Introduction

Local resection of submucosally invasive rectal cancer (T1 stage) is increasingly used. For tumors that extend into or through the muscularis propria layer (T2+ stage), the risk of lymph node metastasis is too high to consider a local resection as the optimal oncological treatment. Discrimination between T1 and T2+ rectal cancer is thus important before embarking on a local procedure. However, there is no reliable imaging method to exclude deep infiltration. Advanced endoscopic imaging has a low sensitivity, MRI and radial (static) endoscopic ultrasound are often overstaging; in addition, for ultrasound there is a lot of intra-observer variation. Linear endoscopic ultrasound (L-EUS) can dynamically assess fixation of the tumor to the muscularis propria layer by testing shiftability. We hypothesize that impaired shiftability could be a predictor of T2+ stage.

Aims & Methods

In this single-center pilot study, L-EUS media, optical and pathological data were prospectively collected from patients referred for local resection of early rectal cancer. Fixation to the muscularis propria layer was visualized by moving the lesion with a biopsy forceps or with the tip of the echoendoscope (shiftability). Impaired shiftability was defined as joined and fixed movement of the tumor and the muscularis propria layer. Shiftability was considered unimpaired when the tumor moved freely over de muscularis propria layer.

Results

We included 91 patients. The sensitivity of advanced endoscopic imaging for T2+ stage tumor was 61.3% and the specificity 86.7%, with a false-negative (understaging) and false-positive (overstaging) rate of 18.8% and 29.6%, Shiftability was assessed in 66 patients; Post-hoc analysis showed no evidence of selection bias in patients in whom shiftability testing was not performed, except for deeply ulcerating lesions (n = 6) in which shiftability testing was often not done for obvious reasons (5 cases not tested).
The sensitivity of impaired shiftability for T2+ stage tumor was 94.4%, the specificity was 97.9%, with a false negative rate of 4.2% and a false-positive rate of 5.6% (p < 0.005). No optical feature or other ultrsonographic static feature (various forms of iso-echogenic extensions from the tumor to muscularis propria layer) could improve this prediction in multivariate logistic regression analysis.

Conclusion

We found excellent sensitivity and specificity of this feature for muscularis propria infiltration, with a sensitivity of 94.4 and a specificity of 97.9%.
Although this should be considered a pilot study, these results are promising and deserve further appraisal in other centers.

References

Beets-Tan RGH, Lambregts DMJ, Maas M, Bipat S, Barbaro B, Curvo-Semedo L et al. Magnetic resonance imaging for clinical management of rectal cancer: updated recommendations from the 2016 European Society of Gastrointestinal and Abdominal Radiology (ESGAR) consensus meeting. Eur Radiol 2018; 28: 1465 – 1475.
Detering R, van Oostendorp SE, Meyer VM, van Dieren S, Bos ACRK, Dekker JWT, Reerink O, van Waesberghe JHTM, Marijnen CAM, Moons LMG, Beets-Tan RGH, Hompes R, van Westreenen HL, Tanis PJ and Tuynman JB, on behalf of the Dutch ColoRectal Audit Group: MRIcT1–2 rectal cancer staging accuracy: a population-based study. BJS 2020; 107: 1372–1382.

Introduction

Chemoradiotherapy (CRT) is a standard non-surgical treatment for esophageal squamous cell carcinoma (ESCC). One of the major disadvantages of CRT is poor local control, and salvage esophagectomy is generally indicated for local failure; however, it is invasive with a high rate of postoperative complications and mortality so that patients often refused or are intolerant to salvage esophagectomy. Alternatively, photodynamic therapy (PDT) with talaporfin sodium (TS) is less invasive salvage treatment for local failure after CRT/ radiotherapy (RT) and was reported to have relatively high local complete response (L-CR) rate and few adverse events (AEs) in the short term. However, long-term outcomes of PDT with TS are unknown.

