Introduction

The obesity paradox, in patients with cancer, is a hypothesis showing patients with obesity have a prolonged overall survival compared to the ones with a normal weight. This paradox is present in different types of cancer, lung cancer, renal cell cancer, and melanoma. For gastrointestinal cancers, there are conflicting results regarding the obesity paradox. Neuroendocrine neoplasms (NENs) are rare cancers arising anywhere in the body but mainly within the gastroenteropancreatic (GEP) tract. NENs differ from other gastrointestinal cancers as they have a relatively good prognosis even in metastatic disease. NENs are classified into three different grades (G1, G2, G3) based on mitotic count and Ki-67 staining. The grades are correlated with overall survival patients with G1 GEP-NENs have significantly better overall survival compared to patients with G2 or G3 GEP-NENs. The presence of the obesity paradox in patients with GEP-NENs is only described in one population-based study from the USA. However real-world data exploring the obesity paradox are lacking.

Aims & Methods

Aim: To explore the presence of the obesity paradox in patients with GEP-NENs in a single centre in the United Kingdom.
A cross-sectional study was performed regarding all patients with GEP-NENs and treatment with monthly somatostatin analogues (SSA’s) between August 2018 and February 2019. During this period all patients weight, height and BMI were collected. Additional demographic and histopathologic data were extracted from the local hospital database. Stable disease was classed as having no change in oncological treatment within 3 months of weight/height screening. Overall survival (OS) was calculated from the moment of weight/height screening until death or the last follow-up appointment (data cut-off June 2022). Kaplan Meier, log-rank tests and Cox regression analysis were performed.

Results

In total 118 patients, n=55 (47%) males with a median age of 67 years (IQR 56.8 – 75) were included. The primary tumour was in the small intestine in n=91 (77%) and pancreas in n=25 (21%) of patients, and grade 1 in n=74 (71%) or grade 2 in n=30 (29%) of patients. In 91 patients (77%) there was stage IV disease. The median period since diagnosis was 40 months (IQR 14 – 84 months) and median period on SSA 23 months (IQR 5.5 – 59 months). The median BMI is 24.8 (IQR 21.7 – 28.7), 7 patients (6%) are underweight (BMI <18.5), 52 patients (44%) had a normal weight (BMI 18.5 – 24.9), 33 patients (28%) were overweight (BMI 25 – 29.9), 26 patients (22%) were obese (BMI >30). There are significant OS differences between BMI categories p-value 0.002. When correcting for age HR 1 (0.97 – 1.05), sex HR 1.3 (0.49 – 3.66), grading 2.06 (0.74 – 5.72), stable disease versus progressive disease HR 5.4 (1.9 – 14.9), the BMI is still significantly associated with OS with HR 0.31 (0.16 – 0.62), p-value 0.002.

Conclusion

This study shows some evidence for the presence of the obesity paradox in a real-world population of patients with GEP-NENs using an SSA. Patients with a low or normal BMI might benefit from extra attention to their nutritional status and nutritional support. Future research should focus on the pathophysiologic mechanism explaining the obesity paradox.

References

DECREASED INPATIENT MORTALITY IN OBESE PATIENTS WITH ABDOMINAL NETS, Evan S. Glazer, Kelley Stanko, Evan S. Ong, Marlon A. Guerrero, ENDOCRINE PRACTICE 2014

Disclosure

Nothing to disclose

Introduction

Endoscopic sleeve gastroplasty (ESG) is a safe and effective procedure for class 1 and 2 obese subjects¹. The effects of smoking habits on weight are well known regarding bariatric surgery^2-6. However, given that this patient population is inherently weight-concerned, understanding the effects of tobacco use on post-operative weight loss in bariatric endoscopy is essential to guiding clinicians in counselling patients in this field.

Aims & Methods

A prospective dataset collecting data on all ESG procedures performed in an Italian tertiary referral centre was assessed retrospectively. Data on smoking habits (smoker, non-smoker, and previous smoker) were collected. Efficacy and safety between the three smoking categories was evaluated using an ANOVA test.

