IntroductionColorectal cancer (CRC) is the third most common type of cancer in the Netherlands. Approximately 90% of patients can be treated with surgery, which is considered potentially curative. ...Postoperative surveillance during the first 5 years after surgery pursues to detect metastases in an early, asymptomatic and treatable stage. Multiple large randomised controlled trials have failed to show any (cancer-specific) survival benefit of intensive postoperative surveillance compared with a minimalistic approach in patients with CRC. This raises the question whether an (intensive) in-hospital postoperative surveillance strategy is still warranted from both a patient well-being and societal perspective. A more modern, home-based surveillance strategy could be beneficial in terms of patients’ quality of life and healthcare costs.Methods and analysisThe multicentre, prospective FUTURE-primary study implements a patient-led home-based surveillance after curative CRC treatment. Here, patients are involved in the choice regarding three fundamental aspects of their postoperative surveillance. First regarding frequency, patients can opt for additional follow-up moments to the minimal requirement as outlined by the current Dutch national guidelines. Second regarding the setting, both in-hospital or predominantly home-based options are available. And third, concerning patient–doctor communication choices ranging from in-person to video chat, and even silent check-ups. The aim of the FUTURE-primary study is to evaluate if such a patient-led home-based follow-up approach is successful in terms of quality of life, satisfaction and anxiety compared with historic data. A successful implementation of the patient-led aspect will be assessed by the degree in which the additional, optional follow-up moments are actually utilised. Secondary objectives are to evaluate quality of life, anxiety, fear of cancer recurrence and cost-effectiveness.Ethics and disseminationEthical approval was given by the Medical Ethics Review Committee of Erasmus Medical Centre, The Netherlands (2021-0499). Results will be presented in peer-reviewed journals.Trial registration numberNCT05656326.
T1 colorectal cancers (T1CRC) are increasingly being treated by endoscopic submucosal dissection (ESD). After ESD of a T1CRC, completion surgery is indicated in a subgroup of patients. Currently, the ...influence of ESD on surgical morbidity and mortality is unknown. The aim of this study was to compare 90-day morbidity and mortality of completion surgery after ESD to primary surgery. The completion surgery group consisted of suspected T1CRC patients from a multicenter prospective ESD database (2014–2020). The primary surgery group consisted of pT1CRC patients from a nationwide surgical registry (2017–2019). Patients with rectal or sigmoidal cancers were selected. Patients receiving neoadjuvant therapy were excluded. Propensity score adjustment was used to correct for confounders. In total, 411 patients were included: 54 in the completion surgery group (39 pT1, 15 pT2) and 357 in the primary surgery group with pT1CRC. Adverse event rate was 24.1% after completion surgery and 21.3% after primary surgery. After completion surgery 90-day mortality did not occur, though one patient died in the primary surgery group. After propensity score adjustment, lymph node yield did not differ significantly between the groups. Among other morbidity-related outcomes, stoma rate (OR 1.298 95%-CI 0.587-2.872, p = 0.519) and adverse event rate (OR 1.162; 95%-CI 0.570-2.370, p = 0.679) also did not differ significantly. A subgroup analysis was performed in patients undergoing rectal surgery. In this subgroup (37 completion and 136 primary surgery), these morbidity outcomes also did not differ significantly. In conclusion, this study suggests that ESD does not compromise morbidity or 90-day mortality of completion surgery.
Background
T1 rectal cancer (RC) patients are increasingly being treated by local resection alone but uniform surveillance strategies thereafter are lacking. To determine whether different local ...resection techniques influence the risk of recurrence and cancer-related mortality, a meta-analysis was performed.
Methods
A systematic search was conducted for T1RC patients treated with local surgical resection. The primary outcome was the risk of RC recurrence and RC-related mortality. Pooled estimates were calculated using mixed-effect logistic regression. We also systematically searched and evaluated endoscopically treated T1RC patients in a similar manner.
