Viscosity and Characteristics of Malignant Ascites.

BACKGROUND/AIM: Malignant ascites is a common condition in patients with terminal cancer. Treatments, such as diuretics, percutaneous drainage of ascites, and abdominal vein shunting have been advocated. However, these treatments have not achieved sufficient palliative effects. Therefore, the development of innovative therapies is mandated, especially for new therapies that require the creation of a fluid simulation of malignant ascites. However, there have been no previous studies on the physical properties of malignant ascites, including viscosity, which are necessary for the development of such a fluid. Therefore, we prospectively investigated the physical properties of malignant ascites. PATIENTS AND METHODS: This single-center, prospective, observational study included 30 patients between November 2021 and January 2023. The primary endpoint was the viscosity of the malignant ascites, and the secondary endpoints included other viscosity studies, biochemical tests, and the presence of malignant cells in the ascites. RESULTS: The median viscosity was 1.105 mPa*S. The viscosity of malignant ascites tended to decrease with increasing temperature, which is common for liquids. Malignant ascites fluid containing malignant cells tended to be more viscous than ascites fluid without malignant cells; furthermore, albumin levels tended to be higher in the former than in the latter. CONCLUSION: Malignant ascites' median viscosity was 1.105 mPa*S. Correlation between viscosity and temperature showed a decreasing trend. These findings contribute valuable insights for future malignant ascites management and device development.

Study protocol for a prospective, multicentre, phase II trial on endoscopic treatment using two fully covered self-expandable metallic stents for benign strictures after hepaticojejunostomy.

INTRODUCTION: The current endoscopic treatment for postoperative benign hepaticojejunostomy anastomotic stricture (HJAS) has a high technical success rate and is highly effective in the short term. However, long-term results have shown a high rate of stenosis recurrence, which indicates an insufficient response to treatment. Three prospective studies on fully covered self-expandable metallic stent (FC-SEMS) treatment for benign HJAS used the stenosis resolution rate as the primary endpoint, and no study has yet used the long-term non-stenosis rate (at 12 months) as the primary endpoint. METHODS AND ANALYSIS: We launched the 'saddle-cross study', which will be conducted as a multicentre, prospective intervention of endoscopic treatment using two modified FC-SEMSs (BONASTENT️ M-Intraductal) that have been improved for benign stenosis in patients with benign HJAS, with the long-term non-restenosis rate (at 12 months) as the primary endpoint. This study aims to evaluate the long-term non-restenosis rate (at 12 months) and safety of the saddle-cross technique for benign HJAS. We plan to enrol 50 participants. ETHICS AND DISSEMINATION: This study has been approved by the Certified Review Board of the National Cancer Center, Japan (CRB3180009). The results will be reported at various conferences and published in international peer-reviewed journals.

Prospective clinical trial of EUS-guided choledochoduodenostomy without fistula dilation for malignant distal biliary obstruction.

Background and Objectives: During EUS-guided choledochoduodenostomy (EUS-CDS), fistula dilation before stent insertion is associated with adverse events (AEs), such as bile leakage and peritonitis. We hypothesized that EUS-CDS without fistula dilation using a novel self-expandable metal stent (SEMS) with a thin delivery system could overcome this problem, and we conducted this study to evaluate its feasibility and safety. Methods: This was an open-label, single-arm, phase II study at a single institution. We planned EUS-CDS without fistula dilation using a fully covered SEMS with a 5.9-Fr delivery system for unresectable malignant distal biliary obstruction. The primary outcome was overall technical success. Secondary outcomes were technical success without fistula dilation, procedure time, functional success, time to recurrent biliary obstruction, and AEs. The planned sample size was 25 patients. Results: In total, 24 patients were included in this study. In 21 patients, EUS-CDS was performed as primary drainage. The overall technical success rate was 100% (24 of 24 patients). The technical success rate without fistula dilation was 96% (23 of 24). The median procedure time was 16 min (range, 10-66 min). The functional success rate was 96% (23 of 24). The median time to recurrent biliary obstruction was 148 days (95% confidence interval, 29-266 days). There were no procedure-related AEs. Furthermore, computed tomography immediately after the procedure showed no leakage of contrast medium into the abdominal cavity in any patient. Conclusions: EUS-guided choledochoduodenostomy without fistula dilation using a fully covered SEMS with a 5.9-Fr delivery system is feasible with a high probability and can be achieved quickly while effectively preventing bile leakage and peritonitis.

