Circulating tumor DNA (ctDNA) is assumed to reflect tumor burden and has been suggested as a tool for prognostication and follow‐up in patients with metastatic pancreatic ductal adenocarcinoma ...(mPDAC). However, the prognostic value of ctDNA and its relation with tumor burden has yet to be substantiated, especially in mPDAC. In this retrospective analysis of prospectively collected samples, cell‐free DNA from plasma samples of 58 treatment‐naive mPDAC patients was isolated and sequenced using a custom‐made pancreatobiliary NGS panel. Pathogenic mutations were detected in 26/58 (44.8%) samples. Cross‐check with droplet digital PCR showed good agreement in Bland–Altman analysis (p = 0.217, nonsignificance indicating good agreement). In patients with liver metastases, ctDNA was more frequently detected (24/37, p < 0.001). Tumor volume (3D reconstructions from imaging) and ctDNA variant allele frequency (VAF) were correlated (Spearman's ρ = 0.544, p < 0.001). Median overall survival (OS) was 3.2 (95% confidence interval CI 1.6–4.9) versus 8.4 (95% CI 1.6–15.1) months in patients with detectable versus undetectable ctDNA (p = 0.005). Both ctDNA VAF and tumor volume independently predicted OS after adjustment for carbohydrate antigen 19.9 and treatment regimen (hazard ratio HR 1.05, 95% CI 1.01–1.09, p = 0.005; HR 1.00, 95% CI 1.01–1.05, p = 0.003). In conclusion, our study showed that ctDNA detection rates are higher in patients with larger tumor volume and liver metastases. Nevertheless, measurements may diverge and, thus, can provide complementary information. Both ctDNA VAF and tumor volume were strong predictors of OS.
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Circulating tumor DNA (ctDNA) attracts much interest as a possible prognostic tool for cancer. Here, the authors showed that the quantity of ctDNA correlated strongly with tumor volume in metastatic pancreatic ductal adenocarcinoma (mPDAC). They conducted a retrospective analysis using samples collected from 58 untreated mPDAC patients. For this study, the authors designed a pancreatobiliary NGS panel, which they used to test the patients’ cell‐free DNA, along with droplet digital PCR. Both ctDNA variant allele frequency and tumor volume predicted overall survival, they found.
To evaluate tumor growth in a series of patients undergoing liver resection after portal vein embolization (PVE).
The regenerative response after PVE leading to compensatory hypertrophy of the ...nonembolized liver segments potentially enhances tumor growth.
Portal vein embolization was performed in 28 patients diagnosed with colorectal metastases between 2004 and 2011. Tumor volume was measured by computed tomography (CT) volumetry before and after PVE. Tumor growth rate (TGR) was measured by CT volumetry and compared with that of a non-PVE control group with colorectal metastases of whom 30 had 2 CT scans preoperatively. Also, newly diagnosed tumors in the future remnant liver (FRL) after PVE and after resection were analyzed.
The median TGR of PVE patients was 0.53 mL/d (interquartile range IQR, 0.02-1.88) versus 0.09 mL/d (IQR, -0.04 to 0.40; P = 0.03) in non-PVE patients. The TGR was 0.15 (IQR, -0.52 to 0.66) mL/d before PVE and 0.85 (IQR, -0.10 to 1.62) mL/d after PVE in the same patients (P = 0.03). Seven patients (25%) showed new tumor lesions in the FRL after PVE, of whom 3 patients (11%) were not resectable. Patients (8 of 19; 42%) after PVE also showed a higher rate of recurrent metastases in the remnant liver at follow-up than non-PVE patients (1 of 28; 4%). Survival was significantly better for non-PVE patients, with a 3-year survival rate of 77% versus 26% in patients undergoing PVE.
Portal vein embolization is associated with increased TGR and new tumor in the FRL and recurrent tumor after resection. Short intervals and interval chemotherapy between PVE and resection are, therefore, advised.
A multicenter, randomized trial of patients with infected necrotizing pancreatitis evaluated immediate drainage within 24 hours after infected necrosis was diagnosed as compared with postponed ...drainage. Immediate drainage was not superior to postponed drainage in reducing complications. Patients assigned to immediate drainage underwent a greater number of invasive procedures.
