Introduction

It has been suggested that the development of cancer chemotherapy resistance may result from the intricate interplay between gene regulation and external environmental factors. Immune biomarkers hold promise as prognostic indicators for the efficacy of chemoradiotherapy; nevertheless, to date, none have been successfully achieved in routine clinical practice.

Aims & Methods

This study is a sub-analysis of data from the prospective IMMUNOREACT 2 trial (NCT04917263) including all the patients who underwent adjuvant therapy. Healthy rectal mucosa adjacent to the cancer was collected during surgery. Gene expression profiling was performed with Nanostring technology using nCounter® PanCancer IO 360™ Panel. Prospectively collected rectal mucosa samples were subjected to flow cytometry to determine the proportion of epithelial cells (Cyt-20⁺) acting as antigen-presenting cells (expressing CD80, CD86, HLA ABC), activated T cells (expressing CD25, CD28, CD38), regulatory T cells (CD4⁺CD25⁺FoxP3⁺) or exhausted T cells (CTLA-4⁺). Non-parametric tests were used for small sample size comparisons. This study aims to evaluate immune biomarkers' role in determining adjuvant therapy's effectiveness in rectal cancer (RC) patients.

Results

A total of 31 patients with RC who underwent adjuvant therapy included in the prospective IMMUNOREACT 2 cohort were analyzed; during a median follow-up time of 20.8 months, 7 patients experienced relapse. Preliminary gene expression analysis on 19 specimens revealed 25 differentially expressed genes between patients who relapsed (n=3) and those who did not (n=16) (Fig. 1 A, B). In particular, in the normal rectal mucosa of patients who relapsed, downregulation of genes associated with macrophages (CD163, CEBPB, MARCO, MS4A2, MS4A4A, MS4A6A, SIGLEC1), inflammation (CCL8, C5, C5AR1, IL11RA, TIE1) and lymphocytes stimulation (VTCN1, TNFSF13B) was observed. Relapse was associated with a high CD8⁺ CD28⁺ cytotoxic lymphocytes mean fluorescence intensity (MFI) (p= 0.05). The accuracy of predicting relapse was AUC=0.765 for CD8⁺CD28⁺ MFI (Fig. 2 A, B).

Conclusion

Our preliminary data suggest that the immune-related markers signature in the healthy peritumoral mucosa might be useful for predicting relapse after adjuvant therapy in rectal cancer patients. Moreover, relapsing patients showed lower stimulation of macrophages and lymphocytes, thus suggesting that impaired immune surveillance might influence adjuvant therapy outcomes. Sampling healthy mucosa might help the decision-making about adjuvant therapy after surgery for rectal cancer.

Introduction

In Hungary, the population-based colorectal carcinoma (CRC) screening programme was introduced at the end of 2018, shortly before the start of the COVID-19 pandemic.

Aims & Methods

The aim of our retrospective cohort study was to evaluate the impact of two presumably opposing causal factors, COVID-19 pandemic and population-based screening, on the incidence and clinical characteristics of CRC. All patients with newly diagnosed CRC from 2014 to 2023 were included and categorized into pre-pandemic (confirmed between 2014-2019), pandemic (confirmed in 2020-2021) and post-pandemic (confirmed in 2022-2023) groups. The extended pre-pandemic period was required to assess the impact of the screening programme, further dividing it into screening-affected (2015, 2016, and 2019) and unaffected (2014, 2017, 2018) subgroups.

Results

A total of 2803 patients were diagnosed with CRC during the study period. The annual number of CRC cases was significantly lower in the pandemic subgroup compared to the pre-pandemic screened and post-pandemic subgroups (254/year, 295/year and 295/year, p=0.009). In addition, in the pandemic subgroup, the incidence rates of CRCs detected at localized stage were significantly lower compared to the other three groups (36.61%, 50.85%, 46.35% and 49.49%, p<0.001). Statistically significant difference in the rate of T1 tumors was only observed between the pandemic and the post-pandemic subgroups (7.09% and 12.20%, p=0.026). In the pandemic period, the annual number of colonoscopies decreased by 64.31% compared to the pre-pandemic period overall, however, the post-pandemic period (n=4574) saw a modest 8.70% increase relative to the pre-pandemic period, offering only partial compensation for the shortage experienced during the pandemic. Furthermore, the annual number of colonoscopies in the extended pre-pandemic subgroup with screening was higher by 20.06% compared to the pre-pandemic subgroup without screening (4591 examinations/year vs 3824 examinations/year) and it was almost the same as the post-pandemic subgroup (4574 examinations/year). Substantially fewer examinations were required to detect a CRC in the pandemic group compared to the pre-pandemic overall and post-pandemic groups (10.67, 15.56, 13.97 and 15.50 examinations, respectively), but within the extended pre-pandemic group, there was no relevant difference between the two subgroups in the mean number of colonoscopies required to detect a CRC (15.56 vs. 13.97).