Results
In 2585 unique T1RC patients (86 studies) undergoing local surgical resection, the overall pooled cumulative incidence of recurrence was 9.1% (302 events, 95% CI 7.3–11.4%;
I
2
= 68.3%). In meta-regression, the recurrence risk was associated with histological risk status (
p
< 0.005; low-risk 6.6%, 95% CI 4.4–9.7% vs. high-risk 28.2%, 95% CI 19–39.7%) and local surgical resection technique (
p
< 0.005; TEM/TAMIS 7.7%, 95% CI 5.3–11.0% vs. other local surgical excisions 10.8%, 95% CI 6.7–16.8%). In 641 unique T1RC patients treated with flexible endoscopic excision (16 studies), the risk of recurrence (7.7%, 95% CI 5.2–11.2%), cancer-related mortality (2.3%, 95% CI 1.1–4.9), and cancer-related mortality among patients with recurrence (30.0%, 95% CI 14.7–49.4%) were comparable to outcomes after TEM/TAMIS (risk of recurrence 7.7%, 95% CI 5.3–11.0%, cancer-related mortality 2.8%, 95% CI 1.2–6.2% and among patients with recurrence 35.6%, 95% CI 21.9–51.2%).
Conclusions
Patients with T1 rectal cancer may have a significantly lower recurrence risk after TEM/TAMIS compared to other local surgical resection techniques. After TEM/TAMIS and endoscopic resection the recurrence risk, cancer-related mortality and cancer-related mortality among patients with recurrence were comparable. Recurrence was mainly dependent on histological risk status.
Graphical abstract
Background
The aim of this study was to investigate the effect of age on CAL and its associated mortality.
Methods
Data were derived from the Dutch ColoRectal Audit. All patients undergoing resection ...for colorectal cancer in the Netherlands between January 2011 and December 2016 were included. Univariable and multivariable logistic regressions were performed to test the effect of age on CAL and its associated mortality.
Results
In total, 45 488 patients were included. The incidence of CAL was 6.4% in patients <60 years old, 5.5% in patients 60‐69 years old, 5.4% in patients 70‐80 years old, and 4.9% in patients ≥80 years old (P < 0.001). Multivariate analysis showed that age was protective for CAL (OR 0.965 per 5 years, 95% CI 0.941‐0.985, P < 0.001). Mortality after CAL was 1.3% in patients <60 years old, 4.8% in patients 60‐69 years old, 12.3% in patients 70‐80 years old, and 27.0% in patients >80 years old (P < 0.001). Older age was associated with mortality following CAL (OR 1.497 per 5 years 95% CI 1.364‐1.647, P < 0.001).
Conclusions
This population‐based study suggests a protective effect of increased age on CAL after colorectal cancer resection. However, older age is strongly associated with mortality after CAL.
Background
Transanal minimally invasive surgery (TAMIS) is emerging as an alternative to transanal endoscopic microsurgery. Quality of life (QOL) and functional outcome are important aspects when ...valuing a new technique. The aim of this prospective study was to assess both functional outcome and QOL after TAMIS.
Methods
From 2011 to 2013, patients were prospectively studied prior to and at least 6 months after TAMIS for rectal adenomas and low-risk T1 carcinomas using a single-site laparoscopy port. Functional outcome was determined using the Faecal Incontinence Severity Index (FISI). Quality of life was measured using functional Faecal Incontinence Quality of Life (FIQL) and generic (EuroQol EQ-5D) questionnaires.
Results
The study population consisted of 24 patients 13 men, median age 59 (range 42–83) with 24 tumours median distance from the dentate line 8 cm (range 2–17 cm); median tumour size 6 cm
2
(range 0.25–51 cm
2
); 20 adenomas; 4 low-risk T1 carcinomas. Post-operative complications occurred in one patient (4 %; grade IIIb according to Clavien Dindo classification). Compared to baseline, FISI remained unaffected (9.8 vs 7.3;
P
= 0.26), FIQL remained unaffected, and EuroQol EQ-5D improved (EQ-VAS: 77 vs 83;
P
= 0.04).
Conclusion
There was no detrimental effect of TAMIS on anorectal function. Overall QOL was improved after TAMIS, probably due to removal of the tumour, and at 6 months was equal to the general population.
Several factors are included in decision making for treatment of patients with locally advanced rectal cancer, including a trade-off between risks and gains of both clinical and functional outcomes. ...However, it is largely unknown which outcomes are most important to patients and whether this differs between patients and clinicians.
Both clinicians and patients treated for locally advanced rectal cancer were invited to fill out an online questionnaire, including a choice-based conjoint experiment. Participants were presented 14 comparisons of two hypothetical case presentations, characterized by different treatments and outcomes of care (6 attributes) and were asked to select the case with the best outcome at that moment. Hierarchical Bayes Estimation was used to calculate the relative importance (RI) of each of the six attributes.