Keywords: Airway obstruction; branchial arch anomalies; third and fourth branchial pouch sinus; endoscopic cauterization; sclerotherapy Article Note: Editor's Note: This Manuscript was accepted for ...publication on August 26, 2020 The authors have no funding, financial relationships, or conflicts of interest to disclose. Byline: M. Matthijs Fockens, Bernadette S. Bakker, Krijn P. Lienden, Frederik G. Dikkers, Carlijn E.L. Hoekstra
Infected necrotising pancreatitis is a potentially lethal disease and an indication for invasive intervention. The surgical step-up approach is the standard treatment. A promising alternative is the ...endoscopic step-up approach. We compared both approaches to see whether the endoscopic step-up approach was superior to the surgical step-up approach in terms of clinical and economic outcomes.
In this multicentre, randomised, superiority trial, we recruited adult patients with infected necrotising pancreatitis and an indication for invasive intervention from 19 hospitals in the Netherlands. Patients were randomly assigned to either the endoscopic or the surgical step-up approach. The endoscopic approach consisted of endoscopic ultrasound-guided transluminal drainage followed, if necessary, by endoscopic necrosectomy. The surgical approach consisted of percutaneous catheter drainage followed, if necessary, by video-assisted retroperitoneal debridement. The primary endpoint was a composite of major complications or death during 6-month follow-up. Analyses were by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN09186711.
Between Sept 20, 2011, and Jan 29, 2015, we screened 418 patients with pancreatic or extrapancreatic necrosis, of which 98 patients were enrolled and randomly assigned to the endoscopic step-up approach (n=51) or the surgical step-up approach (n=47). The primary endpoint occurred in 22 (43%) of 51 patients in the endoscopy group and in 21 (45%) of 47 patients in the surgery group (risk ratio RR 0·97, 95% CI 0·62–1·51; p=0·88). Mortality did not differ between groups (nine 18% patients in the endoscopy group vs six 13% patients in the surgery group; RR 1·38, 95% CI 0·53–3·59, p=0·50), nor did any of the major complications included in the primary endpoint.
In patients with infected necrotising pancreatitis, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing major complications or death. The rate of pancreatic fistulas and length of hospital stay were lower in the endoscopy group. The outcome of this trial will probably result in a shift to the endoscopic step-up approach as treatment preference.
The Dutch Digestive Disease Foundation, Fonds NutsOhra, and the Netherlands Organization for Health Research and Development.
Background Preoperative portal vein embolization is widely used to increase the future remnant liver. Identification of nonresponders to portal vein embolization is essential because these patients ...may benefit from associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), which induces a more powerful hypertrophy response.99m Tc-mebrofenin hepatobiliary scintigraphy is a quantitative method for assessment of future remnant liver function with a calculated cutoff value for the prediction of postoperative liver failure. The aim of this study was to analyze future remnant liver function before portal vein embolization to predict sufficient functional hypertrophy response after portal vein embolization. Methods Sixty-three patients who underwent preoperative portal vein embolization and computed tomography imaging were included. Hepatobiliary scintigraphy was performed to determine pre–portal vein embolization and post–portal vein embolization future remnant liver function. Receiver operator characteristic analysis of pre–portal vein embolization future remnant liver function was performed to identify patients who would meet the post–portal vein embolization cutoff value for sufficient function (ie, 2.7%/min/m2 ). Results Mean pre–portal vein embolization future remnant liver function was 1.80% ± 0.45%/min/m2 and increased to 2.89% ± 0.97%/min/m2 post–portal vein embolization. Receiver operator characteristic analysis in 33 patients who did not receive chemotherapy revealed that a pre–portal vein embolization future remnant liver function of ≥1.72%/min/m2 was able to identify patients who would meet the safe future remnant liver function cutoff value 3 weeks after portal vein embolization (area under the curve = 0.820). The predictive value was less pronounced in 30 patients treated with neoadjuvant chemotherapy (area under the curve = 0.618). A total of 45 of 63 patients underwent liver resection, of whom 5 of 45 developed postoperative liver failure; 4 of 5 patients had a post–portal vein embolization future remnant liver function below the cutoff value for safe resection. Conclusion When selecting patients for portal vein embolization, future remnant liver function assessed with hepatobiliary scintigraphy can be used as a predictor of insufficient functional hypertrophy after portal vein embolization, especially in nonchemotherapy patients. These patients are potential candidates for ALPPS.
