Introduction

Tofacitinib is a relatively novel therapy for immune-mediated inflammatory diseases, including rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. It is a small-molecule drug that exerts its effects by inhibiting Janus kinases. Recently, concerns have been raised about the drug’s safety in terms of cardiovascular side effects and cancer risk.­­

Aims & Methods

This meta-analysis determined the risk of cancer in patients treated with tofacitinib for different clinical indications, compared to both a placebo and other therapies. We searched PubMed (accessed on november 1st 2022) for original articles regarding tofacitinib’s cancer risk when used for rheumatoid arthritis, ulcerative colitis, Crohn’s disease, psoriatic arthritis, and ankylosing spondylitis.

Results

Of the 2047 initial records, 22 articles describing 26 controlled studies (including 22 randomized controlled trials) were selected. In the comparison between tofacitinib and any control treatment, the relative risk (RR) for any cancer was 1.06 (95% CI, 0.86–1.31; p = 0.95). In separate comparisons between tofacitinib and either a placebo or biological therapy, no difference was found in the overall cancer risk (vs. placebo, RR = 1.04; 95% CI, 0.44–2.48; p = 0.95; vs. biological drugs, RR = 1.06; 95% CI, 0.86–1.31; p = 0.58). When tofacitinib was compared to tumor necrosis factor (TNF) inhibitors, the overall cancer RR was 1.40 (95% CI, 1.06–2.08; p = 0.02). Similarly, significant results were obtained for all cancers, except for non-melanoma skin cancer (RR = 1.47; 95% CI, 1.05–2.06; p = 0.03), and for this skin cancer alone (RR = 1.30; 95% CI, 0.22–5.83; p = 0.88).

Conclusion

In conclusion, no difference in the overall cancer risk was found between tofacitinib and either a placebo or biological drugs, while a slightly higher risk was found in patients treated with tofacitinib than anti-TNF agents. Further studies are needed to better define the cancer risk of tofacitinib therapy.

Introduction

Fecal microbiota transplantation (FMT) has been successfully used in a series of diseases in recent years. Most studies have focused on short-term risks, which are mild and generally associated with delivery methods. There have been no reports of FMT safety in the treatment of multiple diseases and long follow-up periods.

Aims & Methods

We performed a retrospective analysis of 11025 patients who underwent FMT in the Tenth People’s Hospital of Tongji University between January 2012 and December 2023. We included patients with various gastrointestinal diseases and patients with extraintestinal diseases that involved intestinal dysfunction. A questionnaire was administered to the included patients during follow-up (2 weeks, 3 months, 1 year, and 5 years after FMT) via telephone and health portal software Haodaifu app).

Results

Most adverse events during short-term follow-up (2 weeks) were related to the method of delivery. The main adverse events in the nasogastric tube group were tube-related respiratory difficulty (40.6%,include sore throat 14.1%, nasal congestion 8.7%, nasal irritation due to nasogastric intubation 17.8%) and nausea/vomiting (12.6%). In the oral capsules group, nausea and vomiting (8.9%) occurred during oral administration because the capsules are associated with a fecal smell and taste, both of which are difficult to remove completely. For colonoscopy and enema routes, the main adverse events were diarrhea (10.7%, 9.9%) and perianal discomfort (15.3%, 8.4%), respectively. Two cases in the colonoscopy group and one case in the enema group were complicated with colon perforation, but remission with conservative treatment. The most frequently reported adverse events were mild or moderate in severity and transient. Those symptoms associated with nasogastric tube administration disappeared after tube removal at the completion of treatment. Several other new symptoms were reported during short-term follow-up, although none occurred in >1% of patients. The most common symptom reported was bloating/flatulence. Although more adverse events were reported in the nasogastric tube group, most were mild. Additionally, patients are more comfortable with the upper gastrointestinal route because they could use it for enteral nutrition support or gastrointestinal imaging according to their medical needs. Based on our clinical experience, we proposed the “Tongji FMT Requirements”and implemented them in our clinic (beginning in 2019) to standardize the indications and timing of FMT treatment and to improve FMT safety. After the implementation of these requirements for 2 years, we compared safety data collected before and after implementation; The application of the requirements has effectively reduced adverse events. The short-term (mainly FMT-related diseases) incidence rate significantly decreased from 32.6% in 2017–2019 to 17.2% in 2019–2021.

