Introduction

Insulinomas are rare, functioning pancreatic neuroendocrine neoplasms (pNEN), whose gold standard therapy is surgical resection. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as a minimally invasive therapeutic option for pancreatic lesions. This study aims at describing a series of patients with pancreatic insulinoma treated with EUS-RFA.

Aims & Methods

This single-center, retrospective study includes all consecutive patients with pancreatic insulinoma undergoing EUS-RFA because unfit for surgery or refusing surgery. EUS-RFA was performed by using a 19G RFA needle, and a dedicated current generator system with a RFA energy of 20 to 50W. Technical success (i.e., the achievement of complete ablation), adverse events rate, and radiologic response within 3 months after EUS-RFA (i.e., complete tumor necrosis) were evaluated. Follow-up was assessed by clinical monitoring and blood test evaluation at least every 6 months for the first year after the procedure. A descriptive statistical analysis was performed for all the variables.

Results

From March 2017 to September 2022, 10 patients (mean age: 67.1 ± 10.1 years; F:M 7:3) were included. The mean size of insulinomas was 11.9 ± 3.3mm. The median number of passes was 6 (1-14) with a median ablation duration of 15 (6-20) seconds per pass. Technical success, immediate post-procedural euglycemia, and complete radiological response by abdominal CT scan were achieved in all cases (100%). Mild procedure-related early adverse are shown in Table 1. Persistent euglycemia was assessed at 6 and 12 months for each treated patient.

Patients, n	10
Technical success, n (%)	10 (100)
Early adverse events, n (%) Mild abdominal pain Bleeding	2 (20) 1 (10)
Late adverse events, n (%)	0 (0)
Euglycaemia within 24 hours	10 (100)
Radiologic complete response within 90 days, n (%)	10 (100)
Clinical remission at 6 months, n (%)	10 (100)
Clinical remission at 12 months, n (%)	9/9 (100)

Conclusion

Data from this case series suggest that EUS-RFA is a feasible and safe therapeutic approach for pancreatic insulinomas with mid-term efficacy.

References

Waung, J.A.; Todd, J.F.; Keane, M.G.; Pereira, S.P. Successful management of a sporadic pancreatic insulinoma by endoscopic ultrasound-guided radiofrequency ablation. Endoscopy 2016, 48 (Suppl. S1), E144–E145
Goldberg SN, Mallery S, Gazelle GS, Brugge WR. EUS-guided radiofrequency ablation in the pancreas: results in a porcine model. Gastrointest Endosc. 1999 Sep;50(3):392-401. doi: 10.1053/ge.1999.v50.98847.
Tsoli M, Chatzellis E, Koumarianou A, Kolomodi D, Kaltsas G. Current best practice in the management of neuroendocrine tumors. Ther Adv Endocrinol Metab. 2018 Oct 31;10:2042018818804698. doi: 10.1177/2042018818804698.

Introduction

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, predominantly diagnosed in patients with chronic liver diseases. The absence of specific biomarkers and the typically asymptomatic progression of the disease lead to delayed diagnosis. Patients with liver disease, including HCC, exhibit alterations in the gut microbiome and increased bacterial permeability, factors that may influence disease progression and patient outcomes. In recent years, there has been a growing interest in exploring circulating microbiome signatures as potential indicators of liver disease stutus, providing a new avenue for understanding HCC.

Aims & Methods

Aims: To identify the signatures of the circulating blood microbiome associated with hepatocellular carcinoma, response to treatment and disease prognosis.
Methods: This study conducted a post-hoc analysis of the SORAMIC clinical trial utilizing peripheral blood plasma samples. For this analysis, blood plasma samples from a cohort of 71 patients with HCC were examined (25 treated with Sorafenib and 46 with SIRT/Sorafenib). Peripheral blood samples were collected at two time points: baseline (prior to the initiation of anti-tumor therapy) with all 71 patients included, and post-therapy (7 to 9 weeks after treatment) with 39 patients included. Additionally, peripheral blood samples were obtained from 52 control subjects, who were endoscopically diagnosed with colonic diverticulosis, to compare against the patient group. The composition of the circulating blood microbiome was assessed through 16S rRNA gene sequencing, targeting the V1-V2 hypervariable regions. Subsequent analyses focused on identifying associations with potential novel biomarkers for diagnosis, prognosis, and response to treatment.

