Pancreatology最新文献

Background

Systemic inflammation and altered metabolism are essential hallmarks of cancer. We hypothesized that the rapid turnover protein transthyretin (TTR) (half-life: 2–3 days), compared with the conventional marker albumin (21 days), better reflects the inflammatory/metabolic dynamics of pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and is a useful prognostic marker.

Methods

Serum TTR and albumin levels were measured in 104 consecutive post-NAT PDAC patients before curative resection. The associations of preoperative TTR and albumin levels with overall survival (OS) after pancreatectomy were retrospectively analyzed.

Results

The mean (SD) TTR and albumin levels were 21.6 (6.4) mg/dL (normal range: ≥22.0 mg/dL) and 3.9 (0.55) g/dL. A low (<22.0 mg/dL) post-NAT TTR level was associated with an advanced tumor stage and higher CEA and CRP levels. Patients with low TTR levels showed significantly worse OS compared with normal levels (3-year OS 39 % vs. 54 %, P = 0.037), although albumin levels did not. We modified prognostic biomarkers of systemic inflammation/metabolism, such as GPS, PNI, and CONUT scores, using the serum TTR instead of albumin level and successfully showed that modified scores were better associated with OS compared with original scores using serum albumin level.

Conclusions

Our data suggest that the TTR level is a promising prognostic biomarker for PDAC patients after NAT.

Background/Objectives

Ambulatory thromboprophylaxis (AT) in patients with pancreatic adenocarcinoma (PAC) reduces venous thromboembolism (VTE) risk and is recommended for patients receiving systemic chemotherapy. We evaluated VTE rates, severity, timing, and risk factors in PAC patients as well as AT rates and initiation times.

Methods

Patients diagnosed with PAC were included. Data collected included patient demographics, medical history, PAC diagnosis, development of VTE, AT, and bleeding episodes. VTE was defined as a DVT or a PE. Patients were classified as receiving AT for VTE prevention if they received a prescription for outpatient anticoagulation.

Results

The cohort included 243 PAC patients. VTE occurred in 24 %. Overall, 52 % developing VTE were hospitalized and 5 % died as a result of the VTE. Of those who developed VTE 50 % were diagnosed within the first 2 months of PAC diagnosis. Univariate predictors of elevated VTE risk included an elevated Onkotev score, metastasis at diagnosis, male gender and not receiving AT. Multivariate predictors of elevated VTE risk included male gender (P = 0.014) and not receiving AT (P = 0.001). Overall, 30 % of patients received AT. The median time from diagnosis to initiation of AT was 43 days. Major bleeding occurred in 5.8 %. Patients receiving AT were not at a significantly increased risk of major bleeding (p = 0.5). Patients with intestinal tumor invasion were at significantly increased risk of major bleeding (P = 0.021).

Conclusion

VTE risk is significant and morbid in PAC patients. AT rates are low, and initiation is often delayed. Therapeutic endoscopists diagnosing PAC may be helpful in AT initiation.

Background

Endoscopic ultrasound (EUS) is the most sensitive method for diagnosing chronic pancreatitis (CP) in its early stages, and Rosemont Classification (RC) is used for its evaluation. Data on the correlation between EUS features and pancreatic exocrine insufficiency (PEI) are limited. We investigated the correlation between the EUS findings and PEI.

Methods

This was a retrospective, monocentric cohort study involving patients prospectively enrolled from 2018 to 2022, with definite or probable CP according to the M-ANNHEIM criteria. All the patients underwent EUS and exocrine function investigations within 12 months of diagnosis. PEI was diagnosed using fecal elastase (FE) or when overt steatorrhea was reversed by pancreatic enzyme replacement therapy. Logistic regression analyses, rank correlation, ROC curve, and area under the curve (AUROC) were performed to evaluate the association between EUS features and PEI, and the accuracy of RC in predicting PEI.

Results

Among 128 patients examined (63.3 % male; mean age, 47 years), 69.5 % were diagnosed with PEI. In multivariate logistic regression among all the RC criteria, only lithiasis in the main pancreatic duct (MPD) was associated with increased risk of PEI (OR 2.92, 95 % CI 1.29–6.61; p = 0.01). Rank analysis showed a weak inverse correlation between RC and FE (Spearman's rho = −0.02; p = 0.03). The accuracy of RC was moderate (AUROC 0.62, p = 0.014).

Conclusions

Among RC EUS features, lithiasis in the MPD is helpful for predicting the risk of PEI, while other findings are of limited utility in evaluating exocrine function.

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.