Introduction

Resection of large non-pedunculated colorectal polyps (LNPCP) located in the rectum varies by institution and region with some, particularly colorectal surgeons, favouring TEM and others endoscopic resection (ER). There is a paucity of data directly comparing these strategies and the procedure of choice remains under debate. Our unit is a tertiary referral centre for complex polyps and early colorectal cancer. All rectal LNPCP were treated by TEM until a change in practice from 2011 when the first-line therapeutic strategy for rectal LNPCP changed to ER.

Aims & Methods

We aimed to report the outcomes of TEM and ER of rectal LNPCP from a large tertiary cohort. Large (≥20mm) rectal adenomas resected by TEM or ER (2009 – 2023) were analysed. From 2009-2011 all rectal adenomas were treated by TEM, after which the primary resection strategy changed to ER. Outcomes were compared between techniques. Given the difference in resection strategy, a composite outcome of septic complications included clinically significant perforation for ER (early or delayed perforation requiring any form of unplanned medical or surgical treatment) and septic complications for TEM (peritonitis or pelvic/anorectal sepsis).

Results

704 rectal adenomas were resected by TEM (n=71), EMR (n=145) and ESD/Hybrid ESD (n=488) with a mean size of 45mm for TEM vs 55mm for ER (p<0.001). 100% of patients undergoing TEM required hospital admission vs 15% for ER (p<0.001), and 100% required general anaesthesia (GA) for TEM vs 26%% for ER (GA or propofol sedation, p<0.001). En bloc resection was achieved for 96% of ESD resections, 54% of TEMS, 28% of EMR and 14% of hybrid ESD (p<0.001). The incidence of complications were similar (9.9% for TEM versus 5.0% for ER, p=0.10). Recurrence occurred in 2.7% after ESD, 21.1% after EMR, 23.6% after Hybrid ESD and 36.4% after TEM (p<0.001). No patients undergoing ER or TEM required surgery as a result of a complication.

Conclusion

Despite significantly larger lesion sizes, ER in our institution provides far superior results for patients than TEM with relatively fewer patients requiring hospital admission and lower recurrence rates, especially with ESD. En bloc resection was more likely with ER as a result of the difficulty achieving en bloc resection for extremely large lesions with TEM, which can invariably be resected en bloc by ESD. These results have led to a policy of ER for all apparently benign rectal tumours regardless of size and, in recent years, ESD as the primary approach for all rectal lesions.

Introduction

The United Kingdom National Institute for Health and Care Excellence recommends Faecal Immunochemical Testing (FIT) for all patients presenting to primary care with symptoms suggestive of colorectal cancer. How use of this test varies across England is unknown, which this study aimed to quantify.

Aims & Methods

Routinely-collected primary care records (Clinical Practice Research Datalink Aurum) were used to assess variations in symptomatic FIT use in adults (≥18 years) between regions and over time in England from 2019 to 2023. Rates were calculated using the population registered to each primary care practice as the denominator, with analysis split by calendar year.
The first coded FIT test with a numerical result per patient each year was extracted from the primary care records. Rates of testing were calculated using Poisson regression, adjusted for other confounders. Results were described between groups, regions and years at the recommended threshold of ≥10 µgHb/g faeces (results above this threshold henceforth referred to as FIT10), describing the proportions likely to have a secondary care referral based on national guidance. Logistic regression was used to compare the impact of year, region, gender and age on the differences in FIT10.

