Clinical Case Summary

A 68-year-old female presented with peripheral oedema and heart block necessitating admission to ICU and insertion of a pacemaker due to electrolyte disturbances secondary to severe malnutrition. She had a background history of jejunoileal bypass for weight loss, performed more than 40 years ago in the UK.
The initial work-up showed iron deficiency anaemia, severe electrolyte abnormalities including hypokalaemia, hypomagnesaemia and hypophosphataemia, as well as hypoalbuminaemia and deranged liver function tests.
Parenteral nutrition was commenced and following discussion at our bariatric MDT, laparoscopic reversal of jejunoileostomy was recommended with restoration of bowel continuity and insertion of gastrostomy tube to supplement nutrition. This was complicated by displacement of gastrostomy tube with imaging evidence of large peri-gastric collections and pneumoperitoneum. The patient returned to theatre for washout and replacement of the gastrostomy tube. A further residual collection posterior to the stomach was drained via endoscopic ultrasound, using a 20mm x 10mm Lumen-apposing metal stent (LAMS). Immediately after stent deployment, copious amounts of feed was drained into the gastric lumen. The stent remained in an excellent position along the greater curvature of the stomach and was subsequently removed after four weeks.
This patient had life-threatening complications due to short bowel syndrome secondary to jejunoileal bypass and underwent successful restoration of anatomy with laparoscopic reversal surgery. The case also highlights the safe and effective use of EUS guided drainage with lumen-apposing metal stent for abdominal collection post laparoscopic surgery and the importance of multi-disciplinary working in complex cases.

Figure 1: Axial CT abdomen view
Jejunoileal bypass was an effective weight loss surgery, but its practice has long been abandoned due to the potential life-threatening metabolic abnormalities that may arise.

References

Menon, A. and Khwaja, H.A. (2018) Complications of jejunoileal bypass

Clinical Case Summary

Introduction: Eating disorders are often overlooked in the management of inflammatory bowel disease (IBD), despite their potential to aggravate malnutrition and reduce treatment effectiveness.
Aims & Methods: This case report aims to raise awareness of the possible coexistence of binge eating disorder (BED) and IBD. A female Crohn’s disease patient with persistent malnutrition and therapeutic resistance disclosed binge eating behavior and was referred for psychiatric care.
Results: Despite clinical remission with infliximab, the patient maintained a BMI of 13.8. After BED diagnosis and psychiatric intervention, her BMI increased to 16.6 with notable emotional improvement.
Conclusion: BED can mimic or worsen IBD complications. Screening for eating disorders and implementing multidisciplinary care—including mental health support—are crucial to optimize outcomes.

References

1) Inflammatory Bowel Disease and Eating Disorders: A systematized review of comorbidity
L Ilzarbe et al. J Psychosom Res. 2017 Nov.
2)Celiac Disease and Inflammatory Bowel Disease Are Associated With Increased Risk of Eating Disorders: An Ontario Health Administrative Database Study
Lakshmimathy Subramanian et al. Clin Transl Gastroenterol. 2024.
3)Shared genetic influences between eating disorders and gastrointestinal disease in a large, population-based sample of adult women and men
Laura A Pascoe et al. Psychol Med. 2024 Apr.
4) Prevalence and Characteristics of Avoidant/Restrictive Food Intake Disorder in Adult Neurogastroenterology Patients
Helen Burton Murray et al. Clin Gastroenterol Hepatol. 2020 Aug.

Introduction

According to the British Society of Gastroenterology (BSG) guidelines on sedation in gastrointestinal endoscopy (2023), minimal to moderate sedation is typically sufficient for level 1/2 endoscopic retrograde cholangiopancreatography (ERCP). However, deep sedation is not routinely available in many centres, potentially affecting patient comfort and procedure completion. This study investigated factors associated with incomplete ERCP procedures, with a particular focus on patient intolerance.

Aims & Methods

A retrospective review of all ERCP’s performed over six months at our tertiary centre was conducted. Data collected included demographics, indication, ERCP grade, sedation used, cannulation rate and completion of procedure (eg complete duct clearance). Achieving the primary therapeutic or diagnostic goal served as the primary outcome. Univariate and multivariable analyses were used to evaluate factors contributing to incomplete procedures.

Results

475 ERCP’s were analysed (median age 67 years; range 18–92; 49.5% female). Successful cannulation was achieved in 458 of 475 procedures (96.4%). Among the 55/475 (11.6%) incomplete ERCPs, 32 (6.7% of all procedures) were abandoned due to patient discomfort—manifested as pain, restlessness, and inability to tolerate the procedure. Univariate analysis showed significantly higher opiate doses (63.8 mg vs. 56.3 mg, p=0.015) and higher midazolam doses (5.0 mg vs. 4.0 mg, p=0.0003) in incomplete procedures. No significant differences were observed for age, sex, inpatient status, ERCP grade, or use of general anaesthesia. Multivariable analysis revealed no independent risk factors for incompletion. Other contributing factors included prolonged procedures (e.g., EUS prior to ERCP) and challenging anatomy.

