Lauromacrogol, as a sclerosing agent, can induce aseptic inflammation and fibrous tissue proliferation to achieve sclerotherapy. Lauromacrogol is widely used not only for vascular sclerotherapy but also for the treatment of different cystic tumors. To evaluate the efficacy and safety of cystic tumor ablation with different concentrations of lauromacrogol solution in a rat endometriosis model, and explore the advantages and disadvantages of this model in simulating pancreatic cystic neoplasm.

An endometriotic cyst model was established in 50 mature female Sprague-Dawley rats. After 4 weeks, successfully modeled cysts were randomly divided into four groups: group A, in which cyst were injected with normal saline; and groups B to D, in which cyst were injected with 1%, 2%, and 3% lauromacrogol solution, respectively. The rats were then fed for 4 more weeks. The abdominal cavity was opened to observe the morphology of the cyst and the degree of damage to surrounding organs. If the ablation procedure failed, the whole cyst was collected; if the ablation procedure was successful, residual scar tissue was collected. The ratio of ablated epithelial cells to the epithelial layer and the intactness of the lamina propria were observed by low- and high-power microscopy.

After ablation, the cysts in normal saline group showed a maintained hemispherical structure, whereas those in three different concentrations of lauromacrogol solution groups showed a flat scar. The effective rate of each group was statistically different. Pairwise comparison of corrected significance levels using the Bonferroni method showed statistically a significant difference between normal saline group and 1% lauromacrogol solution group, 2% lauromacrogol solution group and 3% lauromacrogol solution group.

According to the morphology and pathology of rat endometriotic cysts after ablation, it can be preliminarily concluded that ablation with 1%, 2%, or 3% lauromacrogol solution is an effective and safe therapeutic option. Rat endometriotic cyst model can simulate pancreatic cystic neoplasms to a certain extent.

Endoscopic ultrasound-guided pancreatic cyst ablation (EUS-PCA) is performed as an alternative to surgical resection in selected patients with pancreatic cystic tumors (PCTs). We aimed to directly compare the long-term outcomes between EUS-PCA and surgery for PCTs.

We reviewed a PCT database to identify patients with unilocular or oligolocular PCTs who underwent EUS-PCA or surgery between January 2004 and July 2019. We performed 1:1 propensity score matching based on potential confounding factors. The primary outcome was long-term morbidities. Secondary outcomes included early (≤14 days) and late (>14 days) major adverse events (MAEs), development of diabetes mellitus, readmission, length of hospital stay, and therapeutic efficacy.

A total of 620 patients (EUS-PCA, n = 310; surgery, n = 310) were selected after propensity score matching. The EUS-PCA group showed a lower 10-year rate of cumulative long-term morbidities (1.6% vs 33.5%; P = .001) as well as lower rates of early MAE (1.0% vs 8.7%; P = .001), late MAE (0.3% vs 5.5%; P = .001), and readmission (1.0% vs 15.2%; P = .001). The EUS-PCA group had a shorter hospital stay (3.5 vs 10.3 d; P = .001) and a lower incidence of diabetes mellitus (2.2% vs 22.8%; P = .001), whereas the surgery group had a higher complete resolution rate (76.5% vs 100%; P = .001) and a lower relapse rate (4.6% vs 0.3%; P = .001).

For select patients with PCTs, EUS-PCA showed superior results to surgery in terms of long-term safety profile and preservation of pancreatic function.

Endoscopic ultrasound (EUS) has rapidly evolved from a diagnostic to a therapeutic tool with applications for various pancreaticobiliary diseases. As part of this evolution, EUS-guided chemoablation for neoplastic pancreatic cysts is developing as a minimally invasive treatment option for appropriately selected mucinous cysts, which can spare patients major resective surgery and may reduce progression to pancreatic cancer. Chemotherapeutic cyst ablation has demonstrated encouraging complete resolution rates, while an alcohol-free chemoablation protocol has demonstrated a significant decrease in adverse events without a compromise to complete ablation rates when compared with previous alcohol-based protocols. Most pancreatic cysts are small, low risk, and best managed by surveillance per accepted guidelines. Cysts with features suggestive of overt malignancy are best discussed by a multidisciplinary committee, and surgery is considered if appropriate. However, for patients in the middle ground with cysts that are structurally suitable for chemoablation, alcohol-free chemoablation has been shown to allow effective, safe, and durable results especially for those who are not ideal operative candidates. EUS-guided alcohol-free chemoablation is promising and continues to evolve; however, as a relatively novel treatment option it has areas of uncertainty that will require further investigation and development.

With the introduction of endoscopic retrograde cholangiopancreatography and linear endoscopic ultrasound, interventional pancreaticobiliary (PB) endoscopy has had an enormous impact in the management of pancreatic and biliary diseases. Continuous efforts to improve various devices and techniques have revolutionized these treatment modalities as viable alternatives to surgery. In recent years, trends toward combining endoscopic techniques with other modalities, such as laparoscopic and radiological interventions, for complex PB diseases have emerged using a multidisciplinary approach. Ongoing research and clinical experience will lead to refinements in interventional PB endoscopic techniques and subsequently improve outcomes and reduce complication rates.

Pancreatic cancer is on the rise and expected to become the second leading cause of cancer-related death by 2030. Up to a one-fifth of pancreatic cancers may arise from mucinous pancreatic cysts, which are frequently present in the general population. Currently, surgical resection is the only curative approach for pancreatic cancer and its cystic precursors. However, only a dismal proportion of patients are eligible for surgery. Therefore, novel treatment approaches to treat pancreatic cancer and precancerous pancreatic cysts are needed. Endoscopic ultrasound (EUS)-guided ablation is an emerging minimally invasive method to treat pancreatic cancer and premalignant pancreatic cysts. Different ablative modalities have been used including alcohol, chemotherapy agents, and radiofrequency ablation. Cumulative data over the past two decades have shown that endoscopic ablation of mucinous pancreatic cysts can lead to cyst resolution in a significant proportion of the treated cysts. Furthermore, novel data are emerging about the ability to endoscopically ablate early and locally advanced pancreatic cancer. In this review, we aim to summarize the available data on the efficacy and safety of the different EUS-ablation modalities for the management of premalignant pancreatic cysts and pancreatic cancer.