Conclusion

Our study confirmed the negative impact of COVID-19 pandemic on the CRC epidemiology. The newly introduced population-based CRC screening has only been able to partially compensate this negative effect during pandemic period, however, was moderately compensated by during the pandemic period, but in the post-pandemic period it caused a favorable change in the clinical features of CRC. Our study demonstrates both the effectiveness of the screening programme and that by introducing non-invasive pre-screening of patients (e.g. iFOBT) in a pandemic situation, it can reduce its negative public health impact.

Introduction

The Crohn’s Disease Activity Index (CDAI) is a widely used research tool used to quantify CD patient’ symptoms, evaluate the severity of CD and to determine treatment outcomes.^​

Aims & Methods

The objective of this study was to assess any nuances in treating CD patients with active disease (CDAI score >150), who have remained on the same advanced therapy (biologics/ novel oral molecules) for more than 6 months. The Ipsos CD Therapy Monitor, a multi-centre online medical chart review study of patients with CD was conducted between July – September 2023 among UK, FR, DE, IT & ES gastroenterologists practicing across hospital and private practices. Physicians were screened for practice duration and patient volume. Charts of patients prescribed with advanced therapy were included in the analysis.

Results

208 sampled physicians collectively reported 373 CD patients who were recorded as being on the same advanced therapy for more than 6 months. 286 reported patients were deemed in remission (CDAI score ≤ 150) and 87 patients recorded with active disease (CDAI score >150). Looking at reported CD patient co-morbidities, metabolic conditions were more common in patients with active disease vs those in remission (24% vs 19%)

When looking at extra-intestinal manifestations (EIMs) between the two patient groups, patients with active disease were more likely to experience EIMs vs those in remission.

Table 1: EIMs in reported CD patients (% patients)

CD patients	Patients with active disease (CDAI >150)	Patients in remission (CDAI ≤ 150)
% experienced anaemia	21%	11%
% experienced arthritis	9%	7%
% experienced osteoporosis	6%	2%

A higher proportion of patients with active disease activity were currently receiving non-tumour necrosis factor (TNF) therapy vs those in remission (37% vs 24%) and reported higher steroid usage (% reported patients currently on steroids – 11% vs 3%).

When analysing reasons for prescribing selected advanced therapy between the two patient groups, a greater proportion of patients with active disease had the following reasons specified more frequently by the sampled physicians, vs the patients in remission: ‘To achieve steroid-free remission’ (51% vs 43%), ‘Good safety profile’ (40% vs 35%), and ‘Low incidence of side-effects’ (35% vs 21%).

Conclusion

Comparisons in this study cohort highlighted that active disease in CD patients, as determined by the CDAI score, is associated with a higher number of patient co-morbidities and a greater likelihood of extra-intestinal manifestations; this indicates a more severe or complicated disease burden. As additional development products with new mechanisms of action become available in gastroenterology, non-TNF therapy usage may grow over time to provide more holistic and individualised treatment strategies for CD patients. Further investigation using comparator cohort is warranted.

References

[1] Use of the Crohn’s disease activity index in clinical trials of biological agents, Hugh James Freeman https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725371/

Disclosure

No

Introduction

The early-stage pancreatic cancer (e-PC; stage I/II) detection rate is very low at approximately 25%. The role of general physician is very important for e-PC detection.

Aims & Methods

The aim of this study was to evaluate the effectiveness of the check score sheet used clinical findings to detect e-PC in gastroenterology clinic.
Patients of clinic with a score of ≥ 2 points on clinical findings were enrolled: symptoms of abdominal pain/back pain and/or body weight loss (1 point), high amylase, lipase and/or trypsin (1 point), high carbohydrate antigen 19-9 (CA19-9) (1 point), new-onset or worsened diabetes (2 point), family history of pancreatic cancer (2 points) and ultrasonography (US) findings including direct (e.g., a solid pancreatic tumor) and/or indirect findings (e.g., dilatation of a pancreatic diameter of ≥ 2 mm and/or cystic lesions) (2 points). Abdominal CT and/or EUS (Endoscopic ultrasonography) were performed for all these enrolled patients, and we evaluated about pancreatic disease and pancreatic cancer detection rates of this check score sheet.

