Pancreatic ductal adenocarcinoma (PDAC) has an extraordinarily dense fibrotic stroma that impedes tumor perfusion and delivery of anticancer drugs. Since the extracellular matrix (ECM) comprises the ...bulk of the stroma, it is primarily responsible for the increased interstitial tissue pressure and stiff mechanical properties of the stroma. Besides its mechanical influence, the ECM provides important biochemical and physical cues that promote survival, proliferation, and metastasis. By serving as a nutritional source, the ECM also enables PDAC cells to survive under the nutrient-poor conditions. While therapeutic strategies using stroma-depleting drugs have yielded disappointing results, an increasing body of research indicates the ECM may offer a variety of potential therapeutic targets. As preclinical studies of ECM-targeted drugs have shown promising effects, a number of clinical trials are currently investigating agents with the potential to advance the future treatment of PDAC. Thus, the present review seeks to give an overview of the complex relationship between the ECM and PDAC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Abstract Background Chylous leakage is a relevant clinical problem after major abdominal surgery leading to an increased length of stay. Data sources A systematic search of MEDLINE/PubMed and the ...Cochrane Library was performed according to the PRISMA statement. The search for the MeSH terms “chylous ascites” and/or “lymphatic fistula” retrieved a total of 2,348 articles, of which 36 full-text articles were reviewed by 2 independent investigators. Results Chylous ascites is described with an incidence of up to 11%, especially after pancreatic surgery. The incidence is increasing with the number of lymph nodes harvested. In patients treated with total parenteral nutrition, conservative treatment is demonstrated to be effective in up to 100% of cases. Conclusions The extent of abdominal surgery mainly predicts the risk of chylous ascites. Conservative treatment has been shown to be effective in almost all cases and is the treatment of choice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
IMPORTANCE: In the past decade, the use of neoadjuvant therapy (NAT) has increased for patients with borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Data on pancreatic ...fistula and related overall survival (OS) in this setting are limited. OBJECTIVE: To compare postoperative complications in patients undergoing either upfront resection or pancreatectomy following NAT, focusing on clinically relevant postoperative pancreatic fistula (CR-POPF) and potential associations with OS. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted on data from patients who underwent pancreatic resection for PDAC at the Massachusetts General Hospital from January 1, 2007, to December 31, 2017, EXPOSURES: Pancreatic cancer surgery with or without NAT. MAIN OUTCOMES AND MEASURES: Overall morbidity and CR-POPF rates were compared between NAT and upfront resection. Factors associated with CR-POPF were assessed with univariate and multivariate analysis. Survival data were analyzed by Kaplan-Meier curves and a Cox proportional hazards regression model. RESULTS: Of 753 patients, 364 were men (48.3%); median (interquartile range) age was 68 (61-75) years. A total of 346 patients (45.9%) received NAT and 407 patients (54.1%) underwent upfront resection. At pathologic examination, NAT was associated with smaller tumor size (mean SD, 26.0 15.3 mm vs 32.7 14.4 mm; P < .001), reduced nodal involvement (102 25.1% vs 191 55.2%; P < .001), and higher R0 rates (257 74.3% vs 239 58.7%; P < .001). There were no significant differences in severe complication rate or 90-day mortality. The rate of CR-POPF was 3.6-fold lower in patients receiving NAT vs upfront resection (13 3.8% vs 56 13.8%; P < .001). In addition, factors associated with CR-POPF changed after NAT, and only soft pancreatic texture was associated with a higher risk of CR-POPF (38.5% vs 6.3%; P < .001). Survival analysis showed no differences between patients with or without CR-POPF after upfront resection (26 vs 25 months; P = .66), but after NAT, a worse overall survival rate was observed in patients with CR-POPF (17 vs 34 months; P = .002). This association was independent of other established predictors of overall survival by multivariate analysis (hazard ratio, 2.80; 95% CI, 1.44-5.45; P < .002). CONCLUSIONS AND RELEVANCE: Neoadjuvant therapy may be associated with a significant reduction in the rate of CR-POPF. In addition, standard factors associated with CR-POPF appear to be no longer applicable following NAT. However, once CR-POPF occurs, it is associated with a significant reduction in long-term survival. Patients with CR-POPF may require closer follow-up and could benefit from additional therapy.
