Introduction

Currently, most patients with branch duct intraductal papillary mucinous neoplasms (BD-IPMN) are offered indefinite surveillance, resulting in health care costs with questionable benefits regarding cancer prevention.

Aims & Methods

This study sought to identify patients where the risk of cancer is equivalent to an age-matched population, thereby justifying discontinuation of surveillance. Methods included an International multicenter study involving presumed BD-IPMN without worrisome features (WF) or high-risk stigmata (HRS) at diagnosis who underwent surveillance. Clusters of individuals at risk for cancer development were defined according to cyst size and stability for at least 5 years, and age-matched controls were used for comparison using standardized incidence ratios (SIRs) for pancreatic cancer.

Results

Of 3844 patients with presumed BD-IPMN, 775 (20.2%) developed WF and 68 (1.8%) HRS after a median surveillance of 53 (IQR 53) months. Some 164 patients (4.3%) underwent surgery. Of the overall cohort, 1617 patients (42%) remained stable without developing WF or HRS for at least 5 years. In patients 75 years or older, the SIR was 1.12 (95%CI 0.23-3.39), and in patients 65 years or older with stable lesions below 15mm in diameter after 5 years, the SIR was 0.95 (95%CI 0.11-3.42). The all-cause mortality at 10 years of the entire cohort was 9%, while the disease specific mortality was 0.9%.

Conclusion

The risk of developing pancreatic malignancy in presumed BD-IPMN without WF or HRS after 5 years of surveillance is comparable to that of the general population depending on cyst size and patient age. Surveillance discontinuation could be justified after 5 years of stability in patients older than 75 years with cysts < 30 mm, and in patients 65 years or older who have cysts ≤ 15 mm.

Introduction

Mucinous cystic neoplasms (MCN) are rare cystic pancreatic lesions with an evidenced malignant potential. Although the population who bear MCN is well characterized, the natural history of these lesions has not been elucidated as well as the risk features of malignancy. In a recent single centre study (Vullierme et al., 2021), we identified imaging features suggesting malignant MCN on MRI:
1) ≥ 5mm wall thickness,
2) mural nodule size ≥ 9 mm,
3) enhancing intra-cystic septa and/or
4) heterogenous signal on T2-weighted imaging.

Aims & Methods

The aims of this study were to identify clinical malignancy predictive factors and to validate in a multicentre cohort, the imaging malignancy predictive factors identified previously. In this multicentre retrospective study, patients who underwent pancreatic resection between January 2008 and December 2021 for MCN were included. Pathological review confirmed the presence of ovarian-type stroma. The preoperative imaging (CT and/or MRI) had to be available for a centralized expert radiological review. A multivariable logistic regression was performed to identify predictive factors of malignancy.

Results

A total of 198 patients were included from 13 participant centres. The cohort was constituted of 196 female patients (99%) with a median age of 46 (IQR 37-55) years. At diagnosis, 97 patients (49%) were asymptomatic. Low-grade dysplasia (LGD) was observed in 166 (84%) patients and at least high-grade dysplasia (≥HGD) in 32 (16%) patients, from which 14/32 had invasive carcinoma. An age of diagnosis of ≥55 years and the presence of symptoms at diagnosis was significantly associated with ≥HGD (p=0.028 and p=0.01, respectively). Regarding imaging features: ≥ 5mm wall thickness, a mural nodule size of ≥ 9 mm, presence of enhancing intra-cystic septa, and heterogenous cyst signal on T2-weighted imaging, were all significantly associated with ≥HGD (p=0.005, p=0.009, p=0.006, and p=0.003, respectively). In multivariate analysis, symptoms at diagnosis (OR 2.78, CI95% 1.13-6.89; p=0.027), lesion size ≥4cm (OR 3.29, CI95% 1.05-10.4; p=0.041) and presence of mural nodule (OR 6.58, CI95% 2.77-15.64; p<0.001) were independent predictive factors of ≥HGD.

Conclusion

MCN causing symptoms at diagnosis, measuring ≥ 4cm and with a mural nodule in imaging, should be addressed for surgical resection. The imaging features predictive of malignancy, that are confirmed in this cohort, should also be considered in surgical management decisions.

References

Vullierme MP, Gregory J, Rebours V, Cros J, Abelhady-Attia Y, Vilgrain V, Aguilera Munoz L, Laurent L, Levy P, Sauvanet A, Ronot M. MRI is useful to suggest and exclude malignancy in mucinous cystic neoplasms of the pancreas. Eur Radiol. 2021 Aug 10; PMID: 34374801

Disclosure

No conflict of interest to disclose

Introduction

Acute pancreatitis (AP) is an inflammatory disorder that causes a considerable economic health burden. While the majority of AP shows a mild clinical course, about 10% of patients have moderate or severe disease with major local and systemic complications and a prolonged hospital stay. Still there is a lack of early biomarkers of severity while multiple complicated scoring systems fail to predict the course of disease. Here, we aim to investigate the role of the microbiome to predict the course of AP at admission.

