Introduction

Lower gastrointestinal bleeding (LGIB) is a major medical emergency, and is associated with significant utilization of hospital resources, as well as considerable morbidity and mortality that increases with aging.

Aims & Methods

We aimed to describe patient characteristics, interventions and clinical outcomes of LGIB, and to define the impact of LGIB in elderly patients. This was a retrospective multinational cohort study which included adult patients consecutively presenting LGIB at 10 participating centers over a 12-month period. Data relevant to the initial LGIB episode and for up to 30 days afterwards were collected from patient medical records.

Results

Among the 950 patients included at this moment, 53.5% were men. Patients aged ≥ 65 years comprised 79,7% of the cohort (mean age 74 years); in this group, most comorbidities and use of antiplatelet/anticoagulant therapy were more frequent (p<0.001). 22.8% had a previous LGIB bleeding episode. On admission, hemodynamic instability was present in 12.6% (n=120) and almost 50% required red cell transfusion (n=442). Most patients (81.6%) required hospitalization and 6% of them were admitted in an intensive care unit. The risk scores Oakland (p<0.001) and ABC (p=0.003) were higher in patients ≥65 years. Colonoscopy was the most common investigation (63.8%). Hemostatic endoscopy therapy was performed in 20% of patients. Interventional radiology therapy and surgery were necessary in 7 (0.7%) and 24 (2.5%) patients, respectively. Diverticular bleeding (20.5%) was the most common cause of LGIB, followed by anorectal diseases (12.7%) and ischemic proctitis/colitis (10.3%). Median length of stay was 7 days, 12% of patients rebled during hospitalization and readmission with bleeding occurred in 8.4%. In-hospital mortality was 9% (n=86), with 74 deaths attributed to non-bleeding causes. The multivariate analysis showed that older adults required hospitalization (p<0.001) and longer hospital stays (p<0.001) more frequently, while younger patients had higher ICU admission rates (p=0.018). Antiplatelet (p=0.034) or anticoagulant use (p=0.018), ABC score (p<0.001) and Charlson Comorbidity Index (CCI, p<0.001) were independently associated with in-hospital mortality. The CCI, higher in older patients, also correlated with need of blood transfusions (p=0.035), rebleeding (p=0.048), and re-hospitalization (p=0.027). Table 1 summarizes use of healthcare resources and clinical outcomes.

Conclusion

This study analyzed the epidemiological data of LGIB in a large representative sample of the European population. Despite more accurate diagnostic/therapeutic methods and likely earlier detection, higher use of healthcare resources and worse outcomes have increased which may reflect a higher burden of comorbidities in a progressively aged population. Besides higher prevalence, comorbidities and risk factors in elderly patients, the present study demonstrates that there are several differences in the management of LGIB patients across Europe.

References

1. Abraham NS, Noseworthy PA, Inselman J, et al. Risk of gastrointestinal bleeding increases with combinations of antithrombotic agents and patient age. Clin Gastroenterol Hepatol. 2020;18:337–346 e19.
2. Triantafyllou K, Gkolfakis P, Gralnek IM, et al. Diagnosis and management of acute lower gastrointestinal bleeding: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy. 2021 Aug;53(8):850-868.
3. Sengupta N, Feuerstein JD, Jairath V, et al. Management of Patients With Acute Lower Gastrointestinal Bleeding: An Updated ACG Guideline. Am J Gastroenterol. 2023 Feb 1;118(2):208-231.
4. Oakland K, Guy R, Uberoi R, et al; UK Lower GI Bleeding Collaborative. Acute lower GI bleeding in the UK: patient characteristics, interventions and outcomes in the first nationwide audit. Gut. 2018 Apr;67(4):654-662.
   

Introduction

A grey zone known as the borderline resectable (BR) category, which lies between resectable and unresectable, has been proposed for perihilar cholangiocarcinoma; however, there is no international consensus on this classification. BR can be considered from various perspectives, including local tumor factors, surgical risk, long-term prognosis, liver reserve capacity, and systemic condition.