Results

Between May 2017 and October 2021, 290 subjects underwent ESG. Out of the total, smoking habits were available for 275 subjects: 144 non-smokers (NS; 52,4%), 51 smokers (S; 18,5%) and previous smokers (EX-S; 29,1%). No statistically significant differences in BMI was observed between the three groups.
In each group, no major complication were reported in the perioperative period. Adherence to follow-up was 93,1%, 92,4% and 73,5% for non-smokers, 90,2%, 84,3% and 82,4% for smokers, 91,3%, 90,0% and 71,9% for EX-smokers, at 6,12 and 24 months.
Average TBWL, EWL and WL were similar between the three groups at 6,12 and 24 months (see Table below). In the non-smoker group, five subjects underwent revision procedures (4 Re-ESG, 1 Surgery) after 24 months, whereas one previous smoker underwent Re-ESG after six months. No revision was reported in the smoker group.

Conclusion

Our analysis, with the strengths of a large cohort and a long-term follow-up, showed that smoking habits do not influence the efficacy and safety of ESG for up to 24 months.
Finally, proper counseling of patients should advise the cessation of the smoking habit.

References

¹ Abu Dayyeh BK, et al. Lancet. 2022
² Dittrich L. Surg Obes Relat Dis. 2020
³ łuszyńska P. J Clin Med. 2022
⁴ Chow A. Surg Endosc. 2021
⁵ Mohan S. Surg Endosc. 2021
⁶ Srikanth N. J Addict Dis. 2021

Introduction

Endoscopic sleeve gastroplasty (ESG) is a safe and effective procedure in class 1 and 2 obese subjects.The effects of menopause on weight are well known. However, given that this patient population is inherently weight-concerned, understanding the effects of ESG on women in menopause is essential to guiding clinicians in counselling this patient population.

Aims & Methods

A prospective dataset collecting data on all ESG procedures performed in a tertiary referral centre was assessed retrospectively. Data on fertility status (menopause and non-menopause women) were collected. A comparison was performed using the Mann-Whitney U test.

Results

Between May 2017 and October 2021, 209 women underwent ESG. Out of the total, fertility status was available for 204 women: 79 menopause (M; 38,7%) and 125 non-menopause women (NM; 61,3%).At baseline, non-menopause women were younger, whereas there were no differences in BMI and weight.
Adherence to follow-up was 92,4%, 87,3% and 80,0% for menopause, 88,8%, 90,4% and 72,9% for non-menopause, at 6,12 and 24 months, respectively.
Six months after the procedure, non-menopause women showed significantly higher TBWL, WL and BAROS score compared to the menopausal group. In contrast, EWL showed no significant difference between the groups.Average TBWL, WL and EWL were not significantly different between the groups at 12 and 24 months (as shown in Table below).
Seven menopausal women needed revision procedures (5 Re-ESG, 1 Surgery), whereas ten non-menopausal women underwent revision (8 Re-ESG, two surgery).

Table. Weight loss trajectories of subjects who underwent Endoscopic Sleeve Gastroplasty, based on menopausal status. Data are reported as median (Interquartile range).

Conclusion

Non-menopausal women who undergo ESG show better outcomes in the short term. However, this advantage does not persist in the medium and long term.

Introduction

Obesity, one of the most common co-morbidities in women of reproductive age, contributes to infertility and obesity-related pregnancy complications. On the other hand, pregnancy is a condition in which, physiologically, the pregnant woman undergoes weight gain. Endoscopic Sleeve Gastroplasty (ESG), an organ-sparing bariatric procedure aimed to reduce gastric volume and modify gastric motility with full-thickness endoscopic sutures, may be used for the treatment of obesity in women of childbearing age.

Aims & Methods

A retrospective analysis of a prospective database was conducted to evaluate weight trajectories, the evolution of obesity-related comorbidities, and lifestyle modification in women who became pregnant after ESG.
A comparison was made between childbearing-age women who became pregnant after ESG and non-pregnant women who reached at least the 6-month follow-up after ESG.

