Oncologic outcomes of de-escalating axillary treatment in clinically node-positive breast cancer patients treated with neoadjuvant systemic therapy - A two center cohort study.

BACKGROUND: The aim of the present study was to report the 5-year axillary recurrence-free interval (aRFI) in clinically node-positive breast cancer patients treated according to a de-escalating axillary treatment protocol after neoadjuvant systemic therapy (NST). METHODS: All patients diagnosed in two hospitals between October 2014 and March 2021 were identified retrospectively. Data on diagnostic workup, treatment and follow-up was collected. Adjuvant axillary treatment was considered based on the initial staging using 18F-FDG PET/CT and the results of axillary lymph node marking with a radioactive-iodine seed protocol or a targeted axillary dissection procedure. Follow-up was updated until 27th April 2024. Kaplan-Meier curves were calculated to report the 5-year aRFI with corresponding 95 % confident intervals (95%-CI). RESULTS: A total of 199 patients were included. Axillary pathological complete response was reported in 66 (33.2 %). Based on the treatment protocol and initial clinical staging, no adjuvant axillary treatment was indicated in 30 patients (15 %), while 139 (70 %) received axillary radiotherapy without performance of an axillary lymph node dissection (ALND). The remaining 30 patients (15 %) underwent an ALND with additional locoregional radiotherapy. A median follow-up of 62 months (30-106) showed that 4 (2 %) patients experienced an axillary recurrence after 7, 8, 36 and 36 months, respectively. In all 4 patients, synchronous distant metastases were diagnosed. The estimated 5-year aRFI was 97.8 % (95%-CI 95.6-99.9 %) CONCLUSION: Although longer follow-up should be awaited before final conclusions can be drawn regarding the oncological safety of this approach, the implementation of a de-escalating axillary treatment protocol appears to be safe since the estimated 5-year aRFI is 97.8 %.

Effects of a perioperative educational pathway on ostomy self-care, level of independence and need for visiting nurse services: a comparative observational cohort study.

AIM: Most new ostomy patients are not able to manage ostomy self-care when they are discharged and rely on visiting nurse services for ostomy care. The aim of this study was to determine if a perioperative ostomy educational pathway increases the level of independence and decreases the need for visiting nurse services in new ostomy patients. METHOD: A prospective longitudinal study was conducted between July 2018 and February 2020. Patients who received a colostomy or ileostomy and were treated on the surgery ward were included. Patients who followed a perioperative ostomy educational pathway were compared to a historical control group. The primary outcome measure was the level of independence in ostomy care and the need for visiting nurse services. RESULTS: After discharge, 67.6% of patients in the intervention group (n = 244) were able to independently perform ostomy care and were therefore not relying on visiting nurse services, compared to 15.2% of the patients in the control group (n = 33). The need for visiting nurse services was higher in patients aged ≥70 years (OR 3.20, P < 0.001), those who did not attend the preoperative practice session (OR 3.02, P = 0.002), those with a history of transient ischaemic attack (OR 10.22, P = 0.045) and those with mild cognitive impairment (OR 28.98, P = 0.002). CONCLUSION: A perioperative ostomy educational pathway effectively increased the level of independence and decreased the need for visiting nurse services in new ostomy patients.

Breast conserving surgery with intraoperative electron beam radiation therapy for low-risk breast cancer: Five-year follow-up of 306 patients.

Recent studies have reported a higher than expected risk of ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) and a single dose of electron beam intra-operative radiotherapy (IORT). This finding was the rationale to perform a retrospective single center cohort study evaluating the oncologic results of consecutive patients treated with BCS and IORT. Women were eligible if they had clinical low-risk (N0, ≤2 cm unifocal, Bloom and Richardson grade 1-2), estrogen receptor-positive and human-epidermal-growth-factor-receptor-2-negative breast cancer. Prior to BCS, pN0 status was determined by sentinel lymph node biopsy. Data on oncologic follow-up were analyzed. Between 2012 and 2019, 306 consecutive patients were treated and analyzed, with a median age of 67 (50-86) years at diagnosis. Median follow-up was 60 (8-120) months. Five-year cumulative risk of IBTR was 13.4% (95% confidence interval [CI] 9.4-17.4). True in field recurrence was present in 3.9% of the patients. In 4.6% of the patients, the IBRT was classified as a local recurrence due to seeding of tumor cells in the cutis or subcutis most likely related to percutaneous biopsy. In 2.9% of the patients, the IBRT was a new outfield primary tumor. Three patients had a regional lymph node recurrence and two had distant metastases as first event. One breast cancer-related death was observed. Estimated 5-year overall survival was 89.8% (95% CI 86.0-93.6). In conclusion, although some of IBTR cases could have been prevented by adaptations in biopsy techniques and patient selection, BCS followed by IORT was associated with a substantial risk of IBTR.

