Introduction

Emerging experimental and clinical data suggest that the gut microbiome can significantly influence the antitumor efficacy of key chemotherapy agents, including 5-fluorouracil, oxaliplatin, and docetaxel. These agents form the backbone of the neoadjuvant chemotherapy (NAC) regimen, FLOT, which is widely used for the treatment of locally advanced gastric cancer (GC). However, despite growing evidence from preclinical models, clinical studies investigating the direct association between gut microbiome composition and the response to NAC in GC patients remain scarce.

Aims & Methods

This study aims to address this gap in knowledge by exploring the relationship between the gut microbiome and therapeutic outcomes in this clinical context. In this longitudinal observational study, we explored the association between pre-treatment fecal microbiome composition analyzed via 16S rRNA gene sequencing and histological tumor regression, as assessed by the Becker score, in GC patients undergoing NAC with the FLOT regimen, followed by gastrectomy.

Results

Among the 38 enrolled patients, 19 (50%) achieved a Becker score of 1–2 and were classified as ‘Responders,’ while the other 19 (50%) were classified as ‘Non-responders’. Responders exhibited a higher abundance of Parabacteroides distasonis, Alistipes sp. AL-1, and Bacteroides plebeius. A combined biomarker of these species demonstrated robust predictive accuracy for a favorable response to NAC, with sensitivity of 89%, specificity of 63%, and an AUC of 0.8 (95% CI: 0.66–0.94). In contrast, non-responders showed a predominance of bacterial genera, including Ruminococcaceae UCG-014, Ruminococcus 1, Ruminococcaceae UCG-005, and the [Eubacterium] eligens group. The combined biomarker of these genera demonstrated excellent predictive performance for poor NAC response, with sensitivity of 89%, specificity of 95%, and an AUC of 0.93 (95% CI: 0.85–1.0).

Conclusion

The results of our study support the hypothesis that the pre-treatment gut microbiome composition can serve as a reliable biomarker for predicting both positive and negative responses to NAC in GC patients. By identifying specific microbial signatures associated with chemotherapy outcomes, this research provides critical insights into how microbiome-based strategies might enhance personalized treatment regimens for GC. Future studies are needed to validate these findings and explore potential therapeutic interventions targeting the microbiome to improve clinical outcomes in GC patients.

Clinical Case Summary

The patient was a 39-year-old man admitted to the emergency department for sudden onset of diffuse abdominal pain. The patient had a pathological history of chronic smoking. The clinical history dates back 10 hours to the onset of abdominal pain, initially localized to the epigastrium and rapidly generalized to the entire abdomen, unrelieved by usual treatment and without other associated signs. The patient was conscious, normocardiac, normotensive, slightly tachypneic and apyretic. A diffuse abdominal tenderness was noted, with no other particular pathological signs. Biological work-up revealed hyperleukocytosis at 20430/mm3 , C-reactive protein (CRP) at 5.80 mg/L , no hydroelectrolytic disorders, and the rest of the biological work-up returned normal. Abdominal CT revealed pneumo bubbles with infiltration of mesenteric fat, predominantly at the supra-mesocolic level, in favor of a hollow organ perforation. The patient underwent surgery, which revealed a pre-pyloric gastric perforation measuring approximately 1 cm with a clean edge and the presence of 2 hepatic nodules measuring 0.25 and 0.5 cm in segment II. The rest of the exploration was without anomalies, and the gastric perforation was sutured, with biopsy of the edges of the gastric perforation and biopsy of the hepatic nodules. Histopathological examination revealed the presence of subacute and chronic nonspecific inflammatory remodeling in the gastric margin biopsy, whereas the liver biopsy showed epithelial and gigantocellular granulomatous inflammation with caseous necrosis consistent with tuberculosis.The diagnosis of hepatic tuberculosis was made.The patient was put on standard anti-tuberculosis treatment for 6 months.

