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Chronic watery diarrhea is a frequent symptom. In approximately 10% of the patients, a diagnosis of microscopic colitis (MC) is established. The diagnosis relies on specific, but sometimes subtle, histopathological findings. As the histology of normal intestinal mucosa vary, discriminating subtle features of MC from normal tissue can be challenging and therefore auxiliary stainings are increasingly used. The aim of this study was to determine the variance in number of intraepithelial lymphocytes (IELs) and presence of a subepithelial band in normal ileum and colonic mucosa, according to different stains and digital assessment. Sixty-one patients without diarrhea referred to screening colonoscopy due to a positive feacal blood test and presenting with endoscopically normal mucosa were included. Basic histological features, number of IELs, and thickness of a subepithelial band was manually evaluated and a deep learning-based algorithm was developed to digitally determine the number of IELs in each of the two compartments; surface epithelium and cryptal epithelium, and the density of lymphocytes in the lamina propria compartment. The number of IELs was significantly higher on CD3-stained slides compared with slides stained with Hematoxylin-and-Eosin (HE) (p<0.001), and even higher numbers were reached using digital analysis. No significant difference between right and left colon in IELs or density of CD3-positive lymphocytes in lamina propria was found. No subepithelial band was present in HE-stained slides while a thin band was visualized on special stains. Conclusively, in this cohort of prospectively collected ileum and colonic biopsies from asymptomatic patients, the range of IELs and detection of a subepithelial collagenous band varied depending on the stain and method used for assessment. As assessment of biopsies from patients with diarrhea constitute a considerable workload in the pathology departments digital image analysis is highly desired. Knowledge prov, Chronic watery diarrhea is a frequent symptom. In approximately 10% of the patients, a diagnosis of microscopic colitis (MC) is established. The diagnosis relies on specific, but sometimes subtle, histopathological findings. As the histology of normal intestinal mucosa vary, discriminating subtle features of MC from normal tissue can be challenging and therefore auxiliary stainings are increasingly used. The aim of this study was to determine the variance in number of intraepithelial lymphocytes (IELs) and presence of a subepithelial band in normal ileum and colonic mucosa, according to different stains and digital assessment. Sixty-one patients without diarrhea referred to screening colonoscopy due to a positive feacal blood test and presenting with endoscopically normal mucosa were included. Basic histological features, number of IELs, and thickness of a subepithelial band was manually evaluated and a deep learning-based algorithm was developed to digitally determine the number of IELs in each of the two compartments; surface epithelium and cryptal epithelium, and the density of lymphocytes in the lamina propria compartment. The number of IELs was significantly higher on CD3-stained slides compared with slides stained with Hematoxylin-and-Eosin (HE) (p<0.001), and even higher numbers were reached using digital analysis. No significant difference between right and left colon in IELs or density of CD3-positive lymphocytes in lamina propria was found. No subepithelial band was present in HE-stained slides while a thin band was visualized on special stains. Conclusively, in this cohort of prospectively collected ileum and colonic biopsies from asymptomatic patients, the range of IELs and detection of a subepithelial collagenous band varied depending on the stain and method used for assessment. As assessment of biopsies from patients with diarrhea constitute a considerable workload in the pathology departments digital image analysis is highly desired. Knowledge p

Background In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking. Methods We conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes. Results A total of 10 patients were included in the trial. Median patient age was 70 years (range 54-78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I-III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm 2, p<0.05), along with significant downregulation of messenger RNA gene expression related to neutrophils and upregulation of transcripts encoding cytotoxic functions. Spatial protein analysis showed significant local upregulation of programmed death-ligand 1 (PD-L1) (adjusted p value<0.05) and downregulation of FOXP3 (adjusted p value<0.05). Conclusions Neoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infiltration and upregulation of PD-L1 proficient mismatch repair sigmoid and rectal tumors. Definiti