Results

Between July 2017 and March 2024, 621 patients (mean age 67.6 years, female 391 [63%]), were enrolled in clinic. The 458 pancreatic cystic disease (IPMN and SCN) cases (73.7%), the 28 chronic pancreatitis disease cases (4.5%), the 18 PC patients (2.9%) and the 10 pancreatic solid disease (SPN and NEM) (1.6%) were detected by abdominal CT and/or EUS. The 6 patients with e-PC were detected. The mean clinical finding score of the PC group (3.2 ± 1.4) was significantly higher than that of the overall non-PC group (2.2 ± 0.6) ( p < 0.05). US findings were significantly more frequent in the PC group than in the non-PC group ( p <0.05). Although the sensitivity of direct findings by US was 42.3%, that of indirect-findings was 91.7% in the PC group.

Conclusion

Many pancreatic diseases, which may have potential of pancreatic cancer in future, were detected by this simple check score of ≥ 2 points on clinical findings. And in clinic pancreatic cancers were detected efficiently. Indirect findings by US may play an important role in improving the e-PC detection rate.

Clinical Case Summary

Recently, the concept of neoadjuvant therapy for unresectable locally advanced pancreatic cancer (PC) has received much attention. However, in patients who respond well to neoadjuvant therapy, even if resection is achieved, micro-cancer cells may remain around the major vessels. This may lead to early recurrence. A novel therapeutic strategy is needed to improve prognosis and achieve long-term survival. Under the situations, high-intensity focused ultrasound (HIFU) of new noninvasive therapy is expected as neoadjuvant therapy. A 75-year-old male, who was diagnosed as pancreas body cancer (38mm) infiltrating celiac artery (CA), common hepatic artery (CHA), splenic artery (SPA), and portal vein (PV) by enhanced CT, MRCP and EUS-FNA. There was no indication for surgery, and then chemotherapy (Gem/nab-PTX; GnP) was enforced due to unresectable locally advanced PC (Stage III). The chemotherapy with GnP was administered at 100% dose and performed for 4 courses. The main tumor became smaller (20mm) after 4 months from the diagnosis. However, there was still residual tumor adjacent to the CA, CHA, SPA, and PV (cT4N1aM0: stage III). Therefore, we cauterized the main tumor and the around CA, CHA, SPA, and PV using HIFU system with the aim of obtaining a negative surgical margin for one week before the surgical resection. A total pancreatectomy which included resection of the portal vein, was performed after HIFU therapy. The pathological findings showed that the tumor infiltrated the portal vein that was resected, but no tumor invasion to artery was observed. The surgical margin was negative (R0 resection). In conclusion, the combination of chemo and HIFU therapy may be promising therapies for patients with unresectable locally advanced PC for achieving curative resection.

References

Sofuni A, Asai Y, Tsuchiya T, et al. Novel therapeutic method for unresectable pancreatic cancer the impact of the long term research in therapeutic effect of high intensity focused
ultrasound (HIFU) therapy. Curr Oncol. 2021;28:4845 61.

Disclosure

No COI to report.

Introduction

Surgery represents an important part of the therapeutic armamentarium for the treatment of IBD, and has been associated with variable effects on the psychological profile of patients with inflammatory bowel disease. However, surgical treatment is often distressingly perceived by these patients as the failure of their therapies, and can be a trigger for anguish, anxiety or depression.

Aims & Methods

The aim of this study is to describe the psychological impact of surgery on operated IBD patients.
This is a prospective descriptive monocentric study, conducted at the Department of Hepato-Gastro-Enterology and Proctology "Medicine B" CHU Ibn Sina Rabat, which collected all patients followed for IBD (Crohn's + UC) and who were operated between August 2021 and August 2023, the psychological impact and apprehension regarding surgery will be addressed in this study. Patients of both sexes who agreed to answer the questionnaire were included, and patients who refused to answer the questionnaire and complicated patients who stayed in intensive care were excluded.

Results

43 operated patients were included in our study, including 29 (67.4%) in the emergency setting and 14 (32.6%) scheduled. Mean age was 43 ± 16.17 years. The sex ratio was 1.26 (F/H=24/19). 35 patients (81.4%) were being followed for Crohn's disease and 8 patients (18.6%) for ulcerative colitis (UC), of whom 11 patients (25.5%) had a history of previous resection, and 1 patient (2.3%) was being followed for depression.
The surgical indications were GCA in 12 cases (27.9%), stenosis in 18 cases (41.8%), perforation in 1 case (2.3%), abscess in 8 cases (18.6%), and fistula in 4 cases (9.3%).
Our patients underwent ileo-caecal resection in 22 cases (51.2%), hemicolectomy in 6 patients (14%), coloproctectomy in 3 patients (7%), sub-total colectomy in 11 patients (25.6%), of whom 18 patients (41.9%) had an ostomy.
On the announcement of a possible surgical procedure, the thymic symptoms and feelings expressed by patients can be classified as follows: preoperative anxiety in 18 patients (41.9%), fear of death in 7 patients (16.3%), while 24 patients (55.8%) were indifferent.
The main anxiety-generating concern was postoperative pain in 7 patients (14%), potential complications in 7 patients (16.3%), failure of the procedure in 6 patients (14%), fear of dying in 7 patients (16.3%), and 25 patients (58.1%) expressed no anxiety.
The postoperative psychological experience was unremarkable in 37 patients (86%), 3 patients (7%) reported transient postoperative sadness and 3 patients (7%) developed postoperative depression, prompting consultation with a psychiatrist.

