Introduction

Managing tumoral bleeding poses a significant challenge for endoscopists. Traditional tools such as clips and heat-probes frequently prove inadequate in controlling stubborn bleeding caused by mucosal invasion from these tumors. Hemostatic powder sprays provide a novel solution by applying a combination of minerals and polymers directly onto the tumor surface, forming a mechanical barrier to seal the bleeding site. However, there is a scarcity of data regarding their effectiveness in treating hemorrhagic gastrointestinal neoplasms. This study seeks to evaluate the efficacy of Hemostatic powder spray in patients suffering from gastrointestinal bleeding related to malignancies.

Aims & Methods

This study aimed to evaluate the effectiveness of Hemostatic powder spray compared to standard clinical treatment in controlling gastrointestinal bleeding originating from malignant lesions. The primary outcome measures included the combined rates of rebleeding within 30 days, while secondary outcomes encompassed the combined rates of mortality over any time period.
We gathered relevant data, an extensive search of electronic databases was conducted up to April 2024. Only randomized controlled trials (RCTs) were included in the study, focusing specifically on cases where Hemostatic powder spray was pitted against conventional endoscopic techniques for managing bleeding caused by gastrointestinal tumors.

Results

Three studies involving a total of 162 patients were included in this meta-analysis. Among them, 83 patients underwent treatment with Hemostatic spray powder alone, while 79 patients received conventional hemostatic techniques. The pooled results of the analysis revealed that Hemostatic powder spray was associated with a lower incidence of re-bleeding beyond 30 days from the onset of treatment (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.15-0.84), demonstrating a significant advantage over standard endoscopy in the management of gastrointestinal tumor bleeding (p-value 0.01). Additionally, there was no significant difference observed in all-time mortality between the two treatment groups (OR 0.40, 95% CI 0.19-0.83, p-value 0.09).

Conclusion

Hemostatic spray powders demonstrate significant efficacy in achieving hemostasis for gastrointestinal bleeding associated with malignancies. They should be regarded as a viable alternative to conventional endoscopic methods in such cases. Subsequent research should be structured to assess both the effectiveness and safety of hemostatic spray powders as a primary hemostatic approach compared to traditional endoscopic techniques.

References

1. Pittayanon, Rapat et al. “The efficacy of Hemospray in patients with upper gastrointestinal bleeding from tumor.” Endoscopy international open vol. 4,9 (2016): E933-6. doi:10.1055/s-0042-109863
2. Chen YI, Wyse J, Lu Y, et al. TC-325 hemostatic powder versus current standard of care in managing malignant GI bleeding: a pilot randomized clinical trial. Gastrointest Endosc 2020;91:321–328.
3. Bruno da Costa Martins, et al. Mo1140. Preliminary results of a randomized controlled trial comparing hemostatic powder versus optimal clinical treatment in the management of gastrointestinal bleeding from malignancy, Gastrointestinal Endoscopy, Volume 87, Issue 6, Supplement, 2018, Pages AB415-AB416, ISSN 0016-5107.
4. Martins BC, Abnader Machado A, Scomparin RC, et al. TC-325 hemostatic powder in the management of upper gastrointestinal malignant bleeding: a randomized controlled trial. Endosc Int Open 2022;10:E1350–E1357.
5. Minhem MA, Nakshabandi A, Mirza R, et al. Gastrointestinal hemorrhage in the setting of gastrointestinal cancer: anatomical prevalence, predictors, and interventions. World J Gastrointest Endosc 2021; 13:391–406.
6. Hussein, Mohamed et al. “Hemostatic powder TC-325 treatment of malignancy-related upper gastrointestinal bleeds: International registry outcomes.” Journal of gastroenterology and hepatology vol. 36,11 (2021): 3027-3032. doi:10.1111/jgh.15579

Introduction

Gastric adenocarcinoma (GA) with enteroblastic differentiation (GAED) is a special type of gastric carcinoma with aggressive biological behavior, which is histologically characterized by a glycogen-rich clear cytoplasm and fetal gut-like structures. GAED shows the expression of at least one of the following enteroblastic markers (EMs): glypican-3 (GPC3), spalt-like transcription factor 4 (SALL4), and α-fetoprotein (AFP) (Murakami T et al. Gastric Cancer. 2016;19(2):498-507.)¹. Despite the absence of clear cytoplasm, we often encounter GA with EMs expression (GA with EM); however, the clinicopathological characteristics of GA with EM remain unclear. Regarding this point, we reported that the status of clear cell differentiation within tumors do not affect any clinicopathological or molecular pathological differences in colorectal carcinoma with the expression of enteroblastic markers which is a colorectal counterpart of GEAD (Yamashiro Y et al. Histopathology. 2020;77(3):492-502.)². In addition, CAED has similar clinicopathological and molecular pathological characteristics to GAED, including aggressive behavior, high rates of lymphovascular invasion and liver metastasis and high frequency of TP53 mutation². Therefore, we speculated that the same phenomenon could also be observed in GA.