A novel large surface area microparticle paclitaxel (LSAM-PTX) has unique properties of long retention in cystic spaces while maintaining high drug concentration. We prospectively evaluated the safety and response of EUS-guided fine needle injection (EUS-FNI) of LSAM-PTX to chemoablate branch duct (BD)-IPMNs.

Subjects diagnosed with BD-IPMNs exhibiting at least one worrisome criteria and considered non-surgical were enrolled in a multicenter clinical trial (NCT03188991) and subsequently included in an Expanded Access Protocol (EAP) where they received EUS-FNI of LSAM-PTX (15 mg/mL).

Six BD-IPMNs measuring (mean ± SD) 3.18 ± 0.76 cm in diameter among 5 subjects (mean age: 66 years) were treated by EUS-FNI of LSAM-PTX. A mean of 4 doses of LSAM-PTX (mean dose/cyst: 73 ± 31 mg) were administered, and subjects were followed for up to 32 months. The mean volume reduction/cyst ranged from 42 to 89% (9.58 ± 5.1 ml to 2.2 ± 1.1 ml (p = 0.016)). The mean surface area reduction ranged from 31 to 83% (21.9 ± 8.7 cm2 to 5.7 ± 2.5 cm2 (p = 0.009)). Higher dosing-frequency of EUS-FNI of LSAM-PTX significantly correlated with a reduction in cyst volume (R2 = 0.87, p = 0.03) and surface area (R2 = 0.83, p = 0.04). Comparing pre- and post-ablation samples, molecular analysis of the cyst fluid revealed a loss of IPMN-associated mutations in 5 cases (83.3%), while reemergence was observed in 1 case and persistence in 1 case. Intracystic changes (fibrosis/calcification) were observed in 83.3% (n = 5). One subject developed mild acute pancreatitis (1 of 22 EUS-FNIs of LSAM-PTX).

In this EAP, EUS-FNI of LSAM-PTX into BD-IPMNs was safe and resulted in volume and surface area reduction, morphological changes, and loss of pathogenic mutations.

EUS-guided ethanol ablation is a recently introduced treatment approach for pancreatic cystic lesions (PCLs), including branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs). However, the utility of this procedure is limited because of its relatively low efficacy in treating PCLs.

We retrospectively reviewed patients with PCLs, including those with enlarging suspected BD-IPMNs or those with PCLs measuring >3 cm, who were suboptimal candidates for surgery and had been managed using EUS-guided rapid ethanol lavage (EUS-REL; immediate ethanol lavage performed 4 times, 2015-2022) or surveillance only (SO; 2007- 2022). Propensity score matching (PSM) was performed to minimize bias. The primary outcome was the cumulative incidence rate of BD-IPMN progression. Secondary outcomes were the efficacy and safety of EUS-REL, surgical resection rate (SR), overall survival (OS), and disease-specific survival (DSS) in both groups.

Overall, 169 and 610 patients were included in the EUS-REL and SO groups, respectively. PSM created 159 matched pairs. The radiologic complete resolution rate after EUS-REL was 74%. Procedure-related pancreatitis in the EUS-REL group was 13.0% (n = 22; 19 mild and 3 moderate grade); no severe adverse events were reported. The 10-year cumulative incidence rate of BD-IPMN progression was significantly lower in the EUS-REL group than in the SO group (1.6% vs 21.2%; hazard ratio, 12.35; P = .003). EUS-REL showed a lower tendency of SR compared with that associated with SO. The rates of 10-year OS and 10-year DSS were comparable in both groups.

EUS-REL was associated with a significantly lower 10-year cumulative incidence rate of BD-IPMN progression and a lower tendency of SR, whereas its 10-year OS and DSS rates were similar to those of SO for PCLs. EUS-REL may be a viable alternative to SO for managing patients with enlarging suspected BD-IPMNs or those with PCLs >3 cm who are suboptimal candidates for surgery.

The transcendence of endoscopic ultrasound (EUS) from diagnostic to therapeutic tool has revolutionized management options in the field of gastroenterology. Through EUS-guided methods, pancreaticobiliary obstruction can now be utilized as an alternative to surgical and percutaneous approaches. This modality also allows for gallbladder drainage in patients who are not ideal operative candidates. By utilizing its unique imaging capabilities, EUS also allows for drainage access points in cases of gastric outlet obstruction as well as windows to ablate pancreatic cystic lesions. As technical progress continues to evolve, interventional gastroenterology continues to push the envelope of minimally invasive therapeutic procedures in a multidisciplinary setting. In this comprehensive review, we set out to describe current indications and innovations through EUS.

Since its emergence as a diagnostic modality in the 1980s, endoscopic ultrasound (EUS) has provided the clinician profound access to gastrointestinal organs to aid in the direct visualization, sampling, and subsequent identification of pancreatic pathology. In recent years, advancements in EUS as an interventional technique have promoted the use of local ablative therapies as a minimally invasive alternative to the surgical management of pancreatic neuroendocrine tumors (pNETs) and pancreatic cystic neoplasms (PCNs), especially for those deemed to be poor operative candidates. EUS-guided local therapies have demonstrated promising efficacy in addressing a spectrum of pancreatic neoplasms, while also balancing local adverse effects on healthy parenchyma. This article serves as a review of the current literature detailing the mechanisms, outcomes, complications, and limitations of EUS-guided local ablative therapies such as chemical ablation and radiofrequency ablation (RFA) for the treatment of pNETs and PCNs, as well as a discussion of future applications of EUS-guided techniques to address a broader scope of pancreatic pathology.