Aims & Methods

The study's aim is to define the borderline resectable (BR) of perihilar cholangiocarcinoma based on surgical procedure and preoperative liver function. We examined 1) the comparison of surgical outcomes between extended surgery and standard surgery and 2) the risk of postoperative mortality from liver failure in patients who underwent portal vein embolization.
Study 1) Surgical cases from January 2011 to December 2023 were divided into two groups: the Extended surgery group: left or right trisectionectomy(L3/R3), concomitant hepatic artery resection (AR), hepatopancreaticoduodenectomy (HPD), and the other standard surgery groups. Study 2) The risk of postoperative liver failure in patients who underwent resection after portal vein embolization (PVE) between January 2001 and December 2022 (including HPD) was evaluated

Results

Study 1) A total of 181 patients (59 in the extended surgery group and 122 in the standard surgery group) were included in the study. There were significant differences in operation time (median 798/700 minutes, p<0.01) and blood loss (2000 ml/1295 ml, p<0.01) in the extended surgery group compared to the standard surgery group, but no significant differences in postoperative complication rate (Clavien Dindo 3a or higher: 79%/67%) or in-hospital mortality rate (5%/5%). The 5-year overall survival rate was 34% in the extended surgery group and 50% in the standard surgery group, which was not significantly different by the log-rank test. Study 2: The incidence of liver failure (%) and mortality (%) by surgical technique were R (37/5.7), L3 (30/5), and R3 (54/7.7). ICGK x proportion of remnant liver volume（ICGKF）<0.05 before PVE, operation time >660 minutes, and blood loss >1900 ml were identified as risk factors in univariate and multivariate analyses, and the mortality rate for patients with these three factors was high at 25%.

Conclusion

Patients who required extended surgery with poor pre-PVE liver function (ICGKF<0.05) should be considered BR in perihilar cholangiocarcinoma.

References

1: Nooijen LE, de Boer MT, Braat AE, Dewulf M, den Dulk M, Hagendoorn J, Hoogwater FJH, Lam HD, Molenaar Q, Neumann U, Porte RJ, Swijnenburg RJ, Zonderhuis B, Kazemier G, Klümpen HJ, van Gulik T, Groot Koerkamp B, Erdmann JI.
National consensus on a new resectability classification for perihilar cholangiocarcinoma - A modified Delphi method. Eur J Surg Oncol. 2025 Feb;51(2):107117. PMID: 37880001.
2: Kuriyama N, Usui M, Gyoten K, Hayasaki A, Fujii T, Iizawa Y, Kato H, Murata Y, Tanemura A, Kishiwada M, Sakurai H, Mizuno S, Isaji S.
Neoadjuvant chemotherapy followed by curative-intent surgery for perihilar cholangiocarcinoma based on its anatomical resectability classification and lymph node status. BMC Cancer. 2020 May 11;20(1):405. doi: PMID: 32393197;.
3: Matsuyama R, Mori R, Ota Y, Homma Y, Yabusita Y, Hiratani S, Murakami T, Sawada Y, Miyake K, Shimizu Y, Kumamoto T, Endo I.
Impact of Gemcitabine Plus S1 Neoadjuvant Chemotherapy on Borderline Resectable Perihilar Cholangiocarcinoma.
Ann Surg Oncol. 2022 Apr;29(4):2393-2405. doi: 10.1245/s10434-021-11206-4. Epub
2022 Jan 7. PMID: 34994885.

Introduction

In laparoscopic cholecystectomy (LC), intraoperative cholangiography (IOC) is recommended to clarify biliary anatomy, detect choledocholithiasis and identify complications. IOC interpretation may be performed by either surgeons or radiologists, but it remains unclear which approach is preferable. This study investigates how the type of medical specialist interpreting the IOC affects surgical outcomes and operating time.

Aims & Methods

All LCs registered in the Swedish Registry of Gallstone surgery and Endoscopic retrograde Cholangiopancreatography (GallRik) between January 1, 2009, and December 31, 2020, were included. A complementary survey was distributed to all participating surgical clinics to determine local IOC interpretation practices. Registry and survey data were linked and outcomes were analysed using mixed model analysis and logistic regression.

Results

A total of 118.556 procedures from 61 surgical units were included. Operating time was longer when radiologists assessed the IOC (mean differences 11.3 minutes; 95% CI 1.60-20.89). Intraoperative complications were more common with radiologist interpretation (2.6% vs 1.5%; OR 0.58, 95% CI 0.52-0.63), while postoperative complications were slightly higher with surgeon-led interpretation (8.2% vs 7.3%; OR 1.14, 95% CI 1.08-1.20). Bile duct injury rates (0.3%; OR 1.0, 95% CI 0.79-1.27) and detection of choledocholithiasis (12.4% vs 12.6%; OR 1.02, 95% CI 0.90-0.99) were similar between groups.