Aims & Methods

A total of 688 GA samples on tissue microarray were examined for immunohistochemical (IHC) expression of three EMs (AFP, GPC3, and SALL4), and the correlations between EM expression and clinicopathological factors were analyzed. According to the status of the clear cytoplasm of tumor cells, GA showing IHC expression of EMs was classified as either GAED or GA with EM.

Results

Histological and IHC analysis revealed 94 GAEDs (13.7%), 58 GAs with EM (8.4%), and 536 conventional GAs (CGAs). Both GAED and GA with EM showed frequent lymphovascular invasion, lymph node metastasis, and liver metastasis compared to CGA. However, venous invasion was more frequent in GAED, and vice versa in GA with EM. The five-year overall survival rates for GAED, GA with EM, and CGA were 46.6%, 47.9%, and 58.2%, respectively. GAED and GA with EM showed similar trends in overall survival rates (p = 0.78). GAED had a poorer prognosis than CGA with statistical significance (p = 0.035); however, not for GA with EM (P = 0.157). Furthermore, GA with EM-positive group (GAED and GA with EM) showed a worse overall survival rate than CGA (p = 0.018).

Conclusion

Interestingly, the tumor size tended to be smaller in the EM-positive group than that for CGA group, however, clinicopathologically EM-positive group was more aggressive than CGA group such as higher rate for venous invasion and liver metastasis. These findings suggest that GAED and GA with EM can be clinically classified together as aggressive tumors but can pathologically seem to be slightly different.

References

1. Murakami T et al. Gastric Cancer. 2016;19(2):498-507.
2. Yamashiro Y et al. Histopathology. 2020;77(3):492-502.

Introduction

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease characterized by liver steatosis and inflammation which abnormal immune responses involved in pathogenesis, and there is no approved therapeutic drug. Rhein, one of the main bioactive components of Rheum palmatum, has exerted anti-inflammatory properties. However, the mechanism by which Rhein exerts beneficial effects against NASH is far from elucidated. Here, our study aimed to investigate the therapeutic effects of Rhein on liver steatosis and inflammation and elucidate the related mechanisms of immunoregulation.

Aims & Methods

Male C57BL/6 mice were given high-fat diet for 10 weeks to induce NASH, followed by Rhein suspension administration at a dose of 100mg/kg and 200mg/kg for 4 weeks. The therapeutic effect of NASH was estimated by body weight, liver weight, LW/BW, food intake, the liver appearance and the histological analysis of liver section stained with hematoxylin and eosin. The proportion of lymphocyte cells in the mesenteric lymph nodes (MLNs) was detected by flow cytometry.

Results

Our findings demonstrated that high-fat diet treatment resulted in severe liver inflammation and severe steatosis, while Rhein appreciably reverse these phenomenon, as evidenced by the reduction of body weight, liver wet weight, LW/BW, and liver size in mice. Histological analysis of liver section revealed that administration of Rhein exhibited improvement of severe steatosis, elimination of inflammatory cells and resolution of balloon-like changes when compared to mice in the HFD group. Interestingly, there were no significant differences in food intake among groups of mice, suggesting that the protective effect of Rhein is not achieved by inhibiting appetite. Mechanistically, flow cytometry analysis showed that higher Th1 and Th17 polarized response were detected in the MLN compartments in HFD-induced mice, evidenced by the detection of increased numbers of Th1 cells (CD3+CD4+IFN-γ+) and Th17 cells (CD3+CD4+IL-17+), and Rhein intervention showed significant decrease numbers of Th1 and Th17 in MLNs. In contrast, Rhein treatment significantly increased the numbers of Treg cells (CD3+CD4+Foxp3+) with anti-inflammatory effects in the MLN of NASH mice.

Conclusion

Our results provide novel insights into the protective role of Rhein in modulating the liver steatosis and inflammation, with therapeutic potential for immunology-targeted strategy in the treatment of NASH.

References

[1] Cheng L, Chen Q, Pi R, Chen J. A research update on the therapeutic potential of rhein and its derivatives. Eur J Pharmacol. 2021,899:173908. doi:10.1016/j.ejphar.2021.173908.
[2] Gebru YA, Gupta H, Kim HS, et al. T Cell Subsets and Natural Killer Cells in the Pathogenesis of Nonalcoholic Fatty Liver Disease. Int J Mol Sci. 2021,22(22):12190. doi:10.3390/ijms222212190

Disclosure

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Introduction

The literature regarding the risk of progression to extrahepatic disease and clinical factors associated with the development of metastases in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) is sparse.

