Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment

Background: In solid organ transplant (SOT) recipients, transplant rejection during immune checkpoint inhibitor (ICI) treatment for cancer is a clinical problem. Donor-derived cell-free DNA (dd-cfDNA) can be detected in blood and is a sensitive biomarker for diagnosis of acute rejection in SOT recipients. To our best knowledge, this is the first case report of a kidney transplant recipient with advanced cancer treated with ICI who was monitored with dd-cfDNA. Case presentation: A 72-year old female with a long-standing renal transplant was diagnosed with advanced melanoma in 2018 and was treated with the anti-PD1 antibody nivolumab. Within 12 days after the first administration of nivolumab, dd-cfDNA ratio increased to 23%, suggesting allograft rejection. Her kidney transplant function deteriorated and acute rejection was confirmed by renal transplant biopsy. As the rejection could not be controlled despite immunosuppressive treatment, a transplant nephrectomy was necessary and haemodialysis was started. Immunological analysis of the renal explant showed infiltration of alloreactive, nivolumab-saturated, PD1+ cytotoxic T cells. After transplant nephrectomy, she experienced nivolumab-related toxicity and rapid disease progression. Conclusion: Clinicians prescribing ICIs should be aware that SOT recipients are a

Optimization of Wire-guided Technique With Bracketing Reduces Resection Volumes in Breast-conserving Surgery for Early Breast Cancer

Background: Wire-guided localization (WGL) of early breast cancer can be facilitated using multiple wires, which is called bracketing wire-guided localization (BWL). The primary aim of this study is to compare BWL and conventional WGL regarding minimization of resection volumes without compromising margin status. Secondly, BWL is evaluated as an alternative method for intraoperative ultrasound (US) guidance in poorly definable breast tumors on US. Patients and Methods: In this retrospective cohort study, patients with preoperatively diagnosed breast cancer undergoing wide local excision between January 2016 and December 2018 were analyzed. Patients with multifocal disease or neoadjuvant treatment were excluded from this study. Optimal resection with minimal healthy breast tissue removal was assessed using the calculated resection ratio (CRR). Results: BWL was performed in 17 (9%) patients, WGL in 44 (22%), and US in 139 (70%). The rate of negative margins was comparable in all 3 groups. The CRR was significantly smaller for BWL (0.6) than WGL (1.3) in tumors larger than 1.5 cm. Additionally, BWL (0.8) led to smaller CRRs than US (1.7). This could be explained by the high number of small tumors (≤ 1.5 cm) in the US group for which greater CRRs are obtained than for large tumors (> 1.5 cm) (1.9 vs. 1.4; P = .005). Conclusion: For breast tumors larger than 1.5 cm, BWL achieves more optimal resection volumes without compromising margin status compared with WGL. Moreover, BWL seems a suitable alternative to US in patients with poorly ultrasound-visible breast tumors and patients with a small tumor in a (large) breast. Bracketing wire-guided localization (BWL) to demarcate tumor borders can be used to minimize resection volumes in patients with breast cancer. The sample consisted of 17 patients treated with BWL and 44 patients treated with single wire-guided localization. BWL achieved smaller resection volumes than wire-guided localization without compromising margin status for breast tumors larger than 1.5 cm, which could potentially improve cosmetic outcomes

Electronic Health Program to Empower Patients in Returning to Normal Activities After General Surgical and Gynecological Procedures: Intervention Mapping as a Useful Method for Further Development

BACKGROUND: Support for guiding and monitoring postoperative recovery and resumption of activities is usually not provided to patients after discharge from the hospital. Therefore, a perioperative electronic health (eHealth) intervention ("ikherstel" intervention or "I recover" intervention) was developed to empower gynecological patients during the perioperative period. This eHealth intervention requires a need for further development for patients who will undergo various types of general surgical and gynecological procedures. OBJECTIVE: This study aimed to further develop the "ikherstel" eHealth intervention using Intervention Mapping (IM) to fit a broader patient population. METHODS: The IM protocol was used to guide further development of the "ikherstel" intervention. First, patients' needs were identified using (1) the information of a process evaluation of the earlier performed "ikherstel" study, (2) a review of the literature, (3) a survey study, and (4) focus group discussions (FGDs) among stakeholders. Next, program outcomes and change objectives were defined. Third, behavior change theories and practical tools were selected for the intervention program. Finally, an implementation and evaluation plan was developed. RESULTS: The outcome for an eHealth intervention tool for patients recovering from abdominal general surgical and gynecological procedures was redefined as "achieving earlier recovery including return to normal activities and work." The Attitude-Social Influence-Self-Efficacy model was used as a theoretical framework to transform personal and external determinants into change objectives of personal behavior. The knowledge gathered by needs assessment and using the theoretical framework in the preparatory steps of the IM protocol resulted in additional tools. A mobile app, an activity tracker, and an electronic consultation (eConsult) will be incorporated in the further developed eHealth intervention. This intervention will be evaluated in a multicenter, single-blinded randomized controlled trial with 18 departments in 11 participating hospitals in the Netherlands. CONCLUSIONS: The intervention is extended to patients undergoing general surgical procedures and for malignant indications. New intervention tools such as a mobile app, an activity tracker, and an eConsult were developed. TRIAL REGISTRATION: Netherlands Trial Registry NTR5686; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5686