risk marker associated with relapse (P < .0001). Indeterminate CT findings were observed for 30.8% (21/68) of patients. All patients (9/21) that were ctDNA positive at the time of the indeterminate CT scan later relapsed, contrasting 42.6% (5/12) of those ctDNA negative (P = .0046). Recurrence diagnoses in patients with indeterminate CT findings were delayed (median 2.8 months, P < .0001). ctDNA status is strongly associated with detection of minimal residual disease and early detection of relapse. Furthermore, ctDNA status can potentially contribute to clinical decision‐making in case of indeterminate CT findings, reducing time‐to‐intervention.

Paroxetine, a new, potent and selective serotonin (5-HT) uptake inhibitor has been evaluated in an open study for its clinical effect as well as its effect on the 5-HT concentration in whole blood in 19 patients with depressive illness. Paroxetine was administered in daily doses of 20 to 60 mg. The global evaluation after six to eight weeks showed a marked improvement in 11 patients, a moderate improvement in four and no change in four patients. Assessment with the Hamilton Rating Scale for Depression in ten patients showed a reduction from a mean score of 22.7 to 6.6 in six weeks. Maximal reduction was, however, first seen in three of the patients after 8 to 12 weeks. No correlation between the antidepressant effect and plasma concentrations of paroxetine was found. The only side effects noted with paroxetine were that two patients complained of dry mouth in the beginning of the treatment and a further patient experienced a burning sensation together with periodical light headache. Generally laboratory examinations did not show any trend towards pathological values except in one patient, where a moderate leucopenia was observed. Crista puncture/biopsy showed, however, no specific bone marrow reaction. The 5-HT concentration in whole blood was reduced to about 0.02 micrograms/ml indicating a total depletion of 5-HT from the thrombocytes. The present study indicates that paroxetine possesses a good antidepressive effect in combination with a very low frequency of side effects.

Introduction: We sought to develop and externally validate a novel nomogram to predict recurrence and long-term prognosisof patients undergoing curative liver resection for neuroendocrine liver metastasis (NELM). Methods: Patients who underwent curative liver resection for NELM were identified from an international multicenter database between 1980-2015. A nomogram to predict recurrence was developed and validated externally. Results: Among 279 patients with NELM who underwent resection, multivariable analysis identified primary tumor location(pancreatic vs. others, HR 2.1, 95% CI 1.3-3.4), tumor grade(moderate vs. well, HR 1.9, 95% CI 1.1-3.1; poor vs. well, HR 1.6, 95% CI 0.7-3.3), lymphatic metastasis (HR 2.6, 95% CI 1.4-4.6) and the type of hepatectomy(major resection vs. parenchymal-sparingresection, HR 0.3, 95% CI 0.1-0.6) to be independently associated with recurrence-free survival (RFS). A weighted nomogram was constructed based on the beta-coefficients of the final multivariable model. The nomogram demonstrated a good ability to predict risk of recurrence in both test and external validation cohorts (c-index; test cohort: 0.754; validation cohort: 0.748).Specifically, the calibrated nomogram predicted survival that closely corresponded to actual survival with a good net benefit for most threshold probabilities especially between 20% to 60% in both the development and validation cohorts. Conclusions: A novel nomogram predicted recurrence-free survival rates for patients with NELM with excellent discrimination and calibration. The proposed nomogram may be helpful to discuss with patients their anticipated prognosis following resection of NELM.