Pancreatic cystic lesions (PCLs) are known precursors to pancreatic cancer, one of the deadliest types of cancer worldwide. Surgical removal or pancreatectomies remain the central approach to managing precancerous high-risk PCLs. Endoscopic ultrasound (EUS)-guided therapeutic management of PCLs is a novel management strategy for patients with prohibitive surgical risks. Various ablation techniques have been explored in previous studies utilizing EUS-guided fine needle injection (FNI) of alcohol and chemotherapeutic agents. This review article focuses on EUS-FNI and chemoablation, encompassing the evolution of chemoablation, pancreatic cyst selection, chemotherapy drug selection, including novel agents, and a discussion of its safety and efficacy.

EUS-guided treatments for focal tumor lesions has been developed since 20 years using at onset of the technique mainly local and guided alcohol injection [1-4]. Pancreatic tumors are the most assessed targeted lesions for EUS treatment because of their accessibility and because EUS management could be a safe alternative to surgery. More and more pancreatic tumors are discovered mainly fortuitously due to the advances in conventional imaging (abdominal ultrasound, CT, MRI) resulting in the question of surgical management of an asymptomatic pancreatic lesion ("incidentaloma") [5-8]. The lesions detected include mostly pancreatic cystic neoplasms (PCN) and neuroendocrine tumors (NET) mainly well differentiated. Clinically, NET are mostly non-functional and do not induce secretory disorders [5-8]. Once their nature is yielded by diagnostic tests like EUS-FNA, incidental nonfunctional NET currently lead to difficult management when their largest diameter is less than 2 cm [2,4,9,10]. EUS-guided treatment for pancreatic adenocarcinoma have also been developed with recent prospective observational study and randomized control study [11,12]. Thus, therapeutic surgical choices could be challenged by EUS- guided treatment [2,4,9].

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.

Recently, endoscopic ultrasound (EUS)-guided ablation therapy has been reported as a less invasive therapy for patients with pancreatic neoplasms. Some ablation techniques, including injective ablation (using ethanol or other ablative agents), radiofrequency ablation (RFA), photodynamic therapy, and laser ablation, have been described in the literature. Among these, injective ablation and RFA are more frequently used for treating pancreatic neoplasms. Few studies have evaluated the effectiveness of EUS-guided ethanol ablation (EUS-EA) for potentially malignant solid neoplasms (neuroendocrine neoplasms or solid pseudopapillary neoplasms) and have reported a complete response (CR) rate of 60-80%. In addition, the CR rate after EUS-RFA for these lesions has been reported to be 55-100%, with no additional procedure-related adverse events (AEs). Regarding the amelioration of the symptoms of an insulinoma, the success rates of both the therapies were found to be excellent. Regarding complete tumor ablation, EUS-RFA appeared to be superior to EUS-EA. Although EUS-RFA has been reported as a safe treatment for pancreatic cancers, its effectiveness remains inadequate. Some studies have examined the effectiveness of EUS-guided injection ablation therapy for pancreatic cystic neoplasms (PCNs) and have reported CR rates that range from 35% to 79%. Alcohol-free chemotherapeutic agent ablation appears to be effective, with a low risk of AEs. However, studies on the effectiveness of EUS-RFA for PCNs are limited. In the future, EUS-guided ablation therapy could become a more widely used approach for potentially malignant and malignant pancreatic lesions.

Pancreatic cystic lesions (PCLs) are increasingly being recognized due to improvements and widespread use of cross-sectional imaging. With an estimated prevalence of 15% in general population, incidentally discovered PCLs represent a dilemma in management. While pancreatectomies offer a chance of cure, the morbidity is considerable in patients with high surgical risks. More recently, EUS-guided approaches for cyst ablation are being offered in clinical trials for the management of PCLs. EUS-chemoablation studies have progressed from first investigating safety and efficacy of EUS-guided alcohol lavage to single-agent paclitaxel ablation. Recent studies have shown that alcohol lavage may not be required, and long-term resolution can be achieved by chemoablation alone. EUS-guided lauromacrogol ablation and EUS-guided radiofrequency ablation (RFA) are new techniques that have shown promising results in a few small studies. Overall, the current literature suggests that EUS-guided paclitaxel ablation has better cyst resolution rates compared to other existing minimally invasive techniques including ethanol injection, lauromacrogol ablation, or RFA. This article will review EUS-guided PCL ablation approaches and future directions the field is headed into.

Andrew Canakis.

Pancreatic cysts have always presented as a diagnostic dilemma due to the difficulties in identifying patients with current imaging modalities that could most benefit from surgical intervention. Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystadenomas (MCNs) carry the highest malignant potential of all pancreatic cysts and pancreatic adenocarcinoma carries a high mortality as the fourth leading cause of cancer-related deaths. However, surgery to remove benign cysts also carries a high morbidity and occasional mortality. Opportunities to identify and reduce pre-cancer lesions must be aggressively pursued. Multidetector helical CT (MDHCT) or an up-to-date MRI is the first diagnostic tool to evaluate a suspected pancreatic lesion. Currently, review by a multidisciplinary group who specialize in pancreatic cysts and pancreatic cancer is advised to review factors such as a patient's comorbidities, the type of surgery needed to remove the cyst and the estimated morbidity and mortality associated with the procedure. Some recent data are emerging to assist with identifying those at highest risk such as cyst fluid analysis, laser endomicroscopy, and artificial intelligence (AI). This article reviews the current status, benefits, challenges and future prospects on diagnosis and treatment of pancreatic cysts. Further prospective randomized control trials are needed to determine the optimal management and treatment for patients with pancreatic cysts.

We initially reported EUS-guided lauromacrogol ablation (EUS-LA) to treat pancreatic cystic neoplasms (PCNs); however, its long-term effectiveness remains unknown. This study was performed to further determine the effectiveness of EUS-LA in a larger population with a long-term follow-up based on 5 years of experience with EUS-LA.