Aims & Methods

This retrospective study aimed to clarify the long-term outcomes of PDT with TS for local failure after CRT/RT for ESCC. Patients who underwent PDT with TS for histologically proven local failure of ESCC between December 2012 and December 2021 at the National Cancer Center Hospital East were enrolled. Patients with other active cancers or a prior history of PDT were excluded. Basic indication criteria of PDT were as follows: invasion depth limited to the shallow muscle layer, <1/2 of the esophageal circumference, absence of metastasis, and patient’s refusal or unsuitable physical condition for salvage surgery. We assessed L-CR rate, incidence of AEs, clinical courses after PDT, 3-year overall survival (OS), progression free survival (PFS) and major PFS (mPFS) in which major disease progression after PDT which defined as disease progression requiring more invasive treatment than repeated endoscopic treatment and death from all causes were considered as events. We also assessed pre-PDT factors associated with L-CR. L-CR was defined as no apparent residual tumor, disappearance of post-PDT ulcer and confirmation of the scar formation, and absence of cancer cells in biopsy.

Results

108 patients (92 men; median age 74 years [range, 52-88 years]) were enrolled. Patients with pre-CRT/RT cT1/ T2/ T3/ T4/ unknown were 50/ 22/ 24/ 9/ 3. Those with residual lesion/ local recurrence/ unknown were 63/ 39/ 6. Patients with pre-PDT ycT1a/ T1b/ T2 were 6/ 85/ 17. Pre-PDT median lesion size was 20 mm (range, 4-50 mm). 60 patients achieved L-CR after PDT, 41 had L-nonCR, and 7 were not evaluable. L-CR rate of PDT was 58.8% (60/101). During median follow-up of 23 months (range, 1-90 months), 39 patients (36.1%) finally had no recurrence after PDT. 18 patients, including 8 with L-nonCR after PDT and 10 with local recurrence after achieving L-CR, underwent re-endoscopic treatments alone and remained disease-free afterward. The other 44 patients had major disease progression, and 15 received salvage surgery among them. As for the lesion characteristics associated with L-CR, the lesions with <1/2 circumference and with <20 mm in size were more likely to achieve L-CR than those with ≥1/2 circumference (64.4% vs. 16.7%, P=0.003) and with ≥20 mm (80.0% vs. 45.2%, P=0.001), respectively. The 3-year OS/ PFS/ mPFS of all patients were 78.1%/ 29.8%/ 48.1%. The 3-year OS of L-CR cases was better than that of L-nonCR cases (89.3% vs. 67.7%, P=0.003). There was no grade 3 < AEs. Non-cardiac chest pain (60.2%), skin phototoxicity (4.6%), and esophageal stricture requiring balloon dilatation (4.7%) occurred.

Conclusion

PDT with TS for local failure after CRT/RT for ESCC showed the preferable long-term outcomes. Moreover, achieving local control with PDT could improve prognosis of patients even with local failure after CRT/RT.

Clinical Case Summary

A 67 years old male patient had orotracheal intubation due to COVID-19 infection and respiratory insufficiency. This led to the onset of a tracheoesophageal fistula (caused by the continuous overpressure of the cuff). At admission to our Hospital, the patient was in poor clinical condition and was sent to the intensive care unit. At endoscopy, a 30 mm fistula was found.
After a first multidisciplinary evaluation, surgical treatment was attempted, but this was unsuccessful in the closure of the fistula.
In second place endoscopic suturing with Apollo Overstitch was done (double-channel gastroscope), but also this was unsuccessful in completely closing the fistula and was repeated after 5 days. On the control endoscopy after 3 days, the fistula was still there
A multidisciplinary team composed of endoscopists, anesthesiologists, bronchoscopists, and cardiologists discussed the case again. The decision was to place an Amplatzer atrial septal occluder to close the fistula (Abbott, Illinois, USA). The procedure was technically and clinically successful, and the fistula was finally closed. The patient was weaned off from intubation and then O2 therapy and was discharged after a long rehabilitation.
The stent remained in place. The patient could eat and breathe without difficulty. At 12 months follow-up the patient is completely autonomous, eats everything and is in excellent clinical condition.

