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Aim: Palliative rectal cancer patients typically retain their primary tumour, as trials have concluded no survival benefit of tumour resection in non-curative patients. This patient group is understudied regarding the natural course of the remaining tumour, particularly concerning the need of surgical management.

Method: This was a retrospective study on rectal cancer patients diagnosed between 2007 and 2020 in Region Västerbotten, Sweden. Data were obtained from the Swedish Colorectal Cancer Registry and chart review. Patients were excluded if treated with curative intent, underwent primary tumour resection, had a synchronous colorectal cancer, had locally recurrent colorectal cancer, or refused treatment. Patients were followed from diagnosis until death or end of follow-up. Indications for palliative treatment, tumour-related complications and surgical and oncological management were investigated, with a stratified analysis for study period and patient age.

Results: Some 156 patients remained after applying exclusion criteria. The majority had metastasized and incurable disease (76%). Almost half suffered local complications (44%) and 48% underwent surgical intervention, due to the unremoved primary tumour. Tumour perforation occurred in 7% with a significantly higher risk in patients aged ≤75 years (p = 0.009). Bowel obstruction afflicted 23%, while 40% underwent stoma diversion. Almost half received chemotherapy (48%) and radiotherapy (42%), respectively.

Conclusion: Rectal cancer patients with an unremoved primary tumour face a substantial risk of local complications, often necessitating surgical intervention. Therefore, the benefits of surgical resection should be carefully considered, especially for patients with a longer estimated survival. Further research is needed to accurately identify patients where tumour removal might be beneficial.

Purpose: To evaluate current MRI-based criteria for malignancy in mesorectal nodal structures in rectal cancer.

Method: Mesorectal nodal structures identified on baseline MRI as lymph nodes were anatomically compared to their corresponding structures histopathologically, reported as lymph nodes, tumour deposits or extramural venous invasion. All anatomically matched nodal structures from patients with primary surgery and all malignant nodal structures from patients with neoadjuvant treatment were included. Mixed-effects logistic regression models were used to evaluate the morphological criteria irregular margin, round shape, heterogeneous signal and nodal size, as well as the combined 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus criteria, with histopathological nodal status as the gold standard.

Results: In total, 458 matched nodal structures were included from 46 patients (mean age, 67.7 years ± 1.5 [SD], 27 men), of which 19 received neoadjuvant treatment. The strongest associations in the univariable model were found for short-axis diameter ≥ 5 mm (OR 21.43; 95% CI: 4.13–111.29, p < 0.001) and heterogeneous signal (OR 9.02; 95% CI: 1.33–61.08, p = 0.024). Only size remained significant in multivariable analysis (OR 12.32; 95% CI: 2.03–74.57, p = 0.006). When applying the ESGAR consensus criteria to create a binary classification of nodal status, the OR of malignant outcome for nodes with positive ESGAR was 8.23 (95% CI: 2.15–31.50, p = 0.002), with corresponding sensitivity and specificity of 54% and 85%, respectively.

Conclusion: The results confirm the role of morphological and size criteria in predicting lymph node metastases. However, the current criteria might not be accurate enough for nodal staging.

Background: Large bowel obstruction is a possible complication in patients undergoing neoadjuvant treatment for rectal cancer; however, it may be prevented by placing a pretreatment defunctioning stoma. The aim of this retrospective study was to investigate complication rates in patients with rectal cancer undergoing long-course neoadjuvant therapy, comparing those with and without a prophylactic stoma.

Methods: All patients with rectal cancer undergoing neoadjuvant therapy between 2007 and 2022 in Region Västerbotten, Sweden, were identified using the Swedish Colorectal Cancer Registry. Patients not planned for curative long-course neoadjuvant therapy and those requiring a stoma due to urgent bowel-related issues before treatment were excluded. The primary outcome was the incidence of complications between diagnosis and resection surgery or end of follow-up. The secondary outcomes were 30-day complications following resection, time to treatment (neoadjuvant therapy and surgery), and overall survival. Multivariable regression analysis was used, with adjustment for age, sex, American Society of Anesthesiologists fitness grade, and clinical tumour stage.

Results: Of 482 identified patients, 105 were analysed after exclusion. Among these, 22.9% (24 of 105) received a pretreatment stoma, whereas 77.1% (81 of 105) received upfront neoadjuvant therapy. The complication incidence before resection in the group with a defunctioning stoma and in the group without a defunctioning stoma was 75.0% (18 of 24) and 29.6% (24 of 81) respectively. A considerable number of complications were directly caused by the stoma surgery. Patients in the stoma group had an adjusted OR of 6.71 (95% c.i. 2.17 to 20.76) for any complication. However, for 30-day complications following resection, an adjusted non-significant OR of 2.05 (95% c.i. 0.62 to 6.81) was documented for the stoma group, in comparison with the control group. Neoadjuvant treatment was also delayed for the stoma group (adjusted mean time difference: 21 (95% c.i. 14 to 27) days), whereas the difference was not significant for the time to resection surgery. The median survival after diagnosis was 4.7 years in the stoma group and 12.2 years in the control group (P = 0.015); however, adjustment in the multivariable analysis rendered the estimate non-significant (HR 1.71 (95% c.i. 0.93 to 3.14)).

