Introduction

In recent years, cold snare polypectomy (CSP) for small polyps has become popular, but it is considered inappropriate as a treatment for cancer because of the shallow depth of resection at the muscularis mucosa level and the risk of inadequate pathological evaluation. ¹² Therefore, it is important to diagnose advanced histology (AH) (high grade adenoma or adenocarcinoma) prior to treatment. Based on our retrospective review of colorectal neoplastic lesions smaller than 10 mm, the following six endoscopic findings were extracted as significant predictors of AH findings in the multivariate analysis : (1) surface redness, (2) white spots, using white light image, (3) heterogeneity in mucosal pattern, using non-magnified Narrow band imaging (NBI), (4) irregular vessel or surface pattern(equivalent to JNET Type 2B,3), using magnified NBI, (5) loss of lobulation, and (6) non-polypoid growth, using non-magnified chromoendoscopy using indigo carmine. ³

Aims & Methods

The aim of this study was to evaluate the usefulness of image-enhanced endoscopic findings in real-time prediction of AH for small colorectal polyps. Patients scheduled for colonoscopy were recruited for consent prior to the examination at 9 Japanese institutions, and the presence of the aforementioned AH-predictive endoscopic findings was noted for up to 5 lesions per patient when neoplastic polyps of 5-9 mm were detected. If one of the predictive findings was positive, endoscopic resection using the electric current method or surgical resection was applied. The primary endpoint was the negative predictive value (NPV) of the 6 AH-predicting findings using pathology as the gold standard. Secondary endpoints were NPV of AH prediction by modality combination, odds ratios of each predictors and percentage of non-CSP for T1 cancer. Taking account for practical value, the target threshold of NPV was set for 90%.

Results

A total of 1671 patients were enrolled in the study, of which 517 patients with 849 lesions (80 AH lesions) corresponding to 5-9 mm polyps were included in the analysis. The primary endpoint was 0.945 (95% confidence interval (CI): 0.923-0.961). Secondary endpoints were white light + NBI non-magnified/magnified 0.941 (95%CI: 0.920-0.958), white light + NBI non-magnified 0.934 (95%CI: 0.913-0.952), white light + chromoendoscopy 0.926 (95%CI: 0.904-0.944), and white light 0.922 (95%CI: 0.900-0.940). Odds ratio (95%CI) of each 6 findings were as followings; irregular vessel or surface pattern 5.00 (2.59-9.37), loss of lobulation 4.10(1.61-6.56), white spots 3.32(1.60-6.56), non-polypoid growth 3.24(1.13-8.22), heterogeneity 2.53(1.41-4.42), surface redness 1.41(0.56-3.14). All 6 T1 cancer had multiple predictive findings of AH, and the percentage of non-CSP performed was 100%.

Conclusion

Six predictive findings of AH combined with image-enhanced endoscopy were shown to be useful in determining the indication for CSP (UMIN 000040974).

References

1. Ito A, Suga T, Ota H, et al. Resection depth and layer of cold snare polypectomy versus endoscopic mucosal resection. J Gastroenterol 2018;53:1171-1178.
2. Uraoka T, Takizawa K, Tanaka S, et al. Guidelines for Colorectal Cold Polypectomy (supplement to "Guidelines for Colorectal Endoscopic Submucosal Dissection/Endoscopic Mucosal Resection"). Dig Endosc 2022;34:668-675.
3. Iwai T, Imai K, Hotta K, et al. Endoscopic prediction of advanced histology in diminutive and small colorectal polyps. J Gastroenterol Hepatol 2019;34:397-403.

Introduction

High-risk human papillomavirus (hr-HPV) has been suggested as a risk factor for oesophageal adenocarcinoma (OAC).^1-3 In HPV driven cancers (eg cervical malignancy), associated lymph nodes with a detectable viral load denote metastatic involvement.⁴ To date, there have been no reported studies regarding HPV involvement in lymph nodes of metastatic OAC.⁵

Aims & Methods

Formalin fixed surgically resected specimens were utilised in this study. Eight primary OAC and 16 associated metastatic lymph nodes were analysed for hr-HPV using droplet digital polymerase chain reaction (ddPCR). Viral load was determined and clinical data collected. Utmost care was undertaken to prevent cross-contamination.

Results

The mean age of the patients was 68.6 years. All patients had Siewert Class I or II tumours [T3N1-3,M0 (n=6), T4N3M0 (n=1), T1bN2M0 (n=1)]. 6/8 tumours were positive for hr-HPV DNA. All were genotype 18. There were no other hr-HPV genotypes detected in the primary cancer. The viral load ranged from 1 to 34 copy numbers per 10,000 cells in the primary tumour. 3/16 corresponding lymph nodes obtained from these 8 tumours were positive for hr-HPV; genotype 16 (n=1) and genotype 18 (n=2). These 3 hr-HPV DNA positive lymph nodes corresponded to 2 hr-HPV genotype 18 positive primary OAC. Viral load was measured to be 1 to 2 copy numbers per 10,000 cells in the metastatic lymph nodes.

