LOAd703, an oncolytic virus-based immunostimulatory gene therapy, combined with chemotherapy for unresectable or metastatic pancreatic cancer (LOKON001): results from arm 1 of a non-randomised, single-centre, phase 1/2 study.

BACKGROUND: Pancreatic ductal adenocarcinoma is characterised by low immunogenicity and an immunosuppressive tumour microenvironment. LOAd703, an oncolytic adenovirus with transgenes encoding TMZ-CD40L and 4-1BBL, lyses cancer cells selectively, activates cytotoxic T cells, and induces tumour regression in preclinical models. The aim of this study was to evaluate the safety and feasibility of combining LOAd703 with chemotherapy for advanced pancreatic ductal adenocarcinoma. METHODS: LOKON001 was a non-randomised, phase 1/2 study conducted at the Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA, and consisted of two arms conducted sequentially; the results of arm 1 are presented here. In arm 1, patients 18 years or older with previously treated or treatment-naive unresectable or metastatic pancreatic ductal adenocarcinoma were treated with standard 28-day cycles of intravenous nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 (up to 12 cycles) and intratumoural injections of LOAd703 every 2 weeks. Patients were assigned using Bayesian optimal interval design to receive 500 µL of LOAd703 at 5 × 1010 (dose 1), 1 × 1011 (dose 2), or 5 × 1011 (dose 3) viral particles per injection, injected endoscopically or percutaneously into the pancreatic tumour or a metastasis for six injections. The primary endpoints were safety and treatment-emergent immune response in patients who received at least one dose of LOAd703, and antitumour activity was a secondary endpoint. This study was registered with ClinicalTrials.gov, NCT02705196, arm 2 is ongoing and open to new participants. FINDINGS: Between Dec 2, 2016, and Oct 17, 2019, 23 patients were assessed for eligibility, leading to 22 patients being enrolled. One patient withdrew consent, resulting in 21 patients (13 [62%] men and eight [38%] women) assigned to a dose group (three to dose 1, four to dose 2, and 14 to dose 3). 21 patients were evaluable for safety. Median follow-up time was 6 months (IQR 4-10), and data cutoff was Jan 5, 2023. The most common treatment-emergent adverse events overall were anaemia (96 [8%] of 1237 events), lymphopenia (86 [7%] events), hyperglycaemia (70 [6%] events), leukopenia (63 [5%] events), hypertension (62 [5%] events), and hypoalbuminaemia (61 [5%] events). The most common adverse events attributed to LOAd703 were fever (14 [67%] of 21 patients), fatigue (eight [38%]), chills (seven [33%]), and elevated liver enzymes (alanine aminotransferase in five [24%], alkaline phosphatase in four [19%], and aspartate aminotransferase in four [19%]), all of which were grade 1-2, except for a transient grade 3 aminotransferase elevation occurring at dose 3. A maximum tolerated dose was not reached, thereby establishing dose 3 as the highest-evaluated safe dose when combined with nab-paclitaxel plus gemcitabine. Proportions of CD8+ effector memory cells and adenovirus-specific T cells increased after LOAd703 injections in 15 (94%) of 16 patients for whom T-cell assays could be performed. Eight (44%, 95% CI 25-66) of 18 patients evaluable for activity had an objective response. INTERPRETATION: Combining LOAd703 with nab-paclitaxel plus gemcitabine in patients with advanced pancreatic ductal adenocarcinoma was feasible and safe. To build upon this novel chemoimmunotherapeutic approach, arm 2 of LOKON001, which combines LOAd703, nab-paclitaxel plus gemcitabine, and atezolizumab, is ongoing. FUNDING: Lokon Pharma, the Swedish Cancer Society, and the Swedish Research Council.

Safety and efficacy of a novel suturing device for closure of large defects after endoscopic submucosal dissection (with video).