Clinical Case Summary

A 52-year-old male, liver-transplanted in 2014 for alcohol- and HCV-related cirrhosis (HCV eradicated in 2017 with DAAs), was evaluated in May 2024 due to low-grade evening fevers. His immunosuppression regimen included tacrolimus 1 mg b.i.d., with stable trough levels around 11.5 ng/mL. However, during a routine check-up, tacrolimus levels spiked to 27 ng/mL. The result was confirmed on repeat testing despite Tacrolimus discontinuation.

No changes in liver function were observed, and tacrolimus was temporarily discontinued. The patient was hospitalized and developed mild upper limb tremors. Erythrocytapheresis was performed due to suspected tacrolimus toxicity, reducing levels only modestly (from 22 to 21.2 ng/mL). Given the discrepancy between assay results and clinical context, the lab performed a dilutional linearity test, revealing non-linearity suggestive of assay interference.

Autoantibody screening (RF, ANA, ASMA, LKM, ANCA, etc.) was negative. However, treatment of the sample with heterophile antibody blocking reagent (HBR) significantly reduced tacrolimus concentrations, confirming heterophile antibody interference. The patient underwent plasmapheresis to eliminate interfering antibodies, which normalized tacrolimus readings. Unfortunately, he developed candidemia (Candida parapsilosis) and died from cardiovascular complications.

This case illustrates how heterophile antibodies may falsely elevate tacrolimus levels in immunoassays, potentially leading to inappropriate clinical decisions. Clinicians must consider assay interference when pharmacokinetics and clinical findings are discordant, and collaborate closely with laboratory services to ensure accurate therapeutic drug monitoring.

Clinical Case Summary

A 66-year-old presented with a one-day history of abdominal pain and fevers. Computer tomography imaging (CT) revealed a foreign body in a sigmoid colon diverticulum with perforation and collection. A sigmoidoscopy failed to identify the foreign body. Ultrasound-guided foreign body extraction was unsuccessful. Surgical treatment was deemed high risk due to comorbidities and he was treated conservatively. Twelve days following a second sigmoidoscopy was performed due to persisting collection. A fish bone was found puncturing a sigmoid diverticulum. A through-the-scope (TTS) clip and methylene blue dye were applied. Removal was achieved with a snare. An over-the-scope clip (OTSC) successfully sealed the perforation.
Endoscopy is proving to be an increasingly viable minimally-invasive option for the treatment of foreign body colonic perforations when used early and in the absence of peritonitis or clinical instability¹. Unique to this case is that endoscopic closure was performed one week following perforation with associated collection, factors considered to influence procedure success due to inflammatory change^1,2. A standard TTS clip was unlikely to achieve closure strength. We used the OTSC system, designed to achieve full-thickness closure³. The technical complexity of using the OTSC system was visualisation which requires colonoscope withdrawal and mounting of a cap reducing endoscopic visibility. TTS clip and dye application prior to OTSC application proved beneficial in achieving definitive endoscopic perforation management. This is a technical aspect that to our knowledge has not been documented elsewhere in the literature.
Lessons:
1. Endoscopy can be effective in delayed colonic perforation management avoiding the need for surgery.
2. A three-step technique is proposed: 1) application of a locator (TTS clip and dye) 2) foreign body removal 3) OTSC application of the perforation site.
Fig1 CT image of fish bone and collection
Fig2 Endoscopic image OTSC

References

1) Morais R, Marques M, Macedo G. Endoscopic treatment of a foreign body–associated colonic perforation. Int. J. Colorectal Dis. 2020; 35: 165-167.
2) Rogalski P, Daniluk J, Baniukiewicz A et al. Endoscopic management of gastrointestinal perforations, leaks and fistulas. World J Gastroenterol. 2015; 21: 10542-10552.
3) Kobara H, Mori H, Nishiyama N et al. Over‐the‐scope clip system: A review of 1517 cases over 9 years. JGH. 2019; 34:22-30.

Introduction

Colonic polypectomy is a widely used endoscopic technique for colorectal cancer prevention. However, post-polypectomy bleeding (PPB) and local recurrence remain notable complications. Snare Tip Coagulation (STC) involves the application of thermal coagulation to the resection margin using the tip of the snare after polyp removal. This study aimed to evaluate the clinical efficacy of STC in reducing immediate and delayed PPB, as well as local recurrence, following polypectomy.

