Pancreatic cystic neoplasms (PCN) affect up to 5 % of the general population, with
a relative prevalence increase in recent decades, mostly due to increased life-expectancy
and the improvements in the diagnostic potential and widespread availability of cross-sectional
imaging [1]
[2].
The clinical management of patients affected by PCNs should take into account the
estimation of the underlying malignant potential balanced with the risks associated
with pancreatic surgery. In fact, while some PCNs bear a negligible malignant risk
(i. e. serous cystadenoma), mucinous cystic neoplasms (such as IPMNs and mucinous
cystic neoplasms), cystic neuroendocrine neoplasms and solid pseudopapillary tumors
demonstrate malignant potential in a significant number of cases. Therefore, the differential
diagnosis of PCNs (i. e., mucinous vs. non-mucinous, or other neoplasms), together
with accurate estimates of high-risk stigmata for malignancy is crucial for a correct
treatment strategy [3]. The differential diagnosis of PCNs nature is usually based on cross-sectional imaging,
and EUS with cyst fluid analysis in most patients; however, the diagnostic performance
of conventional imaging, B-mode EUS, and cytology lacks accuracy (50–80 %) [1]
[2].
Several clinical guidelines have been published to guide clinicians in identifying
the best strategy for patients with PCNs. In order to reduce the great burden related
to long-term follow-up and the potentially severe adverse events of pancreatic surgery,
EUS-guided interventions have been proposed to ablate pancreatic cystic epithelium
to decrease, or even abolish, the risk of malignant evolution of PCNs.
In the current issue of Endoscopy International Open, Othman et al. presented the
outcomes of a pilot study designed to assess safety of EUS-fine needle injection (EUS-FNI)
of a novel compound specifically designed for injection into solid tumors, namely
large surface area microparticle paclitaxel (LSAM-PTX) [4]. The authors prospectively enrolled 19 patients with mucinous PCNs and observed
optimal safety, with no procedure or drug-related adverse events. Moreover, there
was no evidence of systemic absorption of injected paclitaxel observed in the study
with nearly 70 % of treated PCNs showing a volume reduction after EUS-FNI of LSAM-PTX.
Othman et al. reported enthusiastic results; however, EUS-guided ablation of PCNs
cannot be considered an effective treatment option at present, due to the limitations
of available evidence. The available literature includes several cases of patients
with pancreatic cysts undergoing EUS-guided ablation with no cyst characterization
and no clear treatment indication. In particular, a meta-analysis of studies reporting
the efficacy of paclitaxel-based EUS-FNI included up to 50 % of patients with serous
cystic neoplasms, pseudocysts or undetermined cysts [6]. Patients’ selection, cyst characterization and treatment indication a priori are paramount in the development of this technique and its future role. Since it
seems impossible to assess the clinical benefit of any intervention without a reliable
estimation of the potential burden of the underlying disease, the correct pre-procedural
assessment of PCNs represents Columbus’ Egg in patients undergoing EUS-FNI.
Recently, an international group of experts published a position statement on EUS-FNI
for PCNs. The manuscript by Teoh et al. included treatment indications which were clearly defined and should be adopted in all subsequent studies, including
the present study [5]. Teoh et al. identified patients with unilocular or oligolocular mucinous cysts,
larger than 3 cm or with proven increase in size over time as the ideal candidates
for EUS-FNI; the international panel contraindicated EUS-FNI in cysts with low malignant
potential. In the present study, Othman et al. adopted cyst fluid analysis for the
definition of mucinous nature of the PCNs, as the authors included 2 patients with
MCNs and 17 with branch duct IPMNs with no mural nodules and no main pancreatic duct
dilation. According to current guidelines, most such PCNs should be referred for clinical
and radiological follow-up, since no high-risk stigmata or even worrisome features
were present.
Local treatment response should be assessed according to proposed criteria [5]. Data interpretation of the effectiveness of EUS-FNI using LSAM-PTX in the current
study could be misinterpreted according to different points of view. The authors stated
that “by week 24 a cyst volume reduction (10–78 %) was seen in 70.6 % of subjects”
[4]; however, according to the proposed criteria [5], 11 out of 17 (65 %) patients who completed the 24-month follow-up showed a null
response (5 volume increase, 6 decrease < 30 %), and the remaining patients showed
only partial responses (volume reduction between 30–78 %). No patient showed a complete
response.
To date, no randomized controlled trials with adequate follow-up have been conducted
comparing surgery and EUS-guided ablation or clinical/radiological surveillance and
EUS-guided ablation, thus the clinical impact of EUS ablation for PCNs is still unknown. Indeed, studies on EUS-radiofrequency
ablation of mural nodules within IPMNs recently reported inspiring results with 100 %
effectiveness [7]. However, long-term follow-up (3 years) of these patients resulted in up to 12 %
incidence of pancreatic cancer [8].
In conclusion, EUS-guided interventions seem to be an effective strategy for the management
of patients with PCNs bearing high-risk potential for malignancy. Moving forward future
rigorous studies on safety and dose-response of novel compounds for EUS-FNI are desperately
needed. Such rigorous studies will be mandatory to ensure an evidence-based comparison
of EUS-guided approaches.