Results

Between 01/01/2019 and 05/06/2023 there were 531,735 FIT results among 495,121 patients and a denominator population of 17,910,681. The number of completed FITs increased from 8,395 in 2019 to 237,708 in 2022 (the last complete year within the study), with a corresponding ~thirty-fold increase from 0.69 tests per 1000 person-years in 2019 (95%CI 0.68-0.71) to 19.57 per thousand person-years in 2022 (95%CI 19.50-19.65). There was large variation in testing between regions, with rates 3.6 times higher in the North East compared to the West Midlands (17.05 per thousand person-years, 95%CI 16.87-17.23 versus 4.72 per thousand person-years, 95%CI 4.67-4.76). These differences persisted to 2022, with less than half the rate in the West Midlands (11.32) compared to the North East (31.85 per thousand person-years).
20.4% of results were FIT10. Despite increased testing, the overall proportion FIT10 did not change over time. 51.7% of all tests FIT10 were in those over 70 years of age. The percentage FIT10 was lower in regions with higher rates of FIT testing, for example FIT10 ranged from 16.7% in the South West (rate of testing 14.62 per thousand person-years) to 25.3% in the South East (rate of testing 8.00 per thousand person-years). After adjusting for year, region, gender and age, this difference persisted (adjusted OR 0.57, 95%CI 0.55-0.58) comparing FIT10 in the South West to the South East. The difference in proportions FIT10 between regions showed some convergence over time, from a range of 16.6%-26.7% (10.1%) in 2021 to 15.8%-23.7% (7.9%) in 2023.

Conclusion

There has been a marked increase over time in the use of FIT for patients with symptoms in primary care, with large and persistent variations between regions of England. The overall proportion FIT10 has not decreased over time with increasing use, however there were large differences in FIT10 between regions that correlated with rates of testing. These regional differences persisted but reduced over time as testing rates increased nationally. It is likely that clinical pathway differences in the implementation of FIT over time and between regions explain the variations we have observed. If used as a guide to referral, such variation could lead to inequalities in colorectal investigation and diagnosis.

Clinical Case Summary

Leiomyomas are benign soft tissue neoplasms that arise from smooth muscle. They are uncommon in the colon. We report two cases of colonic sessile polyps that underwent polypectomy and histology showed leiomyoma.

The first patient previously had a history of polyps with tubular adenoma with low grade dysplasia. A repeat colonoscopy for polyp surveillance was done which found polyps in the ascending colon, and sigmoid. The sigmoid colon polyp was 4mm in size and removed via cold snare polypectomy (Figure 1).
The second patient had underlying non-alcoholic fatty liver disease cirrhosis and iron deficiency anaemia. Colonoscopy showed colonic polyps which were biopsied (Figure 2).

The histology of the first patient’s sigmoid colon polyp showed nodular spindle cell lesion centered in the submucosa/muscularis mucosa. The lesion was composed of spindle cells in fascicles with bland spindled nuclei and eosinophilic cytoplasm. Desmin and SMA stains were done and they were diffusely positive. CD117 stains were negative. DOG1 showed focal nonspecific staining in lesional cells. The overlying lamina propria also showed aggregates of foamy histiocytes and lymphoid aggregates. These were consistent with a leiomyoma.
The second patient’s histology also showed fascicles of spindle cells and immunohistochemistry stain showed positivity for SMA and desmin but negative for CD117 and DOG-1, consistent with leiomyoma.

As the polyps showed smooth margins endoscopically and has similar appearance to hyperplastic polyps, it was likely thought to have a hyperplastic component on top of leiomyoma, hence the patients are to be monitored and followed up for routine surveillance.

References

Miettinen M, Sobin LH, Am J Surg Pathol. 2001;25(11):1433

Introduction

The depth of early gastric cancer is an important factor in determining the treatment plan such as endoscopic resection or surgery. We developed an artificial intelligence (AI) program using deep neural networks to diagnose mucosal and submucosal cancers using endoscopic images. Performance evaluation tests were conducted for clinical applications.

Aims & Methods

A validation dataset was established comprising 204 patients with early gastric cancer who underwent endoscopic resection or surgery at our hospital during 2018–2021. The lesion sites were the upper part in 16 (8%), middle part in 106 (52%), and lower part in 82 (40%) patients. The median lesion size (range) was 14 (2–90) mm; the lesion depth was mucosal cancer in 136 (67%) and submucosal cancer in 68 (33%) patients. Five white-light images per case at a minimum were used (median: 8, range: 5–22). The primary endpoint was sensitivity of mucosal cancer, defined as the lower limit of the 95% confidence interval (CI) > 75%, based on previous reports on the depth diagnosis of early gastric cancer. The secondary endpoints were specificity and accuracy.