BACKGROUND AND AIMS: Endoscopic suturing enables full closure of large defects after endoscopic submucosal dissection (ESD). However, its use is limited by the need for a double-channel endoscope. A novel closure system, the OverStitch Sx (Apollo Endosurgery, Austin, Tex, USA), compatible with any single-channel endoscope, was introduced to address these shortcomings. The aim of this study was to assess the safety and feasibility of OverStitch Sx for the closure of large defects after ESD. METHODS: This is a prospective single-center feasibility study of patients who underwent closure of large defects after ESD using the OverStitch Sx system. Main outcomes of the study are technical and clinical success, same-day discharge rate, and adverse event rate. RESULTS: Thirty-three patients were enrolled. The mean diameter of included lesions was 5.38 ± 2.52 cm. The defect occupied ≥50% of the lumen circumference in 70% of the cases. En-bloc resection, R0 resection, and curative resection were achieved in 97%, 87.5%, and 78.8% of patients, respectively. Technical success and clinical success were seen in 93.9% and 90.9% of the cases, respectively. Same-day hospital discharge was achieved in 77.4% of patients. Total adverse event rate was 35.7%, including delayed bleeding in 1 patient after rectal ESD that was managed conservatively, self-resolving rectal pain in 7 patients, rectal stricture requiring dilation in 1 patient, and temporary dysphagia in 1 patient. No immediate or delayed perforation was reported. CONCLUSIONS: OverStitch Sx enabled safe and effective closure of large defects after ESD. Future trials are needed to determine its superiority over OverStitch for the closure of defects in challenging locations. (Clinical trial registration number: NCT04361227.).

Pancreatic parenchymal changes seen on endoscopic ultrasound are dynamic in the setting of fatty pancreas: A short-term follow-up study.

OBJECTIVES: The impact of fatty pancreas on pancreatic parenchymal changes is unclear. The aim of this study is to assess parenchymal alterations over time in patients with fatty pancreas (FP). METHODS: This is a retrospective study (2014-2021) of patients with FP identified on endoscopic ultrasound (EUS). Subjects with follow up imaging studies including Computed Tomography (CT) scan, Magnetic Resonance Imaging (MRI), and EUS at least two years after the initial EUS were included. RESULTS: A total of 39 patients with a mean age of 51.21 ± 12.34 years were included. Mean initial weight was 80.17 ± 17.75 kg. Diabetes, hepatic steatosis, and EPI were present in 15%, 46% and 33% of the patients at baseline, respectively. In 25 patients with available follow up EUS over 2.4 ± 0.76 years, 16% progressed to chronic pancreatitis (CP) and 24% had progressive parenchymal changes without meeting the criteria for CP. One patient progressed from focal to diffuse FP, while one patient had resolution of FP. In multivariate analysis, progressive parenchymal changes on EUS were associated with an increase in weight over time (p-value 0.04), independent of the effects of gender, alcohol, or tobacco. CONCLUSION: Progressive parenchymal changes were noted in 44%. Our result suggests that FP is a dynamic process with the possibility of progression or regression over time.

Differential Metabolomic Signatures in Patients with Weight Regain and Sustained Weight Loss After Gastric Bypass Surgery: A Pilot Study.

BACKGROUND: While Roux-en-Y gastric bypass (RYGB) is one of the most effective and durable treatment options for obesity and its comorbidities, it is complicated by long-term weight regain in over 20% of patients. AIMS: We sought to determine the metabolite signatures of serum samples of patients with weight regain (RYGB-WR) after RYGB and features distinguishing these patients from patients with sustained weight loss (RYGB-SWL). METHODS: We prospectively analyzed serum samples from 21 RYGB-WR patients, 14 RYGB-SWL patients, and 11 unoperated controls. The main outcome measure was their serum metabolite profile. RESULTS: Weight regain after RYGB was associated with a unique serum metabolomic fingerprint. Most of the statistically different metabolites were involved in amino acid metabolism, one-carbon metabolism, and related nucleotide metabolism. A principal component analysis identified groups of metabolites that correlate with weight regain. Specifically, weight regain was associated with lower serum levels of metabolites related to the serine, glycine and threonine pathway, phenylalanine metabolism, tricyclic acid cycle, alanine and glutamate metabolism, and higher levels of other amino acids. CONCLUSIONS: Weight regain after RYGB is associated with unique serum metabolite signatures. Metabolite profiling may eventually help us to identify markers that could differentiate the patients who will regain weight versus those who will likely sustain weight loss.

Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography, From Training Through Independent Practice.