Aims & Methods

We retrospectively reviewed 156 patients who underwent endoscopic resection—either snare polypectomy or endoscopic mucosal resection (EMR)—for pedunculated or sessile colorectal polyps measuring 6–20 mm at a single center between January 2022 and February 2024. Patients were divided into two groups: those who received STC (n=78) and those who did not (control group, n=78). Primary outcomes included the incidence of PPB within 14 days and local recurrence at 12-month follow-up colonoscopy.

Results

The STC group demonstrated significantly lower rates of early (0.4%) and delayed (1.6%) PPB compared to the control group (1.9% and 3.8%, respectively; p<0.05). Local recurrence was also significantly reduced in the STC group (1.3%) versus the control group (4.8%; p=0.01). No significant differences were observed between the groups regarding procedure time or major complications such as perforation.

Conclusion

Snare Tip Coagulation is a safe and effective adjunctive technique in colorectal polypectomy, significantly reducing the risk of both post-procedural bleeding and local recurrence without increasing procedural complications. STC may offer particular benefit in the resection of medium-sized colorectal adenomas and should be considered for integration into routine endoscopic practice.

References

1. ​Snare Tip Soft Coagulation vs Argon Plasma Coagulation vs No Margin Treatment After Large Nonpedunculated Colorectal Polyp Resection: a Randomized Trial. Douglas K Rex, Gregory B Haber, Mouen Khashab, et al. Clin Gastroenterol Hepatol. 2024 Mar;22(3):552-561.e4.
2. Recurrences of advanced sessile and lateral spreading colorectal adenoma after endoscopic mucosal resection (EMR) thermal ablation versus no adjuvant therapy (RESPECT): a protocol of an international randomized controlled trial. Kemper G, Gerges C, Schoon EJ, Schreuder RM, Schrauwen RRW, Epping LSM, Beyna T, Drenth JPH, Gündug U, Siersema PD, van Geenen EJM; ENDOCARE study group.Trials. 2024 Feb 17;25(1):132. doi: 10.1186/s13063-024-07915-2.

Disclosure

Nothing to disclose

Clinical Case Summary

A 46-year-old man from Bolivia consulted for abdominal pain with watery diarrhoea and occasional rectorrhagia for the last 2 months, associated with asthenia and weight loss. Laboratory tests showed microcytic anaemia, elevated C-reactive protein, positive faecal occult blood and negative stool culture. Colonoscopy (Images 1, 2) revealed deep ulcers in the ileum and colon with discontinuous areas of respected mucosa. Treatment was started with oral methylprednisolone at a dose of 1 mg/kg, with a decrease in the stool rhythm. He returned to the emergency department due to worsening abdominal pain, and was admitted for follow-up care. Histology (Image 3) showed epithelioid granulomas of probable infectious origin, due to the intramacrophagic inclusions, so the corticosteroid treatment was suspended. The quick test for HIV was positive, with a viral load of 79,000 copies/ml and a CD4 count of 88 CD4/ml. Mantoux and IGRA were negative. PCR amplification for Histoplasma spp in ileal biopsy was positive. Amphotericin B was prescribed with prophylaxis of opportunistic infections with trimethoprim-sulfamethoxazole. After 2 weeks, antiretroviral treatment was started. The patient improved, the abdominal pain disappeared and his intestinal rhythm normalised, and he was discharged from hospital. On outpatient follow-up, he was asymptomatic, with resolution of the ulcers in the control colonoscopy and no evidence of fungal structures in the histological examination.
The infection by Histoplasma capsulatum is the most frequent endemic mycosis in the American continent. Intestinal involvement is rare, with a preference for the ileocecal region in the form of deep ulcers that can simulate an outbreak of Crohn disease, as in our case. The use of immunosuppressants, especially anti-TNF-alpha, may worsen its course, highlighting the importance of a broad differential diagnosis, taking into account the patient's epidemiological characteristics.