Introduction

The ability to achieve endoscopic R0 resection in colorectal T1 cancer depends on the submucosal (SM) invasion distance of the malignancy. In this study, we looked for correlations between the SM invasive distance and achievement of R0 resection.

Aims & Methods

We classified fibrosis of the SM layer as noncancerous (Type B) and cancerous (Type C) and further categorized each into three phases from mild (1) to severe (3). Measurements of SM invasion distances for each tumor were based on the criteria specified by the Japanese Society for Cancer of the Colon and Rectum (JSCCR). For 142 patients (70 male and 72 female, average age of 68.1 years), 143 lesions were diagnosed as cancerous fibrosis in subjects who underwent ESD and 1,813 lesions were scored as colorectal epithelial neoplasms, with T1 cancer being diagnosed by postoperative pathological diagnosis. We evaluated the diagnostic ability of cancerous fibrosis in 308 patients including 165 Type B cases. We also compared the degree of SM invasion in Type C-1, C-2, and C-3 malignancies in which we observed macroscopic typing of the 143 Type C lesions. We then scored the degree of SM invasion in R0 resected Type C lesions. Using an ROC curve and a 95% cutoff index, we calculated the maximal SM invasion distance for which R0 resection could be achieved.

Results

The macroscopic subtypes of Type C lesions were as follows: 0-Is+IIa (LST-G (nodular mixed type)): 55, 0-IIa (LST-NG (flat elevated typ)): 23, 0-IIc+IIa (LST-NG(pseudodepressed typ)): 19, 0-Is: 23, 0-IIa+IIc: 15, 0-IIc: 8. Perioperative endoscopy was able to accurately diagnose 83.9% Type C cases and 93.9% of Type B cases. With regard to diagnostic potential, perioperative endoscopy had 83.9% sensitivity, 93.9%, and specificity. Diagnostic precision was 92.3%, PPV was 92.3%, and NPV was 87.0%. Pathology was used to sub-classify the 143 Type C cases based on severity. Seventy-one patients were C-1, 34 were C-2, and 38 were C-3. The mean SM invasion distances in C-1, C-2 and C-3 cases were 801.2 ± 956.1 mm, 1,745 ± 891.6 mm, and 3063.5 ± 2008.4 mm, respectively; differences between each group were significant (p<0.01). We classified macroscopic types of Type C into Flat and Depressed (FD:0-IIa, 0-IIc+IIa, 0-IIa+IIc, 0-IIc) and Protruded (P: 0-Is+IIa, 0-Is ).Although the corresponding values in the P group were larger (C-1:970.6 mm, C-2:2292.3 mm, and C-3:3483.3 mm, respectively), this difference was not statistically significant. The R0 rate according to the invasive distance was 94.7% when SM was <1,500 mm, and 92.9% when SM was <1,000. For SM between 1,000 mm and 1,500 mm the R0 rate was 19/19 (100%).The percentage of cancer-positive cases in the vertical margin (VM (+)) increased proportionally with the degree of invasion. For SM values between 1,500 and 2,000, VM (+) was 79.2%, whereas for SM values of 2,000 or more, the R0 rate decreased to 45.5%. We identified a statistically significant difference (p=0.037) between less than 1,500 mm and 1,500-2,000 mm. The maximum Youden Index was 0.636 and the R0 rate was 95.4%, when the upper limit was less than 1,625 mm.

Conclusion

An SM of less than 1,625 mm (regardless of the macroscopic type) is predictive of an R0 resection for colorectal T1 cancer, and provided the possibility of curative treatment. Also, we infer that the quantitative and qualitative advantages of ESD can help endoscopists avoid the pitfalls associated with preoperative endoscopic diagnosis, which may be useful in clinical practice.