Table 1.Tongji FMT Requirements

Conclusion

FMT appears safe during both short-term and long-term follow-up. The patient group that received FMT did not exhibit an increased incidence of new diseases, and the risk of infection transmission appears to be low. Considering the widespread use of FMT, there is a need for the establishment of a national clinical and patient-reported FMT safety collection system in future.

References

• 1) Kelly CR, Yen EF, Grinspan AM, et al. Fecal microbiota transplantation is highly effective in real-world practice: initial results from the fmt national registry. Gastroenterology 2021;160:183-192
• 2) Mullish BH, Quraishi MN, Segal JP, et al. The use of faecal microbiota transplant as treatment for recurrent or refractory clostridium diffificile infection and other potential indications: Joint british society of gastroenterology (BSG) and healthcare infection society (HIS) guidelines. Gut 2018;67:1920e41
• 3) Saha S, Mara K, Pardi DS, et al. Long-term Safety of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection. Gastroenterology 2021;160:1961-1969
• 4) Zhang S, Chen Q, Kelly CR, et al. Donor Screening for Fecal Microbiota Transplantation in China: Evaluation of 8483 Candidates. Gastroenterology 2022;162:966-968
• 5) Parenteral and Enteral Nutrition Branch of Chinese Medical Association, et al. Chinese experts consensus on standardized methodology and clinical application of fecal microbiota transplantation. Zhonghua Wei Chang Wai Ke Za Zhi 2020;23:5-13
• 6) Wang S, Kou C, Liu Y, et al. Rural-urban differences in the prevalence of chronic disease in northeast China. Asia Pac J Public Health 2015;27:394-406

Introduction

Metabolic-associated fatty liver disease (MAFLD) requires complex treatment based on diet and lifestyle. The understanding of the disease by patients through medical education is an element that could bring them a therapeutic benefit. Since the process is time-consuming and medical factors all over the world are under pressure to use maximum time for diagnostic and therapeutic purposes, an important role can be played by the voluntary activity carried out by medical students, under the guidance of teaching staff, devoted to this purpose.

Aims & Methods

A group of 250 patients with MAFLD, non-cirrhotic, diagnosed in a gastroenterology outpatient clinic, were proposed to participate in an educational program consisting of 3 sessions of 2 hours of interactive course about MAFLD (including notions of anatomy, physiology, diagnosis, evolution, prognosis, complications, risks, treatment, follow-up) in order to appreciate the contribution of medical education to the effectiveness of treatment. The patients did not receive medication but only recommendations regarding lifestyle changes and the Mediterranean diet. They were re-evaluated 6 months after the initial evaluation.

Results

Of the 250 patients, only 126 (50.4%) accepted participation in the educational plan after informed consent, a disappointing proportion; the subgroup of those who did not participate in the course was reported as a control group (the main reason of non-participation was the fact that most of these patients considered to have already enough knowledge about MAFLD), being also invited to be evaluate after 6 months. Educational presentations were given by medical students under the guidance of teaching staff (power-point presentations and informative flyers designed to fix the knowledges about disease) and patients were clinically, laboratory, ultrasound and fibroscan evaluated by attending physicians. Also a questionnaire about quality of life was completed by each patient. Finally, after 6 months, only 85 patients from the control group and 118 from the study group returned for the final evaluation. The final evaluation focused on 4 elements: 1- changes in body mass (decrease of more than 7%), 2- liver ultrasonography (reduction of the degree of steatosis), 3- laboratory analyzes (liver and metabolic tests) and 4- quality of life. In the study group, significantly better results were obtained for parameters 1, 3 and 4: (78%, 87.2%, 84.7%) compared to the reference group (38.8%, 54.1%, 62.3%) which confirms the fact that patient education is an important element in understanding the disease and its treatment. Only in parameter 2 (decrease of steatosis at ultrasonography) there were no significant differences between the two groups (50.8% vs 48.2%), probably due to the too short follow-up time of the patients.