From April 2015 to April 2020, 279 patients suspected of having PCNs were prospectively enrolled, and seventy patients underwent EUS-guided ablation using lauromacrogol alone. Fifty-five patients underwent follow-up, 35 of whom had a follow-up duration of at least 12 months. The effectiveness of ablation was determined based on volume changes.

Among the fifty female and twenty male patients with an overall mean age of 50.3 years, cysts were located in the head/neck of the pancreas in 37 patients (52.9%) and in the body/tail of the pancreas in 33 patients (47.1%). The adverse events rate was 3.6% (3/84), with 14 patients undergoing a second ablation. Among the 55 patients who underwent follow-up, the median cystic volume sharply decreased from 11,494.0 mm3 to 523.6 mm3 (P < 0.001), and the mean diameter decreased from 32.0 mm to 11.0 mm (P < 0.001). Postoperative imaging showed complete resolution (CR) in 26 patients (47.3%) and partial resolution (PR) in 15 (27.3%) patients. CR was observed in 18 (51.4%), and PR was observed in 9 (25.7%) patients among the 35 patients followed for at least 12 months.

EUS-LA was effective and safe for the treatment of PCNs with stable effectiveness based on at least 12 months of follow-up.

Endoscopic ultrasonography-guided ethanol lavage and Taxol injection (EUS-ELTI) for pancreatic cystic lesions have been recently performed in some medical centers. The aim of this study was to optimize patient selection and analyze outcomes of patients who underwent surgeries after EUS-ELTI for pancreatic cystic lesions.

Among 310 patients who underwent EUS-ELTI between January 2007 and December 2014, 23 underwent surgeries after EUS-ELTI owing to incomplete treatment and/or adverse events. Surgical outcomes of patients who underwent surgeries after EUSELTI were evaluated. Clinical outcomes of patients who underwent surgeries after EUS-ELTI were then retrospectively compared with those of patients who underwent upfront surgery for left-sided pancreatic lesions without an EUS-ELTI procedure.

The pathology revealed degenerated cysts in 12 patients, mucinous cyst neoplasms in five, neuroendocrine tumors in two, intraductal papillary mucinous neoplasm (IPMN) in one, solid pseudopapillary tumor in one, pancreatic ductal adenocarcinoma arising from an IPMN in one, and hepatoid carcinoma in one. Twelve patients underwent laparoscopic distal pancreatectomy and five patients underwent open distal pancreatectomy. When clinical outcomes were retrospectively compared between patients who underwent laparoscopic distal pancreatectomy after EUS-ELTI and those who did not receive an EUS-ELTI procedure, the spleen-preserving rate was 0% in the EUS-ELTI group and 61.7% (365/592) in the control group (p < 0.001).

Surgical outcomes are compromised after EUS-ELTI for cystic tumor of the pancreas. Further studies are needed to investigate the efficacy and safety of the EUS-ELTI procedure.

Endoscopic ultrasound-guided ablation (EUS-A) therapy is a minimally invasive procedure for pancreatic-cystic tumors in patients with preoperative comorbidities or in patients who are not indicated for surgical resection. However, histopathologic characteristics of pancreatic cysts after ablation have not been well-elucidated.

Here, we analyzed pathological findings of 12 surgically resected pancreatic cysts after EUS-A with ethanol and/or paclitaxel injection.

Mean patient age was 49.8 ± 13.6 years with a 0.3 male/female ratio. Clinical impression before EUS-A was predominantly mucinous cystic neoplasms. Mean cyst size before and after ablation therapy was similar (3.7 ± 1.0 cm vs. 3.4 ± 1.6 cm; p = 0.139). Median duration from EUS-A to surgical resection was 18 (range, 1-59) months. Mean percentage of the residual neoplastic lining epithelial cells were 23.1 ± 37.0%. Of the resected cysts, 8 cases (67%) showed no/minimal (<5%) residual lining epithelia, while the remaining 4 cases (33%) showed a wide range of residual mucinous epithelia (20-90%). Ovarian-type stroma was noted in 5 cases (42%). Other histologic features included histiocytic aggregation (67%), stromal hyalinization (67%), diffuse egg shell-like calcification along the cystic wall (58%), and fat necrosis (8%).

Above all, diffuse egg shell-like calcification along the pancreatic cystic walls with residual lining epithelia and/or ovarian-type stroma were characteristics of pancreatic cysts after EUS-A. Therefore, understanding these histologic features will be helpful for precise pathological diagnosis of pancreatic cystic tumor after EUS-A, even without knowing the patient's history of EUS-A.

BACKGROUND : Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has been increasingly used for the management of various solid pancreatic tumors. This study aimed to evaluate the feasibility and safety of EUS-RFA for serous cystic neoplasms (SCNs). METHODS : 13 patients with microcystic SCNs with honeycomb appearance underwent EUS-RFA using a 19-gauge RFA needle. Before ablation, cystic fluid was aspirated until a thin layer of fluid remained. RESULTS : EUS-RFA was successful in all patients. Seven patients underwent a single session and the remaining six patients underwent a second session of EUS-RFA. One patient (7.7 %) experienced self-limited abdominal pain after EUS-RFA. During a median follow-up period of 9.21 months (interquartile range [IQR] 5.93 - 15.38), the median volume of the SCNs decreased from 37.82 mL (IQR 15.03 - 59.53) at baseline to 10.95 mL (IQR 4.79 - 32.39) at the end of follow-up. A radiologic partial response was achieved in eight patients (61.5 %). CONCLUSIONS : EUS-RFA is technically feasible and showed an acceptable rate of adverse events for patients with SCNs. A long-term follow-up study is required to evaluate the efficacy of EUS-RFA.

It is difficult to achieve whole tumor ablation using percutaneous ethanol ablation therapy (PEAT) due to the limited diffusion of ethanol.

To determine whether chemotherapy can be an adjuvant therapy to benefit PEAT, we investigated ultrasound-guided percutaneous ethanol-paclitaxel combined therapy (PEPCT) of VX2 carcinoma, a rabbit liver cancer model.