Results

Sensitivity of this program for the diagnosis of mucosal cancer was 91.2% (95% CI: 85.2%–94.9%), indicating the usefulness of this program. Specificity was 66.2% (95% CI: 54.3%–76.3%), and accuracy was 82.8% (95% CI: 77.1%–87.4%).

Conclusion

The AI program developed for diagnosing the depth of early gastric cancer is useful and expected to be applied clinically in the near future.

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with the lowest 5-year survival rate of all cancers due to late diagnosis and lack of effective treatment. One of the challenges of developing molecular diagnosis and molecular targeted therapy for PDAC is the “mismatch” between research models and patients.

Aims & Methods

This study aimed i) to identify common proteins among different research models and patients and accordingly ii) to identify potential hub proteins and signaling pathways involved in the PDAC pathogenesis by using proteomics-based system modeling of multimodal datasets derived from multiple research models and patients. Mouse PDAC cells (derived from a genetically engineered mouse model with KrasG12D/Pdx1-Cre), PDAC orthotopically tumors in C57B/L6 mice (n=5), mouse PDAC spheroids, mouse pancreatic organoids, mouse PDAC organoids, normal mouse pancreatic tissues (n=5), human PDAC tumor tissue samples from treatment-naїve (n=20), neoadjuvant chemotherapy (n=22), and human PDAC organoids were included. Mass spectrometry-based proteomics, Rstudio, Cytoscape 3.10 and pathway enrichment analysis (using ingenuity pathways analysis, including human PDAC transcriptomic in addition) were used.

Results

In the comparison of PDAC models and patients, shared proteins were identified as follows: 60% between the mouse PDAC cells and the mouse PDAC spheroids, 78% between the mouse PDAC cells and the mouse PDAC tissue, 56% between the mouse PDAC spheroids and the mouse PDAC tissue, 66% between the mouse PDAC cells and the mouse PDAC organoids, 54% between the mouse PDAC spheroids and the mouse PDAC organoids, 38% between the mouse PDAC and the human PDAC tissues, 31% between the human PDAC tumor and the human PDAC organoids, and 60% between the mouse and the human PDAC organoids. A total of 1,367 common proteins were identified within all the PDAC models. Among these proteins ACTB, HSP90AA1, HSPA8, HSP90AB1, HSPA4, EEF2, RPS3, RPS20 and GAPDH were the top 10 hub proteins (with >300 node connections). Upon comparison of all eight models, eight proteins were identified as unique to PDAC, namely FAHD1, ARSA, NEK9, SERPINB9, LAMTOR2, SNRPG, TMED3, and RAB1A. There was a correlation in terms of z-score regarding signaling pathways between the mouse PDAC and human PDAC (p<0.001), particularly in activations of nerve growth factor signaling, integrin signaling, and neuregulin signaling. Central hub proteins commonly found in the mouse models included vinculin (membrane-cytoskeletal protein) as one of the high connectivity nodes and β-catenin and probable ubiquitin carboxyl-terminal hydrolase FAF-X (involved in axonal growth and neuronal cell migration) as high centrality nodes. In patients, central hub proteins that were dysregulated after chemotherapy included 14-3-3 protein zeta/delta (encoded by YWHAZ gene), β-catenin and SRC. Among the 47 proteins that were associated with altered metabolism after the chemotherapy in patients, CD44, CTNND1, APOA 1, PARVA, and SCRBS1 were nodes with low degrees, and desmosomes (DSP, KP3, PPL), PRTN3, thrombospondin-2 (THBS2), and DMBT1 were the most down-regulated proteins without nodes, and APOA1, caveolin-1 (encoded by CAV1), LRP1 were the most up-regulated proteins with nodes.

Conclusion

The system modeling identified the common proteins among the research models and patients and the hub proteins and signaling pathways, suggesting the potential translational targets of PDAC.