Conclusion

Therapeutic education of patients with MAFLD can bring more efficiency to the treatment of the disease in non-cirrhotic patients, mainly on body mass control, liver laboratory tests and quality of life, if they accept to participate at educational program.

References

Koutny F, Aigner E, Datz C, Gensluckner S, Maieron A, Mega A, Iglseder B, Langthaler P, Frey V, Paulweber B, Trinka E, Wernly B. Relationships between education and non-alcoholic fatty liver disease. Eur J Intern Med. 2023 Dec;118:98-107. doi: 10.1016/j.ejim.2023.07.039. Epub 2023 Aug 3. PMID: 37541922.
Lee WM, Bae JH, Chang Y, Lee SH, Moon JE, Jeong SW, Jang JY, Kim SG, Kim HS, Yoo JJ, Kim YS. Effect of Nutrition Education in NAFLD Patients Undergoing Simultaneous Hyperlipidemia Pharmacotherapy: A Randomized Controlled Trial. Nutrients. 2021 Dec 13;13(12):4453. doi: 10.3390/nu13124453. PMID: 34960005; PMCID: PMC8709046.

Introduction

Renal disorders are among the extra-intestinal manifestations of inflammatory bowel disease (IBD), and treatments may also lead to renal failure. However, the incidence of end-stage renal disease (ESRD), defined as the need for renal replacement therapy (dialysis and/or renal transplantation (RT)), is poorly known. The primary objective of our study was to assess the incidence of ESRD in IBD patients, and to compare it with the general health insurance scheme population.

Aims & Methods

We conducted a prognostic cohort study based on data from the French National Health Insurance Database(SNDS). Prevalent cases of IBD affiliated to the general health insurance scheme during the period 2011-2020 were identified on the basis of declarations long-term diseases ALD 24 or the presence of 2 hospital stays for IBD with ICD-10 codes or a single stay with reimbursement of specific treatments. Incident cases of ESRD were identified on the basis of a stay with a RT or a period with dialysis sessions for at least 45 days. Crude incidence rates of ESRD were calculated over the period for the IBD and the non-IBD population, with their 95% confidence intervals.

Results

A total of 280,283 IBD patients were included in the study over the period 2011-2020, 134,567 with ulcerative colitis(UC) and 145,716 with Crohn’s disease(CD). The mean age at study inclusion was 39.8 (± 17.1) years. The M/F sex ratio was 0.9. The mean age at incidence of ESRD in the non-IBD population was 65.0 (±17.0) years, the M/F sex ratio cases was 1.7.
Among IBD patients, 534 patients began replacement therapy by dialysis or RT, they were younger than non-IBD patients (60.3(±16.7)years, P<0.001).The mean incidence rate of ESRD over the period was 26.4 per 100,000 person-years (IC95% 23.1-29.6), 480 (89.9%) patients entered ESRD by dialysis, and 54 (10.1%) by preemptive RT. In the non-IBD population the mean rate of ESRD was 15.9 per 100,000 person-years (IC95% 14.8- 17.1; P<0.0001 compared with IBD): 79,606 (94.5%) patients entered ESRD by dialysis, and 4,634 (5.5%) by RT (as compared with IBD,P<0.001). In subgroup analysis, the mean incidence rate of ESRD was 22.8 per 100,000 person-years (IC95% 18.9-26.7) in UC patients and 29.5 (IC95% 25.3-33.6) in CD patients (P<0,0001). The rates of preemptive RT were 12.4% in UC patients (87.6% dialysis) and 8.6% in CD patients (91.4% dialysis).
Over a median follow-up of 6.8 years, the survival rate after ESRD was 40.8% in ESRD-IBD patients VS 34.2% in ESRD non-IBD patients (P<0.001). This difference remained significant for patients under 65 (p<0.0073).
No significant difference for the risk of re-hospitalization after RT (p=0.84), of retransplantation during the follow-up period in RT patients (p=0.67), or for the risk of hospitalization for severe infection (p=0.97) after RT in patients from the general population compared with IBD patients. The same was true for the type of severe infections after RT (p= 0.068) and for the risk of solid and haematological cancer after RT (p=0.48). However, there was a significant difference in the type of first severe infection after RT(p=0.003), but we are waiting for the results to tell us which one.