Conclusion: Patients with rectal cancer who receive a stoma before long-course neoadjuvant therapy, in the absence of urgent symptoms, experience more complications than those without a stoma and a delay with regard to the start of neoadjuvant treatment.

Introduction: Diagnosis and monitoring of metastatic colorectal cancer (mCRC) depend on diagnostic imaging. Circulating carcinoembryonic antigen (CEA) can be analyzed but no optimal, non-invasive biomarker exists. Circulating collagen IV (COL IV) is a promising biomarker in patients with colorectal liver metastases (CLM). This study aimed to evaluate COL IV and other cancer-related and stroma-derived proteins as biomarkers for mCRC.

Materials & methods: Plasma COL IV and 10 other proteins were analyzed with ELISA and Luminex multiplex assays.

Results: mCRC patients have elevated levels of circulating COL IV, CEA, interleukin-8 (IL-8), hepatocyte growth factor (HGF), cytokeratin-19 fragments (CYFRA 21-1), osteopontin (OPN), and migration inhibitory factor (MIF) compared to primary CRC (pCRC) patients. COL IV is elevated in mCRC patients compared to healthy individuals. Levels of COL IV, CEA, OPN, CYFRA 21-1, IL-8, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) were dependent on the metastatic site. OPN, CEA, and HGF are very good at discriminating between mCRC patients and pCRC controls. COL IV is very good at distinguishing between mCRC patients and healthy controls. The combination of OPN + CEA is superior at detecting mCRC than CEA alone. High HGF and COL IV levels correlate to poor prognosis.

Conclusion: OPN, CEA, and HGF are potential biomarkers for mCRC. COL IV is a potential biomarker for CLM. The combination of OPN with CEA is superior to CEA alone in detecting mCRC. Levels of circulating proteins depend on metastatic localization, implying that a combination of markers is better than single markers in detecting mCRC disease. High levels of COL IV and HGF have potential prognostic value.

Background: The immune response has important clinical value in colorectal cancer (CRC) in both prognosis and response to immunotherapy. This study aims to explore tumour immune cell infiltration in relation to clinically well-established molecular markers of CRC.

Methods: Multiplex immunohistochemistry and multispectral imaging was used to evaluate tumour infiltration of cytotoxic T cells (CD8+), Th1 cells (T-bet+), T regulatory cells (FoxP3+), B cells (CD20+), and macrophages (CD68+) in a cohort of 257 CRC patients.

Results: We found the expected association between higher immune-cell infiltration and microsatellite instability. Also, whereas BRAF-mutated tumours displayed increased immune-cell infiltration compared to BRAF wild-type tumours, the opposite was seen for KRAS-mutated tumours, differences that were most prominent for cytotoxic T cells and Th1 cells. The opposing relationships of BRAF and KRAS mutations with tumour infiltration of cytotoxic T cells was validated in an independent cohort of 608 CRC patients. A positive prognostic importance of cytotoxic T cells was found in wild-type as well as KRAS and BRAF-mutated CRCs in both cohorts.

Conclusion: A combined evaluation of MSI status, KRAS and BRAF mutational status, and immune infiltration (cytotoxic T cells) may provide important insights to prognosis and response to immunotherapy in CRC.

Background: Mounting evidence suggests a significant role of the gut microbiota in the development and progression of colorectal cancer (CRC). In particular, an over-representation of oral pathogens has been linked to CRC. The aim of this study was to further investigate the faecal microbial landscape of CRC patients, with a focus on the oral pathogens Parvimonas micra and Fusobacterium nucleatum.

Methods: In this study, 16S rRNA sequencing was conducted using faecal samples from CRC patients (n = 275) and controls without pathological findings (n = 95).

Results: We discovered a significant difference in microbial composition depending on tumour location and microsatellite instability (MSI) status, with P. micra, F. nucleatum, and Peptostreptococcus stomatis found to be more abundant in patients with MSI tumours. Moreover, P. micra and F. nucleatum were associated with a cluster of CRC-related bacteria including Bacteroides fragilis as well as with other oral pathogens such as P. stomatis and various Porphyromonas species. This cluster was distinctly different in the control group, suggesting its potential linkage with CRC.

Conclusions: Our results suggest a similar distribution of several CRC-associated bacteria within CRC patients, underscoring the importance of considering the concomitant presence of bacterial species in studies investigating the mechanisms of CRC development and progression.

