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Simple Summary: In recent years, there have been significant improvements in the treatment of rectal cancer. Preoperative treatment and surgical techniques have advanced, leading to fewer local recurrences, fewer surgical complications, and more complete resections. Recent trials investigating total neoadjuvant treatment aim to decrease distant metastasis and improve overall survival in patients with locally advanced rectal cancer. In addition, adding chemotherapy to the preoperative treatment increases the complete response rate to 30 to 50 percent of patients. This means that no residual tumour is left and that patients can follow a Watch & Wait surveillance program, potentially avoiding surgery, complications, and colostomy. Nonetheless, many factors have to be considered when deciding on a treatment plan for patients with rectal cancer. Ongoing research aims to identify the optimal treatment regimen, considering factors like tumour stage, toxicity of (neo)adjuvant treatment, and patient preference. Over the past decade, the treatment of rectal cancer has changed considerably. The implementation of TME surgery has, in addition to decreasing the number of local recurrences, improved surgical morbidity and mortality. At the same time, the optimisation of radiotherapy in the preoperative setting has improved oncological outcomes even further, although higher perineal infection rates have been reported. Radiotherapy regimens have evolved through the adjustment of radiotherapy techniques and fields, increased waiting intervals, and, for more advanced tumours, adding chemotherapy. Concurrently, imaging techniques have significantly improved staging accuracy, facilitating more precise selection of advanced tumours. Although chemoradiotherapy does lead to the downsizing and -staging of these tumours, a very clear effect on sphincter-preserving surgery and the negative resection margin has not been proven. Aiming to decrease distant metastasis and improve overall survival for locally advanced rectal cancer, systemic chemotherapy can be added to radiotherapy, known as total neoadjuvant treatment (TNT). High complete response rates, both pathological (pCR) and clinical (cCR), are reported after TNT. Patients who follow a Watch & Wait program after a cCR can potentially avoid surgical morbidity and colostomy. For both early and more advanced tumours, trials are now investigating optimal regimens in an attempt to offer organ preservation as much as possible. Multidisciplinary deliberation should include patient preference, treatment toxicity, and likelihood of end colostomy, but also the burden of intensive surveillance in a W&W program. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is diagnosed in approximately 500,000 patients each year in Europe, leading to a high number of patients having to cope with the consequences of resection for colorectal cancer. As treatment options tend to grow, more information on the effects of these treatments is needed to engage in shared decision‐making. This study aims to explore the impact of resection for colorectal cancer on patients' daily life. Methods: Patients (≥18 years of age) who underwent an oncological colorectal resection between 2018 and 2021 were selected. Purposeful sampling was used to include patients who differed in age, comorbidity conditions, types of (neo)adjuvant therapy, postoperative complications and the presence/absence of a stoma. Semi‐structured interviews were conducted, guided by a topic guide. Interviews were fully transcribed and subsequently thematically analysed using the framework approach. Analyses were carried out using the following predefined themes: (1) daily life and activities; (2) psychological functioning; (3) social functioning; (4) sexual functioning; and (5) healthcare experiences. Results: Sixteen patients with a follow‐up period of between 0.6 and 4.4 years after surgery were included in this study. Participants reported several challenges experienced because of poor bowel function, a stoma, chemotherapy‐induced neuropathy, fear of recurrence and sexual dysfunction. However, they reported these as not interfering much with daily life. Conclusion: Colorectal cancer treatment leads to several challenges and treatment‐related health deficits. This is often not recognized by generic patient‐reported outcome measures, but the findings on treatment‐related health deficits presented in this study contain valuable insights which might contribute to improving colorectal cancer care, shared decision making and value‐based health care. [ABSTRACT FROM AUTHOR]