Conclusion

The incidence of ESRD is significantly higher in IBD than in the general data base population, confirming the need for regular monitoring of renal function in our patients.
Survival after ESRD onset, is higher in IBD patients.
The high incidence of RT in the IBD population confirms that access to transplantation is not restricted in this
population.

References

Kirchgesner et al, Gastroenterology 2018
Meyer et al, Aliment Pharmacol Ther. 2020
Tuppin et al, Nephrol Ther 2016

Introduction

Various endoscopic closure procedures including over-the-scope systems and endoscopic hand suturing have been tested in preventing delayed bleeding after endoscopic resection1). Conventional procedures are technically difficult with long procedure time1), which partially explains its limited application in clinical practice. The novel through-the-scope (TTS) helix and tack suture system has been reported with high success rates and acceptable procedure time using in vivo porcine models along with clinical experience2,3). However, past reports have not identified the proficiency rate of the TTS suture system.

Aims & Methods

The objective of this study is to determine the number of cases needed in achieving closure time of literature-based mean closure time. One beginner with less than 400 experiences of upper gastrointestinal endoscopy and one expert with clinical experience of over 500 endoscopic submucosal dissections participated in this study. Both endoscopists were familiarized with the functionality and troubleshooting of the novel TTS suture system via educational videos. Four in vivo porcine models were used to create 24 mucosal defects with diameter of 2-4 cm in the stomach. Each endoscopist were randomly allocated 12 mucosal defects to close with one set of TTS suture system per procedure. The TTS suture system engages four 5 mm helical tacks tethered to a suture thread into the defect margin and approximates the mucosal defect by applying suture tension with a cinch. The primary outcome was the number of procedures required to achieve closure procedure time below the literature-based mean closure time (7.7 minutes) by inverse curve fitting with nonlinear regression. The secondary outcomes were the success rate of complete closure and the incidence of adverse events. Complete closure was defined as over 90% closure of defect in endoscopy image assessed by two certified endoscopy technicians.

Results

Mean (±SD) size of the mucosal defects was 2.9 (±0.2) cm. Both endoscopists required six cases to achieve a closure time of less than 7.7 minutes. The median closure time was 8.2 (IQR: 5.6-10.1) minutes for the expert and 8.0 (IQR: 6.3-9.4) minutes for the beginner (P = 0.8624). The success rates of complete closure were 75.0% (9/12) for the expert and 83.3% (10/12) for the beginner. Neither endoscopist experienced any adverse events.

Conclusion

The novel TTS suture system requires a small number of cases for both expert and beginner to achieve proficiency in endoscopic closure.

References

1) Kobara H, et al. Dig Endosc. 2023;35(2):216-31.
2) Hernandez A, et al. Endosc Int Open. 2021;09:E572-7.
3) Farha J, et al. Endoscopy. Published online: 12 Jan 2023; doi:10.1055/a-1970-5528.

Introduction

Functional diarrhea (FDr) is a disorder of gut-brain interaction (DGBI) characterized by chronic or recurrent diarrhea, not explained by structural or biochemical abnormalities. It is distinct from diarrhea predominant irritable bowel syndrome (IBS) with recurrent symptoms and notably the absence of pain. While functional conditions present with complex, likely heterogenous pathophysiology, we aimed to investigate if proxy measures of sociocultural risk factors have any association with the prevalence of FDr in populations across the world.

Aims & Methods

We performed an ecological study utilising peer-reviewed published datasets reporting country prevalence of FDr¹, Helicobacter pylori (H.p) prevalence² as proxy measures for orofecal infections, and the density of quick service restaurants (QSR) per population as proxy measure for processed food exposure. In addition, we used proxy measures of development including household size, median age, gross domestic product (GDP) per capita. The data were retrieved from publicly accessible datasets (United Nations, CIA, World Bank, commercial/financial reports of a global QSR chain). Spearman rank correlations were used to test univariate associations.

Results

The prevalence of FDr in 33 countries was negatively correlated with both the number of people per QSR (r= -0.44, p= 0.02), and household size (r= -0.69, p <0.0001), while positively correlated with median age (r= 0.58, p= 0.004) and GDP/capita (r= 0.56, p= 0.006). Assocaitions with H.Pylori infection did not reach significance (r= -0.27, p= 0.16).

