European evidence-based guidelines on pancreatic cystic neoplasms

Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring = 40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule > 5 mm, and MPD diameter > 10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN

Outcomes and risk score for distal pancreatectomy with celiac axis resection (DP-CAR) : an international multicenter analysis

Background: Distal pancreatectomy with celiac axis resection (DP-CAR) is a treatment option for selected patients with pancreatic cancer involving the celiac axis. A recent multicenter European study reported a 90-day mortality rate of 16%, highlighting the importance of patient selection. The authors constructed a risk score to predict 90-day mortality and assessed oncologic outcomes. Methods: This multicenter retrospective cohort study investigated patients undergoing DP-CAR at 20 European centers from 12 countries (model design 2000-2016) and three very-high-volume international centers in the United States and Japan (model validation 2004-2017). The area under receiver operator curve (AUC) and calibration plots were used for validation of the 90-day mortality risk model. Secondary outcomes included resection margin status, adjuvant therapy, and survival. Results: For 191 DP-CAR patients, the 90-day mortality rate was 5.5% (95 confidence interval [CI], 2.2-11%) at 5 high-volume (1 DP-CAR/year) and 18% (95 CI, 9-30%) at 18 low-volume DP-CAR centers (P=0.015). A risk score with age, sex, body mass index (BMI), American Society of Anesthesiologists (ASA) score, multivisceral resection, open versus minimally invasive surgery, and low- versus high-volume center performed well in both the design and validation cohorts (AUC, 0.79 vs 0.74; P=0.642). For 174 patients with pancreatic ductal adenocarcinoma, the R0 resection rate was 60%, neoadjuvant and adjuvant therapies were applied for respectively 69% and 67% of the patients, and the median overall survival period was 19months (95 CI, 15-25months). Conclusions: When performed for selected patients at high-volume centers, DP-CAR is associated with acceptable 90-day mortality and overall survival. The authors propose a 90-day mortality risk score to improve patient selection and outcomes, with DP-CAR volume as the dominant predictor

Outcomes After Distal Pancreatectomy with Celiac Axis Resection for Pancreatic Cancer: A Pan-European Retrospective Cohort Study

BACKGROUND: Western multicenter studies on distal pancreatectomy with celiac axis resection (DP-CAR), also known as the Appleby procedure, for locally advanced pancreatic cancer are lacking. We aimed to study overall survival, morbidity, mortality and the impact of preoperative hepatic artery embolization (PHAE). METHODS: Retrospective cohort study within the European-African Hepato-Pancreato-Biliary-Association, on DP-CAR between 1-1-2000 and 6-1-2016. Primary endpoint was overall survival. Secondary endpoints were radicality (R0-resection), 90-day mortality, major morbidity, and pancreatic fistulae (grade B/C). RESULTS: We included 68 patients from 20 hospitals in 12 countries. Postoperatively, 53% of patients had R0-resection, 25% major morbidity, 21% an ISGPS grade B/C pancreatic fistula, and 16% mortality. In total, 82% received (neo-)adjuvant chemotherapy and median overall survival in 62 patients with pancreatic ductal adenocarcinoma patients was 18 months (CI 10-37). We observed no impact of PHAE on ischemic complications. CONCLUSIONS: DP-CAR combined with chemotherapy for locally advanced pancreatic cancer is associated with acceptable overall survival. The 90-day mortality is too high and should be reduced. Future studies should investigate to what extent increasing surgical volume or better patient selection can improve outcomes

Identification of MicroRNA-21 as a Biomarker for Chemoresistance and Clinical Outcome Following Adjuvant Therapy in Resectable Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy.Formalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real-Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52) showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR) for death (HR = 0.316; 95%CI = 0.166–0.600; P = 0.0004) and recurrence (HR = 0.521; 95%CI = 0.280–0.967; P = 0.04). MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells.. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC

Locally advanced pancreatic cancer: Work-up, staging, and local intervention strategies

Locally advanced pancreatic cancer (LAPC) has several definitions but essentially is a nonmetastasized pancreatic cancer, in which upfront resection is considered not beneficial due to extensive vascular involvement and consequent high chance of a nonradical resection. The introduction of FOLFIRINOX chemotherapy and gemcitabine-nab-paclitaxel (gem-nab) has had major implications for the management and outcome of patients with LAPC. After 4–6 months induction chemotherapy, the majority of patients have stable disease or even tumor-regression. Of these, 12 to 35% are successfully downstaged to resectable disease. Several studies have reported a 30–35 months overall survival after resection; although it currently remains unclear if this is a result of the resection or the good response to chemotherapy. Following chemotherapy, selection of patients for resection is difficult, as contrast-enhanced computed-tomography (CT) scan is unreliable in differentiating between viable tumor and fibrosis. In case a resection is not considered possible but stable disease is observed, local ablative techniques are being studied, such as irreversible electroporation, radiofrequency ablation, and stereotactic body radiation therapy. Pragmatic, multicenter, randomized studies will ultimately have to confirm the exact role of both surgical exploration and ablation in these patients. Since evidence-based guidelines for the management of LAPC are lacking, this review proposes a standardized approach for the treatment of LAPC based on the best available evidence