Factors associated with one-year mortality after curative surgery for primary clinical T4 and locally recurrent rectal cancer in elderly patients.

INTRODUCTION: Despite advancements in colorectal cancer care, one-year post-operative mortality rates remain high for elderly patients who have undergone curative surgery for primary clinical T4 rectal cancer (cT4RC) or locally recurrent rectal cancer (LRRC). This study aimed to identify factors associated with one-year mortality and to evaluate the causes of death. MATERIALS & METHODS: This retrospective cohort study included patients aged ≥70 years who underwent surgery with curative intent for cT4RC or LRRC between January 2013 and December 2020. Clinical and follow-up data were collected and analyzed to determine survival rates and investigate factors associated with mortality within one year after surgery. RESULTS: A total of 183 patients (94 cT4RC, 89 LRRC) were included. One-year mortality rates were 16.0% for cT4RC and 28.1% for LRRC (P = 0.064). In cT4RC patients, factors associated with one-year mortality were preoperative anemia (OR 3.83, P = 0.032), total pelvic exenteration (TPE) (OR 7.18, P = 0.018), multivisceral resections (OR 5.73, P = 0.028), pulmonary complications (OR 13.31, P < 0.001) and Clavien-Dindo grade ≥ III complications (OR 5.19, P = 0.025). In LRRC patients, factors associated with one-year mortality were TPE (OR 27.00, P = 0.008), the need for supported care after discharge (OR 3.93, P = 0.041) and Clavien-Dindo grade ≥ III complications (OR 3.95, P = 0.006). The main causes of death in cT4RC and LRRC patients were failure to recover (cT4RC 26.6%, LRRC 28.0%) and disease recurrence (cT4RC 26.6%, LRRC 60.0%). CONCLUSION: In order to tailor treatment in elderly with cT4RC and LRRC, factors associated with increased one-year mortality (e.g. pre-operative anemia, TPE) should be incorporated in the decision-making process. CLINICAL TRIAL REGISTRATION: Not applicable.

Treatment interval in curative treatment of colon cancer, does it impact (cancer free) survival? A non-inferiority analysis.

BACKGROUND: In treatment of colon cancer, strict waiting-time targets are enforced, leaving professionals no room to lengthen treatment intervals when advisable, for instance to optimise a patient's health status by means of prehabilitation. Good quality studies supporting these targets are lacking. With this study we aim to establish whether a prolonged treatment interval is associated with a clinically relevant deterioration in overall and cancer free survival. METHODS: This retrospective multicenter non-inferiority study includes all consecutive patients who underwent elective oncological resection of a biopsy-proven primary non-metastatic colon carcinoma between 2010 and 2016 in six hospitals in the Southern Netherlands. Treatment interval was defined as time between diagnosis and surgical treatment. Cut-off points for treatment interval were ≤35 days and ≤49 days. FINDINGS: 3376 patients were included. Cancer recurred in 505 patients (15.0%) For cancer free survival, a treatment interval >35 days and >49 days was non-inferior to a treatment interval ≤35 days. Results for overall survival were inconclusive, but no association was found. CONCLUSION: For cancer free survival, a prolonged treatment interval, even over 49 days, is non-inferior to the currently set waiting-time target of ≤35 days. Therefore, the waiting-time targets set as fundamental objective in current treatment guidelines should become directional instead of strict targets.

An evaluation of postoperative outcomes and treatment changes after frailty screening and geriatric assessment and management in a cohort of older patients with colorectal cancer.