Efficacy of endoscopic ultrasound-guided tissue acquisition for solid pancreatic lesions 20 mm or less in diameter suspected as neuroendocrine tumors or requiring differentiation.

BACKGROUND: For non-functioning pancreatic neuroendocrine tumors (pNETs) ≤ 20 mm, most guidelines consider follow-up observations as an option; however, the various treatment strategies are defined by size alone, even though the Ki-67 index is important for malignancy grading. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) is the standard for the histopathological diagnosis of solid pancreatic lesions; however, recent results for small lesions remain unclear. Therefore, we examined the efficacy of EUS-TA for solid pancreatic lesions ≤ 20 mm suspected as pNETs or requiring differentiation and the non-increase rate in tumor size in follow-up cases. METHODS: We retrospectively analyzed data of 111 patients (median age = 58 years) with lesions ≤ 20 mm suspected as pNETs or requiring differentiation who underwent EUS-TA. All patients underwent specimen evaluation by rapid onsite evaluation (ROSE). RESULTS: EUS-TA led to a diagnosis of pNETs in 77 patients (69.4%) and tumors other than pNETs in 22 patients (19.8%). The histopathological diagnostic accuracy of EUS-TA was 89.2% (99/111) overall, 94.3% (50/53) for 10-20 mm lesions, and 84.5% (49/58) for ≤ 10 mm lesions, with no significant difference in diagnostic accuracy (p = 0.13). The Ki-67 index was measurable in all patients with a histopathological diagnosis of pNETs. Among 49 patients with a diagnosis of pNETs who were followed up, one patient (2.0%) showed tumor enlargement. CONCLUSIONS: EUS-TA for solid pancreatic lesions ≤ 20 mm suspected as pNETs or requiring differentiation is safe and has adequate histopathological diagnostic accuracy, suggesting that follow-up observations of pNETs with a histological pathologic diagnosis are acceptable in the short term.

Endoscopic Ultrasound-Guided Tissue Acquisition of Pancreaticobiliary Cancer Aiming for a Comprehensive Genome Profile.

In recent years, cancer genomic medicine centered on comprehensive genome profile (CGP) analysis has become widely used in the field of pancreatic cancer. Endoscopic ultrasound-guided tissue acquisition (EUS-TA) has played an important role in pancreatic cancer, and recently, more EUS-TA tissue samples are considered for CGP analysis. Differences exist between the Oncoguide NCC Oncopanel System and Foundation One CDx Cancer Genome Profile, which are CGP tests approved by insurance programs in Japan, including the analysis criteria, optimal needle selection for meeting these criteria, and puncture target. It is important to understand not only the specimen collection factors, but also the specimen processing factors that can increase the success rate of CGP testing. Furthermore, cancer genome medicine is expected to enter an era of increasing turbulence in the future, and endoscopists need to respond flexibly to these changes. Herein, we review the current status of cancer genome medicine in pancreatic and biliary tract cancers and cancer gene panel testing using EUS-TA.

Comparison of the hybrid and partial stent-in-stent method for endoscopic three-segment drainage for unresectable malignant hilar biliary obstruction.

Background and study aims The clinical outcome of the new hybrid drainage method for unresectable malignant hilar biliary obstruction (UMHBO) has not yet been compared with that of the partial stent-in-stent (PSIS) method with three or more stents. Patients and methods Patients with UMHBO underwent drainage of three segments using the hybrid or PSIS method. The clinical outcomes of both methods were compared retrospectively. Results Overall, 54 patients underwent the hybrid (n = 31) or PSIS (n = 23) method of drainage with three or more stents for UMHBO. There were no significant differences in the technical success rate (hybrid vs. PSIS, 87.1 % vs. 87 %), clinical success rate according to per-protocol analysis (81.5 % vs. 70 %), early adverse events rate (14.8 % vs. 10%), late adverse events rate (7.4 % vs. 0 %), and technical success rate of the endoscopic transpapillary reintervention (90.9 % vs. 100 %). Time to recurrent biliary obstruction (TRBO) of the hybrid and PSIS methods was 178 and 231 days, respectively, with no significant difference ( P  = 0.354). Conclusions The choice between the two methods should be made at the physician's discretion.