In total, 94 patients and 128 clinicians completed the questionnaire. For patients, avoiding surgery with permanent stoma was most important (RI 24.4, 95%CI 21.88–26.87) and a 2-year difference in disease-free survival was least important (RI 5.6, 95%CI 4.9–6.2). Clinicians assigned highest importance to avoiding severe and daily worries about cancer recurrence (RI 30.7, 95%CI 29.1–32.4), while this was ranked 4th by patients (RI 17.9, 95%CI 16.5–19.4, p < 0.001).
When confronted with different outcomes within one case description, patients find the duration of disease free survival the least important. In addition, considerable differences were found between the importance assigned by patients and clinicians to clinical and functional outcomes, most notably in avoiding surgery with permanent stoma and worries about recurrence.
To evaluate the feasibility of transanal single port surgery in 15 consecutive patients.
The current method of choice for local resection of rectal tumors is transanal endoscopic microsurgery (TEM), ...a complex and expensive technique. Single access surgery is easy, relatively cheap, and more broadly applied in laparoscopy. Evidence regarding transanal use of single access ports is scarce.
Consecutive patients with a rectal lesion otherwise eligible for TEM were operated using the Single Site Laparoscopic Access System (SSL) and standard laparoscopic instrumentation. Patient, lesion and procedure characteristics, hospitalization length, and peroperative and postoperative complications were recorded.
Fifteen patients were planned for single port transanal surgery. In 2 patients (13.3%), intrarectal retractor expansion failed, and conversion to conventional TEM was necessary. The remaining 13 patients were successfully operated. Rectal lesions (mean diameter 36 mm, standard deviation ±25 mm, mean distance from the dentate line 6 cm ±4.5) included adenoma in 7 patients, T1 adenocarcinoma in 1, T2 adenocarcinoma in 3, carcinoid in 1, and fibrosis only in 1 (after prior polypectomy). All patients were operated in lithotomy position. Resections were en bloc, full thickness, and had complete margins. Resection specimens measured 65 (±35) × 52 (±24) mm. Twelve rectal defects were sutured. One peroperative pneumoscrotum occurred. Mean operating time was 57 (±39) minutes. One patient presented with postoperative hemorrhage, treated conservatively (postoperative morbidity rate 7.7%). Mean hospitalization lasted 2.5 days (±2.7).
Transanal single port surgery via the SSL is feasible and safe and may become a promising alternative to TEM.
The use of cytokines for immunotherapy shows clinical efficacy but is frequently accompanied by severe adverse events caused by excessive and systemic immune activation. Here, we set out to address ...these challenges by engineering a fusion protein of a single, potency-reduced, IL15 mutein and a PD1-specific antibody (anti-PD1-IL15m). This immunocytokine was designed to deliver PD1-mediated, avidity-driven IL2/15 receptor stimulation to PD1
tumor-infiltrating lymphocytes (TIL) while minimally affecting circulating peripheral natural killer (NK) cells and T cells. Treatment of tumor-bearing mice with a mouse cross-reactive fusion, anti-mPD1-IL15m, demonstrated potent antitumor efficacy without exacerbating body weight loss in B16 and MC38 syngeneic tumor models. Moreover, anti-mPD1-IL15m was more efficacious than an IL15 superagonist, an anti-mPD-1, or the combination thereof in the B16 melanoma model. Mechanistically, anti-PD1-IL15m preferentially targeted CD8
TILs and single-cell RNA-sequencing analyses revealed that anti-mPD1-IL15m treatment induced the expansion of an exhausted CD8
TIL cluster with high proliferative capacity and effector-like signatures. Antitumor efficacy of anti-mPD1-IL15m was dependent on CD8
T cells, as depletion of CD8
cells resulted in the loss of antitumor activity, whereas depletion of NK cells had little impact on efficacy. The impact of anti-hPD1-IL15m on primary human TILs from patients with cancer was also evaluated. Anti-hPD1-IL15m robustly enhanced the proliferation, activation, and cytotoxicity of CD8
and CD4
TILs from human primary cancers
, whereas tumor-derived regulatory T cells were largely unaffected. Taken together, our findings showed that anti-PD1-IL15m exhibits a high translational promise with improved efficacy and safety of IL15 for cancer immunotherapy via targeting PD1
TILs.
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