Introduction

Endoscopic surveillance after surgery for colorectal cancer (CRC) has the main objectives of early identification of metachronous lesions and neoplastic recurrence. This study aimed to evaluate the possible benefit of intensified endoscopic surveillance compared to standard recommendations.

Aims & Methods

In this retrospective cohort study, all patients who underwent follow-up colonoscopy after CRC surgery over a period of 6 months were included. Patients with endoscopically treated CRC and patients with postoperative complications were excluded. The recommended follow-up period was considered the 1st year, the 4th year, and the 9th year after surgery and a time period of +/- 6 months to the recommended date was considered. Statistical analysis: Chi-square test; t-student test; Mann-Whitney test.

Results

102 patients (38 women) were included, aged 72±11 years. Patients were divided into two groups, those who followed the recommended protocol (55.9%; n=57) and those who underwent intensified surveillance (44.1%; n=45). No statistically significant differences were identified between the two groups regarding demographics, location of the neoplasm or type of surgery performed. There was only a higher adenoma detection in the intensive surveillance subgroup in the 1st year after surgery (p=0.042), with no differences in the remaining endoscopic controls. None of the advanced adenomas identified in this group required earlier endoscopic surveillance. No advanced adenomas were identified in additional colonoscopies carried out outside the recommended period. The adenoma detection rate didn’t show statistically significant differences between the two groups. An excess of 156 colonoscopies were performed over a total of 361 years of follow-up.

Conclusion

Intensified endoscopic surveillance after CRC surgery does not appear to confer benefit and is a significant burden to endoscopy units, in addition to unnecessary risks and discomfort for patients. Adherence to international recommendations should be promoted among referring physicians and a strict colonoscopy vetting process should be enforced.

Clinical Case Summary

Background/History: A 28-year old male presented with symptoms of chest pain, excessive throat noises, bloating and reported inability to belch with specific triggers inclusive of carbonated drinks. Previous treatment included a trial of PPI therapy, cricopharyngeal dilatation and cricopharyngeal Botox therapy - none proved efficacious. High-resolution oesophageal impedance-manometry (OM) and ambulatory 24-hour oesophageal impedance and pH studies (24hr pHZ) were requested to further investigate his symptoms.
Initial findings - standard protocols: Initial OM demonstrated ostensibly normal findings aside from recurrent weak oesophageal motility. 24hr pHZ showed a normal incidence of acidic and non-acidic reflux, however, there was an unusual pattern of recurrent, prolonged periods of gastric belching with apparent re-swallowing of the air bolus [image 1 - pHZ]. In order to reproduce symptoms in clinic and identify whether the air bolus was able to traverse the upper oesophageal sphincter (UOS), this patient was re-referred for OM with addition of a tailored extended protocol.
Extended OM protocol: Addition of a 330mL carbonated drink with positional changes and prolonged monitoring. Symptoms were replicated in clinic with reported chest pain, throat noises and inability to belch. OM showed a repeating pattern of symptomatic gastro-oesophageal gaseous reflux with retrograde movement of air to the distal UOS, followed by increased oesophageal pressure, and failed UOS relaxation which prevented air being expelled as a belch [image 2]. Final diagnosis - RCPD or Abelchia.
Recommended therapeutic management: High dose (100U), multi-site botulinum toxin A (Botox) injection into the cricopharyngeal muscle. The patient is due to undergo repeat Botox therapy.
Points to be discussed: Why did this patient not respond to initial Botox therapy? Failure of the afferent neural pathway to respond to a sub-optimal dose? Recommendation - repeat Botox (higher dose, multi-site).

References

Karagama, Y. 2021. Abelchia: inability to belch/burp—a new disorder? Retrograde cricopharyngeal dysfunction (RCPD). In: European Archives of Oto-Rhino-Laryngology. 278:5087–5091.
Oude Nijhuis, R. A. B., Snelleman, J. A., . Oors, J. M. et al. 2022. The inability to belch syndrome: A study using concurrent high_resolution manometry and impedance monitoring. In: Neurogastroenterology and Motility. y. 34:e14250.