A six-arm study was designed to quantify the correlation between paclitaxel (PTX) dose and tumor necrosis or cell proliferation, including sham group (2 mL saline, n=6), incremented dose of PTX (0, 12.5, 25, 37.5 mg) in 2.0 mL ethanol (n=6) and a conventional PEAT group (n=6) as comparison. The test was followed by contrast-enhanced ultrasonic (CEUS) before 7-day sacrifice, tumor harvest, and sectioning. Tumor necrosis ratio was radiologically and histologically quantified; modified proliferation index (m-PI) was proposed to quantify the PTX's pharmacological effects. A linear regression model was set to correlate the PTX dose with tumor necrosis ratio or cell proliferation index. The difference of radiological, histological necrosis ratio (HNR) and modified PI in six groups was analyzed via Kruskal-Wallis H-test, Welch analysis of variance and one-way ANOVA.

Incremental increases of PTX (0, 12.5, 25, 37.5 mg) correlated with greater fraction of tumor necrosis (R² = 0.946, P<0.001 for radiological necrosis ratio [RNR], R² = 0.843, P<0.001 forHNR), indicating that one week after procedure PTX's anti-proliferation and ethanol's dehydration co-induced severe tumor necrosis. Correlation analysis further testified a significant association between PTX dose and m-PI (R² = 0.860, P<0.001).

These results suggest a clear role for PTX-induced cytotoxicity and support the use of chemotherapeutic drugs in ablation therapy.

Ablative therapies for locoregional treatment of pancreatic neoplastic lesions developed over the last decade to be applied during surgery are now becoming also available to be utilized under endoscopic ultrasound (EUS) guidance. The advantage of this approach is clear because of the close proximity of the EUS transducer to the target lesion, coupled with developments of specifically designed ablation devices, making the procedure minimally invasive, and potentially sparing patients from the morbidity of this method when performed surgically. EUS-guided ablative techniques that have been applied to pancreatic neoplastic cysts, pancreatic functional and non-functional neuroendocrine neoplasms and pancreatic ductal adenocarcinoma include ethanol injection, radiofrequency ablation (RFA), a combination of bipolar RFA and cryoablation, laser therapy (LT) and photodynamic therapy (PDT). Up to now, most of these procedures have been applied to patients at high surgical risk or who refused surgery. However, more studies evaluating some of these treatments also in selected patients not at surgical risk are becoming available. These studies will pave the road to apply this therapeutic approach to a more extensive number of patients, alone or in association with other therapies, such as immunomodulating drugs. The present manuscript will critically review the available evidence in the field of EUS-guided local ablative treatment of solid and cystic pancreatic neoplasms.

Pancreatic cystic lesions are an increasingly common clinical finding. They represent a heterogeneous group of lesions that include two of the three known precursors of pancreatic cancer, intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN). Given that approximately 8% of pancreatic cancers arise from these lesions, careful surveillance and timely surgery offers an opportunity for early curative resection in a disease with a dismal prognosis. This review summarizes the current evidence and guidelines for the diagnosis and management of IPMN/MCN. Current pre-operative diagnostic tests in pancreatic cysts are imperfect and a proportion of patients continue to undergo unnecessary surgical resection annually. Balancing cancer prevention while preventing surgical overtreatment, continues to be challenging when managing pancreatic cysts. Cyst fluid molecular markers, such as KRAS, GNAS, VHL, PIK3CA, SMAD4 and TP53, as well as emerging endoscopic technologies such as needle-based confocal laser endomicroscopy and through the needle microbiopsy forceps demonstrate improved diagnostic accuracy. Differences in management and areas of uncertainty between the guidelines are also discussed, including indications for surgery, surveillance protocols and if and when surveillance can be discontinued.

The evolution of endoscopic ultrasound (EUS) from a diagnostic to a therapeutic procedure has resulted in a paradigm shift toward endoscopic management of disease states that previously required percutaneous or surgical approaches. The past few years have seen additional techniques and devices that have enabled endoscopists to expand its diagnostic and therapeutic capabilities. Some of these techniques initially were reported more than a decade ago; however, with further device development and refinement in techniques there is potential for expanding the application of these techniques and new technologies to a broader group of interventional gastroenterologists. Lack of formalized training, devices, and prospective data regarding their use in addition to a scarcity of guidelines on implementation of these technologies into clinical practice are contributing factors impeding the growth of the field of interventional EUS. In April 2019, the American Gastroenterological Association's Center for Gastrointestinal Innovation and Technology conducted its annual Tech Summit and a key session focused on interventional EUS. This article is a White Paper generated from the conference, discusses the published literature pertaining to the topic of interventional EUS, and outlines a proposed framework for the implementation of interventional EUS techniques into clinical practice. Three primary areas of interventional EUS are addressed: (1) EUS-guided access; (2) EUS-guided tumor ablation; and (3) endohepatology. There was general agreement among participants on several key components. The introduction of these novel interventions requires better tools, more data on safety/outcomes, and improved training for endoscopists. Participants also agreed that widespread implementation and use of these techniques will require support from Gastrointestinal Societies and other key stakeholders including payers. Continued work by the Gastrointestinal Societies and manufacturers to provide training programs, appropriate equipment/work environments, and policies that motivate endoscopists to adopt new techniques is essential for growing the field of interventional EUS.

Background and study aims  Pancreatic cystic lesions are being increasingly recognized on cross-sectional imaging and mucinous premalignant cysts represent one of the most prevalent types. Endoscopic ultrasound (EUS)-guided chemoablation offers a safe and minimally invasive ablation approach yet with limited efficacy. Patients who develop acute pancreatitis as a complication of chemoablation with alcohol however experience ablation rates up to 100 %. This evidence suggests that recruitment of the body's immune system may represent an avenue to significantly increase the efficacy of EUS-guided chemoablation. Here we illustrate this immune-mediated tumor killing phenomenon through a case presentation at our institution.