In patients with pancreatic ductal adenocarcinoma (PDAC), the tumor microenvironment consists of cellular and stromal components that influence prognosis. Hence, tumor-infiltrating lymphocytes (TILs) ...may predict prognosis more precisely than conventional staging systems. Studies on the impact of TILs are heterogeneous and further research is needed. Therefore, this study aims to point out the importance of peritumoral TILs, tumor-infiltrating neutrophils (TINs), and immune subtype classification in PDAC. Material from 57 patients was analyzed with immunohistochemistry performed for CD3, CD8, CD20, CD66b, α-sma, and collagen. Hot spots with peritumoral TILs and TINs were quantified according to the QTiS algorithm and the distance of TILs hot spots to the tumor front was measured. Results were correlated with overall (OS) and progression-free survival (PFS). High densities of peritumoral hot spots with CD3⁺, CD8⁺, and CD20⁺ TILs correlated significantly with improved OS and PFS. Combined immune cell subtypes predicted improved OS and PFS. High infiltration of CD3⁺ TILs predicted progression after 12 months. The location of TILs' hot spots and their distance to the tumor front did not correlate with patient survival. Peritumoral TILs and the composition of the stroma predict OS and PFS in PDAC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Surgical resection improves survival in pancreatic ductal adenocarcinoma (PDAC) and adjuvant chemotherapy adds an additional survival-benefit. While surgical technique has improved in recent years, ...it remains unclear whether these improvements translate into a survival benefit independent of adjuvant chemotherapy. Thus, we aimed to clarify whether survival of patients who were treated with either Gemcitabine (GEM) or who were observed only in randomized controlled trials on adjuvant chemotherapy of PDAC improved over time.
A systematic search of MEDLINE/PubMed was performed to identify randomized controlled trials on adjuvant chemotherapy of PDAC. The search was limited to studies with arms on GEM monotherapy or postoperative observation and studies were grouped by the median year of enrolment and the use of GEM. Subsequently, a meta-regression on the effect of the median year of enrolment on patient survival was performed.
A total of 13 studies with 2469 patients was included, with median years of enrollment ranging from 1996 to 2015. While disease-free survival decreased in patients with postoperative observation (18.0 vs. 5.0 months, p = 0.001), median survival improved over time in patients with postoperative observation (15.8 vs. 18.4 months, p = 0.01) and in patients treated with adjuvant GEM (22.8 vs. 35.0 months, p < 0.001). One- (p ≤ 0.01) and two-year survival (p = 0.056) improved in both patients treated with adjuvant GEM and those observed only.
Survival after surgical resection of PDAC has improved since 1996, even in patients who did not receive adjuvant chemotherapy. Improved surgical technique and postoperative management are likely to be causative factors.
•Median survival has improved after survival of PDAC since 1996•Median survival improved in patients observed only over time•Median survival improved in patients treated with adjuvant gemcitabine over time
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To assess the perioperative and long-term outcome following pulmonary resection in patients with metachronous metastasis of pancreatic ductal adenocarcinoma (PDAC).
Most patients with PDAC relapse or ...develop tumor spread to secondary organs. Currently, it remains unclear how to proceed with pulmonary metastasis in the metachronous setting. In particular, the role of surgery remains controversial.
Data of patients with pulmonary metachronous metastasis after PDAC collected from 2003 to 2015 in databases of two high-volume pancreatic cancer centers were retrospectively analyzed. Clinical and pathological aspects of primary PDAC as well as the perioperative and long-term outcome following pulmonary metastasectomy (PM) was evaluated, respectively. Patients with synchronous liver metastasis or metastasis to other secondary organs were excluded. Univariate survival analysis was performed.
We identified 15 patients undergoing pulmonary resection for suspected metastasis after primary pancreatic resection. Operative and histopathologic evaluation revealed resectable pancreatic pulmonary metastasis in 11 patients (73.3%). The median disease-free survival (DFS) and overall survival (OS) after PM diagnosis was 18 months and 26 months, respectively. The median time to metachronous metastasis (TMM) was 17 months 3–64 months. Perioperative morbidity was low with only one readmission (8.3%). There was no perioperative mortality. Patients who developed pulmonary metastasis later than 17 months after primary surgery showed better OS compared to those who did earlier (32.2 vs. 14.75 months, p = 0.025). In addition, patients with high-grade tumors had worse survival (12.4 vs. 31 months, p = 0.02). Elevated serum CEA levels or CA 19-9 levels were also not associated with shortened OS.
This study suggests that pulmonary metastasectomy after PDAC is safe and effective. Patients with extended DFS after primary pancreatic surgery as well as favorable tumor grading seem to particularly benefit from pulmonary surgery.