INTRODUCTION: Adequate patient selection is crucial within the treatment of older patients with colorectal cancer (CRC). While previous studies report increased morbidity and mortality in older patients screened positive for frailty, improvements in the perioperative care and postoperative outcomes have raised the question of whether older patients screened positive for frailty still face worse outcomes. This study aimed to investigate the postoperative outcomes of older patients with CRC screened positive for frailty, and to evaluate changes in treatment after frailty screening and geriatric assessment. MATERIALS AND METHODS: Patients ≥70 years with primary CRC who underwent frailty screening between 1 January 2019 and 31 October 2021 were included. Frailty screening was performed by the Geriatric-8 (G8) screening tool. If the G8 indicated frailty (G8 ≤ 14), patients were referred for a comprehensive geriatric assessment (CGA). Postoperative outcomes and changes in treatment based on frailty screening and CGA were evaluated. RESULTS: A total of 170 patients were included, of whom 74 (43.5%) screened positive for frailty (G8 ≤ 14). Based on the CGA, the initially proposed treatment plan was altered to a less intensive regimen in five (8.9%) patients, and to a more intensive regimen in one (1.8%) patient. Surgery was performed in 87.8% of patients with G8 ≤ 14 and 96.9% of patients with G8 > 14 (p = 0.03). Overall postoperative complications were similar between patients with G8 ≤ 14 and G8 > 14 (46.2% vs. 47.3%, p = 0.89). Postoperative delirium was observed in 7.7% of patients with G8 ≤ 14 and 1.1% of patients with G8 > 14 (p = 0.08). No differences in 30-day mortality (1.1% vs. 1.5%, p > 0.99) or one-year and two-year survival rates were observed (log rank, p = 0.26). DISCUSSION: Although patients screened positive for frailty underwent CRC surgery less often, those considered eligible for surgery can safely undergo CRC resection within current clinical care pathways, without increased morbidity and mortality. Efforts to optimise perioperative care and minimise the risk of postoperative complications, in particular delirium, seem warranted. A multidisciplinary onco-geriatric pathway may support tailored decision-making in patients at risk of frailty.

Implementation of an Enhanced Recovery after Surgery Protocol in Advanced and Recurrent Rectal Cancer Patients after beyond Total Mesorectal Excision Surgery: A Feasibility Study.

INTRODUCTION: The implementation of an Enhanced Recovery After Surgery (ERAS) protocol in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) has been deemed unfeasible until now because of the heterogeneity of this disease and low caseloads. Since evidence and experience with ERAS principles in colorectal cancer care are increasing, a modified ERAS protocol for this specific group has been developed. The aim of this study is to evaluate the implementation of a tailored ERAS protocol for patients with LARC or LRRC, requiring beyond total mesorectal excision (bTME) surgery. METHODS: Patients who underwent a bTME for LARC or LRRC between October 2021 and December 2022 were prospectively studied. All patients were treated in accordance with the ERAS LARRC protocol, which consisted of 39 ERAS care elements specifically developed for patients with LARC and LRRC. One of the most important adaptations of this protocol was the anaesthesia procedure, which involved the use of total intravenous anaesthesia with intravenous (iv) lidocaine, iv methadone, and iv ketamine instead of epidural anaesthesia. The outcomes showed compliance with ERAS care elements, complications, length of stay, and functional recovery. A follow-up was performed at 30 and 90 days post-surgery. RESULTS: Seventy-two patients were selected, all of whom underwent bTME for either LARC (54.2%) or LRRC (45.8%). Total compliance with the adjusted ERAS protocol was 73.6%. Major complications were present in 12 patients (16.7%), and the median length of hospital stay was 9 days (IQR 6.0-14.0). Patients who received multimodal anaesthesia (75.0%) stayed in the hospital for a median of 7.0 days (IQR 6.8-15.5). These patients received fewer opioids on the first three postoperative days than patients who received epidural analgesia (p < 0.001). CONCLUSIONS: The implementation of the ERAS LARRC protocol seemed successful according to its compliance rate of >70%. Its complication rate was substantially reduced in comparison with the literature. Multimodal anaesthesia is feasible in beyond TME surgery with promising effects on recovery after surgery.

Limited wedge resection for T1 colon cancer (LIMERIC-II trial) - rationale and study protocol of a prospective multicenter clinical trial.

