Pancreatology最新文献

Background

Early tumor shrinkage (ETS) is a prognostic predictor for patients treated with chemotherapy in colorectal cancer, although scarce studies evaluated its potential in locally advanced pancreatic cancer (LAPC). In this exploratory analysis of JCOG1407, a randomized phase II study comparing modified 5-fluorouracil, levofolinate, irinotecan, and oxaliplatin (mFOLFIRINOX) and gemcitabine plus nab-paclitaxel (GnP), we evaluated whether ETS can predict prognosis of patients with LAPC.

Methods

Of the 126 patients enrolled in JCOG1407, 112 with measurable lesions were included in this study. ETS was defined as a ≥20 % reduction in tumor diameter compared with baseline at the initial imaging assessment 6–10 weeks after initiating chemotherapy. Patients were divided into the ETS (achieved ETS) and non-ETS (failed to achieve ETS) groups based on their ETS status. The impact of ETS on overall survival (OS) was compared using multivariable Cox regression analysis.

Results

Fourteen of 55 (25.5 %) and 24 of 57 (42.1 %) patients in the mFOLFIRINOX and GnP arms, respectively, achieved ETS. In the overall population, mFOLFIRINOX arm, and GnP arm, the median OS in the ETS and non-ETS groups was 27.1 and 20.4, 29.8 and 20.6, and 24.1 and 20.4, months, respectively. The adjusted hazard ratios of OS for the ETS group in the overall population, mFOLFIRINOX arm, and GnP arm were 0.451 (95 % confidence interval [CI]: 0.270–0.754), 0.371 (95 % CI: 0.149–0.926), and 0.508 (95 % CI: 0.255–1.004), respectively.

Conclusions

ETS may be a prognostic predictor in chemotherapy-naïve patients with LAPC treated with mFOLFIRINOX or GnP.

Background

Universal surgical prophylaxis for pancreatoduodenectomy (PD) is practiced, with cephalosporins recommended in most guidelines. Recent studies suggest piperacillin-tazobactam (PTZ) prophylaxis in biliary-stented patients is superior in preventing surgical site infections (SSIs). This study aims to refine surgical prophylaxis recommendations based on the local microbial profile and evaluate the clinical outcomes of biliary-stented compared with non-stented patients.

Methods

This was a retrospective study of all consecutive PD patients at Singapore General Hospital between January 2013 to December 2019. The primary outcome was post-operative SSI rates. Secondary outcomes included rates of ceftriaxone-resistant Klebsiella pneumoniae, Escherichia coli, and Enterococcus species from intraoperative bile cultures and 30-day mortality.

Results

There were 130 biliary-stented and 211 non-stented patients included. Majority of biliary-stented patients received ceftriaxone ± metronidazole prophylaxis (83/130, 63.8 %) while 30/130 (23.8 %) received PTZ. Most non-stented patients received ceftriaxone ± metronidazole prophylaxis (163/211, 77.3 %). Between biliary-stented and non-stented patients, post-operative SSIs (40.8 % vs 38.4 %, p = 0.662), and 30-day mortality rates (1.5 % vs 1.4 %, p = 1.000) were comparable. The adjusted odds of post-operative SSIs was significantly lower in biliary-stented patients prescribed PTZ as compared to non-PTZ prophylaxis (0.29, 95 % CI (0.10–0.79), p = 0.015). Ceftriaxone-resistant Klebsiella spp. and/or Escherichia coli (27.6 % vs 3.8 %, p < 0.001) as well as Enterococcus species (46.1 % vs 11.5 %, p < 0.001), were more prevalent in intraoperative bile cultures of biliary-stented patients, while frequencies in non-stented patients were low.

Conclusion

PTZ prophylaxis effectively reduced SSIs in stented patients post-pancreatoduodenectomy. Based on the local microbial profile, ceftriaxone prophylaxis may be used for prophylaxis in non-stented patients.