Conclusion

Surgeon-led IOC interpretation is associated with shorter operating times and fewer intraoperative complications, without increasing the risk of bile duct injury or missed choledocholithiasis. Routine radiologist involvement may be unnecessary and an inefficient use of resources.

Introduction

Symptomatic uncomplicated diverticular disease (SUDD) is characterized by recurrent gastrointestinal (GI) symptoms in patients with colonic diverticula. Different treatments have been proposed to improve GI symptoms, but with low-level of evidence.

Aims & Methods

We aimed to evaluate the efficacy of a synbiotic formulation combined with a diet rich in fibre (DRF) in improving GI symptoms in SUDD, compared to a DRF and placebo. We conducted a single-centre, no-profit, randomised, double-blind, placebo-controlled trial (Local Ethics Committee n.182 SA_2020). Patients diagnosed with SUDD (colonic diverticula and recurrent abdominal pain with or without altered bowel habits or bloating, in the absence of signs of systemic inflammation) were included. After a 14-day run-in period, all participants completed structured questionnaires [long- and short-lasting abdominal pain, abdominal bloating, Rome IV for IBS, food frequency questionnaire and quality of life (SF-12)], received a dietary counselling, and were randomised to receive either (I) Enterolactis duo (containing the probiotic strain Lacticaseibacillus Paracasei DG and the prebiotic fibre inulin) 1 sachet bid plus advice on DRF (arm A), or (II) Placebo, 1 sachet bid plus advice on DRF (arm B) for 12 weeks. During treatment, patients completed a weekly diary of GI symptoms and bowel habits. At the end of treatment, patients completed all questionnaires again and were followed up after 4 weeks.

Results

After screening 81 patients, 34 (55.9% female; mean age 64±8.6yrs) were included and randomised to arm A (n=17) and arm B (n=17). At baseline, there were no significant differences in terms of clinical characteristics between the two arms. Thirty patients (arm A=14; arm B=16) completed the study. Compliance with the DRF was poor in both arms (0% vs 14.3%). Patients experienced significant improvements in GI symptoms (bloating, short- and long-lasting abdominal pain) and bowel habits compared to baseline in both arms, but no differences were observed between the two arms. Neither arm A nor arm B reported significant changes in the quality of life scores. Mild self-limited adverse events were reported with no differences between arms. Follow-up at 4 weeks showed no clinical changes in either arm, with no differences between arms.

Conclusion

This synbiotic supplementation is as effective as placebo in relieving symptoms in SUDD patients, suggesting the relevant role of the placebo effect also in diverticular disease.

Introduction

Idiopathic Sclerosing Mesenteritis (SM) is a rare fibroinflammatory disease of unknown etiology. The clinical course is generally benign, as has been demonstrated in retrospective studies and large case series.

Aims & Methods

To more accurately determine the natural history of patients with symptomatic SM and describe the clinical features of those with idiopathic SM, we performed a prospective cohort study. Inclusion criteria were adult patients with typical SM symptoms, after ruling out other causes of abdominal pain, who met the Coulier criteria in computed tomography scans for establishing SM diagnosis. We identified 58 patients with symptomatic SM. During the follow-up period, 3 patients were lost and excluded from the analysis. Most patients (95.7%) underwent upper and lower endoscopy and chest imaging to rule out co-existing cancer disease. Secondary SM cases were also excluded (n=5 had a co-existing cancer diagnosis within 6 months of SM diagnosis and n=4 had a pre-existing diagnosis of SM-related autoimmune disease at SM diagnosis). The final cohort of symptomatic idiopathic SM cases consisted of 46 patients. Data were collected prospectively at each site visit from January 2014 to January 2024. Descriptive statistics were used to summarize the results.