Conclusion

Patient discomfort emerged as the primary driver of incomplete ERCPs, highlighting the importance of optimizing sedation strategies and ensuring adequate anaesthetic support. Higher opiate and midazolam doses correlated with incomplete procedures suggesting that deeper sedation may have allowed completion. More detailed research including data from a combination of tertiary and non-tertiary centres is needed to refine sedation practices in line with current BSG guidelines.

Introduction

Musculoskeletal disorders (MSDs) are the leading cause of occupational disease and represent a major public health concern. Endoscopy plays a central role in hepatogastroenterology, and its practice is associated with a high prevalence of MSDs, ranging from 40% to 90% among endoscopists. The increasing complexity of endoscopic procedures may further exacerbate musculoskeletal strain on practitioners. However, few studies have been conducted on this topic, and most rely on observational and self-reported data, limiting their level of evidence. Quantitative studies assessing the impact of digestive endoscopy, particularly endoscopic retrograde cholangiopancreatography (ERCP), on MSD risk under real working conditions remain scarce.

Aims & Methods

To obtain objective and reliable data, we used the KIMEA tool, which analyzes an operator’s movements by generating a digital twin based on data collected through a depth camera and wrist-mounted sensors. This system allows for an objective assessment of musculoskeletal strain by estimating MSD risk using the Rapid Upper Limb Assessment (RULA) method. Our study was conducted on two experienced endoscopists performing a total of 10 ERCP procedures.

Results

Motion analysis revealed an average global RULA score of 4.2, indicating a moderate risk of MSDs. Musculoskeletal strain was predominantly observed in the forearms, particularly in the wrists, which remained in constrained postures for more than 50% of the procedure time. The musculoskeletal load was asymmetrical, with greater strain on the left side. These findings were consistent across all 10 procedures.

Conclusion

Discussion: This study confirms the significant musculoskeletal strain on the upper limbs during ERCP procedures. Our findings align with existing literature. The KIMEA tool appears to be a suitable method for analyzing movements in digestive endoscopy and represents a methodological advancement for the objective evaluation of musculoskeletal strain in this field.
Conclusion: Motion analysis using the KIMEA tool provides objective evidence that ERCP practice poses a risk for MSD development. Further studies with larger sample sizes are needed to strengthen the level of evidence, assess the impact of factors such as age, experience, gender, and procedure type, and promote the integration of ergonomic measures into endoscopic practice to reduce MSD risk.

Introduction

Advanced colorectal neoplasia (ACN) has a high potential for malignancy, and its early detection and removal can effectively reduce the incidence and mortality of colorectal cancer (CRC). A predictive model to estimate the risk of ACN could help direct patients and providers to improve screening efficiency.

Aims & Methods

We aimed to develop a comprehensive risk prediction model specifically for ACN.
A retrospective cross-sectional study was conducted on patients who underwent endoscopy at the Affiliated Wuxi People's Hospital of Nanjing Medical University from January 1, 2021, to December 31, 2023. The researchers collected clinical data, including histopathological results, demographic information, lifestyle features, and medical history. Univariate and multivariable analyses were used to derive a risk prediction model based on the training cohort of the sample, and points were assigned to each variable to create a risk score. Scores with comparable risks were grouped into different risk categories. The model and its scores were tested using the validation cohort.

Results

Among the 2054 participants in the training cohort [mean age, 60 (52, 68) years; 1022 (50.0%) female], the prevalence of ACN was 271 (13.3%). The eight-variable model (sex, age, diabetes, family history of CRC in a first-degree relative, history of colonoscopy history, smoking, gastric histopathological results, and Helicobacter pylori infection history) resulted in two risk categories, with an area under the receiver operating characteristic curve (AUC) of 0.710 (95% CI: 0.679-0.742). In the validation cohort of 495 participants with an ACN prevalence of 62 (12.5%), model performance was comparable (AUC=0.715, 95% CI: 0.649-0.781). The ACN risk was 6.9% and 23.9% in the low- and high-risk groups, respectively, and 14 and 4 participants needed to be screened in the low- and high-risk groups, respectively. Further analysis revealed that three other prediction methods, including the Asia-Pacific Colorectal Screening (APCS) score [0.622 (0.556-0.688), p=0.049], the APCS score-revised edition [0.589 (0.524-0.653), p=0.007], and the colorectal tumor prediction score [0.570 (0.504-0.636), p=0.002], displayed significantly lower AUCs than our prediction ACN model.