BACKGROUND: The sole presence of deep submucosal invasion is shown to be associated with a limited risk of lymph node metastasis. This justifies a local excision of suspected deep submucosal invasive colon carcinomas (T1 CCs) as a first step treatment strategy. Recently Colonoscopy-Assisted Laparoscopic Wedge Resection (CAL-WR) has been shown to be able to resect pT1 CRCs with a high R0 resection rate, but the long term outcomes are lacking. The aim of this study is to evaluate the safety, effectiveness and long-term oncological outcomes of CAL-WR as primary treatment for patients with suspected superficial and also deeply-invasive T1 CCs. METHODS: In this prospective multicenter clinical trial, patients with a macroscopic and/or histologically suspected T1 CCs will receive CAL-WR as primary treatment in order to prevent unnecessary major surgery for low-risk T1 CCs. To make a CAL-WR technically feasible, the tumor may not include > 50% of the circumference and has to be localized at least 25 cm proximal from the anus. Also, there should be sufficient distance to the ileocecal valve to place a linear stapler. Before inclusion, all eligible patients will be assessed by an expert panel to confirm suspicion of T1 CC, estimate invasion depth and subsequent advise which local resection techniques are possible for removal of the lesion. The primary outcome of this study is the proportion of patients with pT1 CC that is curatively treated with CAL-WR only and in whom thus organ-preservation could be achieved. Secondary outcomes are 1) CAL-WR's technical success and R0 resection rate for T1 CC, 2) procedure-related morbidity and mortality, 3) 5-year overall and disease free survival, 4) 3-year metastasis free survival, 5) procedure-related costs and 6) impact on quality of life. A sample size of 143 patients was calculated. DISCUSSION: CAL-WR is a full-thickness local resection technique that could also be effective in removing pT1 colon cancer. With the lack of current endoscopic local resection techniques for > 15 mm pT1 CCs with deep submucosal invasion, CAL-WR could fill the gap between endoscopy and major oncologic surgery. The present study is the first to provide insight in the long-term oncological outcomes of CAL-WR. TRIAL REGISTRATION: CCMO register (ToetsingOnline), NL81497.075.22, protocol version 2.3 (October 2022).

Locally recurrent rectal cancer: Oncological outcomes for patients with a pathological complete response after neoadjuvant therapy.

BACKGROUND: For patients with locally recurrent rectal cancer, it is an ongoing pursuit to establish factors predicting or improving oncological outcomes. In locally advanced rectal cancer, a pCR appears to be associated with improved outcomes. The aim of this retrospective cohort study was to compare the oncological outcomes of patients with locally recurrent rectal cancer with and without a pCR. METHODS: Patients who underwent neoadjuvant treatment and surgery for locally recurrent rectal cancer with curative intent between January 2004 and June 2020 at a tertiary referral hospital were analysed. Primary outcomes included overall survival, disease-free survival, metastasis-free survival, and local re-recurrence-free survival, stratified according to whether the patient had a pCR. RESULTS: Of a total of 345 patients, 51 (14.8 per cent) had a pCR. Median follow-up was 36 (i.q.r. 16-60) months. The 3-year overall survival rate was 77 per cent for patients with a pCR and 51.1 per cent for those without (P < 0.001). The 3-year disease-free survival rate was 56 per cent for patients with a pCR and 26.1 per cent for those without (P < 0.001). The 3-year local re-recurrence-free survival rate was 82 and 44 per cent respectively (P < 0.001). Surgical procedures (for example soft tissue, sacrum, and urogenital organ resections) and postoperative complications were comparable between patients with and without a pCR. CONCLUSION: This study showed that patients with a pCR have superior oncological outcomes to those without a pCR. It may therefore be safe to consider a watch-and-wait approach in highly selected patients, potentially improving quality of life by omitting extensive surgical procedures without compromising oncological outcomes.

The development and implementation of an interactive application for new ostomy patients.

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.

A Multidisciplinary Approach for the Personalised Non-Operative Management of Elderly and Frail Rectal Cancer Patients Unable to Undergo TME Surgery.

Despite it being the optimal curative approach, elderly and frail rectal cancer patients may not be able to undergo a total mesorectal excision. Frequently, no treatment is offered at all and the natural course of the disease is allowed to unfold. These patients are at risk for developing debilitating symptoms that impair quality of life and require palliative treatment. Recent advancements in non-operative treatment modalities have enhanced the toolbox of alternative treatment strategies in patients unable to undergo surgery. Therefore, a proposed strategy is to aim for the maximal non-operative treatment, in an effort to avoid the onset of debilitating symptoms, improve quality of life, and prolong survival. The complexity of treating elderly and frail patients requires a patient-centred approach to personalise treatment. The main challenge is to optimise the balance between local control of disease, patient preferences, and the burden of treatment. A comprehensive geriatric assessment is a crucial element within the multidisciplinary dialogue. Since limited knowledge is available on the optimal non-operative treatment strategy, these patients should be treated by dedicated multidisciplinary rectal cancer experts with special interest in the elderly and frail. The aim of this narrative review was to discuss a multidisciplinary patient-centred treatment approach and provide a practical suggestion of a successfully implemented clinical care pathway.