Introduction

The role of inhaled and subsequently swallowed aeroallergens in treatment outcomes of adults with eosinophilic esophagitis (EoE) is unclear. We hypothesized that the pollen season contributes to the failure of dietary therapy in EoE. In this international two-centre study, we compared six-food elimination diet (SFED) outcomes of EoE patients assessed during versus outside the pollen season.

Aims & Methods

Consecutive adult patients (≥18 years) with EoE who underwent SFED and skin prick test (SPT) for birch and grass pollen were included. Demographics, atopy, SPT results, endoscopy findings (EREFS), and the date of the endoscopy following SFED were retrospectively extracted. Individual sensitization profiles and historical and location specific pollen count data were scrutinized to define whether each patient had been assessed during or outside the pollen season following SFED. For patients without pollen sensitization, Spring was considered as pollen season for comparison purposes. Patients were divided into group A (positive SPT for pollens) or B (negative SPT for pollens). All patients had active EoE before SFED (eosinophils ≥15/high-power field, HPF) and adhered to SFED under the supervision of a dietitian. Response to SFED (eos<15/HPF) was assessed after a minimum of 6 weeks. Data are described as median/interquartile range (Q1-Q3) or as counts/percent. Kruskal-Wallis Rank Sum Test, Pearson’s Chi-Square and Fisher’s exact test were used as appropriate. Significance threshold was p<0.05.

Results

Fifty-eight patients were included, 62.0% had positive SPT for grass and/or birch (group A), while in 37.9% SPT was negative (group B). Significantly more patients from group A also had positive SPT for dust mite, cat and/or dog dander (85.7% vs 31.8%, p<0.001). The two groups were comparable in sex, age, baseline symptoms, atopy, baseline EREFS, and duration of SFED (Table1). The overall SFED response was 56.9%, (95% CI, 44.1%-68.8%) regardless of SPT results and pollen season. When stratifying SFED response according to whether the assessment of the assessment had been performed during or outside the pollen season, patients sensitized to pollens showed significantly lower response to SFED when the assessment was performed during compared to outside the pollen season (21.4% vs 77.3%; p=0.003). Additionally, during the pollen season, patients with positive SPT for pollens had significantly lower response to SFED compared to those with negative SPT (21.4% vs 77.8%; p=0.01). Patients without pollen sensitization did not show seasonal variations in SFED response (66.7% vs 53.8%; p=0.67) (Table 2).

Conclusion

Pollens may have a role in sustaining esophageal eosinophilia in sensitized adults with EoE despite avoidance of trigger foods. SPT for pollens may have a clinical utility in the dietary management of EoE by identifying patients less likely to respond to SFED during pollen season. Further studies are needed to clarify if alternative/combined therapy during pollen season will improve outcomes in sensitized EoE patients undergoing SFED or if elimination diets need to be undertaken outside of the pollen season.

Introduction

Colorectal cancer is one of the most common types of cancer worldwide. The majority of patients are operable at the time of diagnosis. One of the most severe surgical complications is anastomotic leakage (AL). The incidence of AL depends on where the anastomosis is located (1-2% for ileocolic anastomoses, increasing to 10-15% of anastomoses to the rectum). AL leads to prolonged hospital stay, decreased quality of life, increased risk of cancer recurrence, and increased mortality.
Experimental studies have shown that certain bacteria can contribute to the development of AL.
In Denmark, people aged 50-74 years are offered free of charge screening for colorectal cancer. They collect a stool sample at home to be analyzed for the presence for blood (a fecal immunochemistry sample). It is possible to extract bacterial DNA from the fecal sample, to characterize the gut microbiome at the time of sampling.