References

Image 1. Colonoscopy. Terminal ileum with large ulcer with fibrin background, oedema and perilesional erythema.
Image 2. Colonoscopy. Transverse colon with two large deep ulcers with fibrin background and raised edges.
Image 3. Biopsy of ileum. Non-caseating epithelioid granulomas with intramacrophagic inclusions in ileal tissue. HE 40x.

Clinical Case Summary

Condyloma acuminatum represents the clinical expression of epidermal infection caused by the human papillomavirus (HPV) one of the most common sexually transmitted diseases. These lesions range from benign papules to potential precursors of anal squamous cell invasive carcinoma.
Conventional treatments include surgical excision, cryotherapy, immunotherapy and CO₂ laser ablation.Endoscopic approaches such as radiofrequency ablation (RFA) and argon plasma coagulation (APC) are emerging as therapeutic alternatives with promising efficacy and safety profiles.
We report the case of a 49-year-old woman with no relevant medical or surgical history presented with rectal bleeding. Colonoscopy revealed a flat, polypoid lesion circumferentially involving approximately 3–4 cm of distal rectum (Fig1). Biopsy confirmed HPV-6–related condyloma. She underwent transanal minimally invasive surgery (TAMIS) in 2023.
One year later, symptoms recurred. Colonoscopy showed a similar lesion now extending over more than 5 cm of the lower rectum (Fig2-3).Given the lesion's recurrence, extensive involvement, and challenging location, endoscopic RFA was selected as the treatment modality. Using a HALO90° catheter (BARRX Medical Inc.) introduced through a flexible colonoscope, high-energy pulses (1000 pulses at 15 Joules per pulse) were applied to the affected mucosa, achieving near-complete ablation. Residual lesions and the anal canal were subsequently treated with APC (AXIAL catheter, 0.8 L/min, 30 W)(Fig4). The procedure was completed on an outpatient basis without immediate complications.
Post-procedurally, the patient reported transient anal pain and mild bleeding. At 3-month follow-up, mucosal healing was adequate (Fig5), with minor residual lesions successfully treated with APC (Fig6).
This case highlights the utility of combined endoscopic RFA and APC in managing extensive, recurrent rectal condyloma refractory to surgery reducing morbidity and preserving anorectal function.

References

1. Mark Schiffman, Susanne Krüger Kjaer, Chapter 2: Natural History of Anogenital Human Papillomavirus Infection and Neoplasia, JNCI Monographs, Volume 2003, Issue 31, June 2003, Pages 14-19, https://doi.org/10.1093/oxfordjournals.jncimonographs.a003476
2. Ramamoorthy S, Liu YT, Luo L, Miyai K, Lu Q, CarethersJM:Detection of multiple human papillomavirus genotypes in analcarcinoma. Infect Agent Cancer, 2010; 5:17.
3. Wiley DJ, Douglas J, Beutner K, et al.:External genital warts:Diagnosis, treatment, and prevention. Clin Infect Dis, 2002; 35(Suppl 2), S210-24.
4. Goldstone, R.N., Hasan, S.R., Drury, S. et al. A trial of radiofrequency ablation for anal intraepithelial neoplasia. Int J Colorectal Dis 32, 357–365 (2017). https://doi.org/10.1007/s00384-016-2679-2
5. Goldstone, R. N., Hasan, S. R., & Goldstone, S. E. (2017). Brief report: radiofrequency ablation therapy for anal intraepithelial neoplasia: results from a single-center prospective pilot study in HIV+ participants. JAIDS Journal of Acquired Immune Deficiency Syndromes, 76(4), e93-e97.
6. Smulian, A. G., Moore, D. M., Robertson, J. C., & Kralovic, S. M. (2014). Phase I Study Demonstrates Safety and Tolerability of Radiofrequency Ablation (RFA) of the Anal Mucosa. HIV Clinical Trials, 15(1), 36–44. https://doi.org/10.1310/hct1501-36.
7. Bulsiewicz WJ, Shaheen NJ. The role of radiofrequency ablation in the management of Barrett’s esophagus. Gastrointest Endosc Clin N Am 2011; 21: 95-109.