**5. Screening**

The use of EUS in screening patients at increased risk (high-risk individuals [HRIs]) has been suggested due to the lethality of the disease, and the often late-onset of clinical features leading to a very low rate of patients diagnosed at a sufficiently-early stage to undergo curativeintent treatment (15–20%) [30]. In line with the Wilson and Jungner criteria for screening, PC is an important health problem with an acceptable treatment, with a 'latent' phase wherein curative treatment can be undertaken. EUS is a suitable test for early-stage disease that would be likely acceptable to an at-risk population. The questions remain as to whether EUS is yet an accessible test from a resource-availability perspective, and accurately defining HRIs to whom screening could be offered. Subsequent to this, EUS screening of HRIs is yet to be proven to be efficacious, let alone cost-effective to offer as a screening tool.

Identifying HRIs should be based on risk factors for PC. Risk factors such as family history, presence of germline mutations (BRCA1, ATM, PALB2, CDKN2A, and MLH1), Peutz-Jeghers syndrome (PJS), cystic fibrosis, race, ABO blood group, chronic pancreatitis, diabetes mellitus, smoking history, and obesity, are all factors that could be combined to develop a pancreatic risk score. Wang et al. have developed PancPRO, a predictive model for PC using Bayesian modelling to provide risk stratification for developing PC based on family history. It was validated prospectively using the National Familial Pancreas Tumour Registry with an observed to predicted PC ratio of 0.83 (95% CI 0.52–1.20) [36]. The combination of risk stratification algorithms that may include presence of germline mutations may prove to be a more accurate way of identifying HRIs – more research is needed in this area to more-accurately define an at-risk population in which a screening population can be shown to be efficacious and cost effective.

Although no randomised clinical trial has been performed to compare the relative efficacy and safety of CPN via percutaneous versus endoscopic approach, a Cochrane Review of 102 studies concluded that CPN by any modality was associated with reduced pain at 4 weeks (mean difference in visual analogue scale (VAS) −0.42, 95% CI −0.70 to −0.13, p = 0.004). This less than one point improvement of VAS score begs the question of whether this is clinicallysignificant; coupling this data with quality of life would perhaps be more informative. This improvement was maintained at 8 weeks overall, the review noted significant heterogeneity of results at 8 weeks at this time point. Collective data on opioid consumption in these studies also showed a significant benefit in the CPN group [41]. A retrospective cohort study by Kambhampati et al. compared outcomes of patients who underwent either percutaneous or EUS-CPN between 2008 and 2015 at Johns Hopkins University School of Medicine. This study suggested a non-statistically significant reduction in procedural complications for EUS-CPN (7% EUS vs. 11% percutaneous, p = 0.51), as well as a non-significant higher immediate response rate in percutaneous CPN (87% versus 72% in EUS-CPN, p = 0.08). Response was defined as a decrease in numeric pain score by ≥3 points. There was no significant difference in quality of life measures, opiate usage, or pain response at 1 month between groups [42]. An interesting study of note by Wyse et al. looked at early EUS-CPN at the time of diagnosis by EUS of unresectable disease [43]. Patients with pain and suspected PC underwent a diagnostic and staging EUS. If diagnosis of unresectable adenocarcinoma was made, patients were randomised to either early EUS-CPN or conventional pain management. The early EUS-CPN group was found to have non-significant improvements in pain response (measured by the Likert scale) and morphine consumption at 3 months compared to standard analgesia (pain response −28.9 [95% CI −67.0 to 2.8], p = 0.09, morphine consumption −49.5 [95% CI −127.5 to 7.0], p = 0.10). Although not statistically significant, these data do suggest that early EUS-CPN at the time of diagnosis could be considered to assist with the often difficult-to-manage anal-

Endoscopic Ultrasound in Pancreatic Cancer http://dx.doi.org/10.5772/intechopen.75211 81

EUS-guided biliary duct drainage (EUS-BD) can be performed via several methods, but all involve the direct visualisation via EUS of the pre-obstructed biliary tract and puncture of the pre-obstructive system and confirmation with cholangiography. A guidewire is then inserted and the tract is dilated to create a fistula. These techniques rely on accurate EUS images to target the pancreatic duct, common bile duct, or intrahepatic bile ducts (IHBDs) to create a pancreaticogastrostomy, choledocoduodenostomy, or hepaticogastrostomy, respectively.

• Transluminally, where the bile duct or common bile duct is accessed via the stomach or

• Rendezvous, where the ampulla is accessed and the biliary duct is targeted with EUS to fistulise a guidewire to facilitate secondary endoscopic retrograde cholangiopancreatography

• Antegrade, where an IHBD is accessed from the upper intestine to bypass the anatomic

gesic requirements in late-stage PC.

EUS-BD can be performed using several techniques:

(ERCP) and stenting over the guidewire

**6.2. Biliary duct drainage**

duodenum, respectively.

biliary system altogether.

The use of EUS in HRIs has been explored in a review by Bhutani et al. [37]. They identified 10 studies utilising screening EUS in families with identified familial PC, PJS, familial atypical multiple mole melanoma syndrome, and several other mutations incurring increased risk. A total of 512 screening EUSs were performed across the 10 studies. The rate of abnormal EUS results (pancreatic duct dilatation or ectasia, observable solid or cystic masses, or parenchymal changes) in this study population was 212/512 (41%). Clinical outcome measures (rate of curative resection for detected cases, overall survival (OS), etc.) were not reported overall. Several studies have demonstrated the ability of EUS in HRI to identify pancreatic dysplasia and IPMN, with no reported false-positives when these cases with abnormal EUS progressed to surgical resection [38, 39].

The largest of these studies was performed in 216 individuals with one of the following risk factors:


Screening was performed on all of these cases with MRI, CT, and EUS. Ninety-two (42%) of participants had an abnormal EUS (at least one pancreatic mass [cystic n = 84, solid n = 3], or pancreatic duct dilatation [n = 5]). Eighty-two of the abnormal EUS cases were IPMNs, and three were neuroendocrine tumours. Five participants went on to have surgical resection, returning three cases of pancreatic dysplasia in <3 cm IPMNs, multiple intraepithelial neoplasms. No cases were identified by CT or MRI that were undetected by EUS. This study lends support to the potential for pancreatic screening in HRIs and supports the choice of EUS as the screening modality over CT and EUS. Further investigation to properly define the characteristics of the at-risk sub-population is needed. The optimal timing and frequency of screening also requires further exploration. The potential merits of screening will need to be balanced against the resource-cost, access, and scalability considerations before routine EUS screening can be supported.