Background and study aims Colorectal cancer is one of the most common malignancies, with approximately 20 % of patients having metastatic disease. Local symptoms from the tumor remain a common issue and affect quality of life. Electroporation is a method to permeabilize cell membranes with high-voltage pulses, allowing increased passage of otherwise poorly permeating substances such as calcium. The aim of this study was to determine the safety of calcium electroporation for advanced colorectal cancer. Patients and methods Six patients with inoperable rectal and sigmoid colon cancer were included, all presenting with local symptoms. Patients were offered endoscopic calcium electroporation and were followed up with endoscopy and computed tomography/magnetic resonance scans. Biopsies and blood samples were collected at baseline and at follow-up, 4, 8, and 12 weeks after treatment. Biopsies were examined for histological changes and immunohistochemically with CD3/CD8 and PD-L1. In addition, blood samples were examined for circulating cell-free DNA (cfDNA). Results A total of 10 procedures were performed and no serious adverse events occurred. Prior to inclusion, patients reported local symptoms, such as bleeding (N = 3), pain (N = 2), and stenosis (N = 5). Five of six patients reported symptom relief. In one patient, also receiving systemic chemotherapy, clinical complete response of primary tumor was seen. Immunohistochemistry found no significant changes in CD3 /CD8 levels or cfDNA levels after treatment. Conclusions This first study of calcium electroporation for colorectal tumors shows that calcium electroporation is a safe and feasible treatment modality for colorectal cancer. It can be performed as an outpatient treatment and may potentially be of great value for fragile patients with limited treatment options.

Cancersygdomme er årsag til høj morbiditet og mortalitet og fylder meget i sundhedssystemet inden for både kliniske og diagnostiske specialer. I 2020 blev der registreret knap 20 mio. nye tilfælde af cancer og 10 mio. cancerrelaterede dødsfald på verdensplan [1]. En god prognose afhænger i høj grad af detektion af cancersygdommen i et tidligt stadie, inden canceren har spredt sig til lymfeknuder eller andre organer. Lokaliserede lymfeknudemetastaser på diagnosetidspunktet forekommer hyppigt, og risikoen øges i takt med primærtumorens udbredelse angivet som T-stadie [2]. Andre faktorer, herunder tumorens størrelse, den histologiske subtype og differentieringsgraden, er ligeledes af betydning for tumorens potentiale til at sprede sig via lymfesystemet [3]. Et stigende antal ældre i befolkningen kombineret med øget levealder og bedre behandlingsmuligheder betyder unægteligt, at man vil se en stigning i antallet af patienter med mere end én malign sygdom. Der kan enten være tale om samtidige eller tidsmæssigt adskilte diagnosetidspunkter. Ved mistanke om cancer vil udredningen ud over klinisk undersøgelse, blodprøver og billeddiagnostiske undersøgelser bestå i, at der tages biopsier fra tumoren, og de sendes til undersøgelse på en patologiafdeling. Hvis der er tale om en malign tumor, forsøges det primære udgangspunkt bestemt på baggrund af biopsimaterialet. For patienter, der får foretaget resektion af en tumor, bliver operationspræparatet efterfølgende grundigt undersøgt, og der bliver foretaget en endelig stadieinddeling. Herudover vil der blive undersøgt for tilstedeværelse af specifikke risikofaktorer som f.eks. kar- og nerveindvækst. Den histologiske undersøgelse er således af afgørende betydning for behandlingsforløbet og danner baggrund for vurdering af behovet for efterfølgende onkologisk behandling. Af og til påvises ved den histologiske undersøgelse uventede fund som kollisionstumorer og kollisionsmetastaser, som der ikke var nogen mistanke, Cancer is a cause of high morbidity and mortality. It is not uncommon for a patient to have more than one primary tumour. This review summarises the knowledge of collision tumours which are defined as two adjacent neoplasms in the same organ, while a collision metastasis is the rare occurrence of two different primary cancers metastasising to the same anatomical site. Identification of collision metastasis is a diagnostic challenge and relies on histopathological examination. As it might have profound impact on prognosis and treatment decisions, it is important to create awareness among both pathologists and clinicians of this phenomenon.