Results

Between January 2018 and December 2021, a total of 150 childbearing-age women underwent ESG at a large Italian tertiary medical center. Out of the total, 18 patients (12,0 %) reported a desire for pregnancy associated with unsuccessful attempts in the 12 months preceding ESG.
Eleven patients (mean age 33,4±6,2 years) became pregnant after the procedure, following a mean time interval of 5,5±3,9 months. The mean preconception BMI was 31,9±4,0 kg/m² (with a mean reduction of 7,24±4,0 kg/m² after ESG). Three patients were affected by hyperinsulinemia (H-INS), while an additional patient had both H-INS and high blood pressure (HBP). Three women reported difficulty in becoming pregnant before the ESG: two were affected by PCOS.
Total body weight loss (TBWL) of at least 5% was achieved before pregnancy in all patients (73% reached a TBWL ≥ 10%).
Six out of eleven (55%) patients had weight gain in the ranges recommended by the Institute of Medicine (IOM) during pregnancy. Among the 18 women with a reported desire for maternity associated with difficult attempts in the previous 12 months, 16,6 % (3/18) managed to start and carry out a pregnancy.
TBWL (%) was 18,08±8,00, 10,35±11,53, and 12,08±8,49, at the beginning of pregnancy, at the delivery, and at the first follow-up (mean interval, 5,18±3,57 months).
No significant differences in WL, TBWL, EWL, BMI, BAROS, and QoL were found between the pregnancy and non-pregnancy groups (99 childbearing-age women) up to 24 months after ESG.

Conclusion

ESG produces adequate weight loss before pregnancy in patients with obesity and is potentially a useful treatment option for women who have difficulty becoming pregnant, such as those with PCOS. Pregnancy after ESG does not adversely affect weight loss outcomes after delivery as lifestyle changes induced by ESG are maintained after pregnancy and allow for a gradual loss of weight gained during pregnancy.

Introduction

Double-headed capsules enable the non-invasive one-step endoscopic evaluation of both the small bowel and colon (pan-intestinal capsule endoscopy, PCE).

Aims & Methods

We aim to evaluate the diagnostic accuracy and safety of PCE vs. the current standard of care (conventional colonoscopy) as the first-line examination in patients with iron deficiency anaemia (IDA) and/or overt bleeding after a non-diagnostic upper endoscopy (suspected mid or lower gastrointestinal bleeding, MLGIB).
We conducted a prospective, single-centre, single-blinded cohort study including consecutive patients with suspected MLGIB. All patients were submitted to PCE, followed by same-day colonoscopy under deep sedation. The physicians performing PCE and conventional colonoscopies were independent and blinded to each other’s observations. The diagnostic yield for potentially haemorrhagic lesions (PHL) was compared for efficacy analysis, and adverse events were assessed for both examinations. The gold standard diagnosis was defined by consensus panel. This trial has been registered in ClinicalTrials.gov (ID NCT04782986).

Results

We included 100 consecutive patients with suspected MLGIB, mean age 66.5 (18-92) years, 65% female gender, presenting with IDA (81%) or overt bleeding (19%). Mean haemoglobin level was 8.4 (4.1-12.8) g/dL and 40% were inpatients. For PCE, the PillCam Crohn’s® capsule was used in 88 patients, and PillCam COLON® 2 in the remaining. Patients with overt bleeding performed PCE within 2 weeks in 70% of cases, 15% in the first 72h after the bleeding episode. PCE was complete in 76% of cases, vs. colonoscopy 95% (p<0.01). The quality of bowel preparation was adequate in 72% of PCE vs. 85% of colonoscopies (p=0.012). Overall, PHL were diagnosed, based on the combination of PCE + colonoscopy, in 46% of patients, corresponding to small bowel and/or colon angioectasias in more than two-thirds (69.6%) of cases. PHL were detected by both examinations in 13/46 (28.3%), only by colonoscopy in 3/46 (6.5%), and only by PCE in 30/46 (65.2%) of cases (p<0.01). Overall, colonoscopy detected PHL in 23% of the entire cohort, which means 50% (23/46) of all patients with PHL according to the consensus panel, while for PCE the overall diagnostic yield was 44%, meaning 95.7% (44/46) of all PHL (p<0.01). Considering the gold standard diagnosis for PHL, colonoscopy had a sensitivity of 23/46=50%, specificity 54/54=100%, positive predictive value (PPV) 23/23=100% and negative predictive value (NPV) 54/77=70,1%, while for PCE the sensitivity was 44/46=95.7%, specificity 54/54=100%, PPV 44/44=100% and NPV 54/56=96.4%. Thirty-one percent of patients had PHL accessible to ileocolonoscopy; in those cases, the PCE was able to make the diagnosis in 29/31 (93.5%) vs. conventional colonoscopy in 23/31 (74.2%) of cases, p<0.01. Regarding safety, no significant adverse events occurred with PCE, vs. 2% (cardiopulmonary) with conventional colonoscopy.