Results

Patients with HCC had significantly diminished α-diversity of the circulating blood microbiome as compared to controls. Significant differences were also observed in between microbial communities of these two cohorts based on Bray-Curtis dissimilarity index. Patients with HCC had significantly higher levels of Proteobacteria and Bacteroidetes and lower levels of Firmicutes and Campylobacterota. Differential abundance analysis revealed that families of Gordoniaceae, Cryomorphaceae, Burkholderiaceae, Comamonadaceae, Enterobacteriaceae were significantly enriched in patients with HCC. At the genus level, patients with HCC had higher levels of Gordonia, Fluviicola, Burholderia, Limnohabitans and Escherichia/Shigella and lower levels of Corynebacterium. HCC patients, who responded to treatment with SIRT/Sorafenib showed an increase in blood bacterial diversity, enrichment of families Burkholderiales incertae sedis, Arcobacteraceae, Peptostreptococcaceae, Moraxellaceae, genera Sphaerotilus, Aliacrobacter, Rhodoluna, Giesbergeria, Microbacterium, Romboutsia, Arcicella, Pseudorhodoferax and depletion in families Gordoniaceae, Cryomorphaceae and genera Cloacibacterium, Gordonia, Limnohabitans, Fluviicola after the treatment. Levels of Acinetobacter, Enhydrobacter and Micrococcus in the blood before the HCC treatment were associated with patient prognosis.

Conclusion

Patients with HCC exhibit a unique circulating blood microbiome profile characterized by reduced bacterial diversity. Response to treatment is linked to an increase in α-diversity and changes in the circulating microbiome profile. Specific members of the circulating microbiome show potential prognostic capabilities, suggesting their utility as biomarkers for predicting disease progression and treatment outcomes in HCC.

Clinical Case Summary

Management of bleeding GIST is challenging, especially in metastatic disease. Emergent surgery for bleeding GIST lesions has a high rate of morbility and mortality in comparison to elective procedures (1). A safe and accurate method to obtain a permanent hemostasis is needed. Several endoscopic procedures are available although with limited efficacy due to the complex neoangiogenesis of these tumours that remains out of reach of contact endoscopic techniques (2). EUS-guided therapy of bleeding GIST injecting cyanoacrylate or ethanol has been published. After one adverse event of spurting bleeding after EUS-guided injection of cyanoacryalte, our group first reported the EUS-guided coil puls cyanoacrylate injection therapy for bleeding GIST in two patients (3). We report our experience in five consecutive cases of bleeding GIST successfully treated under EUS-guidance (Table 1). Given the rich network of arteries in some cases, we aim to deploy coils into de tumor .
One adverse event was observed. An intratumoral bleeding after the punction of a 22G needle, successfully managed by EUS-guided deployment of a coil plus CYA. The clinical outcome in these five patients was uneventful until scheduled surgery was performed or palliative therapy in the fifth patient with a metastatic GIST with oncologic progression disease.