Conclusion

Utilising publicly available data, the prevalence of FDr across diverse countries are linked to various markers of social development and a proxy marker of processed food consumption.

References

1. Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide Prevalence and Burden of Functional Gastrointestinal Disorders, Results of Rome Foundation Global Study. Gastroenterology 2021;160:99-114 e3.
2. Hooi JKY, Lai WY, Ng WK, et al. Global Prevalence of Helicobacter pylori Infection: Systematic Review and Meta-Analysis. Gastroenterology 2017;153:420-429.

Disclosure

Nil

Introduction

In recent years remarkable progress has been made in the treatment of malignant tumors, including minimally invasive surgery¹⁾, the development of chemotherapy including immune checkpoint inhibitors²⁾, drugs to prevent chemotherapy induced side effects³⁾. As a result, the prognosis was improved, the number of patients with multiple primary malignant tumors increased. However, there is currently no evidence to support a specific treatment for multiple primary malignant tumors. Therefore, patient consent must be obtained, and options should be selected according to institution policies.

Aims & Methods

Aims: This study aimed to investigate the clinical outcomes and prognosis of patients who underwent endoscopic submucosal dissection (ESD) for early-stage gastric cancer (EGC) complicated with advanced primary malignant tumors of other organs, with 5-year absolute survival rate of less than 50 %.
Methods: This study enrolled 26 patients with advanced malignant tumors of other organs, with 5-year absolute survival rates of less than 50 %, who were selected from 3,703 patients with gastric cancer who underwent ESD at our hospital. Clinicopathological characteristics and outcomes of ESD were evaluated.

Results

Patient median age was 75.0 (50-90) years. The median tumor diameter was 20.0 (5-110) mm. Advanced malignant tumors of other organs included 5 patients with hepatocellular carcinoma, 5 with prostate cancer, 4 with esophageal cancer, 4 with colorectal cancer, 3 with lung cancer, 1 with renal cell carcinoma, 1 with breast cancer, 1 with gingival cancer, 1 with multiple myeloma, and 1 with malignant lymphoma. The clinical stages were cStage II in 6 patients, cStage III in 2, and cStage IV in 18, all evaluated under treatment or before treatment. In terms of EGC locations, there were 6 (23 %) U region patients, 6 (23 %) M region, and 14 (54 %) L region. Macroscopic types were 0-I 2 (7 %), 0-IIa 9 (35 %), 0-IIa+I 1 (4 %), 0-IIc 13 (50 %), and 0-IIc+IIa 1 (4 %). The main histological types included 23 (88%) with differentiated type, 3 (12%) with undifferentiated type, 18 (69 %) with pT1a, 3 (12 %) with pT1b1, and 5 (19 %) with pT1b2. Rates of en bloc resection were 100 %, curative resection was 62 %, noncurative resection was 38 % (including 5 patients with pT1b2, 1 patient with UL positive, 3 patients with undifferentiated and lesion size bigger than 20 mm, and 1 patient was positive for vertical margin). Adverse events included delayed bleeding in 1 (4%) patient, delayed perforation in 1 (4%), and postoperative pneumonitis in 1 (4%), all of which resulted in DIC and death within 30 days after ESD. The prognosis was death from advanced malignant tumors of other organs in 11 patients, death from other causes in 3 patients, and survival in 9 patients that did not suffer death due to EGC.

Conclusion

Although ESD was useful for local resection of EGC complicated with advanced malignant tumors, DIC triggered by an adverse event should be noted.

References

1) Uyama I, Suda K, Nakauchi M, et al. Clinical advantages of robotic gastrectomy for clinical stage I/II gastric cancer: a multi-institutional prospective single-arm study. Gastric Cancer 2019; 22(2): 377-385.
2) Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WEE, Poddubskaya E, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373: 123-135.
3) Mellar Davis, David Hui, Andrew Davies, et al. MASCC antiemetics in advanced cancer updated guideline. Supportive Care in Cancer 2021; 29: 8097–8107.