Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group.

BACKGROUND: Upfront primary tumor resection (PTR) has been associated with longer overall survival (OS) in patients with synchronous unresectable metastatic colorectal cancer (mCRC) in retrospective analyses. The aim of the CAIRO4 study was to investigate whether the addition of upfront PTR to systemic therapy resulted in a survival benefit in patients with synchronous mCRC without severe symptoms of their primary tumor. PATIENTS AND METHODS: This randomized phase III trial was conducted in 45 hospitals in The Netherlands and Denmark. Eligibility criteria included previously untreated mCRC, unresectable metastases, and no severe symptoms of the primary tumor. Patients were randomized (1 : 1) to upfront PTR followed by systemic therapy or systemic therapy without upfront PTR. Systemic therapy consisted of first-line fluoropyrimidine-based chemotherapy with bevacizumab in both arms. Primary endpoint was OS in the intention-to-treat population. The study was registered at ClinicalTrials.gov, NCT01606098. RESULTS: Between August 2012 and February 2021, 206 patients were randomized. In the intention-to-treat analysis, 204 patients were included (n = 103 without upfront PTR, n = 101 with upfront PTR) of whom 116 were men (57%) with median age of 65 years (interquartile range 59-71 years). Median follow-up was 69.4 months. Median OS in the arm without upfront PTR was 18.3 months (95% confidence interval 16.0-22.2 months) compared with 20.1 months (95% confidence interval 17.0-25.1 months) in the upfront PTR arm (P = 0.32). The number of grade 3-4 events was 71 (72%) in the arm without upfront PTR and 61 (65%) in the upfront PTR arm (P = 0.33). Three deaths (3%) possibly related to treatment were reported in the arm without upfront PTR and four (4%) in the upfront PTR arm. CONCLUSIONS: Addition of upfront PTR to palliative systemic therapy in patients with synchronous mCRC without severe symptoms of the primary tumor does not result in a survival benefit. This practice should no longer be considered standard of care.

Evaluation of sex hormone profile and semen parameters in acromegalic male patients.

OBJECTIVE: To investigate the changes in semen quality and bioavailable testosterone concentrations in acromegalic male patients according to their disease activity and compare them with patients with non-functional pituitary adenoma (NFA) and healthy controls (HC). METHODS: Twenty-four acromegalic patients with active disease, 22 acromegalic patients in remission, 10 HCs, and 10 patients with NFA were included. RESULTS: Total and calculated bioavailable testosterone concentrations were lower in patients with pituitary disease. Patients with acromegaly had more severely impaired total testosterone levels and semen parameters in comparison to HCs and patients with NFA. The degree of impairment was more prominent in acromegalic patients with active disease than acromegalic patients in remission. Acromegalic patients in remission had residual impairments in both semen quality and testosterone concentrations. Patients with NFA had the lowest concentrations of calculated bioavailable testosterone, followed by acromegalic patients with active disease and acromegalic patients in remission. Increasing growth hormone (GH) levels were found to be associated with both more severely impaired semen quality and androgen concentrations. CONCLUSION: Growth hormone hypersecretion can disturb reproductive biology and thereof semen quality. The reduction in semen quality and androgen levels may not fully recover upon disease control. Clinicians should be aware of the increased risk of impaired semen parameters and reduced total/bioavailable levels in acromegalic patients, especially in the setting of active disease.

Local recurrence rate in a national Danish patient cohort after curative treatment for rectal cancer.

AIM: Several trials have shown that preoperative (chemo)radiotherapy (CRT) reduces local recurrence rates (LRRs) in rectal cancer (RC). The use of CRT varies greatly between countries. It is unknown whether the restrictive use of CRT in Denmark results in a higher LRR relative to other countries. The aim was to evaluate the LRR in a national Danish consecutive cohort of patients with RC. METHODS: All data from patients with RC in Denmark in 2009-2010 who were operated on with curative intent were retrieved from the Danish Colorectal Cancer Group database. Patients with metastases at the time of diagnosis, patients with synchronous colon cancer, and patients, in whom only local surgical procedures were performed, were excluded. In total, 1633 patients met the inclusion criteria. Clinical follow-up was at least five years with a cut-off date of 31 December 2015. RESULTS: Clinical follow-up was 5.4 years (median) with an interquartile range of 4.5-6.1 years. Of all included patients, 479 (29%) were treated with preoperative long-course CRT. Local recurrence was found in 68 patients, resulting in an LRR of 4.2%, and 182 (11%) patients developed distant metastases. Five-year overall survival was 74% (95% CI: 71.64-75.91). CONCLUSIONS: Five-year follow-up of curatively treated patients with RC in Denmark revealed a low LRR. This figure is identical to those reported in other Nordic countries, despite Denmark's considerably stricter guidelines for CRT. The obtained results justify the currently adopted restrictive use of preoperative CRT in Denmark.

Venous thrombosis in pancreaticobiliary tract cancer: outcome and prognostic factors.

BACKGROUND: The differences in outcome among cancer patients with incidental vs. symptomatic venous thromboembolism (VTE) are unknown. In this study, patients with extrahepatic pancreaticobiliary tract cancer (PBC) were selected for a prospective cohort study between February 2008 and February 2011. METHODS: At the time of cancer diagnosis, all patients were examined for deep vein thrombosis with bilateral compression ultrasonography (biCUS). Computed tomography pulmonary angiography was also performed to diagnose pulmonary embolisms. After inclusion, the patients were followed up with clinical examinations, blood collections, and biCUS. RESULTS: A total of 121 PBC patients were enrolled. At the time of cancer diagnosis, 15 patients had experienced a VTE (12.4%, 95% confidence interval [CI] 7.1-19.6), including six symptomatic and nine incidental cases. A total of 25 first-time VTE events were identified (20.7%; 95% CI 13.8-29.0). Patients with a VTE had reduced survival, with a median overall survival (OS) of 4.4 months (95% CI 2.2-11.5). The median OS of the patients with incidental VTE was 3.0 months (95% CI 0.1-15.0), which was not different from the median OS of the patients with symptomatic VTE (5.0 months; 95% CI 2.1-14.5). The median OS was 11.9 months (95% CI 8.1-14.7) in the PBC patients with no VTEs. CONCLUSION: The occurrence of a VTE event in a PBC patient within the first months of the disease is associated with significantly increased mortality.

[Preventive strategies against infections in autologous bone marrow transplantation]. / Infektionsstrategi ved autolog knoglemarvstransplantation.

The routine microbial surveillance, the prophylatic antibiotic regime and the management of infections were retrospectively evaluated in 26 autologous bone marrow transplantation episodes. The surveillance specimens indicated that ciprofloxacin prophylaxis was effective in minimising gram-negative functions. The comparison between specimens taken before and during the granulocytopenic period showed a shift towards more yeast, otherwise there were no big differences. The surveillance specimen could not identify the causative organisms in case of fever. The proven infections comprised four cases of bacteriaemia and one case of gastro-enteritis. Two patients died from disseminated Aspergillus infection not diagnosed prior to death. In 11 episodes the cause of fever remained unknown. Both fungal infections were related to nearby building construction work. None of the patients with bacterial infections were in a serious clinical condition. In the future the number of routine microbial surveillance specimens will be reduced. The aim of surveillance will be to monitor the potential occurrence of fluoroquinolone resistance, and more attention will be paid to possible fungal infections. The antibacterial policy will be continued.