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.

Introduction

Endoscopic submucosal dissection (ESD) is increasingly being used as a minimally invasive treatment option for early gastric cancer (EGC), with a very low risk of lymph node metastasis.

Aims & Methods

This study aimed to evaluate the short-, medium-, and long-term clinical outcomes of patients undergoing gastric ESD at a tertiary hospital center. Patients undergoing ESD for superficial gastric lesions (SGLs) between September 2015 and January 2023 were prospectively evaluated. Demographic, clinical (comorbidities, medication, and relevant family history), endoscopic (location, size, and morphology of the lesion, resection scar evaluation), and pathological data (from the resected specimen, mapping biopsies, and scar biopsies) were collected.

Results

Since 2015, 195 patients with SGLs (mean age 70.7±9.8 years, 58.6% male) underwent ESD, with a median follow-up time of 28 months (interquartile range 13-54). Most patients presented with intestinal metaplasia only in the antrum (n=72) or in the antrum and corpus (n=60), and the most frequent location of SGLs was the antrum (64.6%). Resection was R0 in 95.4% of cases and curative in 87.7% (only one non-curative case had no free horizontal margins). During the follow-up period, 15 metachronous lesions and 8 recurrences were identified, on average 24.1±3.4 months after the index procedure. It should be noted that most recurrences (n=5) were identified at the 36- and 48-month reevaluation endoscopies. The complication rate was 3.6%, corresponding to 3 intra-procedural perforations (2 treated endoscopically) and 4 cases of significant bleeding after the procedure were registered.

Conclusion

Endoscopic submucosal dissection is safe and effective, with a high cure rate and low complication and recurrence rates. The identification of mostly late recurrences suggests the need to develop risk assessment tools that allow for defining personalized follow-up intervals.

Introduction

Endoscopic submucosal dissection (ESD) is a common treatment for low-risk gastric cancers, but postoperative bleeding, affecting 0%-15.6% of patients, remains a concern. With aging populations and increased antithrombotic agent use, post-ESD bleeding may soon become even more frequent. Fibrin glue with polyglycolic acid (PGA) sheets has shown promise in preventing post-ESD bleeding, but challenges exist, especially when applying sheets against gravity in gastrointestinal ulcers. Moreover, the PGA sheets themselves can be difficult to manipulate and place onto the ulcer bed. The envelope method, developed in 2017, involves storing PGA sheets in a protective envelope that is carried alongside the endoscope, preventing exposure to saliva or mucus which commonly occurs when PGA sheets are individually passed down the endoscope channel. The envelope then adheres to the gastric wall, and clean PGA sheets can be drawn easily using forceps. This method has demonstrated efficient PGA sheet delivery and fixation but was only found to be effective for gravitational ulcers.

Aims & Methods

The study aims to evaluate the envelope method's efficacy in treating both gravitational and anti-gravitational post-ESD ulcers in living porcine stomachs.Gravitational and anti-gravitational artificial ulcers were created via ESD in living porcine stomachs, using a standardized template as a sizing guide. PGA sheets were then applied to each ulcer, employing the conventional and envelope methods six times each. To standardize the ulcer location and characteristics, the sheets were removed after application, and reapplied over the same ulcer bed. To account for minute changes in ulcer environment over time, the method of re-application was alternated between the conventional and envelope methods. The delivery time of PGA sheets and the endoscopic and histological observations of the treated ulcer surfaces were comparatively analyzed. The ulcers were measured with an endoscopic scale, and the delivery time was presented in min/cm² to allow for subtle differences in ulcer size.

Results

The envelope method showed significantly shorter application times compared to the conventional method for both gravitational (1.0 min/cm² vs 0.32 min/cm², p=0.002) and anti-gravitational ulcers (1.2 min/cm² vs 0.50 min/ cm² p=0.002). In endoscopic examinations, the envelope group demonstrated appropriately applied PGA sheets in anti-gravitational ulcers, with flat sheets and minimal overlapping, while the conventional group showed uneven sheets and clumping. Histologically, the envelope method provided uniform coverage of the ulcer floor with a mixture of PGA sheets and fibrin glue, while the conventional method left gaps between sheets.