•Total pulmonary metastasectomy of metachronic disease after PDAC is safe with little perioperative morbidity and mortality.•Extended DFS after primary pancreatic surgery favors benefits from pulmonary surgery.•Low grade pancreatic tumors are more likely to profit from pulmonary metastasectomy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
ZusammenfassungHintergrundZystische Läsionen an der Bauchspeicheldrüse werden immer häufiger akzidentell bei meist asymptomatischen Patienten entdeckt. Die klinische Einordnung solcher Zufallsbefunde ...gestaltet sich oft schwierig und verunsichert Ärzt:innen wie Patient:innen gleichermaßen.FragestellungStand der aktuellen Empfehlungen zum Umgang mit zystischen Pankreasläsionen.Material und MethodenSelektive Literaturrecherche in PubMed unter Berücksichtigung aktueller Leitlinien.ErgebnisseEssenziell ist die korrekte diagnostische Einordnung der zystischen Läsion, da sich hieraus das weitere Vorgehen ergibt. Eine Resektion wird in der Regel für muzinös-zystische Neoplasien (MCN), solide pseudopapillare Neoplasien (SPN) und intraduktale papillar-muzinöse Neoplasien (IPMN) mit relevanten Risikomerkmalen wie deutlicher Hauptgangdilatation empfohlen. Die IPMN ohne Risikomerkmale sollten regelmäßige kontrolliert werden, sofern Komorbiditäten und Lebenserwartung eine Resektion im Verlauf noch zulassen. Die serös-zystischen Neoplasien (SCN) sind benigne und müssen nur bei klinischen Beschwerden reseziert werden. Entzündliche Pankreaszysten sollten nur unter bestimmten Umständen behandelt werden.
Neoadjuvant chemotherapy has become a powerful tool to convert borderline resectable (BRPC) and locally advanced pancreatic cancers (LAPC) into a resectable scenario. However, data analyzing the ...optimal type of therapy are scarce. In the present multicenter retrospective study, we evaluated the influence of FOLFIRINOX (FFX) and gemcitabine (GEM)-based neoadjuvant therapy on patient prognosis.
Data on 239 patients from 7 centers across Europe was gathered using an online database. Patients having received their first cycle of chemotherapy for BRPC/LAPC before 06/2017, with a minimum follow-up of 12 months, were included in the intention-to-treat analysis.
Patients treated with neoadjuvant FFX (n = 135) or gemcitabine + nab-paclitaxel (GNP) (n = 38) had significantly improved radiological response according to RECIST criteria as compared to single-agent GEM (n = 16), with a partial/complete response of 59.3%, 55.3% and 6.25% respectively (p = 0.001). Treatment with FFX (n = 135) and GNP (n = 38) resulted in higher resection rates compared to GEM (73.3%, 81.6% and 43.8%; p = 0.01 and p = 0.005). Regardless of regimen, patients who were resected had significantly prolonged overall survival compared to non-resected patients (p < 0.01). Complete pathological responses (ypT0 ypN0) were predominantly observed with FFX (p = 0.01). Adjuvant GNP in addition to successful neoadjuvant therapy and surgery resulted in a trend towards improved median survival as compared to postoperative observation (47.0 vs. 30.1 months, p = 0.06).
Representing one of the largest studies published so far, our results reveal that patients with BRPC/LAPC should be offered either FFX or GNP to improve chances of resection and with this also survival.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Non-resectability is common in patients with pancreatic ductal adenocarcinoma (PDAC) due to local invasion or distant metastases. Then, biliary or gastroenteric bypasses or both are often established ...despite associated morbidity and mortality. The current study explores outcomes after palliative bypass surgery in patients with non-resectable PDAC.
From the prospectively maintained German StuDoQ|Pancreas registry, all patients with histopathologically confirmed PDAC who underwent non-resective pancreatic surgery between 2013 and 2018 were retrospectively identified, and the influence of the surgical procedure on morbidity and mortality was analyzed.
Of 389 included patients, 127 (32.6%) underwent explorative surgery only, and a biliary, gastroenteric or double bypass was established in 92 (23.7%), 65 (16.7%) and 105 (27.0%). After exploration only, patients had a significantly shorter stay in the intensive care unit (mean 0.5 days SD 1.7 vs. 1.9 3.6, 2.0 2.8 or 2.1 2.8; P < 0.0001) and in the hospital (median 7 days IQR 4-11 vs. 12 10-18, 12 8-19 or 12 9-17; P < 0.0001), and complications occurred less frequently (22/127 17.3% vs. 37/92 40.2%, 29/65 44.6% or 48/105 45.7%; P < 0.0001). In multivariable logistic regression, biliary stents were associated with less major (Clavien-Dindo grade ≥ IIIa) complications (OR 0.49 95% CI 0.25-0.96, P = 0.037), whereas-compared to exploration only-biliary, gastroenteric, and double bypass were associated with more major complications (OR 3.58 1.48-8.64, P = 0.005; 3.50 1.39-8.81, P = 0.008; 4.96 2.15-11.43, P < 0.001).
In patients with non-resectable PDAC, biliary, gastroenteric or double bypass surgery is associated with relevant morbidity and mortality. Although surgical palliation is indicated if interventional alternatives are inapplicable, or life expectancy is high, less invasive options should be considered.
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