Peritoneal metastases (PM) are common in patients with colorectal cancer. Patients with PM have a poor prognosis, and for those who are not eligible for cytoreductive surgery (CRS) with or without ...hyperthermic intraperitoneal chemotherapy (HIPEC), palliative chemotherapy is currently the only option. Recently, we conducted a phase I trial (INTERACT) in which irinotecan was administered intraperitoneally (IP) to 18 patients ineligible for CRS‐HIPEC. The primary objective was to evaluate covariates influencing the PK profile of irinotecan and SN‐38 after IP administration. Secondly, a population PK model was developed to support the further development of IP irinotecan by improving dosing in patients with PM. Patients were treated with IP irinotecan every 2 weeks in combination with systemic FOLFOX‐bevacizumab. Irinotecan and SN‐38 were measured in plasma (588 samples) and SN‐38 was measured in peritoneal fluid (267 samples). Concentration‐Time data were log‐transformed and analyzed using NONMEM version 7.5 using FOCE+I estimation. An additive error model described the residual error, with inter‐individual variability in PK parameters modeled exponentially. The final structural model consisted of five compartments. Weight was identified as a covariate influencing the SN‐38 plasma volume of distribution and GGT was found to influence the SN‐38 plasma clearance. This population PK model adequately described the irinotecan and SN‐38 in plasma after IP administration, with weight and GGT as predictive factors. Irinotecan is converted intraperitoneal to SN‐38 by carboxylesterases and the plasma bioavailability of irinotecan is low. This model will be used for the further clinical development of IP irinotecan by providing dosing strategies.
Purpose
The usefulness of restaging by magnetic resonance imaging (MRI) after chemoradiotherapy (CTx/RTx) in patients with locally advanced rectal cancer has not yet been established, mostly due to ...the difficult differentiation between viable tumor and fibrosis. MRI with dynamic contrast-enhanced (DCE) sequences may be of additional value in distinguishing malignant from nonmalignant tissue. The aim of this study was to assess the accuracy of tumor, nodal staging, and circumferential resection margin (CRM) involvement by MRI with DCE sequences after CTx/RTx.
Methods
The accuracies were assessed by MRI on T2-weighted magnetic resonance (MR) images with DCE sequences in patients with locally advanced rectal cancer after a long course of CTx/RTx. MR images were assessed by two independent radiologists.
Results
For tumor staging and CRM involvement, MRI with DCE sequences had an accuracy of 45 and 60 %, respectively. The accuracy for nodal staging was 93 %. On MRI, malignant lymph nodes had a median diameter of 8 mm (range, 4–18) and benign lymph nodes a median diameter of 4 mm (range, 3–11). A significant indicator for benign nodes was hypointensity on T2-weighted images
(p
< 0.001) and early complete arterial phase enhancement on DCE-weighted images (
p
< 0.001). A significant indicator for malignant nodes was heterogeneity on T2-weighted images (
χ
2
,
p
< 0.000) and early incomplete arterial phase enhancement on DCE (
p
< 0.001).
Conclusions
MRI with DCE is a useful tool for nodal staging after CTx/RTx. The addition of DCE sequences did not improve the accuracy of determining the tumor stage, CRM involvement, and in detecting complete response.
IntroductionRepetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients with isolated unresectable ...colorectal peritoneal metastases (PM) in several centres worldwide. However, little is known about its feasibility, safety, tolerability, efficacy, costs and pharmacokinetics in this setting. This study aims to explore these parameters in patients with isolated unresectable colorectal PM who receive repetitive ePIPAC-OX as a palliative monotherapy.Methods and analysisThis multicentre, open-label, single-arm, phase II study is performed in two Dutch tertiary referral hospitals for the surgical treatment of colorectal PM. Eligible patients are adults who have histologically or cytologically proven isolated unresectable PM of a colorectal or appendiceal carcinoma, a good performance status, adequate organ functions and no symptoms of gastrointestinal obstruction. Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled ePIPAC-OX (92 mg/m2 body surface area (BSA)) with intravenous leucovorin (20 mg/m2 BSA) and bolus 5-fluorouracil (400 mg/m2 BSA) every 6 weeks. Four weeks after each procedure, patients undergo clinical, radiological and biochemical evaluation. ePIPAC-OX is repeated until disease progression, after which standard palliative treatment is (re)considered. The primary outcome is the number of patients with major toxicity (grade ≥3 according to the Common Terminology Criteria for Adverse Events v4.0) up to 4 weeks after the last ePIPAC-OX. Secondary outcomes are the environmental safety of ePIPAC-OX, procedure-related characteristics, minor toxicity, postoperative complications, hospital stay, readmissions, quality of life, costs, pharmacokinetics of oxaliplatin, progression-free survival, overall survival, and the radiological, histopathological, cytological, biochemical and macroscopic tumour response.Ethics and disseminationThis study is approved by an ethics committee, the Dutch competent authority and the institutional review boards of both study centres. Results are intended for publication in peer-reviewed medical journals and for presentation to patients, healthcare professionals and other stakeholders.Trial registration number NCT03246321, Pre-results; ISRCTN89947480, Pre-results; NTR6603, Pre-results; EudraCT: 2017-000927-29, Pre-results.
Background
Bilateral adrenalectomy (BLA) is a treatment option to alleviate symptoms in patients with ectopic Cushing’s syndrome (ECS) for whom surgical treatment of the responsible nonpituitary ...tumor is not possible. ECS patients have an increased risk for complications, because of high cortisol levels, poor clinical condition, and metabolic disturbances. This study aims to evaluate the safety and long-term efficacy of endoscopic BLA for ECS.
Methods
From 1990 to present, 38 patients were diagnosed and treated for ECS in the Erasmus University Medical Center, a tertiary referral center. Twenty-four patients were treated with BLA (21 endoscopic, 3 open), 9 patients were treated medically, and 5 patients could be cured by complete resection of the adrenocorticotropic hormone (ACTH)-producing tumor. The medical records were retrospectively reviewed and entered into a database. For evaluation of the efficacy of BLA, preoperative biochemical and physical symptoms were assessed and compared with postoperative data.
Results
Endoscopic BLA was successfully completed in 20 of the 21 patients; one required conversion to open BLA. Intraoperative complications occurred in two (10%) patients, and postoperative complications occurred in three (14%) patients. Median hospitalization was 9 (2–95) days, and median operating time was 246 (205–347) min. Hypercortisolism was resolved in all patients. Improvements of hypertension, body weight, Cushingoid appearance, impaired muscle strength, and ankle edema were achieved in 87, 90, 65, 61, and 78% of the patients, respectively. Resolution of diabetes, hypokalemia, and metabolic alkalosis was achieved in 33, 89, and 80%, respectively.
Conclusion
Endoscopic BLA is a safe and effective treatment for patients with ectopic Cushing’s syndrome.