Background objectives

The aim of this study was to determine the role of site-specific metastatic patterns over time and assess factors associated with extended survival in metastatic PDAC. Half of all patients with pancreatic ductal adenocarcinoma (PDAC) present with metastatic disease. The site of metastasis plays a crucial role in clinical decision making due to its prognostic value.

Methods

We examined 56,757 stage-IV PDAC patients from the National Cancer Database (2016–2019), categorizing them by metastatic site: multiple, liver, lung, brain, bone, carcinomatosis, or other. The site-specific prognostic value was assessed using log-rank tests while time-varying effects were assessed by Aalen's linear hazards model. Factors associated with extended survival (>3years) were assessed with logistic regression.

Results

Median overall survival (mOS) in patients with distant lymph node-only metastases (9.0 months) and lung-only metastases (8.1 months) was significantly longer than in patients with liver-only metastases (4.6 months, p < 0.001). However, after six months, the metastatic site lost prognostic value. Logistic regression identified extended survivors (3.6 %) as more likely to be younger, Hispanic, privately insured, Charlson-index <2, having received chemotherapy, or having undergone primary or distant site surgery (all p < 0.001).

Conclusion

While synchronous liver metastases are associated with worse outcomes than lung-only and lymph node-only metastases, this predictive value is diminished after six months. Therefore, treatment decisions beyond this time should not primarily depend on the metastatic site. Extended survival is possible in a small subset of patients with favorable tumor biology and good conditional status, who are more likely to undergo aggressive therapies.

Dysregulation of the epigenomic landscape of tumor cells has been implicated in the pathogenesis of pancreatic cancer. However, these alterations are not only restricted to neoplastic cells. The behavior of other cell populations in the tumor stroma such as cancer-associated fibroblasts, immune cells, and others are mostly regulated by epigenetic pathways. Here, we present an overview of the main cellular and acellular components of the pancreatic cancer tumor microenvironment and discuss how the epigenetic mechanisms operate at different levels in the stroma to establish a differential gene expression to regulate distinct cellular phenotypes contributing to pancreatic tumorigenesis.

Introduction

Inflammation-induced dysregulation of the coagulation cascade and vascular stasis in hospitalized patients with acute necrotizing pancreatitis (ANP) serve as a milieu for venous thromboembolism (VTE). Deep vein thrombosis (DVT) and pulmonary embolism (PE) are often underrecognized. We evaluated the incidence and risk factors for VTE in a cohort of patients with ANP.

Methods

All adult patients with ANP at our center between 2009 and 2022 were followed for three months after index hospitalization and categorized into cases and controls based on development of VTE. Demographic, clinical, and radiologic characteristics during admission were compared. A multivariable analysis was done to identify independent predictors for VTE. A p value of <0.05 was taken as significant.

Results

Among 643 ANP patients, 512 [males-350, median age-52 years] were eligible for inclusion. VTE developed in 64 (12.5 %) patients – 28 DVT (5 %), 22 PE (4 %) and both in 14 (3 %) after a median 16 days from the diagnosis of ANP. Significant independent predictors for VTE on multivariable analysis were age ≥60 years (OR 1.91; 95 % CI 1.04–3.53), peri-pancreatic extent of necrosis (OR 7.61; 95 % CI 3.94–14.70), infected necrosis (OR 2.26; 95 % CI 1.13–4.50) and total length of stay ≥14 days (OR 4.08; 95 % CI 1.75–9.50).

Conclusions

The overall incidence of VTE in our cohort of patients with ANP was 12.5 %, which was usually diagnosed within one month of hospitalization. High-risk patients can be stratified based on clinical and imaging characteristics and may benefit from intensive DVT screening and prophylaxis during hospitalization and following discharge.

Background

Acute pancreatitis is a common disease that is usually mild and self-limiting. Early discharge of patients with mild acute pancreatitis, with the use of supporting outpatient services including remote monitoring or smartphone applications, might be safe and could reduce the healthcare demand. The objective of this review was to provide a comprehensive overview of existing strategies aimed at facilitating early discharge of patients diagnosed with mild acute pancreatitis and to assess clinical outcomes, feasibility and costs associated with these strategies.