Aims & Methods

We aimed to assess the incidence of extrahepatic recurrence and to identify clinically relevant risk factors for the development of metastases in patients with HCC treated with TACE as first-line treatment.
From the Italian Liver Cancer (ITA.LI.CA) database, data of 981 HCC patients undergoing TACE as first-line treatment were retrieved and retrospectively analyzed. Incidence of extrahepatic recurrence was compared between two groups according to the diameter of the largest liver lesion at the time of TACE (HCC ≤ 3 cm vs. HCC > 3 cm). Multivariate Cox regression was used to identify predictor of extrahepatic recurrence.

Results

During a median follow-up of 27.0 months (IQR, 13.2-49.0) the overall recurrence rate was 75.4%. Only 78/981 patients (8.0%) had an extrahepatic tumor localization at first recurrence (5.4% in the ≤3 cm group and 10.7% in the >3 group; p=0.002), while the overall extrahepatic recurrence rate was 26.0% (21.2% and 31.0% patients in the ≤3 cm and >3 cm groups, respectively; p=0.0006) (Figure 1). Compared to those with larger tumors, patients with HCC ≤ 3 cm had a significantly longer recurrence-free survival (12.0 [95% CI 10.7-13.3] vs. 9.7 [95% CI 8.2-11.2] months; p=0.02) and overall survival (52.5 [95% CI 45.5-59.4] vs. 34.7 [95% CI 30.7-38.7] months; p<0.0001). HCC size ≥ 3 cm, multifocality and AFP levels were independent predictors of extrahepatic recurrence.

Conclusion

Although the majority of patients treated with TACE do not develop metastases during their lifespan, knowledge of risk factors for extrahepatic recurrence (HCC size, multifocality, AFP levels) may help to assess patient prognosis and to identify patients deserving closer follow-up in order to start early systemic therapy.

Introduction

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer. The median survival after resection is about 60 months. However, when regional lymph node (LN) metastases are found, survival drops to only 20 months. Survival for patients with extraregional LN involvement (i.e., stage IV disease) is even worse. These patients may benefit from preoperative or palliative treatment rather than upfront surgery. Recently, the European Association for the Study of the Liver (EASL) and International Liver Cancer Association (ILCA) clinical practice guidelines advocated the use of endoscopic ultrasound (EUS) with tissue acquisition (TA) of LN for presumed resectable iCCA patients, if a positive LN would alter management. The aim of this study was to evaluate the yield of EUS with TA of LN in presumed resectable iCCA patients and to determine its impact on clinical decision making.

Aims & Methods

In this retrospective, multicentre cohort study, patients with potentially resectable iCCA who underwent preoperative EUS from 2010-2020 were included. The impact of EUS-TA was defined as the percentage of patients who did not undergo surgical exploration due to positive LN found with EUS-TA. Extraregional LN (e.g., aortocaval and celiac trunc) were distinguished from regional LN. EUS was not performed in a standardized manner and TA was performed at the discretion of the endosonographist.

Results

A total of 56 patients were included. The EUS reports described 71 LN (29 regional; 42 extraregional) in 46 patients (82%). EUS-TA was performed of 55 LN, with a yield (i.e., malignancy confirmed) in 21 LN of 19 patients (35%). Fifteen patients (27%) had positive extraregional LN. Surgical exploration was precluded due to positive LN in 17 patients (30%). Fifteen patients (27%) did not undergo surgical exploration for other reasons, such as tumour progression. The remaining 24 patients (43%) underwent surgical exploration of whom 8 (33.3%) underwent a resection, after a median period of 1.5 months. Five patients (21%) had positive LN at surgical exploration that were not detected at EUS, including 2 patients with extraregional LN.

Table 1. Baseline characteristics of the included patients

Conclusion

Preoperative EUS in patients with resectable iCCA had a yield of 35% of patients with TA-confirmed positive LN. In 30% of patients the multidisciplinary team and the patient decided to withhold surgery because of positive LN. The ongoing POELH trial (NCT05678218) prospectively investigates standardized preoperative LN assessment.

Disclosure

R.P. Voermans is a consultant for and receives grants for investigator-initiated studies from Boston Scientific. M.J. Bruno serves as a consultant and receives support for industry and investigator-initiated studies from Boston Scientific and Cook Medical and receives support for investigator-initiated studies from Pentax Medical, 3 M, Interscope, and Mylan. The other authors declare that they have no conflicts of interest.