BACKGROUND & AIMS: It is unclear whether participation in competency-based fellowship programs for endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) results in high-quality care in independent practice. We measured quality indicator (QI) adherence during the first year of independent practice among physicians who completed endoscopic training with a systematic assessment of competence. METHODS: We performed a prospective multicenter cohort study of invited participants from 62 training programs. In phase 1, 24 advanced endoscopy trainees (AETs), from 20 programs, were assessed using a validated competence assessment tool. We used a comprehensive data collection and reporting system to create learning curves using cumulative sum analysis that were shared with AETs and trainers quarterly. In phase 2, participating AETs entered data into a database pertaining to every EUS and ERCP examination during their first year of independent practice, anchored by key QIs. RESULTS: By the end of training, most AETs had achieved overall technical competence (EUS 91.7%, ERCP 73.9%) and cognitive competence (EUS 91.7%, ERCP 94.1%). In phase 2 of the study, 22 AETs (91.6%) participated and completed a median of 136 EUS examinations per AET and 116 ERCP examinations per AET. Most AETs met the performance thresholds for QIs in EUS (including 94.4% diagnostic rate of adequate samples and 83.8% diagnostic yield of malignancy in pancreatic masses) and ERCP (94.9% overall cannulation rate). CONCLUSIONS: In this prospective multicenter study, we found that although competence cannot be confirmed for all AETs at the end of training, most meet QI thresholds for EUS and ERCP at the end of their first year of independent practice. This finding affirms the effectiveness of training programs. Clinicaltrials.gov ID NCT02509416.

Setting minimum standards for training in EUS and ERCP: results from a prospective multicenter study evaluating learning curves and competence among advanced endoscopy trainees.

BACKGROUND AND AIMS: Minimum EUS and ERCP volumes that should be offered per trainee in "high quality" advanced endoscopy training programs (AETPs) are not established. We aimed to define the number of procedures required by an "average" advanced endoscopy trainee (AET) to achieve competence in technical and cognitive EUS and ERCP tasks to help structure AETPs. METHODS: American Society for Gastrointestinal Endoscopy (ASGE)-recognized AETPs were invited to participate; AETs were graded on every fifth EUS and ERCP examination using a validated tool. Grading for each skill was done using a 4-point scoring system, and learning curves using cumulative sum analysis for overall, technical, and cognitive components of EUS and ERCP were shared with AETs and trainers quarterly. Generalized linear mixed-effects models with a random intercept for each AET were used to generate aggregate learning curves, allowing us to use data from all AETs to estimate the average learning experience for trainees. RESULTS: Among 62 invited AETPs, 37 AETs from 32 AETPs participated. Most AETs reported hands-on EUS (52%, median 20 cases) and ERCP (68%, median 50 cases) experience before starting an AETP. The median number of EUS and ERCPs performed per AET was 400 (range, 200-750) and 361 (range, 250-650), respectively. Overall, 2616 examinations were graded (EUS, 1277; ERCP-biliary, 1143; pancreatic, 196). Most graded EUS examinations were performed for pancreatobiliary indications (69.9%) and ERCP examinations for ASGE biliary grade of difficulty 1 (72.1%). The average AET achieved competence in core EUS and ERCP skills at approximately 225 and 250 cases, respectively. However, overall technical competence was achieved for grade 2 ERCP at about 300 cases. CONCLUSION: The thresholds provided for an average AET to achieve competence in EUS and ERCP may be used by the ASGE and AETPs in establishing the minimal standards for case volume exposure for AETs during their training. (Clinical trial registration number: NCT02509416.).

EUS-guided intrahepatic portosystemic shunt with direct portal pressure measurements: a novel alternative to transjugular intrahepatic portosystemic shunting.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunting involves the creation of a low-resistance channel between the portal vein (PV) and the hepatic vein (HV), and is routinely performed under angiography. The aims were to evaluate (1) safety and technical feasibility; (2) procedural duration; and (3) subjective workload assessment of EUS-guided intrahepatic portosystemic shunt (EIPS). METHODS: Five Yorkshire pigs were used in the study. The HV or inferior vena cava (IVC) was identified using a linear-array echoendoscope and accessed with a 19-G FNA needle preloaded with a digital pressure wire. Mean pressure was recorded. The needle was advanced into the PV, where pressure measurements were again taken, and ultimately exchanged over a guidewire. A lumen-apposing metal stent was deployed under EUS and fluoroscopic guidance, with distal and proximal ends positioned inside the PV and HV (IVC), respectively. Dilation was performed, and pressure measurements repeated. The National Aeronautics and Space Administration (NASA) Task Load Index (TLI) was scored. Animals survived 2 weeks before necropsy. RESULTS: EIPS was successful in 5 out of 5 pigs. Mean time required for EUS identification, needle access, pressure measurement, and stent placement was 43 (31-55) minutes. NASA TLI scores revealed moderate workload. Mean baseline pressure measurements were PV 7.0 (5-9) and HV/IVC 5.0 (3-7) mm Hg and PV 6.3 (5-7) and HV/IVC 6.0 (4-7) mm Hg after. All animals survived 2 weeks. No bleeding was seen on necropsy. CONCLUSIONS: This study demonstrates the technical feasibility of EIPS using LAMS, with direct portal pressure measurement, in a survival model. In addition, the procedure was performed quickly with moderate technical demand.