Results

In total, 46 patients with idiopathic SM were included, of whom 56.5% were females and 43.5% were males with a mean age at diagnosis of 62 years. Overweight or obese were 62.8%, and 37.2% had normal weight. SM was histologically confirmed in 13%. Features of IgG4-related disease were present in 21.7% with other organ involvement (13% pancreas, 10.9% bile ducts, 2.2% orbit, and 2.2% lymph nodes). Multiple organ involvement was observed in 6.5%. All patients who presented with an abdominal mass (8.7%) developed features similar to IgG4-related disease. Elevated serum IgG4 levels at diagnosis were found in 7 of 36 patients (19.4%). All patients presented with abdominal pain, followed by bloating (84.8%), nausea (43.5%), anorexia (39.1%), weight loss (37%), vomiting (30.4%), dyspepsia (19.6%), diarrhea (19.6%), constipation (13%), fever (8.7%), icterus (4.3%), early satiety (4.3%), sarcopenia (4.3%), and peripheral edema (2.2%). Hospitalization was required in 37%, and severe complications were observed in 30.4% [ileus (15.2%), acute pancreatitis (8.7%), acute cholangitis (8.7%), abdominal mass (8.7%), chronic pancreatitis (4.3%), mesenteric thrombosis (2.2%), and obstructive lymphadenopathy (2.2%)]. Surgical intervention was performed in 13%. During the disease course, most patients (84.8%) were treated with colchicine in combination or not with corticosteroids (54.3%), antiplatelets (50%), and low-molecular heparin (28.3%).

Conclusion

In this prospective cohort study, we observed an aggressive clinical course with severe intra-abdominal complications in a substantial proportion of patients with idiopathic SM (30.4%). Almost one in four patients (21.7%) manifested other organ involvement, identical to IgG4-related disease, indicating that some idiopathic SM cases could be part of the IgG4 disease spectrum. These observations suggest that idiopathic SM requires clinical vigilance similar to that applied to IgG4-related disease.

References

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Disclosure

No potential conflicts of interest

Clinical Case Summary

Background: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors that rarely present with gastrointestinal (GI) bleeding due to tumor erosion. GISTs commonly arise in the stomach, followed by the small bowel. They are typically diagnosed through histopathology and immunohistochemistry.¹ The presence of mucosal ulceration and tumor locations outside the stomach are linked with a greater risk of tumor progression to malignancy.^1,2 This case highlights a benign ulcerated jejunal GIST presenting as GI bleeding.
Case summary: A 42-year-old male presented with dark stools and light-headedness over five days. On examination, he was hypotensive, tachycardic, tachypneic, and had pallor. Laboratory tests revealed normocytic normochromic anemia, with a significant one-day drop in hemoglobin (from 7.2 g/dL to 6.4 g/dL). Upper GI endoscopy and colonoscopy were normal, but double-balloon enteroscopy [Figure 1] revealed a subepithelial lesion distal to the duodenojejunal flexure, and an overlying ulcer. These findings were suggestive of GIST and were corroborated by a contract-enhanced CT abdomen scan, which revealed a well-defined, homogenously-enhancing solid exophytic lesion (30 x 22 x 26 mm) arising from the proximal jejunal loops. He underwent resection anastomosis with complete en-bloc surgical removal of the lesion. Histopathological analysis of the resected specimen showed spindle cells arranged in a long, fascicular pattern, with minimal pleomorphism, low mitotic index, without any necrosis or epithelioid cells [Figure 2]. Immunohistochemistry confirmed the GIST which displayed diffuse immunopositivity for CD117 and DOG1 markers. His hemoglobin levels were stable on regular follow-ups, and there was no documented recurrence six months later.
Conclusion: GISTs can present with GI hemorrhage and should be suspected in cases of unexplained GI bleeding. Early diagnosis and complete surgical resection are key to favorable outcomes.

References

1. Parab TM, DeRogatis MJ, Boaz AM, Grasso SA, Issack PS, Duarte DA, Urayeneza O, Vahdat S, Qiao JH, Hinika GS. Gastrointestinal stromal tumors: a comprehensive review. J Gastrointest Oncol. 2019 Feb;10(1):144-154. doi: 10.21037/jgo.2018.08.20.
2. Carter BM, Bronsert MR, Wilky BA, McCarter MD. Mucosal Ulceration in Gastrointestinal Stromal Tumor is an Independent Predictor of Progression-Free Survival. J Surg Res. 2023 Apr;284:221-229. doi: 10.1016/j.jss.2022.11.076.

Introduction

The CRAFITY (CRP and AFP in ImmunoTherapY) score is a biomarker composed of CRP and AFP that predicts clinical outcomes of patients undergoing immunotherapy for hepatocellular carcinoma (HCC), independently of Child-Pugh score and performance status [1]. We previously validated its utility in predicting the prognosis of patients with HCC receiving atezolizumab and bevacizumab therapy [2].