A prospective cohort study to evaluate continuous wound infusion with local analgesics within an enhanced recovery protocol after colorectal cancer surgery.

AIM: To reduce detrimental opioid-related side effects, minimising the postoperative opioid consumption is needed, especially in older patients. Continuous wound infusion (CWI) with local analgesics appears to be an effective opioid-sparing alternative. However, the added value of CWI to an enhanced recovery protocol after colorectal cancer (CRC) surgery is unclear. The aim of this study was to evaluate the outcomes of CWI after CRC surgery within a strictly adhered to enhanced recovery protocol. METHODS: In this multicentre prospective observational cohort study, patients who underwent CRC surgery between May 2019 and January 2021 were included. Patients were treated with CWI as adjunct to multimodal pain management within an enhanced recovery protocol. Postoperative opioid consumption, pain scores and outcomes regarding functional recovery were evaluated. RESULTS: A cohort of 130 consecutive patients were included, of whom 36.2% were ≥75 years. Postoperative opioids were consumed by 80 (61.5%) patients on postoperative day 0, and by 28 (21.5%), 27 (20.8%), and 18 (13.8%) patients on postoperative days 1, 2, and 3, respectively. Median pain scores were <4 on all days. The median time until first passage of stool was 1.0 (IQR: 1.0-2.0) day. Postoperative delirium occurred in 0.8%. Median length of hospital stay was 3.0 days (IQR: 2.0-5.0). CONCLUSION: In patients treated with CWI, low amounts of postoperative opioid consumption, adequate postoperative pain control, and enhanced recovery were observed. CWI seems a beneficial opioid-sparing alternative and may further improve the outcomes of an enhanced recovery protocol after CRC surgery, which seems especially valuable for older patients.

MRI tumour regression grade in locally recurrent rectal cancer.

BACKGROUND: This study aimed to investigate the agreement between magnetic resonance tumour regression grade (mrTRG) and pathological regression grade (pTRG) in patients with locally recurrent rectal cancer (LRRC). Also, the reproducibility of mrTRG was investigated. METHODS: All patients with LRRC who underwent a resection between 2010 and 2018 after treatment with induction chemotherapy and neoadjuvant chemo(re)irradiation in whom a restaging MRI was available were retrospectively selected. All MRI scans were reassessed by two independent radiologists using the mrTRG, and the pTRG was reassessed by an independent pathologist. The interobserver agreement between the radiologists as well as between the radiologists and the pathologist was assessed with the weighted kappa test. A subanalysis was performed to evaluate the influence of the interval between imaging and surgery. RESULTS: Out of 313 patients with LRRC treated during the study interval, 124 patients were selected. Interobserver agreement between the radiologists was fair (k = 0.28) using a two-tier grading system (mrTRG 1-2 versus mrTRG 3-5). For the lead radiologist, agreement with pTRG was moderate (k = 0.52; 95 per cent c.i. 0.36 to 0.68) when comparing good (mrTRG 1-2 and Mandard 1-2) and intermediate/poor responders (mrTRG 3-5 and Mandard 3-5), and the agreement was fair between the other abdominal radiologist and pTRG (k = 0.39; 95 per cent c.i. 0.22 to 0.56). A shorter interval (less than 7 weeks) between MRI and surgery resulted in an improved agreement (k = 0.69), compared with an interval more than 7 weeks (k = 0.340). For the lead radiologist, the positive predictive value for predicting good responders was 95 per cent (95 per cent c.i. 71 per cent to 99 per cent), whereas this was 56 per cent (95 per cent c.i. 44 per cent to 66 per cent) for the other radiologist. CONCLUSION: This study showed that, in LRRC, the reproducibility of mrTRG among radiologists is limited and the agreement of mrTRG with pTRG is low. However, a shorter interval between MRI and surgery seems to improve this agreement and, if assessed by a dedicated radiologist, mrTRG could predict good responders.

Functional Bowel Complaints and the Impact on Quality of Life After Colorectal Cancer Surgery in the Elderly.