Suppressing quantum errors by scaling a surface code logical qubit

Practical quantum computing will require error rates that are well below what is achievable with physical qubits. Quantum error correction offers a path to algorithmically-relevant error rates by encoding logical qubits within many physical qubits, where increasing the number of physical qubits enhances protection against physical errors. However, introducing more qubits also increases the number of error sources, so the density of errors must be sufficiently low in order for logical performance to improve with increasing code size. Here, we report the measurement of logical qubit performance scaling across multiple code sizes, and demonstrate that our system of superconducting qubits has sufficient performance to overcome the additional errors from increasing qubit number. We find our distance-5 surface code logical qubit modestly outperforms an ensemble of distance-3 logical qubits on average, both in terms of logical error probability over 25 cycles and logical error per cycle ($2.914\%\pm 0.016\%$ compared to $3.028\%\pm 0.023\%$). To investigate damaging, low-probability error sources, we run a distance-25 repetition code and observe a $1.7\times10^{-6}$ logical error per round floor set by a single high-energy event ($1.6\times10^{-7}$ when excluding this event). We are able to accurately model our experiment, and from this model we can extract error budgets that highlight the biggest challenges for future systems. These results mark the first experimental demonstration where quantum error correction begins to improve performance with increasing qubit number, illuminating the path to reaching the logical error rates required for computation.Comment: Main text: 6 pages, 4 figures. v2: Update author list, references, Fig. S12, Table I

Measurement-induced entanglement and teleportation on a noisy quantum processor

Measurement has a special role in quantum theory: by collapsing the wavefunction it can enable phenomena such as teleportation and thereby alter the "arrow of time" that constrains unitary evolution. When integrated in many-body dynamics, measurements can lead to emergent patterns of quantum information in space-time that go beyond established paradigms for characterizing phases, either in or out of equilibrium. On present-day NISQ processors, the experimental realization of this physics is challenging due to noise, hardware limitations, and the stochastic nature of quantum measurement. Here we address each of these experimental challenges and investigate measurement-induced quantum information phases on up to 70 superconducting qubits. By leveraging the interchangeability of space and time, we use a duality mapping, to avoid mid-circuit measurement and access different manifestations of the underlying phases -- from entanglement scaling to measurement-induced teleportation -- in a unified way. We obtain finite-size signatures of a phase transition with a decoding protocol that correlates the experimental measurement record with classical simulation data. The phases display sharply different sensitivity to noise, which we exploit to turn an inherent hardware limitation into a useful diagnostic. Our work demonstrates an approach to realize measurement-induced physics at scales that are at the limits of current NISQ processors

Non-Abelian braiding of graph vertices in a superconducting processor

Indistinguishability of particles is a fundamental principle of quantum mechanics. For all elementary and quasiparticles observed to date - including fermions, bosons, and Abelian anyons - this principle guarantees that the braiding of identical particles leaves the system unchanged. However, in two spatial dimensions, an intriguing possibility exists: braiding of non-Abelian anyons causes rotations in a space of topologically degenerate wavefunctions. Hence, it can change the observables of the system without violating the principle of indistinguishability. Despite the well developed mathematical description of non-Abelian anyons and numerous theoretical proposals, the experimental observation of their exchange statistics has remained elusive for decades. Controllable many-body quantum states generated on quantum processors offer another path for exploring these fundamental phenomena. While efforts on conventional solid-state platforms typically involve Hamiltonian dynamics of quasi-particles, superconducting quantum processors allow for directly manipulating the many-body wavefunction via unitary gates. Building on predictions that stabilizer codes can host projective non-Abelian Ising anyons, we implement a generalized stabilizer code and unitary protocol to create and braid them. This allows us to experimentally verify the fusion rules of the anyons and braid them to realize their statistics. We then study the prospect of employing the anyons for quantum computation and utilize braiding to create an entangled state of anyons encoding three logical qubits. Our work provides new insights about non-Abelian braiding and - through the future inclusion of error correction to achieve topological protection - could open a path toward fault-tolerant quantum computing

Pancreatic cystic neoplasms: Different types, different management, new guidelines

Pancreatic cystic neoplasms (PCN) include different types of cysts with various biological behavior. The most prevalent PCN are intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), and serous cystic neoplasm (SCN). Management of PCN should focus on the prevention of malignant progression, while avoiding unnecessary morbidity of surgery. This requires specialized centers with dedicated multidisciplinary PCN teams. The malignant potential of PCN varies enormously between the various types of PCN. A combination of computed tomography, magnetic resonance imaging/magnetic resonance cholangiopancreatography, and endoscopic ultrasound with or without fine needle aspiration is typically needed before a reliable diagnosis can be made. Several guidelines discuss the management of PCN; however, most of these are non-evidence-based without clear consensus on the optimal treatment and follow-up strategy. The 2018 European guidelines on PCN are the first evidence-based guidelines to include IPMN, MCN, SCN, and all other PCN. This guideline advises a more conservative approach to side-branch IPMN and MCN smaller than 40 mm and more often a surgical approach in IPMN with a main duct dilatation beyond 5 mm. The goal of this review is to summarize the different types and management of the most common PCN based on the current literature and guidelines