Visceral Medicine最新文献

Background: The advent of next-generation sequencing technologies has enabled the identification of molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) with different biological traits and clinically targetable features.

Summary: Although current chemotherapy trials are currently exploiting this knowledge, these molecular subtypes have not yet sufficiently caught the attention of surgeons. In fact, integration of these molecular subtypes into the timing of surgery can in theory improve patient outcome. Here, we present the molecular subtypes of PDAC from the surgeon's perspective and a clinically applicable algorithm that integrates the molecular subtyping of PDAC preoperatively into the decision of primary surgery versus neoadjuvant therapy. Furthermore, we point out the potential of "tailored" (in addition to conventional) neoadjuvant treatment for exploiting the molecular subtypes of PDAC.

Key messages: We believe that for surgeons, the preoperative knowledge on the subtype of PDAC can properly guide in deciding between upfront surgery versus neoadjuvant treatment for improving patient outcome.

Introduction: Several endoscopic methods can be employed to manage post-bariatric leaks. However, endoluminal vacuum therapy (EVT) and endoscopic internal drainage (EID) are relatively new methods, and studies regarding these methods are scarce. We performed a systematic review of the literature and a meta-analysis to evaluate the efficacy of EVT and EID.

Methods: Databases were searched for eligible studies. The clinical success of leak closure was the primary outcome of interest. A proportional meta-analysis was performed for pooling the primary outcome using a fixed-effects model. A meta-analysis or descriptive analysis of other outcomes was performed based on the data availability.

Results: Data from 3 EVT and 10 EID studies (n = 279) were used for evidence synthesis. The leak closure rates (95% confidence interval [CI]) of EVT and EID were 85.2% (75.1%-95.4%) and 91.6% (88.1%-95.2%), respectively. The corresponding mean treatment durations (95% CI) were 28 (2.4-53.6) and 78.4 (50.1-106.7) days, respectively. However, data about other outcomes were extremely limited; thus, a pooled analysis could not be performed.

Conclusions: Both EVT and EID were effective when used as the first-line treatment for post-bariatric leaks. However, larger studies must be conducted to compare the efficacy of the 2 interventions.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that has no effective early detection method or treatment to date.

Summary: The normal cell type that initiates PDAC, or its cellular origin, is still unknown. To investigate the contribution of distinct normal epithelial cell types to PDAC tumorigenesis, genetically engineered mouse models were used to show that both acinar and ductal cells are capable of giving rise to PDAC. These studies indicated that genetic mutations and pancreatic injury interact differently with each cellular origin to affect their predilection and process for forming PDAC. In this review, we summarize recent findings using various genetically engineered mouse models in the identification and characterization of the PDAC cell of origin. We also discuss potential implications for cellular origin on tumor development, PDAC transcriptional subtype, and disease prognosis of patients.

Key message: Although it is clear that both ductal and acinar cells have the potential to form PDAC, whether cellular origin can indeed influence patient prognosis and whether knowledge of cellular origin will aid in the diagnosis or treatment of patients in the future will need further study.

Background: Pancreatic cancer (PDAC) - even if deemed resectable - has still a dismal prognosis and is the seventh leading cause of global cancer-related death with rising incidence worldwide.

Summary: Surgical resection at best in combination with adjuvant systemic chemotherapy is the only potentially curative treatment. Surgical treatment has substantially improved over the last years with significantly reduced perioperative morbidity and mortality. Even when deemed radiologically resectable, the majority of PDAC is likely to have micrometastases, leaving most PDAC patients with an advanced stage. Recent 5-year overall survival was up to 46% in patients eligible for surgery with intensified adjuvant chemotherapy. Eligible for curative surgery are about one-third of the patients, and only 20% of these patients have the option for cure with surgery and adjuvant chemotherapy. Standards of care in treating PDAC patients include various mostly combinational chemotherapy approaches in the advanced and adjuvant setting. Moreover, first targeted therapies for individualizing treatment, e.g., specific subgroups like BRCA1/2 germline mutated patients, were established lately. Neoadjuvant concepts are currently part of research. This review focuses on current and future multimodal treatment options of PDAC and the impact of molecular profiling for individualizing treatment.

Key messages: State of the art in pancreatic cancer therapy is multimodal and includes novel strategies to allow molecular defined subgroup-specific treatment.

Background: The incidence and mortality of pancreatic ductal adenocarcinoma (PDAC) are increasing recently. Most patients with PDAC are diagnosed at advanced stage because of the high invasiveness of cancer cells and the lack of typical early symptoms. Therefore, early diagnosis of PDAC is very important to improve the prognosis. Exosomes play crucial role in intercellular communication and deliver the contents to recipient cells to regulate their biological behaviors. Recent evidence suggests emerging role of exosomes in the carcinogenesis of a variety of cancers including PDAC. Long noncoding RNAs (LncRNAs) have been reported to be involved in the development of PDAC. It has been proved that LncRNAs have the potential to be biomarkers and therapeutic targets for PDAC. Moreover, increasing number of studies focus on the role of exosomal LncRNAs in PDAC.

Summary: In this review, we summarize the current status on our understanding of the role of exosomal-derived LncRNAs in the progression and metastasis of PDAC.

Key messages: We focus on challenges in the potential of exosomal-derived LncRNAs as novel diagnostic and prognostic markers and therapeutic targets of PDAC. In addition, we provide an overview about the demonstrated important role of exosomal LncRNAs in the progression of PDAC.