With the development of cross-sectional imaging modalities and the increasing attention being paid to physical examinations, the prevalence of pancreatic cystic neoplasms (PCNs) has increased. PCNs comprise a broad differential spectrum with some PCNs having low or no malignant potential and others having high malignant potential. The morbidity and mortality rates related to major pancreatic surgical resection are high. Long-term surveillance may not only increase the financial burden and psychological stress for patients but also result in a missed malignancy. Minimally invasive endoscopic ultrasound (EUS)-guided ethanol ablation was first reported in 2005. Several other agents, such as paclitaxel, lauromacrogol, and gemcitabine, were reported to be effective and safe for the treatment of PCNs. These ablative agents are injected through a needle inserted into the cyst via transgastric or transduodenal puncture. This treatment method has been substantially developed in the last 15 years and is regarded as a promising treatment to replace surgical resection for PCNs. While several reviews of EUS-guided ablation have been published, no systematic review has evaluated this method from patient preparation to follow-up in detail. In the present review, we systematically describe EUS-guided injective ablation with regard to the indications, contraindications, preoperative treatment, endoscopic procedure, postoperative care and follow-up, evaluation method, treatment efficiency, safety profile, tips and tricks, and current controversies and perspectives.

Pancreatic cysts are common and often incidentally detected on abdominal imaging. Their prevalence in asymptomatic individuals depends on the screening modality used. The incidence of these lesions increases with age and may be detected in nearly half of elderly patients undergoing high-resolution magnetic resonance imaging. Some, but not all, pancreas cysts have malignant potential. The overall risk is small but induces significant anxiety for the patient. When determining management options, it is important to consider the patient's age, medical comorbidities, and surgical risks as well as the wishes of the patient. Current strategies include imaging surveillance or surgical resection. Before embarking on cyst surveillance, a clinician must factor in patients' risk of developing malignancy, their life expectancy, medical comorbidities, and if they are a surgical candidate. Surgery poses significant adverse events and mortality, whereas radiographic surveillance imposes healthcare costs and psychological distress to patients with the looming possibility of malignancy. The development and use of endoscopic ultrasound cyst ablation is a minimally invasive alternative in treating pancreatic cystic lesions. This review focuses on the modalities of ethanol ablation, paclitaxel ablation, and radiofrequency ablation of pancreatic cystic lesions.

Background and aim  Recently, several guidelines with divergent recommendations on management of pancreatic cystic neoplasm have been published but the role of endoscopic ultrasound (EUS)-guided pancreatic cyst ablation has not been thoroughly addressed. The aim of the current paper is to explore the issues surrounding EUS-guided pancreatic cyst ablation by generating a list of clinical questions and providing answers based on best scientific evidence available. Methods  An expert panel in EUS-guided pancreatic cyst ablation was recruited from members of the Asian EUS group and an international expert panel. A list of clinical questions was created and each question allocated to one member to generate a statement in response. The statements were then discussed in three Internet conference meetings between October 2016 and October 2017. The statements were changed until consensus was obtained. Afterwards, the complete set of statements was sent to all the panelist to vote on strength of the statements, classification of the statement sand grading of the evidence. Results  Twenty-three statements on EUS-guided drainage of pancreatic cyst ablation were formulated. The statements addressed indications for the procedures, technical aspects, pre-procedure and post-procedure management, management of complications, and competency and training in the procedures. Conclusion  The current set of statements on EUS-guided pancreatic cyst ablation are the first to be published by any endoscopic society. Clinicians interested in developing the technique should reference these statements and future studies should address the key issues raised in the document.

Pancreatic cystic lesions represent a growing public health dilemma, particularly as our population ages and cross-sectional imaging becomes more sensitive. Mucinous cysts carry a clinically significant risk of developing pancreatic cancer, which carries an extremely poor prognosis. Determining which cysts will develop cancer may be challenging, and surgical resection of the pancreas carries significant morbidity. The goal of this paper is to review the rationale for cyst ablation and discuss prior and current research on cyst ablation techniques and efficacy. Indications, contraindications, and factors related to optimal patient selection are outlined.

Endoscopic ultrasound-guided chemoablation of pancreatic cysts has been performed in neoplastic cysts, with varying levels of efficacy. Safety concerns arose due to the risk of pancreatitis in alcohol-based treatments; however, the most recent data using a non-alcohol chemoablation cocktail suggests that ablation is effective without the need for alcohol, resulting in a significantly more favorable adverse event profile. Endoscopic ultrasound-guided chemoablation of neoplastic pancreatic cysts is a promising, minimally invasive approach for treatment of cysts, with recent significant advances in safety and efficacy, suggesting that it should play a role in the treatment algorithm.

Background and study aims  Endoscopic ultrasound (EUS)-guided chemoablation with ethanol lavage, followed by infusion with paclitaxel, has been found to be effective for treatment of mucinous pancreatic cysts. However, there are notable adverse events (AEs) associated with ethanol and its undesirable inflammatory effects on local tissue and vessels. The recent ChARM trial demonstrated that removing ethanol from the cyst ablation process resulted in equivalent efficacy while significantly reducing associated AEs. Encouraged by these results, we speculated that alcohol-free chemoablation can be applied to treatment of solid tumors, as described in our case with a patient with severe and symptomatic recurrent hypoglycemia in the setting of multifocal insulinomas. As a result, the patient saw a significant reduction in symptoms. EUS-guided alcohol-free chemoablation may represent a new alternative to previously established therapies that will ultimately reduce risk of AEs.