Conclusion

The impact of surgery in IBD patients not only concerns the body, but also has an effect on psychological well-being.
This study found that the pre-operative period induces a significant burden of anxiety in these patients, and depression in some.

Introduction

High-resolution anoscopy (HRA) plays a central role in the detection and treatment of precursors of anal squamous cell carcinoma (ASCC). The visual characterization of high-grade intraepithelial lesions (HSIL) is hampered by a limited interobserver agreement. Artificial intelligence (AI) algorithms have shown high levels of efficiency in detecting and differentiating HSIL from low-grade squamous intraepithelial lesions (LSIL) in HRA images. Nevertheless, these studies have been conducted using a digital videoproctoscope, whose use is not predicted in the standards of the International Anal Neoplasia Society (IANS). Our aim was to develop a deep learning system for automatic detection and differentiation of HSIL versus LSIL using HRA images from both conventional and digital proctoscopes.

Aims & Methods

A convolutional neural network (CNN) was developed based on 151 HRA exams from 137 patients undergoing HRA at two large volume centres (GH Paris Saint-Joseph, Paris, France and Emílio Ribas Infecciology Institute, São Paulo, Brazil), using conventional HRA (KLP 200 LED®, Kolplast) and digital HRA (THD Proctostation®, THD SpA). A total of 58,498 images were included, 29,212 images containing HSIL and 29,286 LSIL. Partial subanalyses were performed to evaluate the performance of the CNN in the subset of images with no staining (n=2,820), acetic acid (n=27,191), lugol (n=10,011), and after treatment of the anal canal (n=11,047). For these subanalyses, training, and testing datasets comprised 90% and 10% of each class's total number of images. The sensitivity, specificity, accuracy, positive and negative predictive values, and area under the curve (AUC) were calculated.

Results

The overall accuracy of the CNN in distinguishing HSIL from LSIL during the testing stage was 98.6%. The algorithm had an overall sensitivity and specificity of 97.3% and 99.1%, respectively. The overall AUC was 0.99. For staining with acetic acid, HSIL was differentiated from LSIL with an overall accuracy of 96.4%, while for lugol and after therapeutic manipulation these values were 96.6% and 99.3%, respectively. The AUC ranged between 0.98 and 1.00 in these particular subgroups.

Conclusion

The introduction of AI algorithms to HRA may enhance the early diagnosis of ASCC precursors, and this system showed to perform adequately across conventional and digital HRA interfaces. Improving the detection of ASCC precursors may improve the treatment outcomes and prognosis. The developed AI model is the first model capable of performing adequately in different clinical sub settings and in different systems available on the market.

References

1. Hillman, R.J.; Cuming, T.; Darragh, T.et al. 2016 IANS International Guidelines for Practice Standards in the Detection of Anal Cancer Precursors. J Low Genit Tract Dis 2016; 20: 283-291.
2. Mistrangelo, M.; Salzano, A. Progression of LSIL to HSIL or SCC: is anoscopy and biopsy good enough? Tech Coloproctol 2019; 23: 303-304.
3. Deshmukh, A.A.; Suk, R.; Shiels, M.S.et al. Recent Trends in Squamous Cell Carcinoma of the Anus Incidence and Mortality in the United States, 2001-2015. J Natl Cancer Inst 2020; 112: 829-838.
4. Palefsky, J.M.; Lee, J.Y.; Jay, N.et al. Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer. New England Journal of Medicine 2022; 386: 2273-2282.
5. Neukam, K.; Milanés Guisado, Y.; Fontillón, M.et al. High-resolution anoscopy in HIV-infected men: Assessment of the learning curve and factors that improve the performance. Papillomavirus Res 2019; 7: 62-66.
6. Saraiva, M.M.; Spindler, L.; Fathallah, N.et al. Artificial intelligence and high-resolution anoscopy: automatic identification of anal squamous cell carcinoma precursors using a convolutional neural network. Tech Coloproctol 2022; 26: 893-900.
7. Pathologists, C.o.A. Protocol for the Examination of Excision Specimens From Patients With Carcinoma of the Anus. 2021; 4.2.0.