Background: In rectal cancer, watch and wait for patients with a cCR after neoadjuvant treatment has an established evidence base. However, there is a lack of consensus on the definition and management of a near-cCR. This study aimed to compare outcomes in patients who achieved a cCR at first reassessment versus later reassessment. Methods: This registry study included patients from the International Watch & Wait Database. Patients were categorized as having a cCR at first reassessment or at later reassessment (that is near-cCR at first reassessment) based on MRI and endoscopy. Organ preservation, distant metastasis-free survival, and overall survival rates were calculated. Subgroup analyses were done for nearcCR groups based on the response evaluation according to modality. Results: A total of 1010 patients were identified. At first reassessment, 608 patients had a cCR; 402 had a cCR at later reassessment. Median follow-up was 2.6 years for patients with a cCR at first reassessment and 2.9 years for those with a cCR at later reassessment. The 2-year organ preservation rate was 77.8 (95 per cent c.i. 74.2 to 81.5) and 79.3 (75.1 to 83.7) per cent respectively (P = 0.499). Similarly, no differences were found between groups in distant metastasis-free survival or overall survival rate. Subgroup analyses showed a higher organ preservation rate in the group with a near-cCR categorized exclusively by MRI. Conclusion: Oncological outcomes for patients with a cCR at later reassessment are no worse than those of patients with a cCR at first reassessment. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to assess the clinical and oncological outcome of a selected group of stage IV rectal cancer patients managed by the watch‐and‐wait approach following a (near‐)complete response of the primary rectal tumour after radiotherapy. Method: Patients registered in the Dutch watch‐and‐wait registry since 2004 were selected when diagnosed with synchronous stage IV rectal cancer. Data on patient characteristics, treatment details, follow‐up and survival were collected. The 2‐year local regrowth rate, organ‐preservation rate, colostomy‐free rate, metastatic progression‐free rate and 2‐ and 5‐year overall survival were analysed. Results: After a median follow‐up period of 35 months, local regrowth was observed in 17 patients (40.5%). Nine patients underwent subsequent total mesorectal excision, resulting in a permanent colostomy in four patients. The 2‐year local regrowth rate was 39.9%, the 2‐year organ‐preservation rate was 77.1%, the 2‐year colostomy‐free rate was 88.1%, and the 2‐year metastatic progression‐free rate was 46.7%. The 2‐ and 5‐year overall survival rates were 92.0% and 67.5%. Conclusion: The watch‐and‐wait approach can be considered as an alternative to total mesorectal excision in a selected group of stage IV rectal cancer patients with a (near‐)complete response following pelvic radiotherapy. Despite a relatively high regrowth rate, total mesorectal excision and a permanent colostomy can be avoided in the majority of these patients. [ABSTRACT FROM AUTHOR]

Background: Young-onset rectal cancer, in patients less than 50 years, is expected to increase in the coming years. A watch-and-wait strategy is nowadays increasingly practised in patients with a clinical complete response (cCR) after neoadjuvant treatment. Nevertheless, there may be reluctance to offer organ preservation treatment to young patients owing to a potentially higher oncological risk. This study compared patients aged less than 50 years with those aged 50 years or more to identify possible differences in oncological outcomes of watch and wait. Methods: The study analysed data from patients with a cCR after neoadjuvant therapy in whom surgery was omitted, registered in the retrospective-prospective, multicentre International Watch & Wait Database (IWWD). Results: In the IWWD, 1552 patients met the inclusion criteria, of whom 199 (12.8 per cent) were aged less than 50 years. Patients younger than 50 years had a higher T category of disease at diagnosis (P=0.011). The disease-specific survival rate at 3 years was 98 (95 per cent c.i. 93 to 99) per cent in this group, compared with 97 (95 to 98) per cent in patients aged over 50 years (hazard ratio (HR) 1.67, 95 per cent c.i. 0.76 to 3.64; P=0.199). The cumulative probability of local regrowth at 3 years was 24 (95 per cent c.i. 18 to 31) per cent in patients less than 50 years and 26 (23 to 29) per cent among those aged 50 years or more (HR 1.09, 0.79 to 1.49; P=0.603). Both groups had a cumulative probability of distant metastases of 10 per cent at 3 years (HR 1.00, 0.62 to 1.62; P=0.998). Conclusion: There is no additional oncological risk in young patients compared with their older counterparts when following a watch-and-wait strategy after a cCR. In light of a shared decision-making process, watch and wait should be also be discussed with young patients who have a cCR after neoadjuvant treatment. [ABSTRACT FROM AUTHOR]