Endoscopic ultrasound (EUS)-guided pancreatic cyst ablation with alcohol lavage or paclitaxel-based regimens are investigative modalities. To evaluate the safety and efficacy of EUS-guided pancreatic cyst ablation with alcohol lavage or paclitaxel-based regimens. A systematic review of computerized bibliographic databases was carried out for studies of EUS-guided pancreatic cyst ablation with alcohol lavage or paclitaxel-based regimens from January 1980 to February 2018. EUS-guided cyst ablation-related outcomes (cyst resolution) and complications. Data were extracted from six studies (N=207 patients) for EUS-guided cyst ablation with alcohol lavage and eight studies (N=347 patients) for EUS-guided cyst ablation with paclitaxel-based regimens. The pooled proportion of patients with complete cyst resolution was 68/207 (32.8%) for EUS-guided cyst ablation with alcohol lavage and 221/347 (63.6%) for EUS-guided cyst ablation with paclitaxel. Postablation adverse events with EUS-guided ablation with alcohol lavage were 44/207 (21.7%), and those with EUS-guided ablation with paclitaxel-based regimens were 52/347 (15%). Limitations of this study are because of the variability in study design and regimens tested, paucity of randomized trials, and differences in pancreatic cyst types receiving treatment. EUS-guided cyst ablation appears to be effective and safe. The effect on pancreatic cancer incidence is unknown; EUS-guided pancreatic cyst ablation modalities require further improvement and validation to determine their role in the treatment of patients with pancreatic cystic lesions.

The decision of the appropriate treatment for pancreatic cystic lesions (PCLs) is becoming increasingly important as the number of incidentally found PCLs increases. A range of modalities have been attempted because there has been an increasing demand for minimally invasive treatment for PCLs due to the large burden of a surgical resection. Endoscopic treatment using endoscopic ultrasonography (EUS), a representative of minimally invasive therapy, can be categorized into two types: ablation therapy by the injection of drugs and topical thermal coagulative therapy through the high topical energy. A number of studies reported the feasibility and efficacy of these treatments; the most common is EUS-guided ablation for PCLS with ethanol alone or in combination with anticancer drugs. Although ablation therapies with drug injection have proven safety and feasibility, there is no consensus regarding the actual treatment effects and indications of these modalities. EUS-guided radiofrequency ablation was recently attempted as a representative method of local thermal coagulation, but further studies will be needed because of the lack of evidence of its feasibility and safety. In addition, a range of treatments for malignant tumors rather than PCLs have been attempted, such as EUS-guided photodynamic therapy, EUS-guided neodymium-doped yttrium aluminum garnet laser, and high-intensity focused ultrasound, based on the data from animal experiments. Through further study, endoscopic treatment is expected to become established as a useful treatment modality for PCLs.

With the increase in the use of cross-sectional diagnostic imaging, there has been a concomitant rise in the rate of detected pancreatic cystic lesions. Recent years have seen the rise of newly developed therapeutic modalities to treat pancreatic lesions via ablation. Specifically, through the use of endoscopic ultrasound-guided therapy, endoscopists can potentially ablate these lesions safely and with minimally invasive techniques. In this manuscript we review 4 major endoscopic ultrasound-guided ablative therapies: radiofrequency ablation, ethanol injection, chemo ablation, and cryoablation. We also review the efficacy and safety of these techniques and future directions in the management of cystic pancreatic lesions.

The growing incidence of cystic pancreatic tumours has become a major problem in daily clinical practice. These patients usually undergo follow-up programmes of questionable clinical efficacy that put significant strain on endoscopy units. Safe and effective alternatives to surgery are desperately needed in these cases. The aim of this study was to critically review the utility of ablative therapies in cystic pancreatic tumours.

Pancreatic intraductal papillary-mucinous neoplasm is a rare primary neoplasm of unknown pathogenesis. This kind of tumor represents 0.2-2.7% of all pancreatic cancers and they may proceed to malignant lesions. In this study, we describe a case of pancreatic intraductal papillary-mucinous tumor (4.3 cm) with normal tumoral markers and nuclear atypia. We perform also a systematic review of the literature on MEDLINE and find only one relevant study that used microwave ablation for the palliative treatment of pancreatic tumor. We describe the case of a 70-year-old Caucasian male who was diagnosed with a pancreatic tumor with biliary tree dilatation. The patient underwent computed tomography (CT), percutaneous biopsy, and an endoscopic positioning of prosthesis in the biliary tree. Due to the worsening of jaundice and cholestasis, and considering the severe systemic disease status, palliative surgery with microwave thermoablation in the head of pancreas was performed. No complications were observed. The hospitalization lasted for 11 days after surgery, with normal liver and pancreatic lab tests at discharge. The patient followed a line of chemotherapy for 6 months with a complete response for 8 months. One month after the treatment, a staging CT scan was performed showing the size of the cephalopancreatic lesion had decreased from 43 to 35 mm with signs of complete ablation. The patient had a total response at the imaging of 10 months. One year later, a CT scan follow-up showed progression of the pancreatic disease. The disease remained stable for 18 months. The patient died due to cardiovascular complications with an overall survival of 30 months. Microwave ablation in our case report has been demonstrated to be feasible and safe without complications. It can be used as a phase of multimodality treatment in patients with severe systemic disease status and advanced intraductal papillary-mucinous neoplasm.

Endoscopic ultrasonography (EUS)-guided therapy with ethanol injection or catheter-based radiofrequency ablation for pancreatic neoplasm has been conducted as a potential alternate treatment modality for patients who are not eligible for surgery. On the basis of the limited number of studies available, EUS-guided ablation therapy with the aforementioned methods for small pancreatic neoplasms has demonstrated promising technical feasibility and safety profiles. To be considered as a legitimate alternative option to surgery, however, EUS-guided ablation therapy must provide a long-term efficacy profile along with the consensus among experts regarding its treatment parameter. This review focuses on the clinical issues and future perspectives of EUS-guided therapy for pancreatic neoplasm.

Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are the mainstays of interventional endoscopic practice. EUS occupies a central role in the diagnosis of pancreatobiliary neoplasms and offers a platform for a wide range of direct tumor therapies. Initial steps have demonstrated the feasibility of such applications in animal models and pilot studies. Larger clinical trials and incorporation of EUS-based therapies into cooperative cancer studies might demonstrate an impact in the clinical prognosis of patients with pancreatic cancer. ERCP plays an important role in elucidating indeterminate biliary strictures and in treating patients with malignant biliary obstruction who are symptomatic or have borderline-resectable or unresectable disease. ERCP-directed ablative therapies enable neoadjuvant and palliative intervention in patients with malignant biliary obstruction, in particular perihilar cholangiocarcinoma. Additional comparative, multicenter studies are needed to better understand the safety and efficacy of endobiliary brachytherapy, photodynamic therapy, and radiofrequency ablation in patients with pancreatobiliary malignancies.

Pancreatic cysts are very common with the majority incidentally identified. There are several types of pancreatic cysts; some types can contain cancer or have malignant potential, whereas others are benign. However, even the types of cysts with malignant potential rarely progress to cancer. At the present time, the only viable treatment for pancreatic cysts is surgical excision, which is associated with a high morbidity and occasional mortality. The small risk of malignant transformation, the high risks of surgical treatment, and the lack of high-quality prospective studies have led to contradictory recommendations for their immediate management and for their surveillance. This guideline will provide a practical approach to pancreatic cyst management and recommendations for cyst surveillance for the general gastroenterologist.

Pancreatic cancer is a lethal disease and usually is diagnosed at advanced stages of disease. This study assessed the effects of intratumoral ethanol injection using an endoscopic ultrasound (EUS) probe on the control of pancreatic cancer in a mouse orthotopic xenograft model.

The subcutaneous and orthotopic human pancreatic cancer cell mouse xenograft models were established. Different concentrations of ethanol (0-95%) were injected into subcutaneous xenograft tumors. In the orthotopic tumor model, ethanol was injected into the tumor lesions under the guidance of a high-frequency EUS probe. Tumor volume, relative tumor volume (RTV), and histopathology were evaluated. The serum amylase level was analyzed at baseline and 24 h after treatment in the orthotopic tumor model.

Injection of 40-95% ethanol induced tumor necrosis in the subcutaneous tumor model, while there was no statistical difference between the RTVs of the two groups (P = 0.81). In the orthotopic tumor model, the RTV of the 80% ethanol treatment group was less than that of the saline injection group (P < 0.01); and histologically, there was a large area of necrosis observed in the 80% ethanol group. The serum amylase level was slightly elevated at 24 h after injection and returned to the baseline level at 7 days.

Injection of 80% ethanol into xenograft tumor lesions of orthotopic pancreatic cancer resulted in tumor necrosis, and the procedure was safe and effective. Future studies will further confirm its antitumor activity as well as assess its safety and feasibility.

With the development of imaging techniques, the detection rate of pancreatic cystic neoplasms (PCNs) has increased. The surgical morbidity and mortality rates of PCNs are quite high. This study is intended to evaluate the safety and effectiveness of a minimally invasive treatment, EUS-guided PCN ablation with lauromacrogol.

From April 2015 to May 2016, 120 patients with PCNs were enrolled to undergo EUS. We prospectively studied 29 of the 120 patients who underwent EUS-guided ablation with lauromacrogol. The follow-up contrast-enhanced CT or magnetic resonance image was conducted at 3 months and then 6 months after ablation. We determined the effectiveness of ablation by the changes in the volume of the cysts.

Twenty-nine patients were enrolled in the study, and 7 of them underwent a second ablation; therefore, there were 36 treatments. The mean tumor diameter was 28.6 ± 14.5 mm preoperation, whereas the diameter postoperation was 13.4 ± 10.5 mm. Mild pancreatitis occurred in 2 patients and moderate fever in 1; they occurred in the cysts located in the head/uncinate. Among the 29 treatments with complete follow-up of 9 months (range, 3-15), 11 had complete response and 9 had partial response. The resolution rate was 37.9% (11/29) with 36.4% (8/22) in the cysts of the head/uncinate and 42.9% (3/7) in the body/tail (P > .05).

EUS-guided PCN ablation with lauromacrogol is safe and efficient. Adverse event rates seem to be higher in the head/uncinate than in the body/tail, but their resolution rates are similar. Further studies involving larger populations and longer follow-ups are warranted.

Endoscopic ultrasound (EUS)-guided chemoablation with ethanol lavage followed by infusion of paclitaxel is effective for the treatment of mucinous pancreatic cysts. However, complications arise in 3%-10% of patients, presumably linked to the inflammatory effects of ethanol. We aimed to determine whether alcohol is required for effective pancreatic cyst ablation, if removing alcohol from the ablation process would improve complication rates, and whether a multi-agent chemotherapeutic cocktail could increase the rate of complete cyst resolution compared with findings reported from previous trials using alcohol followed by paclitaxel alone.

Between November 2011 and December 2016, we conducted a single-center, prospective, double-blind trial of 39 patients with mucinous-type pancreatic cysts. Patients were randomly assigned to 1 of 2 groups that underwent EUS-guided pancreatic cyst lavage with either 80% ethanol (control) or normal saline (alcohol-free group). Cysts in both groups were then infused with an admixture of paclitaxel and gemcitabine. Primary outcomes were the rates of complete ablation 12 months after the procedure, and rates of serious and minor adverse events within 30 days of the procedure.

At 12 months, 67% of patients who underwent alcohol-free EUS-guided cyst chemoablation had complete ablation of cysts compared with 61% of patients in the control group. Serious adverse events occurred in 6% of patients in the control group vs none of the patients in the alcohol-free group. Minor adverse events occurred in 22% of patients in the control group and none of the patients in the alcohol-free group. The overall rate of complete ablation was 64%.

In this prospective, randomized, controlled trial, we found that alcohol is not required for effective EUS-guided pancreatic cyst ablation, and when alcohol is removed from the ablation process, there is a significant reduction in associated adverse events. A multi-agent chemotherapeutic ablation admixture did not appear to significantly improve rates of complete ablation compared with the current standard of alcohol lavage followed by paclitaxel alone. ClinicalTrials.gov ID: NCT01475331.