BACKGROUND: The Low Anterior Resection Syndrome (LARS) is commonly reported after colorectal cancer surgery and significantly impairs quality of life. The prevalence and impact of LARS in the elderly after rectal cancer as well as colon cancer surgery is unclear. We aimed to describe the prevalence of LARS complaints and the impact on quality of life in the elderly after colorectal cancer surgery. MATERIALS AND METHODS: Patients were included from seven Dutch hospitals if they were at least one year after they underwent colorectal cancer surgery between 2008 and 2015. Functional bowel complaints were assessed by the LARS score. Quality of life was assessed by the EORTC QLQ-C30 and EORTC QLQ-CR29 questionnaires. Outcomes in patients ≥70 years were compared to a reference group of patients <70 years. RESULTS: In total 440 rectal cancer and 1183 colon cancer patients were eligible for analyses, of whom 133 (30.2%) rectal and 536 (45.3%) colon cancer patients were ≥70 years. Major LARS was reported by 40.6% of rectal cancer and 22.2% of colon cancer patients ≥70 years. In comparison, patients <70 years reported major LARS in 57.3% after rectal cancer surgery (p=0.001) and in 20.4% after colon cancer surgery (p=0.41). Age ≥70 years was independently associated with reduced rates of major LARS after rectal cancer surgery (OR 0.63, p=0.04). Patients with major LARS reported significantly impaired quality of life on almost all domains. CONCLUSION: Elderly should not be withheld a restorative colorectal cancer resection based on age alone. However, a substantial part of the elderly colorectal cancer patients develops major LARS after surgery, which often severely impairs quality of life. Since elderly frequently consider quality of life and functional outcomes as one of the most important outcomes after treatment, major LARS and its impact on quality of life should be incorporated in the decision-making process.

Metabolic positron emission tomography/CT response after induction chemotherapy and chemo(re)irradiation is associated with higher negative resection margin rate in patients with locally recurrent rectal cancer.

AIM: Positron emission tomography (PET)/CT can be used to monitor the metabolic changes that occur after intensified treatment with induction chemotherapy and chemo(re)irradiation for locally recurrent rectal cancer (LRRC). This study aimed to analyse the correlation between the PET/CT response and final histopathological outcomes. METHODS: All LRRC patients who underwent induction chemotherapy prior to surgery between January 2010 and July 2020 and were monitored with pretreatment and post-treatment PET/CT were included. Visual qualitative analysis was performed, and patients were scored as having achieved a complete metabolic response (CMR), partial metabolic response (PMR) or no response (NR). The histopathological response was assessed according to the Mandard tumour regression (TRG) score and categorized as major (TRG 1-2), partial (TRG 3) or poor (TRG 4-5). The PET/CT and TRG categories were compared, and possible confounders were analysed. RESULTS: A total of 106 patients were eligible for analysis; 24 (23%) had a CMR, 54 (51%) had a PMR and 28 (26%) had NR. PET/CT response was a significant predictor of the negative resection margin rate, achieving 96% for CMR, 69% for PMR and 50% for NR. The overall accuracy between PET score and pathological TRG was 45%, and the positive predictive value for CMR was 63%. A longer interval between post-treatment PET/CT and surgery negatively influenced the predictive value. CONCLUSION: Metabolic PET/CT response evaluation after neoadjuvant treatment proves to be a complementary diagnostic tool to standard MRI in assessing tumour response, and may play a role for treatment planning in LRRC patients.

Neither inflammatory bowel disease nor immunosuppressants are associated with an increased risk of severe COVID-19: an observational Dutch cohort study.

Conflicting data about inflammatory bowel disease [IBD] and immunosuppressants are risk factors for severe COVID-19 confuse patients and healthcare providers. Clinical reports with longer follow-up are lacking. A retrospective search was performed for severe COVID-19 (hospital admission and/or mortality) one year after the SARS-CoV-2 outbreak in an IBD cohort from one of the most affected Dutch regions. Cohort characteristics were explored by value-based healthcare data, including immunotherapy. COVID-19 cases were detected by ICD-10 codes and further examined for IBD determinants (including medication) and COVID-19 characteristics (intensive care admission, respiratory support, treatment, mortality). The national mortality register was consulted, ensuring detection of patients that died without admission. Results were compared with regional and national general population registries. The IBD cohort consisted of 1453 patients (51% Crohn's disease, 54% women, 39.9% using immunotherapy), including children. Biologics use increased during the study. Eight cases (0.55%) had severe COVID-19: seven were hospitalized (0.48%, 95% confidence interval [CI] 0.21-1.04), and two died (0.14%, CI 0.002-0.55). Six patients had comorbidity, one used immunotherapy, and four had no medication. Both deceased patients were older than 80 years, had severe comorbidity, but used no immunotherapy. Hospitalization occurred significantly more in the IBD cohort than regionally (0.18%, CI 0.17-0.19, p = 0.015), but not significantly more than nationally (0.28%, CI 0.279-0.284). Mortality was equal in IBD patients, regionally (0.11%, CI 0.10-0.12) and nationally (0.13%, CI 0.125-0.128). Neither IBD nor immunosuppressants are associated with increased risks of severe COVID-19 in an observational study with one-year follow-up.