Novel fork-tip needles versus standard needles for EUS-guided tissue acquisition from solid masses of the upper GI tract: a matched cohort study.

BACKGROUND: There are very few available data on the novel SharkCore™ needles for EUS-FNB. AIM: Comparison of the performance of the SharkCore™ needles with the standard EUS-FNA needles for the diagnosis of solid upper GI masses. PATIENTS AND METHODS: Single-center, retrospective cohort study in an academic tertiary referral hospital. Patients were matched 1:1 for the site of the lesion and the presence or absence of rapid on-site evaluation (ROSE). RESULTS: A total of 102 patients were included. There was no statistically significant difference in the mean number of passes (3.3 ± 1.3 versus 3.4 ± 1.5; p = .89). Similar results were observed at the subgroup with ROSE (4.3 ± 1.3 versus 3.7 ± 1.5; p = .26). More histological specimens were obtained with the SharkCore™ needles compared to standard needles (59 versus 5%; p < .001). Diagnostic test characteristics were not significantly different (sensitivity: 91.5 versus 85.7; specificity: 100 versus 100%; accuracy: 92.2 versus 85.4% for SharkCore™ versus standard needles, p > .05 in all cases). At multivariable analysis, there was no statistically significant difference in the mean number of passes in all patients (p = .23) and in the ROSE subgroup (p = .66). However, the SharkCore™ needle obtained significantly more histological material than the standard needle (odds ratio 66; 95% confidence interval: 11.8, 375.8, p < .001). There was no significant difference in complication rates (p = .5). LIMITATIONS: Retrospective study, single-center. CONCLUSION: The SharkCore needles were similar to standard FNA needles in terms of the number of passes to reach diagnosis, but obtained significantly more histological specimen.

Preclinical endoscopic training using a part-task simulator: learning curve assessment and determination of threshold score for advancement to clinical endoscopy.

BACKGROUND: Preclinical simulator training has the potential to decrease endoscopic procedure time and patient discomfort. This study aims to characterize the learning curve of endoscopic novices in a part-task simulator and propose a threshold score for advancement to initial clinical cases. METHODS: Twenty novices with no prior endoscopic experience underwent repeated endoscopic simulator sessions using the part-task simulator. Simulator scores were collected; their inverse was averaged and fit to an exponential curve. The incremental improvement after each session was calculated. Plateau was defined as the session after which incremental improvement in simulator score model was less than 5%. Additionally, all participants filled out questionnaires regarding simulator experience after sessions 1, 5, 10, 15, and 20. A visual analog scale and NASA task load index were used to assess levels of comfort and demand. RESULTS: Twenty novices underwent 400 simulator sessions. Mean simulator scores at sessions 1, 5, 10, 15, and 20 were 78.5 ± 5.95, 176.5 ± 17.7, 275.55 ± 23.56, 347 ± 26.49, and 441.11 ± 38.14. The best fit exponential model was [time/score] = 26.1 × [session #]-0.615; r 2 = 0.99. This corresponded to an incremental improvement in score of 35% after the first session, 22% after the second, 16% after the third and so on. Incremental improvement dropped below 5% after the 12th session corresponding to the predicted score of 265. Simulator training was related to higher comfort maneuvering an endoscope and increased readiness for supervised clinical endoscopy, both plateauing between sessions 10 and 15. Mental demand, physical demand, and frustration levels decreased with increased simulator training. CONCLUSION: Preclinical training using an endoscopic part-task simulator appears to increase comfort level and decrease mental and physical demand associated with endoscopy. Based on a rigorous model, we recommend that novices complete a minimum of 12 training sessions and obtain a simulator score of at least 265 to be best prepared for clinical endoscopy.

Safety and efficacy of fistula closure by endoscopic suturing: a multi-center study.