Introduction

The distinction between eosinophilic esophagitis (EoE) and other causes of dysphagia in clinical practice can be difficult without histology. In addition, failure to collect esophageal biopsies represents one of the reasons for a delayed diagnosis in patients with EoE. Current guidelines recommend multiple esophageal biopsies in all patients reporting dysphagia although this may not be cost-effective.

Aims & Methods

To optimize resources allocation in the diagnostic workup of EoE, we developed and thereafter validated on an independent cohort of patients two point-of-care machine learning (ML) tools to predict a diagnosis of EoE: 1) based on clinical history data alone and 2) based on clinical-endoscopic findings, prior to the results of esophageal biopsies. This was a two-step multi-center international study conducted in three European tertiary referral centers for EoE (London, Pisa, and Padua). We build predictive ML models based on retrospectively extracted clinical data alone (age at diagnosis, sex, presence or absence of heartburn, chest pain, postprandial nausea/dyspepsia, history of food impaction requiring endoscopic removal, allergic rhinitis, asthma, nasal polyposis) and on clinical and upper endoscopy (EGDS) (exudates, rings, edema, furrows, stricture) data collected from 273 EoE and 55 non-EoE dysphagia (NED) patients in London. We performed an external validation of the models on an independent cohort of 93 prospectively enrolled patients reporting dysphagia at Pisa and Padua University Hospitals. The performance of the models was described with area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). We then developed a freely downloadable software for use in clinical practice at the point-of-care.

Results

The machine learning model trained on clinical data alone showed AUC of 0.82, and sensitivity, specificity, PPV, and NPV of 0.75, 0.82, 0.82, 0.75, respectively, for the diagnosis of EoE in the external validation cohort. Among clinical data alone, the patients’ age at diagnosis and sex had the highest predictive ability. The machine learning model trained on a combination of clinical and endoscopic data showed AUC of 0.93, and sensitivity, specificity, PPV, and NPV of 0.88, 0.95, 0.95, 0.87, respectively, in the external validation cohort. Among clinical and endoscopic data, the patients’ age at diagnosis, esophageal rings at endoscopy, and sex had the highest predictive ability. The models’ performance in the development and external validation cohorts is reported in Table 1.

Conclusion

The international external validation of our ML tools, as well as the freely available software, allow generalizability of our findings to other settings. Our software can be easily used at the point-of-care to optimize resources allocation in the diagnostic workup of EoE and 1) Support the clinical suspicion of EoE even in the absence of endoscopic findings, 2) Support decision making in performing repeat EGDS in patients in whom biopsies had been omitted, 3) Support decision making in performing repeat EGDS in patients with persistent EoE symptoms who had non-diagnostic levels of eosinophils at a previous EGDS performed while on proton-pump inhibitors, 4) Avoid unnecessary biopsies in very low-risk patients.

Clinical Case Summary

SARS-COV2 infection has accumulated more than 670 million cases since its onset in 2019. Its clinical spectrum varies from asymptomatic patients to bilateral pneumonia with a mortality rate of 1%. Digestive symptoms include nausea, abdominal pain and diarrhea. Multiple complications as hepatitis, pancreatitis, cholecystitis, mesenteric ischemia or venous thrombosis have also been described.
We present the case of a 60-year-old woman who came to ER for abdominal pain. A CT showed acute cholecystitis with a 30mm liver abscess and choledocholithiasis. It was treated with empirical Piperacillin-Tazobactam, thromboprophylaxis and drainage by ERCP. During admission the patient presented bilateral SARS-COV2 pneumonia requiring Dexamethasone and Remdesivir. Due to the reappearance of abdominal discomfort, an US was performed showing a new left portal thrombosis. Given these findings, a coagulation study was performed, with no genetic or cytological alterations. Finally it was decided to maintain antibiotic for 6 weeks and anticoagulation, performing outpatient US control, with deferred surgical treatment.
The portal thrombosis is a complication mostly related to chronic liver diseases and hepatic tumors, being much rarer the septic portal thrombophlebitis associated with abdominal infections or related to proliferative neoplasms. On the other hand, SARS-COV2 infection triggers an inflammatory reaction after binding to ACE-II receptor that leads to a generalized prothrombotic environment. In relation to this process, PTE, DVT and in multiple other locations has been described. One of the the most infrequent locations is abdominal, with very few cases described in the literature.
The scarce clinical repercussion of portal thrombosis and the serious complications derived from it, added to the high prevalence of SARS-COV2, means that we should early rule out this process in patients with abdominal infections with regular evolution and active or recent SARS-COV2 infection.