Conclusion

The developed and validated prediction model performed well in identifying individuals with ACN at high risk in asymptomatic Chinese populations. Colonoscopy examinations in these patients were necessary, as they not only facilitated early detection of ACN but also enabled timely intervention to prevent CRC.

Introduction

Esophageal squamous cell carcinoma (ESCC) is a major global health concern, with a high recurrence rate after chemoradiotherapy (CRT). Despite being a curative approach, CRT alone is often insufficient, leading to local recurrence in 30–40% of cases (1). Salvage treatments such as surgery and endoscopic resection have limitations, particularly in patients with comorbidities or advanced lesions (2). Photodynamic therapy (PDT) using talaporfin sodium (TS) has emerged as a promising, minimally invasive salvage treatment, offering advantages such as reduced phototoxicity and repeatability (3). Since its approval in Japan in 2015, TS-PDT has gained traction, yet further clinical evidence is needed to validate its efficacy and safety. This study aims to evaluate the clinical outcomes of TS-PDT as a salvage treatment for locally recurrent or residual ESCC following CRT or radiotherapy (RT).

Aims & Methods

A retrospective study was conducted at Nagoya City University Hospital between May 2016 and December 2023. A total of 29 patients with histologically confirmed local recurrence or residual ESCC post-CRT/RT were included. Eligible patients had lesions classified as ≤T2, without lymph node or distant metastasis. TS-PDT was administered with a diode laser (664 nm) 4–6 hours post-intravenous TS injection (40 mg/m²). Patients were monitored for adverse events, local complete response (L-CR), progression-free survival (PFS), and overall survival (OS). Kaplan–Meier analysis was used for survival estimation, and comparisons between single and multiple PDT sessions were evaluated.

Results

Table 1. The best response to PDT
	Local-CR	Non L-CR	L-CR rate
patients	22	5	81.5%
lesions	36	5	87.8%
T1b lesions	28	1	96.6%
T2 lesions	8	4	66.7%

Among the 29 patients (23 males, 6 females; median age, 72 years), TS-PDT achieved an L-CR rate of 82.1% per patient and 87.8% per lesion, with superior outcomes in T1b lesions (96.6%) compared to T2 lesions (66.7%) (Table1). The median local PFS was 1,324 days, and the median PFS was 912 days. OS was not reached during follow-up, with a 3-year survival rate of 70.7%. Seventeen patients underwent a single PDT session, while 12 required multiple sessions. The 3-year OS rate was 83.3% in the single-session group and 44.4% in the multiple-session group. No skin phototoxicity was observed. Adverse events included esophageal strictures (1 case, asymptomatic) and esophageal perforations (2 cases), one of which required surgical intervention.

Conclusion

TS-PDT demonstrated high local control rates and favorable survival outcomes, making it a promising salvage therapy for ESCC recurrence post-CRT/RT (4). Despite some adverse events, its minimal invasiveness and reduced phototoxicity enhance its applicability, particularly in elderly or high-risk patients. The effectiveness of multiple PDT sessions supports its role as a flexible treatment strategy. Further multicenter prospective trials are warranted to optimize patient selection, treatment protocols, and long-term outcomes, solidifying TS-PDT as a key salvage therapy for recurrent ESCC (5).

References

1. Hironaka S, Ohtsu A, Boku N, et al.: Nonrandomized comparison between definitive chemoradiotherapy and radical surgery in patients with T(2-3)N(any) M(0) squamous cell carcinoma of the esophagus. Int J Radiat Oncol Biol Phys 57: 425-433, 2003.
2. Tachimori Y, Kanamori N, Uemura N, Hokamura N, Igaki H and Kato H: Salvage esophagectomy after high-dose chemoradiotherapy for esophageal squamous cell carcinoma. J Thorac Cardiovasc Surg 137: 49-54, 2009.
3. Yano T, Kasai H, Horimatsu T, et al.: A multicenter phase II study of salvage photodynamic therapy using talaporfin sodium (ME2906) and a diode laser (PNL6405EPG) for local failure after chemoradiotherapy or radiotherapy for esophageal cancer. Oncotarget 8: 22135-22144, 2017.
4. Ikebuchi Y, Yoshida A, Kurumi H, et al.: Salvage Photodynamic Therapy Using Talaporfin Sodium for Local Failure of Esophageal Squamous Cell Carcinoma. Yonago Acta Med 64: 120-125, 2021.
5. Kai K, Nakashima K, Kawakami H, et al.: Clinical Impact of the Charlson Comorbidity Index on the Efficacy of Salvage Photodynamic Therapy Using Talaporfin Sodium for Esophageal Cancer. Intern Med 63: 903-910, 2024.