Methods

PubMed, Cochrane, Embase, and Web of Science were systematically searched, to identify studies that evaluated strategies to reduce the length of hospital stay in patients with mild acute pancreatitis.

Results

Five studies, including 84 to 419 patients each, were identified and described three different early discharge protocols. The early discharge strategies resulted in a median length of hospital stay of a minimum of 6 to a maximum of 23 h in these studies. Early discharge compared to usual care did not result in increased 30-day readmissions. Additionally, no occurrences of complications or mortality were observed in either group. A significant reduction in overall costs was reported ranging from 43.1 % to 85.4 %.

Conclusions

Early discharge of patients with mild acute pancreatitis seems both feasible and safe. Further studies are warranted, since focus on safe early discharge could significantly reduce inpatient healthcare utilization and associated costs.

Background

PDAC cells upregulate carbonic anhydrase 9 (CA9) expression in order to survive in hypoxic tumor environments, which plays a key role in tumor progression. However, the relationship between CA9 expression and preoperative treatment has not been clarified. We evaluated the clinical impact of CA9 expression on the efficacy of neoadjuvant chemoradiotherapy (NACRT) in pancreatic ductal adenocarcinoma (PDAC).

Methods

We investigated CA9 expression in 273 surgical specimens and 20 serum samples obtained from patients with PDAC and evaluated their clinical outcomes. We analyzed the function of CA9 using human pancreatic cancer cell lines.

Results

CA9 was positively expressed in 36.2 % of patients who underwent NACRT, which was significantly lower than those who underwent upfront surgery (US) (58.9 %, p < 0.001). Interestingly, patients who were CA9-positive in the US group had a significantly poorer prognosis than that of those in the NACRT group (median survival time [MST], 21.5 months vs. 49.2 months, p < 0.001), while there was no significant difference between patients who were CA9-negative in the US and NACRT groups (MST, 45.8 months vs. 46.3 months, p = 0.357). Moreover, serum CA9 levels tended to correlate positively with CA9 expression in cancer tissues. In-vitro experiments demonstrated that CA9 expression was reduced after treatments with radiation and chemoradiation therapy (RT/CRT), and that CA9 knockdown suppressed the impact of RT/CRT on cancer cell proliferation.

Conclusions

CA9 may act as a target molecule for RT/CRT, highlighting its clinical importance as a valuable biomarker for more stringent indications for NACRT.

Background

Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) usage has been associated with pancreatic ductal adenocarcinoma (PDAC) prevention, though epidemiological data have not reliably demonstrated this. The aim of this study is to identify if aspirin and other NSAIDs are effective in the primary prevention of PDAC in a large UK prospective cohort.

Methods

A nested case-control study was conducted using the UK Biobank cohort. Incident PDAC cases (n = 1129 of whom 239 (21.2 %) were using aspirin) were age and sex-matched with cancer-free controls (n = 8822 of whom 1752 (19.9 %) were using aspirin). Conditional logistic regression models were used to generate odds ratios (ORs) and 95 % confidence intervals (CI) for risk of PDAC with and without regular use of aspirin, non-aspirin NSAIDs and all NSAIDs respectively. Exploratory analyses were carried out assessing interactions with diabetes mellitus (DM) as a condition with increased pancreatic cancer risk.

Results

Regular aspirin use at initial recruitment was independently associated with a decreased risk of PDAC (OR [95 % CI] = 0.80 [0.68–0.95] P = 0.01). Regular non-aspirin NSAID use was not associated with a risk reduction of PDAC (OR [95 % CI] = 1.01 [0.84–1.23] P = 0.88). Exploratory analyses showed that in those with DM; regular aspirin use reduced risk of PDAC (OR [95 % CI] = 0.60 [0.42–0.85] P = 0.004) compared to non-use.

Discussion

Regular aspirin use is associated with a reduction in risk of PDAC. The reduced risk is more apparent in participants with DM.