Background In colorectal cancer, the effects of immune checkpoint inhibitors are mostly limited to patients with deficient mismatch repair tumors, characterized by a high grade infiltration of CD8+T cells. Interventions aimed at increasing intratumoral CD8+T-cell infiltration in proficient mismatch repair tumors are lacking.Methods We conducted a proof of concept phase 1/2 clinical trial, where patients with non-metastasizing sigmoid or rectal cancer, scheduled for curative intended surgery, were treated with an endoscopic intratumorally administered neoadjuvant influenza vaccine. Blood and tumor samples were collected before the injection and at the time of surgery. The primary outcome was safety of the intervention. Evaluation of pathological tumor regression grade, immunohistochemistry, flow cytometry of blood, tissue bulk transcriptional analyses, and spatial protein profiling of tumor regions were all secondary outcomes.Results A total of 10 patients were included in the trial. Median patient age was 70 years (range 54–78), with 30% women. All patients had proficient mismatch repair Union of International Cancer Control stage I–III tumors. No endoscopic safety events occurred, with all patients undergoing curative surgery as scheduled (median 9 days after intervention). Increased CD8+T-cell tumor infiltration was evident after vaccination (median 73 vs 315 cells/mm2, p<0.05), along with significant downregulation of messenger RNA gene expression related to neutrophils and upregulation of transcripts encoding cytotoxic functions. Spatial protein analysis showed significant local upregulation of programmed death-ligand 1 (PD-L1) (adjusted p value<0.05) and downregulation of FOXP3 (adjusted p value<0.05).Conclusions Neoadjuvant intratumoral influenza vaccine treatment in this cohort was demonstrated to be safe and feasible, and to induce CD8+T-cell infil

Aim It is often safe to treat pT1 tumours with local resection due to the low risk of lymph node metastasis. The risk of lymph node metastasis in pT2 colon cancer is less well investigated. The recommendation for patients diagnosed with T2 colon cancer is a segmental resection including regional lymph nodes. The aim of this work was to determine the risk of lymph node metastasis in pT2 colon cancer and identify the possible associated clinical and pathological risk factors for lymph node metastasis. Method PubMed and Embase were systematically searched for studies describing patients with T2 colon cancer and lymph node status after histopathological assessment. Lymph node metastasis and the effect of histological and clinical factors were included. Results Overall, 5489 studies were screened, and 10 studies consisting of a total of 91 460 patients were included in the review. The overall risk of lymph node metastasis was 19.3% (95% confidence interval 19.0%–19.5%). A meta-analysis was not possible as very few studies described the clinical and pathological risk factors for lymph node metastasis. Conclusion The risk of lymph node metastasis in patients with pT2 colon cancers is higher than for pT1. The studies included patients operated on from 1985 to 2015 with variations in surgical procedure, pathological handling, and definition of lymph node metastasis. Further studies reporting risk factors for lymph node metastasis in pT2 colon cancer are warranted as more data are needed to determine if local resection for a subgroup of patients could be an alternative treatment modality., Aim: It is often safe to treat pT1 tumours with local resection due to the low risk of lymph node metastasis. The risk of lymph node metastasis in pT2 colon cancer is less well investigated. The recommendation for patients diagnosed with T2 colon cancer is a segmental resection including regional lymph nodes. The aim of this work was to determine the risk of lymph node metastasis in pT2 colon cancer and identify the possible associated clinical and pathological risk factors for lymph node metastasis. Method: PubMed and Embase were systematically searched for studies describing patients with T2 colon cancer and lymph node status after histopathological assessment. Lymph node metastasis and the effect of histological and clinical factors were included. Results: Overall, 5489 studies were screened, and 10 studies consisting of a total of 91 460 patients were included in the review. The overall risk of lymph node metastasis was 19.3% (95% confidence interval 19.0%–19.5%). A meta-analysis was not possible as very few studies described the clinical and pathological risk factors for lymph node metastasis. Conclusion: The risk of lymph node metastasis in patients with pT2 colon cancers is higher than for pT1. The studies included patients operated on from 1985 to 2015 with variations in surgical procedure, pathological handling, and definition of lymph node metastasis. Further studies reporting risk factors for lymph node metastasis in pT2 colon cancer are warranted as more data are needed to determine if local resection for a subgroup of patients could be an alternative treatment modality.