Safety of biliary drainage with 6-mm metallic stent for preoperative obstructive jaundice in pancreatic cancer: PURPLE SIX STUDY.

BACKGROUND AND AIM: The 10-mm self-expandable metal stent (SEMS) is the standard for endoscopic transpapillary biliary drainage before pancreatic cancer surgery. However, the efficacy of stents thinner than 10 mm has not been adequately validated. Therefore, we aimed to evaluate the safety of a 6-mm fully covered SEMS (FCSEMS) for distal malignant biliary obstruction (DMBO) during preoperative chemotherapy for pancreatic cancer. METHODS: This was a single-arm, multicenter, prospective phase II study of endoscopic transpapillary initial biliary drainage for DMBO before pancreatic cancer surgery. The primary endpoint was stent-related adverse events, and the key secondary endpoint was the non-recurrent biliary obstruction (non-RBO) rate during the observation period for both resectable (R) and borderline resectable (BR) pancreatic cancers. RESULTS: The study enrolled 33 patients, among whom 32 received the study treatment. There were 23 and 9 cases of R and BR pancreatic cancers, respectively. The technical and clinical success rates were 97.0% and 90.1%, respectively. The stent-related adverse event rate was 3.1% (n = 1, acute pancreatitis) (95% confidential interval, 0.00-16.2), which met the criteria to be considered safe. The overall non-RBO rate during the observation period (median 96 days) was 78.1% (82.6% and 66.7% for R and BR pancreatic cancer cases, respectively). CONCLUSIONS: The 6-mm FCSEMS is an extremely safe metallic stent with a low stent-related adverse event rate of 3.1% for preoperative biliary drainage in pancreatic cancer. It is considered the optimal stent for preoperative biliary drainage in terms of the non-RBO rate. UMIN Clinical Trial Registry (UMIN-CTR 000041704).

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.

Clinical features of germline BRCA1/2 or ATM pathogenic variant positive pancreatic cancer in Japan.

BACKGROUND: There has been increasing interest into the role of germline BRCA1/2 pathogenic variants (gBRCA PV) and gATM PV and likely PV (PV and LPV; PV + LPV) in the carcinogenesis and treatment of pancreatic cancer (PC), but the clinical features have not been well described. METHODS: Patients with confirmed gBRCA PV and gATM PV + LPV PC treated at our hospital between April 2016 and December 2021, were retrospectively evaluated for clinical characteristics and outcomes. RESULTS: Twenty-two patients harbored gBRCA PV and three patients harbored gATM PV + LPV. Of the gBRCA PV patients, 81.8 % received platinum-based chemotherapy with favorable treatment outcomes with an objective response rate of 50.0 % (95 % CI: 23.0-77.0), median progression free survival (PFS) of 334 days, and median overall survival (OS) of 926 days from the initiation of first-line chemotherapy. The annual number of patients with gBRCA PV was two patients per year before January 2021 (when BRACAnalysis became available in Japan), and ten patients during the 10 months thereafter. Four patients (20 %) with gBRCA PV developed soft-tissue metastasis with progression. Two patients with gATM PV + LPV received platinum-based chemotherapy and the best response of those patients was partial response and stable disease and their OS from the initiation of first-line chemotherapy was 1192 and 989 days, and PFS was 579 and 140 days, respectively. CONCLUSION: The diagnosis of gBRCA PV-positive PC has increased revealed in recent years. These tumors appear to be sensitive to platinum-based chemotherapy, with long term survival observed in gATM PV + LPV-positive patients.

Endoscopic ultrasound-assisted rendezvous by transgastric approach in malignant extrahepatic bile duct stricture.

Endoscopic ultrasonography rendezvous (EUS-RV) is useful in cases of difficult deep biliary cannulation. However, in malignant extrahepatic bile duct strictures (MEHBDS), transduodenal routes are challenging and the transgastric approach often requires fistula dilation. We report a case of resectable MEHBDS in which transgastric puncture from the antrum of the stomach as EUS-RV was useful.

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.

A novel endoscopic technique using fully covered self-expandable metallic stents for benign strictures after hepaticojejunostomy: the saddle-cross technique (with video).

BACKGROUND: In recent years, the number of patients with hepaticojejunostomy anastomotic strictures has increased. Balloon dilation and placement of multiple plastic stents have proven effective for hepaticojejunostomy anastomotic strictures. However, for refractory strictures, there is often a need for repeated endoscopic procedures within a short period. This study aimed to assess the efficacy and safety of the new saddle-cross technique, which uses two fully covered self-expandable metallic stents. METHODS: This was a retrospective analysis of 20 patients with benign hepaticojejunostomy anastomotic strictures who underwent placement of two fully covered self-expandable metallic stents at the National Cancer Center, Japan, from November 2017 to June 2021. RESULTS: The technical and clinical success rates were 100% (20/20). The median time of the procedure was 61 (range 25-122) min. The scheduled stent removal rate was 70% (14/20). Spontaneous dislodgement of the stent was observed on computed tomography in five patients (25.0%). The non-restenosis rate 12 months after the saddle-cross technique was 88.2% (15/17). Procedure-related early adverse events included mild ascending cholangitis in three patients (15.0%) and sepsis in one patient (5.0%). Procedure-related late adverse events included mild ascending cholangitis in three patients (15.0%) and bile duct hyperplasia in one patient (5.0%). CONCLUSIONS: The saddle-cross technique performed using two fully covered self-expandable metallic stents resulted in promising long-term stricture resolution with a high technical success rate. Based on these findings, the saddle-cross method can be considered an option for the standard procedure for benign hepaticojejunostomy anastomotic strictures.

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.

Use of endoscopic ultrasound-guided biliary drainage as a rescue of re-intervention after the placement of multiple metallic stents for malignant hilar biliary obstruction.

BACKGROUND/PURPOSE: Endoscopic transpapillary re-intervention (ETP-RI) after multiple self-expandable metallic stent (SEMS) placement for unresectable malignant hilar biliary obstruction (MHBO) is challenging, but endoscopic ultrasound-guided biliary drainage (EUS-BD) could be an alternative following failed ETP-RI. We investigated appropriate re-intervention (RI) methods in MHBO after multiple SEMS placement and evaluated RI with EUS-BD (EUS-RI) benefits following ETP-RI failure. METHODS: Patients requiring RI after multiple SEMS placement for MHBO between October 2017 and April 2021 were enrolled. Patients' characteristics, metallic-stent type, stent-placement configuration, overall survival, stent patency, re-intervention results, and re-intervention technical and clinical success rates were reviewed. RESULTS: Forty-nine patients underwent ETP-RI for MHBO. ETP-RI's technical success rate was 69.4%. Of 15 failed ETP-RI cases, all underwent EUS-RI, achieving technical and clinical success rates of 86.7% and 100%, respectively. Time to recurrent biliary obstruction (TRBO) after RI was significantly different between EUS-RI and ETP-RI (212 vs 84 days; P = .01). On multivariate analysis, EUS-RI was the only factor associated with TRBO (odds ratio: 4.48; 95% confidence interval: 1.01-19.91; P = .04). Acute pancreatitis and bile peritonitis were present in 6.1% of ETP-RI and 13.3% of EUS-RI cases, respectively; both improved conservatively. CONCLUSIONS: EUS-RI was effective and safe in difficult ETP-RI cases after multiple SEMS placement for MHBO.