Clinical Case Summary

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in clinical practice. These patients have up to 50 times higher risk of developing cancer in comparison to the general population, with gastric adenocarcinoma being the leading cause of death in this population.
We describe a case of a 33-year-old woman with a history of CVID and Addison's disease, who was admitted for upper gastrointestinal hemorrhage with hemodynamic instability refractory to combined endoscopic hemostasis (noradrenaline, hemoclips, thermocoagulation and hemostatic spray) after partial resection of a 40 mm semipediculated gastric polyp (figures 1,2), finally requiring selective arterial embolization to control bleeding. Histological and immunohistochemical studies revealed gastric adenocarcinoma HER2+ with conserved expression of proteins encoded by DNA repair genes.
Multiple studies have demonstrated a dysfunctional immune system at the level of the non-neoplastic gastric mucosa of these patients, characterized by high rates of CD4+, CD8+, Foxp3+, GATA3+, PD-L1 and low numbers of CD20+ B-lymphocytes and CD138+ plasma cells compared to individuals without CVID. In addition, the expression of GATA3+ by cytotoxic T lymphocytes is identified in the literature as a mechanism for tumor escape from immunological surveillance and T-cell depletion. On the other hand, few studies have focused on analyzing the monogenic causes of CVID. This could be an interesting field of study since genes, such as NF-Kb1 deficiency, which is the most common monogenic cause of CVID, have in turn been directly related to the pathogenesis of gastric cancer in individuals without CVID. All this is very important when it comes to being able to stratify our patients according to the risk of developing malignant gastric pathology in order to establish standardized screening recommendations and to be able to carry out individualized follow-ups in order to detect premalignant lesions.

References

Bruns L, Panagiota V, von Hardenberg S, et al. Common Variable Immunodeficiency-Associated Cancers: The Role of Clinical Phenotypes, Immunological and Genetic Factors. Front Immunol. 2022;13:742530. Published 2022 Feb 17.
Pecoraro A, Crescenzi L, Varricchi G, Marone G, Spadaro G. Heterogeneity of Liver Disease in Common Variable Immunodeficiency Disorders. Front Immunol. 2020;11:338. Published 2020 Feb 28. doi:10.3389/fimmu.2020.00338
Pikkarainen S, Martelius T, Ristimäki A, Siitonen S, Seppänen MRJ, Färkkilä M. A High Prevalence of Gastrointestinal Manifestations in Common Variable Immunodeficiency. Am J Gastroenterol. 2019 Apr;114(4):648-655.
Pulvirenti F, Pecoraro A, Cinetto F, et al. Gastric Cancer Is the Leading Cause of Death in Italian Adult Patients With Common Variable Immunodeficiency. Front Immunol. 2018;9:2546. Published 2018 Nov 5.
Gullo I, Costa C, Silva SL, et al. The Dysfunctional Immune System in Common Variable Immunodeficiency Increases the Susceptibility to Gastric Cancer. Cells. 2020;9(6):1498. Published 2020 Jun 19.

Introduction

Gastroesophageal reflux disease (GERD) patients with atypical symptoms represents a diagnostic and therapeutic challenge. In particular, the diagnosis of GERD is often suspected by ENT surgeons according to laryngoscopic findings, but their sensitivity and specificity for diagnosis is low. The aim of this study was to assess the prevalence of GERD in patients with atypical symptoms undergoing laryngoscopic examination and pH monitoring.