Conclusion

PCE is safe and more effective than conventional colonoscopy in identifying PHL both in the small bowel and the colon, and could be considered as a first-line examination in patients with IDA or overt bleeding after a non-diagnostic upper endoscopy. In more than half of patients with suspected MLGIB, PCE does not detect any PHL either in the small bowel or the colon, dismissing any further invasive endoscopic investigations.

Disclosure

Medtronic provided financial support to the acquisition of some of the capsules which were used in the trial

Introduction

Chronic fatigue is a debilitating symptom and has major impacts on the quality of life of patients with chronic inflammatory conditions. In IBD, an estimated 50% of patients suffer from persistent fatigue despite successful treatment of intestinal inflammation. During active disease flares, this number jumps to 80% (Borren et al. 2018). Tryptophan metabolites are not only associated with disease activity in UC and CD, but also with chronic fatigue (Kavyani et al. 2022). Thus, our aims are (1) to characterize the relationship between fatigue and tryptophan derivatives and (2) to understand the metabolic dynamics arising when fatigue symptoms improve following therapeutic intervention.

Aims & Methods

In a prospective open label cohort of patients with moderate-to-severe Crohn’s disease (CD, n = 71) and ulcerative colitis (UC, n = 94) assigned to biologics therapy or JAK inhibitors, fatigue was assessed by the fatigue subscale of the Functional Assessment of the Chronic Illness Therapy – Fatigue (FACIT-F) questionnaire at therapy induction and 2 and 14 weeks thereafter. A FACIT-F score of <30.1 was considered severe fatigue while a score of >40 was considered no relevant fatigue. Clinical response at week 14 was defined as Crohn’s Disease Activity Index (CDAI) <150 and reduction of Partial Mayo Clinical Score (PMCS) >50% vs. baseline, respectively. We used targeted mass spectrometry to quantify the levels of 13 tryptophan derivatives and neopterin in a subset of patient serum in the weeks following therapy induction (at 0, 2, and 14 weeks, n = 120 individuals).

Results

Half of the recruited patients had severe fatigue at baseline (50.3%). Of the 120 patients who reached week 14 and had FACIT-F scores available, severe fatigue was experienced by 45.9% of the patients who did not respond to therapy and the rate was reduced to 13.2% in therapy responders. We found 8 metabolites positively associated with FACIT-F: tryptophan, kynurenic acid, kynurenine, picolinic acid, xanthurenic acid, serotonin, indole-3-proprionic acid, and quinaldic acid, while neopterin was negatively associated (FDR < 0.05). Four of these metabolites changed dynamically as a function of the extent of fatigue improvement: tryptophan, kynurenine, xanthurenic acid, and serotonin (FDR < 0.05). In all cases, the rate of change of these metabolites increased as a function of fatigue improvement.

Conclusion

Fatigue is linked to a diverse array of tryptophan metabolites. Notably, all of the significantly associated tryptophan derivatives were positively associated with FACIT-F, meaning that as fatigue symptoms improve, tryptophan metabolite levels increase. Many of these metabolites have previously been linked to symptom severity in IBD: for example, tryptophan, kynurenic acid and xanthurenic acid all tend to increase with symptom alleviation (Nikolaus et al. 2017, Michaudel et al. 2022). While the kynurenine-to-tryptophan ratio is elevated in active IBD (Nikolaus et al. 2017), this ratio did not convey a specific, fatigue-related signature. Considering that some patients continue to suffer from persistent fatigue even during disease quiescence, further work is needed to disentangle the impact of tryptophan metabolism on therapy response from its role on fatigue improvement.

Disclosure

F. Tran receives scientific funding from Sanofi, received consulting fee's from LEK Consulting and speaker's fees from Lilly, Janssen, Falk, Abbvie, Celltrion, onkowissen.de, CED Service GmbH. S. Schreiber reports consulting fees from Abbvie, Arena, BMS, Biogen, Celltrion, Celgene, IMAB, Gilead, MSD, Mylan, Pfizer, Fresenius, Janssen, Takeda, Theravance, Prevention Bio, Protagonist and Falk.