Background and aim: Endoscopic closure of fistulas is desirable but remains a challenge, especially for gastrogastric fistulas. The aim of this study was to assess the success rate for the closure of gastrointestinal fistulas using an endoscopic suturing device. Patients and methods: Electronic records at three medical centers were reviewed to identify patients who underwent sutured fistula closure as recorded on a central database. Demographic details, clinical variables, and details of the endoscopic procedure were recorded. Results: A total of 56 patients (mean age 54 ± 12.7 years) underwent fistula closure. Gastrogastric fistulas were most common (n = 29; 51.8 %). Sixteen patients (28.6 %) had undergone previous failed attempts at closure. Immediate success was universal (n = 56; 100 %). Thirteen patients had persistent closure without any need for further therapies, while 17 underwent additional endoscopic procedures, with successful closure in 4 /17. Only one patient had abdominal pain requiring hospital admission. Conclusion: Sutured closure of fistulas in a single session is safe and can be expected, even in what are known to be challenging cases. Sequential closure for recurrences is sometimes successful in the longer term.

Facilitating endoscopic submucosal dissection: the suture-pulley method significantly improves procedure time and minimizes technical difficulty compared with conventional technique: an ex vivo study (with video).

BACKGROUND: The lack of countertraction in endoscopic submucosal dissection (ESD) results in increased technical demand and procedure time. Although the suture-pulley method for countertraction has been reported, its effectiveness compared with the traditional ESD technique remains unclear. OBJECTIVE: To objectively analyze efficacy of countertraction using the suture-pulley method for ESD. DESIGN: Prospective ex vivo animal study. SETTING: Animal laboratory. INTERVENTIONS: Twenty simulated gastric lesions were created in porcine stomachs by using a standard circular template 30 mm in diameter. In the control arm (n = 10), ESD was performed by using the standard technique. In the suture-pulley arm (N = 10), a circumferential incision was made, and an endoscopic suturing device was used to place the suture pulley. MAIN OUTCOME MEASUREMENTS: The primary outcome of this study was total procedure time. RESULTS: The median total procedure time with the suture-pulley method was significantly shorter than the traditional ESD technique (median, 25% to 75%, interquartile range [IQR]: 531 seconds [474.3-549.3 seconds] vs 845 seconds [656.3-1547.5 seconds], P < .001). The median time (IQR) for suture-pulley placement was 160.5 seconds (150.0-168.8 seconds). Although there was a significantly longer procedure time for proximal versus middle/lower stomach lesions with traditional ESD (median, 1601 seconds; IQR, 1547.5-1708.8 seconds vs median, 663 seconds; IQR, 627.5-681.8 seconds; P = .01), there was no significant difference in procedure time for lesions of various locations when using the suture-pulley method. Compared with traditional ESD, the suture-pulley method was less demanding in all categories evaluated by the NASA Task Load Index. LIMITATIONS: Ex vivo study. CONCLUSIONS: The suture-pulley method facilitates direct visualization of the submucosal layer during ESD and significantly reduces procedure time and technical difficulty. In addition, the benefit of the suture-pulley method was seen for both simple and more complicated ESDs.

Closure of refractory gastrocutaneous fistula with endoscopically guided percutaneous suturing with the use of miniature biopsy forceps.

Video 1Closure of a refractory gastrocutaneous fistula with endoscopically guided percutaneous suturing with the use of miniature biopsy forceps.

Relief of malignant gastric outlet obstruction with lumen-apposing metallic stent-assisted percutaneous endoscopic gastrostomy tube after Roux-en-Y gastric bypass.

Video 1Xxx.

Endoscopic vacuum therapy for treatment of spontaneous and iatrogenic upper gastrointestinal defects.

BACKGROUND/AIMS: Endoscopic vacuum therapy (EVT) can heal a variety of defects within the gastrointestinal (GI) tract via applying negative pressure, which reduces the defect size, aspirates the infected fluid, and promotes granulation tissue. Here we present our experience with EVT as it relates to both spontaneous and iatrogenic upper GI tract perforations, leaks, and fistulas. METHODS: This retrospective study was conducted at four large hospital centers. All patients who underwent EVT between June 2018 and March 2021 were included. Data on multiple variables were collected, including demographics, defect size and location, number and intervals of EVT exchanges, technical success, and hospital length of stay. Student t-test and the chi-squared test were used to analyze the data. RESULTS: Twenty patients underwent EVT. The most common defect cause was spontaneous esophageal perforation (50%). The most common defect location was the distal esophagus (55%). The success rate was 80%. Seven patients were treated with EVT as the primary closure method. The mean number of exchanges was five with a mean interval of 4.3 days between exchanges. The mean length of hospital stay was 55.8 days. CONCLUSION: EVT is a safe and effective initial management option for esophageal leaks and perforations.