CASE	AGE	LOCALZATION SIZE OF THE ARTERY	CLINICAL PRESENTATION	EUS-GUIDED PROCEDURE NEEDLE CYANOACRYLATE/COILS	ADVERSE EVENTS	CLINICAL OUTCOME SCHEDULED SURGERY
1	82	Duodenal Bulb 2 mm	Recurrent melena Two unsuccessful endoscopic injection and clipping therapy	22 gauge 1 mL CYA	None	Uneventful 4 years
2	72	Fundus 5 mm	Hematemesis and hypovolemic shock	22 gauge 1 mL CYA 19 gauge 1 coil (6 mm/20cm long) 2 mL CYA	Bleeding after injection of 1 mL CYA Hemostasis after deployment of 1 coil and 2 mL CYA	Uventful 3 years
3	79	Fundus 4 mm	Hematemesis and hypovolemic shock	19 gauge 1 coil (6mm/14 mm long)	None	Uneventful
4	43	Fundus 3 mm	Melena	19 gauge 3 coils (3 mm/14cm long) 2 mL CYA	None	Uneventful 2 years
5	63	Body Metastatic GIST with oncologic progressiion Several 4 mm arteries	Hypovolemic shock	19 gauge 1 session: 5 coils (14mm/14 cm long) plus 2 mL CYA 2 session (anemia): 6 coils (6 mm/14 cm) plus 1 mL CYA	None	Uneventful on palliative care 6 weeks

EUS-guided therapy of bleeding GIST was effective in these five cases and could be another safe and accurate endoscopic procedure in bleeding GIST aiming to obtain hemostasis until scheduled surgical therapy is carried out or as palliative therapy. In these cases there were not observed recurrent bleeding in spite of a rich network of arterial vessels.

References

(1) Liu Q, Kong F, Zhou J, et al. Management of hemorrhage in gastrointestinal stromal tumors: a review. Cancer Manag Res. 2018;10:735-43.
(2) Venezia G, Asnaghi G, Manca A, et al. Successful use of Hemospray as a bridge to surgery in life-threatening bleeding from a gastrointestinal stromal tumor of the stomach. Endoscopy 2016;48:E232-E233.
(3) Romero-Castro R, Jimenez-Garcia VA, Irisawa A, et al. Endoscopic ultrasound-guided angiotherapy in bleeding gastrointestinal stromal tumors with coil deployment and cyanoacrylate injection. Endoscopy. 2021;53(4):E124-E5.

Disclosure

Rafael Romero Castro is consultant to Cook Medical since 28th, 2023.

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).

		WL (kg)	EWL (%)	TBWL (%)	BAROS
6-months follow-up	Menopause (n=73)	15,0 (10)	50,8 (24,7)	15,2 (8,6)	3,5 (1,5)
	Non-menopausa (n=111)	17,0 (9,0)	54,9 (34,6)	17,2 (8,6)	4,0 (2,0)
	p	0,017	0,068	0,0190	0,039
12-months follow-up	Menopause (n=69)	13,0 (11,0)	47,8 (31,4)	14,1 (13,0)	3,5 (2,3)
	Non-menopausa (n=113)	16,0 (13,5)	52,5 (41,5)	16,3 (13,5)	3,5 (2,8)
	p	0,162	0,318	0,223	0,506
24-months follow-up	Menopause (n=40)	13,0 (15,6)	40,5 (39,3)	13,6 (14,8)	2,6 (2,9)
	Non-menopausa(n=62)	10,0 (11,8)	35,4 (45,0)	10,4 (13,4)	2,5 (3,4)
	p	0,4	0,716	0,519	0,776

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

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.

	Smoker	Non-Smoker	Ex-Smoker
6-months TBWL (%)	18,1 (5,6)	16,9 (6,4)	18,1 (6,4)
6-months EWL (%)	53,8 (20,4)	53,3 (23,6)	54,7 (21,8)
6-months WL (kg)	20,4 (7,2)	17,9 (8,0)	19,7 (7,7)
12-months TBWL (%)	17,0 (9,1)	15,7 (9,1)	16,0 (10,1)
12-months EWL (%)	51,0 (29,8)	49,4 (30,9)	48,3 (30,4)
12-months WL (kg)	19,0 (10,6)	15,5 (10,3)	17,3 (12,1)
24-months TBWL (%)	12,2 (12,5)	13,3 (10,0)	14,9 (8,7)
24-months EWL (%)	32,5 (37,0)	39,6 (29,8)	43,6 (24,4)
24-months WL (kg)	14,4 (14,0)	14,7 (11,9)	16,2 (10,6)

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