Introduction

Colorectal cancer (CRC) therapy faces significant challenges, including drug resistance, tumour heterogeneity, metastatic progression, and treatment-associated toxicity. CRC and other cancers exhibit increased levels of Fe(II) due to dysregulated iron metabolism, which can act as a trigger for selective prodrug activation. In this study, we explore the therapeutic potential of a novel tumour-activated prodrug platform based on 1,2,4,5-tetraoxane scaffold that is selectively activated in cancer cells with high levels of labile Fe(II). As a proof-of-concept, we evaluated the therapeutic potential of 5b, a prodrug coupled with doxorubicin (DOX), which releases this cytotoxic payload upon activation by the labile Fe(II) pool in the cytoplasm of cancer cells.

Aims & Methods

The therapeutic potential and mechanism of action of 5b was evaluated both in vitro and in vivo. IC₅₀ values were determined across multiple cancer cell lines and compared to non-tumorigenic cells. To confirm iron-dependency, HCT116 cell viability was assessed upon co-incubation with 5b and iron chelator deferoxamine (DFO). Co-incubation with apoptosis inhibitor Z-VAD-FMK (Zvad) or ferroptosis inhibitor liproxstatin-1 was used to assess cell death mechanism. The sub-cellular location of 5b activation was evaluated by fluorescence microscopy. In vivo efficacy was evaluated in a xenograft mouse model using immunocompromised mice implanted with HT29 cells and intraperitoneal administrations of 5b, assessing tumour burden and systemic toxicity.

Results

Prodrug 5b effectively reduced cell viability in CRC cells HCT116 and HT29, as well as in glioblastoma (U251), prostate cancer (PC3) and breast cancer (MCF7) cells, with IC₅₀ values ranging from 1.64 to 6.69 µM. Notably, 5b was over 2000 times less toxic than DOX in non-tumorigenic cells AML12 (5b IC₅₀ = 398.2 µM vs. DOX IC₅₀ = 0.18 µM). Taking advantage of DOX intrinsic fluorescence properties (while 5b pro-drug is non-fluorescent), we used fluorescence microscopy analysis to confirm that 5b released its fluorescent DOX payload in the cytoplasm, after activation by labile Fe(II). The significant decrease in cell viability induced by 5b (p < 0.0001) was rescued by the iron chelator DFO and by the ferroptosis inhibitor liproxstatin-1 (p < 0.01) but not by pan-caspase inhibitor Zvad, suggesting that ferroptosis may be the primary mechanism of cell death. In vivo, 5b significantly reduced the relative tumour volume (p < 0.05), demonstrating greater efficacy than DOX, with only minor cardiotoxicity side-effects (multifocal loci of fibrosis affecting of 0.2% of left ventricle volume).

Conclusion

Prodrug 5b efficiently released its DOX payload in response to the cytoplasmatic labile Fe(II), effectively reducing cancer cell viability both in vitro and in vivo, while demonstrating significantly lower toxicity compared to DOX itself. Given its Fe(II)-dependent activation, 5b represents a promising strategy to exploit cancer cell iron addiction for cancer therapy. Future work should further validate ferroptosis as cell death mechanism, optimize the selection of cytotoxic payloads for tumours with dysregulated iron metabolism, and assess its efficacy in relation to KRAS mutational status. Funding: CMPR: PTDC/MED-FAR/3492/2021, LCF/PR/HR21/52410028; RM: 2022.07857.PTDC, PTDC/MED-QUI/30021/2017; VM: 10.54499/2023.11531.PEX; DMS: LCF/TR/CI22/52660003

Disclosure

The authors declare that this work is associated with intellectual property protection under the following patents/patent requests:
- Diogo Magalhães e Silva, Rui Moreira, Francisca Lopes, Cecília Rodrigues, Vanda Marques, “1,2,4,5-tetraoxane compounds, a drug delivery system based in said compounds useful in diagnoses and therapy, and methods thereof”, Portuguese Patent Application nº PT117644 from 16-12-2021;
- Diogo Magalhães e Silva, Rui Moreira, Francisca Lopes, Cecília Rodrigues, Vanda Marques, “Drug delivery systems based on endoperoxides useful in diagnosis and therapy, and methods thereof”, PCT Application nº PCT/IB2022/062107 from 13-12-2022;
- Diogo Magalhães e Silva, Rui Moreira, Francisca Lopes, Cecília Rodrigues, Vanda Marques, “Drug delivery systems based on endoperoxides useful in diagnosis and therapy, and methods thereof”, European Patent Office Application nº EP4448107 from 23-10-2024;
- Diogo Magalhães e Silva, Rui Moreira, Francisca Lopes, Cecília Rodrigues, Vanda Marques, “Drug delivery systems based on endoperoxides useful in diagnosis and therapy, and methods thereof”, United States Patent and Trademark Office patent application nº US20250064840 from 27-02-2025.