POST-ERCP PANCREATITIS IN PERIAMPULLARY MALIGNANCIES – A HARBINGER FOR POST-OPERATIVE COMPLICATIONS AND PANCREATIC FISTULAS

Background
Pancreatic ductal adenocarcinoma (PDAC) exists in several morphological subtypes differing in prognostic significance. However, to date, a clinico-morphological correlation of these subtypes in the context of neoadjuvant therapy (NAT) has not been performed. The aim of this study was 1) to investigate the frequency of the different PDAC morphologies in patients undergoing radical intent pancreatectomy after NAT; and 2) to determine the prognostic impact of the presence of a secondary morphology in the primary tumor.

Methods
All patients who underwent pancreatic resection after NAT for PDAC (2013-2019) at one academic institution were enrolled. All pathological samples were included in toto and reviewed by experienced pathologists. The presence of a secondary morphology in the primary tumor specimen was determined according to a morphological cut-off ≥10%. Tumor regression grade (TRG) was classified according to the MDACC Scoring system. The clinico-pathological characteristics and the survival of the cohort were studied by means of conventional statistical analyses.

Results
Among the 401 included patients 205 (51,5%) received Folfirinox, 134 (33,7%) gemcitabine/nab-paclitaxel. The median follow-up was 28.0 months, and the median disease specific survival (DSS) was 29.7 months. The median DSS associated to the principal tumor morphologies and their relative frequencies is shown in the Table. Gland forming PDAC with conventional morphology (n=167, 41,6%) was the most frequent subtype. Overall, no significant difference in DSS was observed. After pairwise comparison, the papillary morphology shown a significant higher survival rate compared to other less frequent subtypes (cribiform, p<0.019; gyriform, p<0.008; micropapillary, p<0.048; and adenosquamous, p<0.006). Overall, 247 (61,1%) displayed only a single principal tumor morphology, while 154 (38,4%) presented an additional secondary morphology in the primary tumor. PDACs harboring a secondary tumor morphology shown a significantly more advanced pathological profile and a higher TRG, as well as significantly shorter DSS and recurrence free survival (RFS) (Figure). At multivariable Cox regression, the presence of a secondary tumor morphology was independently associated with worse DSS (HR 1.881, 95% CI 1.384-2.557, p<0.001) and RFS (HR 1.635, 95% CI 1.230-2.175, p<0.001).

Conclusion
In patients receiving pancreatectomy after NAT, the presence of a secondary morphology in the primary tumor is frequent, occurring in over one third of the cases. This feature is associated with a less favorable pathological profile and a higher TRG, and represents an independent predictor of shorter DSS and RFS. Based on these findings, including a detailed morphological description in pancreatectomy pathology reports might provide valuable prognostic information and possibly help post-surgical decision-making.

Background: Surgical resection is necessary for the curative treatment of periampullary malignancies. Many patients will undergo endoscopic retrograde cholangiopancreatography (ERCP) prior to surgery, for obstructive jaundice or diagnostic purposes. Post-ERCP pancreatitis (PEP) is one of the most common complications of this procedure, but its impact on postoperative outcomes is not well studied. We hypothesize that patients who experience PEP will experience worse postoperative outcomes.

Methods: All patients with periampullary malignancies who underwent surgical resection between 2017-2020 at a single, high-volume institution were reviewed from a prospectively maintained database. Post-ERCP pancreatitis was defined as clinically significant pancreatitis requiring post-procedure or prolonged admission, as outlined by Cotton et al (1991). Groups were compared with Mann-Whitney U-tests for continuous variables and chi-squared or Fisher’s exact tests for categorical variables. Multivariable analysis was performed with logistic regression.

Results: Four hundred fifty-five patients underwent surgical resection for periampullary malignancy in the studied time frame, of which 317 patients underwent preoperative ERCP: 237(74.8%) for pancreatic cancer, 51(16.1%) ampullary cancer, 22(6.9%) distal cholangiocarcinoma, 4(1.3%) duodenal cancer, and 2(0.9%) pancreatic neuroendocrine tumors. A total of 27(8.8%) patients developed post-ERCP pancreatitis. Groups were comparable in demographics, comorbidities, clinical stage and tumor resectability. There was no significant difference in frequency of neoadjuvant therapy (NAT) (p=0.16). PEP was associated with greater estimated blood loss during surgery (300[300] vs 500[550] mL, p=0.03). There was no significant difference in operative time, post-operative length of stay, 30-day readmission rate and 30- and 90-day mortality rate. While overall complication rates did not differ between groups (p=0.12), PEP patients experienced higher rates of complications Clavien-Dindo class III or above (10.7% vs 33.3%, p<0.01), including clinically relevant postoperative pancreatic fistulas (CR-POPF) (7.9% vs 25.9%, p<0.01). On multivariable analysis, PEP remained independently associated with CR-POPF after adjusting for gland texture, duct diameter, EBL, and pathology (OR 4.88, 95% CI: 1.62–14.68, p<0.01), as well as class III or higher complications after adjusting for age, EBL, pathology, and other factors (OR 6.79, 95% CI: 2.22–18.89, p<0.01).

Conclusions: Patients with periampullary malignancies who develop PEP are at higher risk for major complications after surgery, including clinically relevant postoperative pancreatic fistulas. Post-ERCP pancreatitis should be considered a strong risk factor for postoperative morbidity and CR-POPF, suggesting that PEP patients may require alternative fistula mitigation approaches.