Aims & Methods

In this study, we investigated the applicability of the CRAFITY score in patients with unresectable HCC treated with the combination of durvalumab and tremelimumab (Dur/Tre). In this multicenter study, a total of 325 patients who received the STRIDE regimen between March 2023 and December 2024 were included. Baseline characteristics were as follows: median age, 73.0 (IQR 68.0–78.0) years; sex (male/female), 272/53; performance status (0/1/≥2), 252/58/15; etiology (hepatitis B/C/B+C/non-B, non-C), 55/88/3/179; Child-Pugh score (5/6/≥7), 137/133/73; BCLC stage (≤A/B/≥C), 22/91/212; neutrophil-to-lymphocyte ratio (NLR), 2.97 (1.98–4.31); CRP, 0.44 (0.15–1.59) mg/dL; AFP, 58.1 (5.0–1921.0) ng/mL; observation period, 7.9 (4.1–13.3) months; and treatment line (first-line/second-line or beyond), 121/204 patients.

Results

Patients were stratified by CRAFITY score (0/1/2): 120/149/56, and significant differences were observed among the groups for most baseline characteristics, except for sex, body mass index (BMI), and prothrombin time (PT). Median progression-free survival (PFS) was 3.8 months (95% CI: 3.0–4.3), and median overall survival (OS) was 17.0 months (95% CI: 14.1–NA). Best response rates based on RECIST version 1.1 were: complete response (CR) 2.1%; partial response (PR) 16.8%; stable disease (SD) 30.9%; progressive disease (PD) 50.2%; with an objective response rate (ORR) of 18.9% and disease control rate (DCR) of 49.8%. Significant differences in best response (p = 0.042) and DCR (p = 0.043) were observed across CRAFITY score groups. The incidence of immune-related adverse events (imAEs, ≥10% in any category) was 25.8% for skin toxicity, 21.8% for hepatotoxicity, 12.9% for diarrhea/enteritis, and 10.2% for fever. No significant differences in adverse events, including other imAEs, were found among CRAFITY groups. In multivariate analysis, both treatment line (second-line or later: HR 1.47; 95% CI: 1.11–1.96; p = 0.007) and CRAFITY score of 2 (HR 1.62; 95% CI: 1.08–2.42; p = 0.020) were independently associated with PFS. Additionally, in multivariate analysis, non-B non-C etiology (HR 0.63; 95% CI: 0.43–0.93; p = 0.020), CRAFITY score of 1 (HR 2.00; 95% CI: 1.22–3.27; p = 0.006), and score of 2 (HR 3.42; 95% CI: 1.91–6.12; p < 0.001) were independently associated with OS. For the prediction of 12-month OS, the integrated discrimination improvement (IDI) was 0.007 (95% CI, 0.022 to 0.137; p < 0.001) for AFP and 0.066 (95% CI, 0.018 to 0.135; p < 0.001) for CRP, respectively, when compared with the CRAFITY score. Similarly, the net reclassification improvement (NRI) was 0.360 (95% CI, 0.092 to 0.474; p = 0.002) for AFP and 0.170 (95% CI, 0.024 to 0.348; p = 0.016) for CRP, indicating the superior prognostic performance of the CRAFITY score. Subgroup analyses showed significant differences in OS by CRAFITY score among patients with Child-Pugh class A, NLR less than 3, and BCLC stage C or higher.

Conclusion

The CRAFITY score appears to be a promising prognostic biomarker for patients with unresectable HCC treated with Dur/Tre.

References

1. Bernhard Scheiner, Katharina Pomej, Martha M. Kirstein et al. Prognosis of patients with hepatocellular carcinoma treated with immunotherapy – development and validation of the CRAFITY score. J Hepatol. 2022; 76 (2): 353-363.
2. Takeshi Hatanaka, Satoru Kakizaki, Atsushi Hiraoka et al. Prognostic impact of C-reactive protein and alpha-fetoprotein in immunotherapy score in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: a multicenter retrospective study. Hepatol Int. 2022; 16 (5): 1150-1160.

Disclosure

Toshifumi Tada: lecture fees from AbbVie, AstraZeneca, Eisai, and Chugai
Atsushi Hiraoka: lecture fees from Eisai, Bayer, Eli Lilly, and Otsuka
Hidenori Toyoda: lecture fees from AbbVie, Eisai, Gilead, Terumo, and Bayer