Conclusion

This is the first time that hr-HPV has been detected in both the primary OAC and associated nodal metastases giving credence to the role of this pathogen in this malignancy.

References

1. Rajendra S, Wang B, Snow ET, et al. Transcriptionally active human papillomavirus is strongly associated with Barrett's dysplasia and esophageal adenocarcinoma. Am J Gastroenterol 2013; 108: 1082-93.
2. Wang B, Rajendra S, Pavey D, et al. Viral load and integration status of high-risk human papillomaviruses in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. Am J Gastroenterol 2013; 108: 1814-6.
3. Li X, Gao C, Yang Y, Zhou F, Li M, Jin Q, Gao L. Systematic review with meta-analysis: the association between human papillomavirus infection and oesophageal cancer. Aliment Pharmacol Ther 2014; 39: 270-81.
4. Kobayashi Y, Yoshinouchi M, Tianqi G, Nakamura K, Hongo A, Kamimura S, Mizutani Y, Kodama J, Miyagi Y, Kudo T. Presence of human papilloma virus DNA in pelvic lymph nodes can predict unexpected recurrence of cervical cancer in patients with histologically negative lymph nodes. Clin Cancer Res. 1998;4:979–983.
5. Sharma P, Gautam SD, Rajendra S. Importance of investigating high-risk human papillomavirus in lymph node metastasis of esophageal adenocarcinoma. World J Gastroenterol 2020; 26(21): 2729-273.

Introduction

Endoscopic intermuscular dissection (EID) has been shown to be an effective technique to remove deep submucosal invasive rectal cancers. However, selecting tumours suitable for this technique has been challenging both endoscopically and radiologically, due to a lack of knowledge and confidence in the anatomical characterisation of early rectal cancers (ERC). This has limited attempts at rectal-preserving local excision, but has also led to incomplete resection of deeper invasive cancers. We aimed to determine if the application of a novel systematic approach for staging rectal lesions on MRI can more accurately identify tumours suitable for local excision in the intermuscular plane, by identifying preservation of at least 1 mm of muscularis propria on MRI.

Aims & Methods

Twelve Dutch abdominal radiologists participated in a one-day training session by an expert radiologist who developed and validated the systematic reporting approach for assessing ERC on MRI. After training, 12 study radiologists and 1 expert radiologist reported a retrospective cases series of pseudonymised MRI scans, blinded to pathological outcome data. Scans were derived from consecutive patients from 2 academic centers in the Netherlands who were suspected of having (at least) deep submucosal invasive rectal cancer at optical diagnosis between 2018 and 2022. All scans were matched to clinical and pathological outcome data. Our primary outcome was the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI in identifying tumours suitable for a local excision in the intermuscular plane, based on preservation of ≥ 1 mm of muscularis propria on MRI, and compared to pathological staging (≤ pT2 limited to the circular m. propria). Secondary outcome was the inter-observer reliability between study and expert radiologists.

Results

246 patients were included (median age 67 years [IQR 13], 71.1% male, 86.6% ASA I/II), of which 186 (75.6%) would retrospectively have been suitable candidates for a local excision in the intermuscular plane based on the pathology data (≤ pT2 limited to the circular m. propria). MRI accuracy in identifying these tumours as locally resectable was 81.7% (95% CI 76.3 - 86.3) for expert radiologist diagnosis and 78.5% (95% CI 72.7 - 83.5) for the trained study radiologists (range individual radiologists: 64.1% - 94.6%). Sensitivity, specificity, PPV, and NPV were 86.0%, 68.3%, 89.4%, and 61.2% for expert diagnosis, and 80.5%, 72.4%, 90%, and 54.6% for trained study radiologists, respectively. The percentage of locally resectable cancers overstaged by MRI was 14.0% based on expert radiologist assessment and 19.5% for the trained study radiologists, and the percentage of understaged cancers was 31.7% and 27.3%, respectively. Expert and study radiologists showed overall moderate inter-observer reliability (kappa 0.46; 95% CI 0.34 - 0.59). Inter-observer reliability among study radiologists was moderate as well (kappa 0.44; 95% CI 0.32 - 0.57).

Conclusion

MRI has not previously been considered useful for identification of ERC suitable for endoscopic local excision. This study shows our approach to select rectal cancers for excision in the intermuscular plane is accurate, easily taught and reproducible. This can improve care by enabling better case selection for rectal-preserving local excisions such as EID. Further prospective research is needed to evaluate the clinical impact of this approach.