Diagnostic Ability of Endoscopic Ultrasound-Guided Tissue Acquisition Using 19-Gauge Fine-Needle Biopsy Needle for Abdominal Lesions.

Attempts at performing endoscopic ultrasound-guided tissue acquisition (EUS-TA) with a 19G needle are increasing because histological diagnosis and comprehensive genomic profiling are a necessity. However, the diagnostic ability of the 19G fine-needle biopsy (FNB) needle, especially the third-generation FNB needle, is unclear and has been retrospectively reviewed. The 19G TopGain needle was used in 147 patients and 160 lesions between September 2020 and December 2021. The technical success rate of the biopsies was 99.4% (159/160). The early adverse event rate was 4.1% (6/147), and moderate or severe adverse event rate occurrence was 2.0% (3/147). The sensitivity, specificity, and accuracy of the 19G TopGain needle for 157 lesions with a confirmed diagnosis were 96.7%, 100%, and 96.8%, respectively. Rescue EUS-TA using the 19G TopGain needle was performed for nine lesions, and a successful diagnosis was made in six of these lesions (66.7%). The diagnostic ability of EUS-TA using the third-generation 19G TopGain needle was favorable. However, the use of 19G FNB needles may increase adverse events. Therefore, EUS-TA with a 19G FNB needle is mainly indicated in lesions where comprehensive genomic profiling may be necessary or the diagnosis could not be determined via EUS-TA using the 22G needle.

Usefulness of a laser-cut covered metal stent with a 7F delivery sheath in endoscopic ultrasound-guided biliary drainage without fistula dilation.

Background and study aims Recently, the utility of endoscopic ultrasound-guided intervention without fistula dilation (EUS-IV WoD) has been reported to prevent adverse events. We clinically evaluated cases in which EUS-IV WoD was attempted using a novel self-expandable metallic stent (SEMS); this is a fully covered, laser-cut SEMS that has a tapered and stiff tip specifically designed for a 0.025-inch guidewire and a relatively thin, 7F delivery system. Patients and methods We retrospectively evaluated cases wherein EUS-IV WoD was attempted using the novel SEMS between March and December 2021. Results Treatment of 11 patients by EUS-IV WoD with the novel SEMS was attempted. The technical success rate for EUS-IV was 100 % and the clinical success rate was 100 %; the success rate for EUS-IV WoD was 72.8 %. Of these, the procedural success rate for EUS-IV WoD was 100 % in EUS-biliary drainage (BD) and 57.1 % in non-EUS-BD. Early adverse events were observed in 27.3 % of patients (3/11): mild abdominal pain in two patients and moderate bleeding in one patient. The abdominal pain cases were both cases of EUS-IV WoD failure and required fistula dilation. Conclusions The novel stent may be useful for EUS-IV WoD, especially in EUS-BD.

Fine-needle biopsy with 19G needle is effective in combination with endoscopic ultrasound-guided tissue acquisition for genomic profiling of unresectable pancreatic cancer.

OBJECTIVES: Comprehensive genomic profiling (CGP) has been approved in Japan since June 2019, enabling mutation-specific therapy. Although tissue sampling via endoscopic ultrasound-guided tissue acquisition (EUS-TA) is standard in pancreatic cancer, reports on obtaining appropriate samples for CGP, especially for the OncoGuide NCC Oncopanel System (NOP) and FoundationOne CDx (FOne), are lacking. Therefore, we investigated the success rate and factors related to appropriate EUS-TA sampling for CGP analysis suitability in unresectable pancreatic ductal adenocarcinoma (UR-PDAC). METHODS: Participants comprised 150 UR-PDAC patients who underwent EUS-TA and tumor sample evaluation for CGP analysis suitability between June 2019 and December 2021. The proportion of patients meeting the criteria was evaluated considering tumor size, puncture lesion, presence of metastasis, type and size of puncture needle, suction method, number of punctures, and puncture route. RESULTS: In total, 39.2% (60/153) of samples met NOP analysis suitability criteria and 0% met FOne analysis suitability criteria. The suitability rate was significantly higher with 19G fine-needle biopsy (FNB) (56.0%; 42/75) than with 22G FNB (32.6%; 14/43) and 22G fine-needle aspiration (11.4%; 4/35). Nineteen-gauge needle (odds ratio [OR] 2.53; 95% confidence interval [CI] 1.15-5.57; P = 0.021) and FNB (OR 3.57; 95% CI 1.05-12.20; P = 0.041) were independent factors contributing to NOP analysis suitability. Among 30 patients who underwent actual NOP analysis, the analysis success rate was 100% (30/30). CONCLUSION: In sample collection via EUS-TA, 19G and FNB needles contribute to NOP analysis suitability.