Clinical Case Summary

Diaphragmatic flutter (DF) is a rare condition characterized by rhythmic, repetitive, and involuntary contractions of the diaphragm and other respiratory muscles, with variable clinical presentation including epigastric pulsations, sleep disturbances, dyspnea, hyperventilation, hiccups, abdominal pain, gastroesophageal reflux and belching, often leading to delays in diagnosis and ineffective treatments. Diagnostic tools were previously limited to thoracic videofluoroscopy and electromyography.
Patient 1: A 22yr male, with abdominal spasms, constant nausea and reflux during adolescence with poor response to omeprazole.Endoscopy and gastric emptying scintigraphy did not reveal the root of the problem. The condition was intermittent, and psychological evaluation was normal. Due to disabling symptoms, high-resolution esophageal manometry (HREM) was performed, revealing absent motility and additionally observing abdominal spasms associated with oscillating increases in intragastric pressure, pharyngeal contraction and repetitive diaphragmatic spasms. Biofeedback therapy (BT) was conducted with symptomatic control.
Patient 2: A 47yr, male with a 10-year history of abdominal spasms, evaluated by neurology, which ruled out structural abnormalities via cranial magnetic resonance imaging and electromyography. He received multiple medications without symptomatic improvement. The condition was intermittent, with periods of remission. Upon symptom recurrence HREM was performed, showing normal motility but a pattern similar to the previous case. BT achieved optimal symptom control.
Discussion: DF is a rare entity. Cases reported in the literature are generally initially managed by neurologists, with minimal involvement from gastroenterologists. However, it is proposed that HREM assessment, which demonstrates a specific pattern, can facilitate diagnosis without the need for invasive studies. Likewise, BT appears to be effective in the short term, improving patients' quality of life.

References

Ramirez JD, Gonzales M, Hoyos JA, Grisales L. Diaphragmatic flutter: a case report and literature review. Neurología. 2015;30(4): 249-251. 2

Iliceto G, Thompson PD, Day BL, et al. Diaphragmatic flutter, the moving umbilicus syndrome, and "belly dancer's" dyskinesia. Mov Disord 1990;5:15–22

Disclosure

Nothing to disclose

Introduction

Rectal cancer represent 30% of colorectal cancer with 46,220 new cases estimated in the United States in 2024. About 98% of rectal cancer patients have rectal adenocarcinoma. Gastrointestinal (GI) squamous cell neoplasm (SCN) is very rare with no enough studies to estimate its incidence and clinical features. Thus, our aim was to assess the risk of developing second primary GI SCN following chemo(radio)therapy after rectal adenocarcinoma.

Aims & Methods

We used the Surveillance Epidemiology and End Results (SEER) database to obtain the data of 145,789 patients with first primary rectal adenocarcinoma. We used MP-SIR session to calculate the standardized incidence ratios (SIR) ratio as (observed/Expected) with a latency exclusion period of 0 months, Excess risk (ER) was calculated per 10.000 and 95% Confidence Interval (CI). The results were significant if P> 0.05.

Results

Out of 145.789 patients with rectal adenocarcinoma, 4333 patients developed second primary SCN. Among who developed second primary GI SCN, 21.9% received chemotherapy with an O/E of 4.07 (P˂0.05, CI: 4.50 - 3.67, ER=74.53) while 3.25% received radiotherapy with an O/E of 2.23 (P ˂ 0.05, CI: 2.60- CI: 1.90, ER=42.59). The group who had no systemic therapy had an O/E of 2.83 (P˂ 0.05, 95%CI: 2.93–2.74, ER=57.27). The group who received combined chemoradiotherapy had a 2-fold increased risk of developing second primary GI SCN (O/E =2.34, P˂ 0.05, CI:2.44- 2.24, ER=34.88). There was a significant increase in the 0-11 months interval in the four groups. The group who received chemotherapy O/E was 11.73 (P ˂ 0.05, 95 % CI: 13.27– 10.32, ER=233.48) and the group who received radiotherapy had increased O/E to 5.16 (P˂0.05, ER=150.85, 95%CI: 6.51–4.03).

Conclusion

Chemotherapy increases the risk of multiple primary GI SCN after the first primary rectal adenocarcinoma, especially in the first year after diagnosis. Chemo(radio)therapy have a significantly high risk second primary GI SCN with different potential and variations across different intervals. Thus, more attention to be given for the screening of second primary GI malignancies after chemo(radio)therapy administration.