Conclusion

The envelope method enables swift transportation and accurate fixation of PGA sheets within living porcine stomachs. This approach is applicable for addressing both gravitational and anti-gravitational ulcers, and may have utility in the prevention of post gastric ESD bleeding.

Introduction

Control of intraoperative bleeding is vital in endoscopic submucosal dissection (ESD) for gastric neoplasms. We developed an ESD method specialized for hemostasis (Spray-ESD) focusing on the Spray coagulation mode (VIO3; ERBE) with high voltage, easy spark control, and improved incision performance.

Aims & Methods

This study aimed to determine the efficacy of Spray-ESD for gastric neoplasms compared to conventional ESD (C-ESD).
An open-label, randomized, controlled trial was conducted from June 2021 to February 2022 at five centers in Japan, and patients with gastric neoplasms meeting the absolute indication for ESD were included in the study. (The clinical registration number is UMIN000034353) Patients were randomized 1:1 to Spray-ESD or C-ESD, and the outcomes of both groups were compared. ESD was performed with an electrosurgical knife: ProKnife. Hemostatic forceps: Hemostat-Y was used for soft coagulation when bleeding was difficult to control. The primary endpoint was the completion rate of ESD using the knife alone without hemostatic forceps. Secondary endpoints were the number and duration of hemostatic forceps use, ESD procedure time, radical cure, and safety.

Results

We analyzed 130 registered cases (Spray-ESD: 65 cases, C-ESD: 65 cases). The completion rate of ESD using the knife alone was significantly higher in Spray-ESD (83.1% vs. 13.8%, P<0.001). The number and duration of hemostatic forceps use were significantly lower in Spray-ESD (median: 1 vs. 3.5 times, P<0.001; 2.0 min vs. 5.5 min, P<0.001). ESD procedure time was not significantly different between the two groups (48.0 min vs. 56.0 min, P=0.11). Both groups had equally high resection rates (complete en bloc resection rate: 100% vs. 95.4%, P=0.24; curative resection rate: 90.8% vs. 87.7%, P=0.78), with a low adverse events rate. (3.1% [posterior bleeding in 2 cases] vs. 6.2% [intraoperative perforation in 1 case, posterior bleeding in 3 cases], P=0.68).

Conclusion

Spray-ESD has been shown to significantly reduce major bleeding requiring hemostats while maintaining a high en bloc resection rate; mastery of the Spray coagulation mode allows for safe ESD with reduced bleeding risk.

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

Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is the most prevalent hepatic disorder worldwide. While histology remains the gold standard, a shift is evident in emerging studies favoring Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) over biopsy as a reliable alternative for steatosis assessment. Similarly, Controlled Attenuation Parameter (CAP) enables the noninvasive assessment of liver steatosis.

Aims & Methods

To assess the accuracy of CAP for MASLD diagnosis as defined by MRI-PDFF. We performed a cross-sectional, diagnostic accuracy study with prospectively collected data. We included consecutive adult participants with type 2 diabetes (T2D) and increased body mass index (BMI ≥25 kg/m²). We used receiver operating characteristic (ROC) curve analyses to assess the accuracy of CAP for diagnosing MASLD (MRI-PDFF ≥5%), and hepatic fat content (HFC) ≥10%. For each ROC analysis, we calculated the area under the ROC (AUROC) alongside 95% Confidence Intervals (CIs), and cutoffs for ruling out (sensitivity >90%) and ruling in (specificity >90%) the target condition. For each cutoff, we calculated the negative (NPV) and positive predictive values (PPV), as well as negative (LRn) and positive (LRp) likelihood ratios with their 95% CIs.