Aims & Methods

We retrospectively evaluated patients with atypical symptoms with or without typical symptoms associated referred to Gastroenterology Units of six tertiary Italian centres between January and December 2020. Of 477 patients, we enrolled 277 patients who underwent both 24 hours pH-impedance monitoring off-therapy and laryngoscopy. Diagnosis of GERD was made according to Lyon Consensus, and we considered the novel impedance metrics (baseline impedance and post reflux swallow-induced peristaltic wave index) when pH-impedance monitoring was inconclusive in order to add confidence to diagnosis of GERD. Three patients with hypersensitive esophagus were excluded.

Results

The most common atypical symptom was cough (90/274). Laryngoscopic examination showed pathological findings in 195 patients (71.2%), and the most frequent feature detected was posterior laryngitis (77.4%). GERD was diagnosed in 80/274 patients (29.2%) on pH impedance monitoring. Upper endoscopy was made in 269 patients and 5 of them had B grade esophagitis. The prevalence of GERD diagnosis in patients with or without positive laryngoscopy examination was not statistically significant (p=0.075). No difference in the number of proximal refluxes was observed in patients with positive or negative laryngoscopy (65/195, 33.3% vs 19/79, 24.1%; p= 0.133). Sensitivity and specificity of laryngoscopy in diagnosing GERD is 78.8% and 32.0% respectively (PPV= 32.3%; NVP= 28.4%).

Conclusion

Laryngoscopic examination has a poor specificity in diagnosing GERD in patients with atypical symptoms. This study may underline that pathological laryngoscopy findings could only pose a suspect of an underlying GERD, but its diagnosis would still need to be confirmed by impedance-pH monitoring, even in patients with atypical symptoms.

Introduction

CD is a chronic progressive disease associated with bowel damage and disability and with a globally increasing prevalence. Contemporary reports on the clinical presentation, disease outcomes, and treatment choices in newly diagnosed patients across Europe are important to inform physicians.

Aims & Methods

To describe the clinical characteristics in a contemporary European cohort of recently diagnosed CD patients. The Crohn´s Disease Cohort (CROCO) is an ongoing multicentre, European, prospective cohort study of recently diagnosed CD patients (within 12 months following diagnosis) intended to characterize bowel damage progression and disability. Herin, we report on the characteristics of CD-patients at inclusion in the study.

Results

Between Aug/21-April/24, 316 patients (58% male, 47% smoker or ex-smokers) with a median age at diagnosis of 34.4 (IQR 24.8; 49.6), were recruited from 17 centres. The median delay between symptoms onset and diagnosis was 6.5 months (IQR 2; 17.5); median disease duration at the time of inclusion was 3.9 months (IQR 1.6; 7.6); Ileal involvement (L1/L3) was reported in 86%. Overall, 15% had perianal disease and 28% had extra-intestinal manifestations, the most frequent being arthritis/arthralgia. One-third (32%) had evidence of either stricturing (B2) (17%) or penetrating (B3) (15%) phenotype; 7% had an intestinal-related surgery, and 2% perianal surgery. Fifty-nine (21%%) patients had at least one CD-related hospitalization. Median faecal calprotectin was was 236µg/g (IQR 75; 731) and median C-reactive protein was 4mg/L (IQR 1.2; 11). Regarding the therapies receiveid from diagnosis to inclusion, 54% of the patients had received systemic steroids, 18% 5ASA, 10% IM monotherapy, and 43% started biological therapy (126 anti-TNF, 6 anti-IL 12/23 and 3 anti-integrin).

Conclusion

In this prospective cohort of newly diagnosed CD-patients, more than one-third of the patients presented with a complicated phenotype despite a short delay between onset of symptoms and diagnosis. Steroids remain frequently used, however early and effective therapy was started in approximately in 40% of patients, highlighting the changing paradigm in CD treatment.