Proportion of unresectable pancreatic cancer specimens obtained by endoscopic ultrasound-guided tissue acquisition meeting the OncoGuide™ NCC Oncopanel System analysis suitability criteria: a single-arm, phase II clinical trial.

BACKGROUND: There are limited studies on the results of comprehensive genomic profiling testing for pancreatic cancer tissue specimens by endoscopic ultrasound-guided tissue acquisition (EUS-TA). This study aimed to evaluate the proportion of specimens obtained by EUS-TA using a 19-gauge (G) fine-needle biopsy (FNB) needle for unresectable pancreatic cancer (UR-PC) that met the OncoGuide™ NCC Oncopanel System (NOP) analysis suitability criteria. METHODS: In this single-arm, prospective, phase II study, EUS-TA was performed using a 19G FNB biopsy needle in patients with suspected UR-PC based on a contrast-enhanced computed tomography scan. The primary endpoint was the proportion of patients who met the NOP analysis suitability criteria, with a threshold, expected value, α-error, and power of 40%, 70%, 0.025, and 0.9, respectively, and the planned number of enrolled patients was 33. The NOP analysis suitability criteria were defined as tumor cell content ≥ 20% and tissue size ≥ 4 mm2. RESULTS: Thirty-three patients were enrolled. The procedural success rate was 100%, and the cytodiagnosis of class V was observed in all patients. The proportion of patients meeting the NOP analysis suitability criteria was 63.6% (95% CI 47.22-80.05), which satisfied the predefined criteria to be considered valid. Adverse events occurred in 9.0% of the patients. CONCLUSIONS: The proportion of patients with UR-PC who met the NOP analysis suitability criteria for EUS-TA using a 19G FNB needle was effective for achieving the primary endpoint, making it a valid test method. Adverse events occurred at a higher rate than that previously reported.

Endoscopic ultrasound-guided choledochoduodenostomy without fistula dilation using a stent with a 5.9-Fr delivery system: Comparison to a conventional procedure with fistula dilation.

Objectives: To evaluate the feasibility and safety of endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) without fistula dilation using a novel self-expandable metal stent (SEMS). Methods: This retrospective study examined patients who underwent EUS-CDS for malignant distal biliary obstruction between October 2017 and May 2021 at the National Cancer Center, Japan. The primary outcome was a technical success without fistula dilation. Secondary outcomes were the overall technical success, clinical success, adverse events (AEs), procedure time, recurrent biliary obstruction (RBO), and time to RBO (TRBO). Results: Forty-one patients were enrolled; 31 patients underwent EUS-CDS with fistula dilation using a conventional SEMS with 7.5-8.5-Fr delivery system (conventional SEMS group), and 10 patients underwent EUS-CDS without fistula dilation using the novel SEMS with a 5.9-Fr delivery system (novel SEMS group). In the novel SEMS group, the rate of technical success without fistula dilation was 90%. There were no differences in overall technical success (100% vs. 97%, p = 1.00), clinical success (80% vs. 90%, p = 0.58), and overall AEs (10% vs. 23%, p = 0.65) rates between the novel and conventional SEMS groups. In the novel SEMS group, no early AEs were observed and no bile leakage into the abdominal cavity was observed on the computed tomography scan after the procedure. The median procedure time was significantly shorter in the novel SEMS group (17 min vs. 24 min, p = 0.03). RBO and median TRBO did not differ between the 2 groups. Conclusions: EUS-CDS without fistula dilation using the novel SEMS with a 5.9-Fr delivery system is technically feasible, straightforward, quick, and safe.

A novel partially covered metallic stent with a 20-mm long distal bare portion for EUS-guided hepaticogastrostomy.

Video 1EUS-guided hepaticogastrostomy with a novel partially covered self-expandable metallic stent for a patient with biliary obstruction owing to gallbladder cancer.