Results

We included 113 participants (58.4% males, mean age 59.6 years). Most participants (95.6%) had a BMI ≥30 kg/m². CAP measurements were performed with the M probe in 36.3% of the participants, and the remaining (63.7%) were scanned with the XL probe. MRI-PDFF values ranged from 1.9% to 37.8% covering the whole spectrum of steatosis. The prevalence of MASLD was 72.6%. The AUROC of CAP for MASLD diagnosis was 0.82 (0.74 to 0.89). The threshold for ruling out MASLD was 249 dB/m yielding a sensitivity (Sens) of 90.2% (81.7 to 95.7), specificity (Sp) 35.5% (19.2 to 54.6), LRp 1.40 (1.07 to 1.83), LRn 0.27 (0.12 to 0.62), PPV 78.7% (73.8 to 82.9) and NPV 57.9% (37.9 to 75.6). Similarly, the threshold for ruling in MASLD was 328 dB/m yielding a Sens, Sp, LRp, LRn, PPV and NPV of 47.6% (36.4 to 58.9), 90.3% (74.2 to 98.0), 4.91 (1.64 to 14.75) and 0.58 (0.46 to 0.74), 92.9% (81.2 to 97.5) and 39.4% (34.0 to 45.2), respectively. The AUROC of CAP for detecting HFC ≥10% was 0.81 (0.73 to 0.88). CAP thresholds for ruling out/in HFC ≥10% were 271 dB/m and 345 dB/m respectively. CAP measurements with IQR < 30 dB/ did not improve the accuracy of CAP for MASLD diagnosis

Conclusion

CAP has acceptable diagnostic accuracy in identifying patients with MRI-PDFF defined MASLD. Thresholds below 249 and 271 dB/m can be used to exclude MALSD and HFC ≥10% with adequate sensitivity. Similarly, CAP values over 328 and 345 dB/m can rule in MASLD and HFC ≥10% respectively.

Disclosure

This study was supported by the Hellenic Association for the Study and Education of Diabetes Mellitus

Introduction

Endoscopic submucosal dissection (ESD) is a common treatment for early-stage gastrointestinal cancers, but managing delayed bleeding from post-ESD ulcers can be challenging. With more patients taking antithrombotic drugs, reliable bleeding prevention methods are crucial. This study presents the Dumpling technique, a new solution for preventing delayed bleeding from these ulcers.

Aims & Methods

Dumpling technique: The technique involves using a double-lumen catheter to inject fibrin glue into the pocket created after suturing an artificial ulcer post-ESD. This technique not only covers the ulcer but also provides a tamponade effect through compression. The fibrin glue is encased by the sutured mucosa, giving it the appearance of a dumpling. An important point of this technique is the use of a double-lumen catheter for fibrin glue injection. Fibrin glue consists of a fibrinogen solution and thrombin solution. Single-lumen catheters cannot be used because the two solutions begin to form a gel in just a few seconds when mixed. One advantage of this technique is that it combines existing products, so no new product development time is required.
An artificial ulcer was created in the resected bovine rectum by ESD flow, fixed to a jig, and a defect of 2.7 mm in diameter was created using an Aorta/Vein Punch. Pig blood that had lost coagulability was then injected to create a hemorrhage model. First, pressure resistance was measured after clip sutures only. Next, the same ulcer was used as is, the blood was washed out, fibrin glue was injected, and pressure resistance was measured again and compared between the two groups (Clip suture group vs Dumpling technique group). In addition, to confirm the feasibility of the technique, the Dumpling technique was performed endoscopically on porcine explanted stomach and bovine explanted rectum, and the excised specimens were evaluated.

Results

The mean ± SD pressure resistance in the bleeding model was 40.2 ± 14.0 mmHg in the clip suture group and 134.5 ± 36.8 mmHg in the Dumpling technique group (N = 5). Feasibility checks confirmed that suture spacing could be performed endoscopically without problems by setting the suture spacing to allow catheter tip insertion. The resection specimen was confirmed to be sufficiently filled with fibrin glue in the pocket.

Conclusion

This study suggests that the Dumpling technique improves the bleeding prevention effect of ulcer closure. Although various methods of ulcer suturing are still being developed, the injection of fibrin glue itself is expected to be adoptable by many clinicians because it does not require high skill if the tip of the catheter can be inserted through the gap between the sutures. We plan to confirm the feasibility of the Dumpling method in an in vivo study using pigs, followed by a clinical trial to confirm the effectiveness of the Dumpling technique.

Disclosure

Mr. Takegawa is employees of KM Biologics Co., Ltd. and the fibrin glue (BOLHEAL®) used in this article is manufactured by KM Biologics Co., Ltd.