Aims & Methods

The objective of the study was to use third-generation sequencing methods to analyze screening fecal samples in a cohort of colorectal cancer patients, and to characterize and compare the gut microbiome between patients with or without postoperative AL.
Fecal samples sent to the Colorectal Cancer Screening Program that tested positive for blood, from 2016-2018, were place in a biobank and stored at -80 ⁰C. By combining the biobank with data from the Danish Colorectal Cancer Group, we identified 18 patients who had surgery for colonic or rectal cancer in the period and suffered a postoperative AL (AL group). We matched these patients in a 1:2-ratio, with 36 patients without AL (Control group). We analyzed the 16S ribosomal RNA genes in the screening fecal samples with third-generation sequencing (Oxford Nanopore Technologies).

Results

The data are preliminary, as the data analysis has not yet been completed.
The AL-group and Control group were similar on basic demographic parameters (age, gender, type of resection, smoker status and ASA classification). The gut microbiome composition was significant different in the two groups, based on the two main components of a principal coordinate analysis (PCoA) chart (PERMANOVA, p-value = 0.01).
The Bacteroidota phylum was more abundant in the Control group (p < 0.05). On the order level, Campylobacterales and Bacteroidales were more abundant in the Control group (p < 0.001). On family level, Campylobacteraceae were more abundant in the Control group (p < 0.001), whereas Burkholderiaceae were abundant in the AL-group (p < 0.001). The AL-group also had more Ralstonia and Burkholderia at genus level (p < 0.001), whereas the Control group had more Campylobacter and Oridobacter genera (p < 0.001).

Conclusion

The preoperative gut microbiome composition in colorectal patients with subsequent anastomotic leakage were significantly different from the control group without anastomotic leakage. Campylobacter and Oridobacter seem protective against AL, whereas Ralstonia and Burkholderia seem harmful. We are awaiting further analysis for the species level.
Further studies should focus on validating our results, including changes in the gut microbiome prior to surgery - for instance the impact of bowel preparation – and on estimating the predictive value of our findings.

Introduction

Barrett’s mucosal neoplasia can be endoscopically cured with minimal risk of lymph node metastasis while submucosally invasive neoplasia poses higher risk and usually requires surgery. Endoscopic optical diagnosis is often challenging to differentiate between the two. We aim to develop an artificial intelligence (AI) system using a deep neural network to stage Barrett’s neoplasia into mucosal (LGD, HGD, pT1a) and submucosally invasive (pT1b) lesions.

Aims & Methods

A VGG16-based deep neural network was used for the staging AI system. The model was trained with 69 images which were carefully selected from 79,159 frame images with histological ground truth. As a pre-trained model for training, the model from initial Barrett’s detection and delineation system was used, which was trained for 1,090,171 images from 161 Barrett's patients¹. We tested staging AI on pre-recorded images and its performance was compared to two experts who regularly perform Barrett's endoscopic resections.

Results

68 neoplastic images (white light, enhanced imaging, near focused/magnification) were used. 43 were mucosal (2 LGD, 31 HGD, 10 pT1a) and 25 were submucosal (6 pT1bSM1 and 19 pT1bSM2/3). The sensitivity, specificity and accuracy of AI were 80%, 84% and 82% while that of experts were 74%, 78% and 76% with no statistical difference (p=0.507).

Conclusion

This suggests that the staging AI system is good at differentiating submucosal neoplasia and it can perform as well as experts. It has the potential to help guide expert clinicians to decide if endoscopic resection of Barrett's neoplasia can be curative while helping non-expert to achieve more yield in targeted biopsy. However, more work is still needed to further refine and validate this staging AI model.

References

1. Mohamed Abdelrahim, Masahiro Saiko, Naoto Maeda, Ejaz Hossain, Asma Alkandari, Sharmila Subramaniam, Adolfo Parra-Blanco, Andres Sanchez-Yague, Emmanuel Coron, Alessandro Repici, Pradeep Bhandari, Development and Validation of Artificial Neural Networks Model for Detection of Barrett’s Neoplasia, a Multicenter Pragmatic Non-Randomized Trial, Gastrointestinal Endoscopy (2022)