Background and Aims The long-term safety and efficacy of allogeneic bone marrow-derived mesenchymal stromal cell [bmMSC] therapy in perianal Crohn's disease [CD] fistulas is unknown. We aimed to provide a 4-year clinical evaluation of allogeneic bmMSC treatment of perianal CD fistulas. Methods A double-blind dose-finding study for local bmMSC therapy in 21 patients with refractory perianal fistulising Crohn's disease was performed at the Leiden University Medical Center in 2012–2014. All patients treated with bmMSCs [1 x 107 bmMSCs cohort 1, n = 5; 3 × 107 bmMSCs cohort 2, n = 5; 9 × 107 bmMSCs cohort 3, n = 5] were invited for a 4-year evaluation. Clinical events were registered, fistula closure was evaluated, and anti-human leukocyte antigen [HLA] antibodies were assessed. Patients were also asked to undergo a pelvic magnetic resonance imaging [MRI] and rectoscopy. Results Thirteen out of 15 patients [87%] treated with bmMSCs were available for long-term follow-up. Two non-MSC related malignancies were observed. No serious adverse events thought to be related to bmMSC therapy were found. In cohort 2 [ n = 4], all fistulas were closed 4 years after bmMSC therapy. In cohort 1 [ n = 4] 63%, and in cohort 3 [ n = 5] 43%, of the fistulas were closed, respectively. In none of the patients anti-HLA antibodies could be detected 24 weeks and 4 years after therapy. Pelvic MRI showed significantly smaller fistula tracts after 4 years. Conclusions Allogeneic bmMSC therapy for CD-associated perianal fistulas is also in the long-term a safe therapy. In bmMSC-treated patients, fistulas with closure at Week 24 were still closed after 4 years. [ABSTRACT FROM AUTHOR]

Based on more than 11 years of follow-up, autopsy-based analysis of recurrence in the Dutch D1-D2 Trial permits meaningful assessment of patterns of failure with respect to the Maruyama Index (MI). We previously reported that a low Maruyama Index was an independent predictor of both overall and disease-specific survival. Autopsy results are available for 441 deaths on study. Distant-only failure (15% vs 13%) was no different between the MI categories, but isolated “regional” failure (8% for MI < 5 group vs 21%) and “regional + distant” failure (19% for MI < 5 group vs 36%) occurred less frequently in the MI < 5 group ( P < 0.001). We conclude that “low Maruyama Index” surgery enhances regional control and survival but does not alter the occurrence of isolated distant metastases unassociated with regional failure. Our results speak to the substantial survival value of local-regional control in this disease. [ABSTRACT FROM AUTHOR]

In case of suspicion of a T1 colorectal tumor, the tumor should not be biopsied but removed completely (so-called en-bloc resection). With more recent endoscopic techniques, T1 colorectal tumors can be more often radical resected. If at least one of the following four characteristics is present, there is a high-risk T1 colorectal tumor and it is recommended to consider surgical resection with adequate lymphadenectomy; poor differentiation, presence of (lymphatic) angioinvasion, high-grade tumor budding (grade 2-3) and a positive resection margin (where the malignant cells approach the cut edge to 0.1mm). The risk of recurrent disease after endoscopic resection of a high-risk T1 colorectal tumor without additional surgery is not well known. Scheduled surgery for bowel cancer at an early stage is associated with the same risk of a serious complication and/or death as scheduled surgery at a more advanced stage.