Disclosure

JB: Reports grants and personal fees from AbbVie, grants and personal fees from Janssen-Cilag, personal fees from Celgene, grants and personal fees from MSD, personal fees from Pfizer, grants and personal fees from Takeda, grants and personal fees from Tillots Pharma, personal fees from Samsung Bioepis, grants and personal fees from Bristol Myers Squibb, grants from Novo Nordisk, personal fees from Pharmacosmos, personal fees from Ferring, personal fees from Galapagos, outside the submitted work. NA: received speaker fees from Ferring and Janssen. PE: educational grants Jannsen; SV: Speaker fees from Abbvie, Ferring, Janssen Takeda. IR-L: has received financial support for travelling and educational activities from or has served as an advisory board member for Abbvie, Adacyte, Celltrion, Chiesi, Danone, Dr. Falk Pharma, Ferring, Faes Farma Janssen, Galapagos, MSD, Otsuka Pharmaceutical, Pfizer, Roche, Takeda, and Tillotts Pharma. IO: has served as speaker and/or consultant and has received educational funding from MSD, Abbvie, Pfizer, Takeda, Janssen, Faes Farma and Chiesi, and has received research funding from Abbvie and Faes Farma. DD: Lecture fee/consultancy from: Takeda, Pfizer, Janssen, Ferring, AbbVie, Eli-Lilly. SS: received consulting fees and advisory board fees from Takeda, AbbVie, Merck, Ferring, Pharmacocosmos, Warner Chilcott, Janssen, Falk Pharma, Biohit, TriGenix, Celgene, and Tillots Pharma; speaker honoraria from AbbVie, Takeda, Celltrion, Pfizer, Biogen, AbbVie, Janssen, Merck, Warner Chilcott, and Falk Pharma. VH: Has served as consultant, has served as speaker, has received travel support or research funding from MSD, AbbVie, Ferring, Dr. Falk Pharma, Tillotts Pharma, Pfizer, Takeda, Janssen, KernPharma Biologics, Adacyte, Sandoz, Biogen, Fresenius-Kabi, FAES Farma and Galapagos. MN: received board membership, consultancy, or lecture fees from Abbvie, Amgen, Biogen, Celltrion, Ferring, Fresenius-Kabi, Galapagos, Janssen, Lilly, Mayoli-Spindler, MSD, Nordic Pharma, Pfizer, Takeda, Viatris. MF: Lecture and consulting fees from Abbvie, Pfizer, Tillots, Takeda, Gilead, Arena, Sandoz, Celltrion, Galapagos, Celgene, Boehringer, Biogen, Viatris, Amgen, Fresenius, Celltrion, CTMA, Ferring and Janssen. MA: Speaker and consulting fees from Abbvie, Pfizer, Ferring and Janssen. BB: Speaker and consulting fees from Janssen, Takeda, Sofar, Alfasigma, Doxapharma. BB: Speaker and consulting fees from Janssen, Takeda, Sofar, Alfasigma, Doxapharma. RCU: has received consulting and/or advisory board fees from AbbVie, Bristol Myers Squibb, Celltrion, Janssen, Lilly, Pfizer, Roivant, Takeda. JC: receiving research grants from AbbVie, Janssen Pharmaceuticals and Takeda; receiving payment for lectures from AbbVie, Amgen, Anaptysbio, Allergan, Inc. Ferring Pharmaceuticals, Shire, and Takeda; receiving consulting fees from AbbVie, Amgen, Arena Pharmaceuticals, Boehringer Ingelheim, BMS, Celgene Corporation, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Genentech, Galxo Smith Kline, Japan Gastroenterological Endoscopy Society, Janssen Pharmaceuticals, Kaleido Biosciences, Imedex, Immunic, Iterative Scopes, Merck, Microba, Morgan, Lewis & Bockius LLP, Novartis, Otsuka Pharmaceutical Development PBM Capital, Pfizer, Protagonist Therapeutics Sanofi, Takeda, TiGenix, Vifor; and hold stock options in Intestinal Biotech Development. JT: Grant - AbbVie, Janssen Personal Fees - Pfizer, Janssen, Abbvie, sandoz.