Colorectal cancer is caused by a sequence of somatic genomic alterations affecting driver genes in core cancer pathways1. Here, to understand the functional and prognostic impact of cancer-causing somatic mutations, we analysed the whole genomes and transcriptomes of 1,063 primary colorectal cancers in a population-based cohort with long-term follow-up. From the 96 mutated driver genes, 9 were not previously implicated in colorectal cancer and 24 had not been linked to any cancer. Two distinct patterns of pathway co-mutations were observed, timing analyses identified nine early and three late driver gene mutations, and several signatures of colorectal-cancer-specific mutational processes were identified. Mutations in WNT, EGFR and TGFβ pathway genes, the mitochondrial CYB gene and 3 regulatory elements along with 21 copy-number variations and the COSMIC SBS44 signature correlated with survival. Gene expression classification yielded five prognostic subtypes with distinct molecular features, in part explained by underlying genomic alterations. Microsatellite-instable tumours divided into two classes with different levels of hypoxia and infiltration of immune and stromal cells. To our knowledge, this study constitutes the largest integrated genome and transcriptome analysis of colorectal cancer, and interlinks mutations, gene expression and patient outcomes. The identification of prognostic mutations and expression subtypes can guide future efforts to individualize colorectal cancer therapy.

Aim: To investigate whether patients with endoscopically untraversable rectal cancer may benefit from a defunctioning stoma created before neoadjuvant therapy or resectional surgery.

Methods: This retrospective study comprise patients diagnosed with rectal cancer during 2007–2020 in Region Västerbotten, Sweden. The primary outcome was time between diagnosis and any treatment, while survival and the incidence of complications were secondary outcomes. Excluded were patients without endoscopic obstruction, patients already having a stoma, patients with recurrent disease, palliative patients, and patients receiving a stoma shortly after diagnosis due to any urgent bowel-related complication. Data were obtained from the Swedish Colorectal Cancer Registry and medical records. Kaplan–Meier failure curves were drawn, and a multivariable Cox regression model was employed for confounding adjustment.

Results: Out of 843 patients, 57 remained after applying exclusion criteria. Some 12/57 (21%) patients received a planned stoma before treatment, and the remainder received upfront neoadjuvant therapy or surgery. Median time to any treatment was 51 days for the planned stoma group and 36 days for the control group, with an adjusted hazard ratio of 0.28 (95% confidence interval: 0.12–0.64). Complications occurred at a rate of 5/12 (42%) and 7/45 (16%) in the planned stoma group and control group, respectively. Survival was similar between groups.

Conclusion: A planned stoma results in treatment delay, but it remains unclear whether this is clinically relevant. Complications were more common in the planned stoma group, although the data are limited. While larger studies are needed, it seems feasible to avoid defunctioning stomas even in endoscopically obstructing rectal cancers.

Microbiota dysbiosis may affect both the development and progression of colorectal cancer (CRC). Large metagenomic studies have highlighted specific oral bacteria linked to CRC including Porphyromonas gingivalis. Few studies have however analysed the implications of this bacterium in CRC progression and survival. In this study, we investigated the intestinal presence of P. gingivalis by qPCR in both faecal and mucosal samples from two different patient cohorts, including patients with precancerous dysplasia or CRC, as well as controls. P. gingivalis was detected in 2.6-5.3% of CRC patients and significantly different levels of P. gingivalis were found in faeces of CRC patients compared to controls (P = 0.028). Furthermore, an association was found between the presence of P. gingivalis in faeces and tumour tissue (P < 0.001). Our findings further suggested a potential link between mucosal P. gingivalis and tumours of MSI subtype (P = 0.040). Last but not least, patients with faecal P. gingivalis were found to have a significantly decreased cancer-specific survival (P = 0.040). In conclusion, P. gingivalis could be linked to patients with CRC and to a worse patient prognosis. Further studies are needed to elucidate the role of P. gingivalis in CRC pathogenesis.

The importance of the tumour microbiome in different aspects of colorectal cancer (CRC) has been increasingly recognised, but many questions remain. The aim of this study was to explore the effect of specific CRC associated microbes on the tumour immune response, which has a considerable prognostic value in CRC. We applied specific qPCR to detect Parvimonas micra and Fusobacterium nucleatum in tumour tissues from an immunologically well-characterised cohort of 69 CRC patients. This cohort included detailed analyses of immune profiles based on flow cytometry and transcriptomics in tumour tissue and blood, along with comprehensive analyses of molecular subtypes. P. micra and F. nucleatum were detected in 24% and 64% of tumour tissues, respectively. We found a significant association of P. micra with high-grade tumours and tumours of CMS1 subtype. F. nucleatum was significantly associated with right-sided tumours, microsatellite instability, and CMS1 tumours. The immunological analyses revealed significant associations of P. micra with activated CD69+ T lymphocytes and increased antigen-presenting HLA-DR+ B lymphocytes. P. micra was also positively associated with M1 and M2 macrophage traits. The impact of P. micra tumour colonisation on the immune response was further assessed using transcriptomics in validation of our findings. No associations were found between F. nucleatum and immune profiles in this study. Our findings support novel associations between P. micra and the immune response in CRC. A better understanding of these interactions might help to identify important predictive and prognostic tools as well as new targets for therapy.