Background Colorectal cancer (CRC) is among the most frequently diagnosed cancers. Approximately 20-30% of stage I-III CRC patients develop a recurrent tumour or metastases after curative surgical ...resection. Post-operative follow-up is indicated for the first five years after curative surgical resection. As intensified follow-up after curative surgical resection has shown no effect on survival, patient organisations and policy makers have advocated for a more patient-centred approach to follow-up. The objective of this study is to successfully implement patient-led, home-based follow-up (PHFU) in six hospitals in The Netherlands, with as ultimate aim to come to a recommendation for a patient-centred follow-up schedule for stage I-III CRC patients treated with surgical resection with curative intent. Methods This study is designed as a stepped-wedge cluster-randomised trial (SW-CRT) in six participating centres. During the trial, three centres will implement PHFU after six months; the other three centres will implement PHFU after 12 months of inclusion in the control group. Eligible patients are those with pT2-4N0M0 or pT1-4N1-2M0 CRC, who are 18 years or older and have been free of disease for 12 months after curative surgical resection. The studied intervention is PHFU, starting 12 months after curative resection. The in-hospital, standard-of-care follow-up currently implemented in the participating centres functions as the comparator. The proportion of patients who had contact with the hospital regarding CRC follow-up between 12-24 months after curative surgical resection is the primary endpoint of this study. Quality of life, fear of cancer recurrence, patient satisfaction, cost-effectiveness and survival are the secondary endpoints. Discussion The results of this study will provide evidence on whether nationwide implementation of PHFU for CRC in The Netherlands will be successful in reducing contact between patient and health care provider. Comparison of PROMs between in-hospital follow-up and PHFU will be provided. Moreover, the cost-effectiveness of PHFU will be assessed. Trial registration Dutch Trail Register (NTR): NL9266 (Registered on January 1st, 2021). Keywords: Follow-up studies, Colorectal neoplasms, Surveillance, Telemedicine, Aftercare
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim
Guidance throughout the entire process of ostomy surgery is warranted to improve self‐management and reduce healthcare consumption. The aim of this study was to develop an interactive application ...to educate patients scheduled for ostomy surgery and to evaluate patient satisfaction and implementation.
Method
A literature study and a cross‐sectional study among patients and nurses was performed to evaluate the relevance of different topics (e.g., ostomy materials, self‐care, complications, impact) for an interactive application in ostomy surgery. The interactive application, StoManager, was developed in collaboration with patients and healthcare providers. The implementation of the application was evaluated among 30 patients scheduled for ostomy surgery to investigate usability, patient satisfaction, compliance, the need for home nursing care services, and the number of contact moments with the ostomy nurse.
Results
StoManager contained all topics considered relevant by patients and healthcare providers, including information on ostomy surgery, ostomy self‐care and ostomy‐related complications. Patient‐reported outcome measures were incorporated to monitor the patient's health status during treatment. The usability scores of StoManager were above average. Patients rated StoManager with an overall score of 7.5 (SD 1.5) out of 10. The response rate to the patient‐reported outcome measures was 79.3%. At discharge, 28/30 (93.3%) patients did not need home nursing care services for ostomy care.
Conclusions
An interactive application to support patients throughout the entire process of ostomy surgery is feasible. Patients were satisfied with StoManager and its usability, which might result in improved self‐management and decreased healthcare consumption. A more patient‐specific approach could further improve the perceived quality and value of the application.
Abstract Surgery plays an important role in the treatment of patients with limited metastatic disease of colorectal cancer (CRC). Long term survival and cure is reported in 20-50% of highly selected ...patients with oligometastatic disease who underwent surgery. This paper describes the role of surgery of the primary tumour in patients with unresectable stage IV colorectal cancer. Owing to the increased efficacy of chemotherapeutic regimens in stage IV colorectal cancer, complications from unresected primary tumours are relatively infrequent. The risk of emergency surgical intervention is less than 15% in patients with synchronous metastatic disease who are treated with chemotherapy. Therefore, there is a tendency among surgeons not to resect the primary tumour in case of unresectable metastases. However, it is suggested that resection of the primary tumour in case of unresectable metastatic disease might influence overall survival. All studies described in the literature (n = 24) are non-randomised and the majority is single-centre and retrospective of nature. Most studies are in favour of resection of the primary tumour in patients with symptomatic lesions. In asymptomatic patients the results are less clear, although median overall survival seems to be improved in resected patients in the majority of studies. The major drawback of all these studies is that primarily patients with a better performance status and better prognosis (less metastatic sites involved) are being operated on. Another limitation of these studies is that few if any data on the use of systemic therapy are presented, which makes it difficult to assess the relative contribution of resection on outcome. Prospective studies on this topic are warranted, and are currently being planned. Conclusion Surgery of the primary tumour in patients with synchronous metastasised CRC is controversial, although data from the literature suggest that resection might be a positive prognostic factor for survival. Therefore prospective studies on the value of resection in this setting are required.
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