Bile Salt and FGF19 Signaling in the Early Phase of Human Liver Regeneration.

The involvement of bile salt-fibroblast growth factor 19 (FGF19) signaling in human liver regeneration (LR) is not well studied. Therefore, we studied aspects of bile salt-FGF19 signaling shortly after liver resection in patients. We compared plasma bile salt and FGF19 levels in arterial, portal and hepatic venous blood, calculated venous-arterial differences (ΔVA), and determined hepatic transcript levels on two intra-operative time points: before (< 1 hour) and immediately after (> 2-3 hours) liver resection (i.e., following surgery). Postoperative bile salt and FGF19 levels were assessed on days 1, 2, and 3. LR was studied by computed tomography (CT)-liver volumetry. Following surgery, the liver, arterial, and portal bile salt levels were elevated (P < 0.05). Furthermore, an increased amount of bile salts was released in portal blood and extracted by the remnant liver (P < 0.05). Postoperatively, bile salt levels were elevated from day 1 onward (P < 0.001). For FGF19, intra-operative or postoperative changes of ΔVA or plasma levels were not observed. The bile salt-homeostatic regulator farnesoid X receptor (FXR) was markedly up-regulated following surgery (P < 0.001). Cell-cycle re-entry priming factors (interleukin 6 [IL-6], signal transducer and activator of transcription 3 [STAT3], and cJUN) were up-regulated following surgery and were positively correlated with FXR expression (P < 0.05). Postoperative hyperbilirubinemia was preceded by postsurgery low FXR and high Na+/Taurocholate cotransporting polypeptide (NTCP) expression in the remnant liver coupled with higher liver bile salt content (P < 0.05). Finally, bile salt levels on postoperative day 1 were an independent predictor of LR (P < 0.05). Conclusion: Systemic, portal, and liver bile salt levels are rapidly elevated after liver resection. Postoperative bile salts were positively associated with liver volume gain. In the studied time frame, FGF19 levels remained unaltered, suggesting that FGF19 plays a minor role in human LR. These findings indicate a more relevant role of bile salts in human LR.

Rate and predictors of nodal pathological complete response following neoadjuvant endocrine treatment in clinically biopsy-proven node-positive breast cancer patients.

BACKGROUND: Data on effectiveness and optimal use of neoadjuvant endocrine therapy (NET) in clinically biopsy-proven node-positive breast cancer is lacking. This study examined the incidence of axillary pathological complete response (pCR) on NET in clinically biopsy-proven node-positive breast cancer patients. Secondary, patient and tumour characteristics, as well as the optimal duration of NET in relation to the occurrence of axillary pCR were investigated. MATERIAL AND METHODS: Patients diagnosed with primary hormone receptor positive, HER2 negative breast cancer between 2014 and 2019, with at least one positive axillary lymph node (pathologically proven), treated with NET were selected from the Netherlands Cancer Registry. The incidence of axillary pCR in combination with patient, tumour and treatment characteristics was analysed. RESULTS: In a population of 561 patients, an axillary pCR of 7.3% on NET was observed. Median length of treatment was 8.1 months in the patients without vs. 8.8 months in those with axillary pCR, with no statistically significant difference. A p-value <0.30 was found for age, histologic type, clinical tumour status, hormone receptor status and the type of NET in univariable analysis. After multivariable logistic regression analyses, none of these variables were independently associated with the likelihood of an axillary pCR. CONCLUSION: The rate of axillary pCR after NET in HR + HER2-clinically biopsy-proven node-positive breast cancer patients is low. Factors independently associated with the likelihood of an axillary pCR could not be identified. More research is warranted regarding optimizing the duration of NET and the prognostic value of residual disease in the axilla after NET.