Aims & Methods

In 16 European centers buccal and rectal swabs were collected from 450 AP patients within the first 72h of hospital admission. All samples were sequenced with Oxford Nanopore Technologies. Primary endpoints are the association of orointestinal microbiome with revised Atlanta classification and severity. Secondary endpoints are the association with mortality and length of hospital stay.

Results

In total, 832 samples from 424 patients were sequenced, 26 patients met exclusion criteria. After normalization of microbial data 409 buccal samples and 391 rectal samples remained for subsequent analysis. Significant differences were observed in beta diversities for rev. Atlanta classification (Bray Curtis, p-value 0.009**), severity (Bray Curtis, p-value 0.008**), mortality (Bray Curtis, p-value 0.006**) and length of hospital stay (Bray Curtis, p-value 0.043*) in rectal but not buccal swabs. Notably, these results remain significant after factoring in 74 potential confounding variables such as alcohol consumption, smoking status, and antibiotics. No differences were observed in alpha-diversity. Classifier for severity was built with different abundant taxa achieving an AUROC of 80%.

Conclusion

The rectal but not oral microbiome has the ability to predict the course of acute pancreatitis at admission of the patient.

Introduction

The majority of pancreatic ductal adenocarcinomas (PDAC) are incurable at presentation but population-based screening is not recommended. Surveillance of asymptomatic high-risk individuals (HRI) with a strong family history or inherited pathogenic genetic variant associated with PDAC can lead to early detection but the survival benefit is unproven

Aims & Methods

We compared the overall survival (OS) and stage distribution of surveillance-detected PDACs in with a control population of patients with PDAC in the United States.
Methods: HRI enrolled in the Cancer of the Pancreas Screening (CAPS) studies from 1998-2021 included individuals who had at >= 1 first-degree relative with PDAC, and who were part of a kindred with at least 1 pair of affected first-degree relatives (familial pancreatic cancer), or were carriers of a gene associated with hereditary pancreatic cancer (ATM, BRCA1, BRCA2, PALB2, STK11 or CDKN2A pathogenic germline variant and/or familial atypical mole melanoma FAMMM, Lynch syndrome, or Peutz-Jeghers syndrome. Those HRIs underwent surveillance with endoscopic ultrasonography (EUS) and magnetic resonance imaging (MRI) and who developed PDAC were compared to matched control patients with PDAC in the National Cancer Institute (NCI) Surveillance, Epidemiology and End Resuts (SEER) Research Plus database. We matched SEER controls to each eligible CAPS case by age at diagnosis, gender, tumor location, and year-of-diagnosis and compared tumor stage and overall survival. We also performed sensitivity analyses to account for lead time bias and to compare resectable PDAC outcomes.

Results

Characteristic	CAPS PDAC Cases N=26	Matched SEER PDAC Controls N=1504	p value
American Joint Committee on Cancer (AJCC) stage - number (%)			< 0.001
1	10 (38.5%)	155 (10.3%)
2	8 (30.8%)	377 (25.1%)
3	1 (3.8%)	163 (10.8%)
4	7 (26.9%)	809 (53.8%)

A total of 1731 HRIs (mean age 60.3 years, 65% women, 52% familial pancreatic cancer relatives) enrolled in the CAPS surveillance program between 1998 and June 2021. 26 PDACs were diagnosed (mean age 65.8 years) at median or 5.8 years (range 1.1-11.2 years) from baseline. Fewer CAPS PDACs were well-differentiated and more were moderately to poorly differentiated compared to controls (5.3% vs. 14.4%, p=0,03). The PDAC size in the CAPS cohort was smaller than in controls (2.5 vs. 3.6cm p<0.001). Resectable T1 tumors (27.3%) were also more common in CAPS cases than in controls (T1 4.4%) (p<0.001). There was significant down-staging in the CAPS participants (38.5% AJCC Stage I, 30.8% Stage II) vs. controls (Stage I: 10.3%, Stage II: 25.1%, p<0.001). At diagnosis, only 26.9% of all CAPS PDACs were distantly metastatic, compared to 53.8% of controls (p=0.01). All CAPS participants who developed PDAC lived longer than 1504 controls (median overall survival (OS): 61.7 months CAPS vs. 8 months controls, 5-year OS: 50% CAPS vs 9% controls, p<0.001). Hazard ratios for the likelihood of death in all controls with PDAC (4.2,95% CI 2.3-7.6, p<0.001) as well as only resectable PDACs (HR = 3.3 95% CI 1.6, 6.7, p=0.001) compared to CAPS patients were comparable after accounting for 3-, 6-, and 12-month lead time bias.

Conclusion

Surveillance of asymptomatic HRI with EUS/MRI leads to detection of lower stage, smaller PDACs, with associated decreased mortality and improved survival in this cohort of patients. The very high long term survival rates for surveillance-detected PDAC are unlikely to be due to lead time bias.