A novel approach to the removal of a silastic band via the peroral endoscopic tunneling-silastic bandectomy technique.

Video 1The peroral endoscopic tunneling-silastic bandectomy technique to remove a silastic band causing a vertical banded gastroplasty stenosis. This method is a viable alternative to surgical removal of foreign bodies outside the gastrointestinal lumen.

Comparison of endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography outcomes using various technical approaches.

Background and study aims Roux-en-Y gastric bypass presents an anatomic challenge for patients needing ERCP. EUS-directed transgastric ERCP (EDGE) offers high clinical success but carries considerable risk of adverse events (AEs) with no standardized technical approach. In our study, we review the safety and efficacy of our various EDGE technical approaches. Patients and methods A retrospective single-center study of all patients who underwent EDGE procedures between February 2018 and November 2019. Primary outcomes included comparing the technical and clinical success, AEs, and lumen-apposing metal stent (LAMS) migration rates per access route (gastrogastric vs jejuno-gastric), number of procedure stages (single-stage vs two-stage), and stent size (15 mm vs 20 mm). Secondary outcomes included LAMS migration characteristics and management. Results Thirty-two EDGE procedures were performed in 29 patients, including 17 single-stage and 15 two-stage procedures, 23 gastrogastric, and nine jejuno-gastric routes, fourteen 15-mm and 17 20-mm LAMS. Overall technical and clinical success rates were 96.9 % and 87.1 %, respectively, without any significant difference between groups. The overall AE rate was (34.4 %) and was significantly lower in the 20-mm LAMS group compared to the 15-mm group (17.6 % vs 57.1 %, P  = 0.03). Compared to two-stage procedures, there was no significant difference in AEs with single-stage procedures (35.3 % vs 33.3 %, P  = 0.33). The LAMS migration rate was (25 %) with no significant difference between groups. Most migrations were around the index procedure and managed endoscopically (62.5 %). Conclusions EDGE offers high clinical success rates but AE rates remain significant. In our series, a 20-mm LAMS resulted in a significantly lower AE rate than the 15-mm LAMS. Large multicenter studies are recommended to identify technical factors leading to an optimal EDGE procedure.

Early phase trial of intracystic injection of large surface area microparticle paclitaxel for treatment of mucinous pancreatic cysts.

Background and study aims Mucinous pancreatic cystic lesions (PCLs) have the potential for malignant transformation, for which the only accepted curative modality is surgery. A novel intracystic therapy with large surface area microparticle paclitaxel (LSAM-PTX) may treat PCLs without local or systemic toxicities. Safety and preliminary efficacy of LSAM-PTX for the treatment of PCLs administered by endoscopic ultrasound-guided fine-needle injection (EUS-FNI) was evaluated. Patients and methods Ten subjects with confirmed PCLs (size > 1.5 cm) received intracystic LSAM-PTX via EUS-FNI at volumes equal to those aspirated from the cyst in sequential cohorts at 6, 10, and 15 mg/mL in a standard "3 + 3" dose-escalation protocol. The highest dose with acceptable safety and tolerability was taken into the confirmatory phase where nine additional subjects received two injections of LSAM-PTX 12 weeks apart. Subjects were followed for 6 months after initial LSAM-PTX treatment for endpoints including: adverse events (AEs), tolerability, pharmacokinetic analysis of systemic paclitaxel drug levels, and change in cyst volume. Results Nineteen subjects completed the study. No dose-limiting toxicities, treatment-related serious AEs, or clinically significant laboratory changes were reported. Systemic paclitaxel concentrations did not exceed 3.5 ng/mL at any timepoint measured and fell below 1 ng/mL by Week 2, supporting the lack of systemic toxicity. By Week 24 a cyst volume reduction (10-78 %) was seen in 70.6 % of subjects. Conclusions Intracystic injection of LSAM-PTX into mucinous PCLs resulted in no significant AEs, a lack of systemic absorption, and resulted in reduction of cyst volume over a 6 month period.