In rheumatoid arthritis (RA) the cause for loss of tolerance and anti-citrullinated protein antibody (ACPA) production remains unidentified. Mouse studies showed that lymph node stromal cells (LNSCs) ...maintain peripheral tolerance through presentation of peripheral tissue antigens (PTAs). We hypothesize that dysregulation of peripheral tolerance mechanisms in human LNSCs might underlie pathogenesis of RA.
Lymph node (LN) needle biopsies were obtained from 24 RA patients, 23 individuals positive for RA-associated autoantibodies but without clinical disease (RA-risk individuals), and 14 seronegative healthy individuals. Ex vivo human LNs from non-RA individuals were used to directly analyze stromal cells. Molecules involved in antigen presentation and immune modulation were measured in LNSCs upon interferon γ (IFNγ) stimulation (
= 15).
Citrullinated targets of ACPAs were detected in human LN tissue and in cultured LNSCs. Human LNSCs express several PTAs, transcription factors autoimmune regulator (AIRE) and deformed epidermal autoregulatory factor 1 (DEAF1), and molecules involved in citrullination, antigen presentation, and immunomodulation. Overall, no clear differences between donor groups were observed with exception of a slightly lower induction of human leukocyte antigen-DR (HLA-DR) and programmed cell death 1 ligand (PD-L1) molecules in LNSCs from RA patients.
Human LNSCs have the machinery to regulate peripheral tolerance making them an attractive target to exploit in tolerance induction and maintenance.
Decision making on optimal treatment strategy in patients with initially unresectable colorectal cancer liver metastases (CRLM) remains complex because uniform criteria for (un)resectability are ...lacking. This study reports on the feasibility and short-term outcomes of The Dutch Colorectal Cancer Group Liver Expert Panel.
The Expert Panel consists of 13 hepatobiliary surgeons and 4 radiologists. Resectability assessment is performed independently by 3 randomly assigned surgeons, and CRLM are scored as resectable, potentially resectable, or permanently unresectable. In absence of consensus, 2 additional surgeons are invited for a majority consensus. Patients with potentially resectable or unresectable CRLM at baseline are evaluated every 2 months of systemic therapy. Once CRLM are considered resectable, a treatment strategy is proposed.
Overall, 398 panel evaluations in 183 patients were analyzed. The median time to panel conclusion was 7 days (interquartile range IQR 5–11 days). Intersurgeon disagreement was observed in 205 (52%) evaluations, with major disagreement (resectable vs permanently unresectable) in 42 (11%) evaluations. After systemic treatment, 106 patients were considered to have resectable CRLM, 84 of whom (79%) underwent a curative procedure. R0 resection (n = 41), R0 resection in combination with ablative treatment (n = 26), or ablative treatment only (n = 4) was achieved in 67 of 84 (80%) patients.
This study analyzed prospective resectability evaluation of patients with CRLM by a panel of radiologists and liver surgeons. The high rate of disagreement among experienced liver surgeons reflects the complexity in defining treatment strategies for CRLM and supports the use of a panel rather than a single-surgeon decision.
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Determining the resectability of locally advanced pancreatic cancer (LAPC) after induction chemotherapy is complex since CT-imaging cannot accurately portray tumor response. We hypothesized that ...CA19-9 response adds to RECIST-staging in predicting resectability of LAPC.
Post-hoc analysis within a prospective study on LAPC (>90° arterial or >270° venous involvement). CA19-9 response was determined after induction chemotherapy. Surgical exploration was performed in RECIST-stable or -regressive disease. The relation between CA19-9 response, resectability and survival was assessed.
Restaging in 54 patients with LAPC after induction chemotherapy (mostly FOLFIRINOX) identified 6 RECIST-regressive, 32 RECIST-stable, and 16 patients with RECIST-progressive disease. The resection rate was 20.3% (11/54 patients). Sensitivity and specificity of RECIST-regression for resection were 40% and 87% whereas the positive predictive value (PPV) and negative predictive value (NPV) were 67% and 68%. Using a 30% decrease of CA19-9 as cut-off, 9/10 patients were correctly classified as resectable (90% sensitivity, PPV 43%) and 3/15 as unresectable (20% specificity, NPV 75%). In the total cohort, a CA19-9 decrease ≥30% was associated with improved survival (22.4 vs. 12.7 months, p = 0.02).
Adding CA19-9 response after induction chemotherapy seems useful in determining which patients with RECIST non-progressive LAPC should undergo exploratory surgery.
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