Precancerous neoplastic cells can move through the pancreatic ductal system.

Most adult carcinomas develop from noninvasive precursor lesions, a progression that is supported by genetic analysis. However, the evolutionary and genetic relationships among co-existing lesions are unclear. Here we analysed the somatic variants of pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas. After inferring evolutionary relationships, we found that the ancestral cell had initiated and clonally expanded to form one or more lesions, and that subsequent driver gene mutations eventually led to invasive pancreatic cancer. We estimate that this multi-step progression generally spans many years. These new data reframe the step-wise progression model of pancreatic cancer by illustrating that independent, high-grade pancreatic precursor lesions observed in a single pancreas often represent a single neoplasm that has colonized the ductal system, accumulating spatial and genetic divergence over time.

How the mechanobiome drives cell behavior, viewed through the lens of control theory.

Cells have evolved sophisticated systems that integrate internal and external inputs to coordinate cell shape changes during processes, such as development, cell identity determination, and cell and tissue homeostasis. Cellular shape-change events are driven by the mechanobiome, the network of macromolecules that allows cells to generate, sense and respond to externally imposed and internally generated forces. Together, these components build the cellular contractility network, which is governed by a control system. Proteins, such as non-muscle myosin II, function as both sensors and actuators, which then link to scaffolding proteins, transcription factors and metabolic proteins to create feedback loops that generate the foundational mechanical properties of the cell and modulate cellular behaviors. In this Review, we highlight proteins that establish and maintain the setpoint, or baseline, for the control system and explore the feedback loops that integrate different cellular processes with cell mechanics. Uncovering the genetic, biophysical and biochemical interactions between these molecular components allows us to apply concepts from control theory to provide a systems-level understanding of cellular processes. Importantly, the actomyosin network has emerged as more than simply a 'downstream' effector of linear signaling pathways. Instead, it is also a significant driver of cellular processes traditionally considered to be 'upstream'.

Fistula-in-ano: when to cut, tie, plug, or sew.

INTRODUCTION: Management of fistula-in-ano requires understanding of both perianal and rectal anatomy, as well as the surgical approaches available to ensure the highest possible postoperative continence and wound healing. Further, high rates of recurrence with medical management commonly bring these patients under the care of the colorectal surgeon after variable periods of failed conservative management. Novel techniques provide surgeons with tools to treat increasingly complex fistulas with a focus on maintaining sphincteric functionality and limiting recurrence. METHOD: This manuscript presents our practice, including perioperative decision making regarding surgical approach, in managing patients with fistula-in-ano. CONCLUSION: Familiarity with these techniques prepares the general surgeon and colorectal surgeon to improve wound healing and functional outcomes in these patients, especially with complex disease involving the external and internal anal sphincters.

EUS characteristics of Nissen fundoplication: normal appearance and mechanisms of failure.

BACKGROUND: In patients who develop symptoms after Nissen fundoplication, the precise mechanism of failure can be difficult to determine. Current testing modalities do not demonstrate sufficient anatomic detail to definitively determine the mechanism. This observational study establishes that EUS can determine fundoplication integrity and hiatal anatomic relationships after Nissen fundoplication. METHODS: EUS was performed on the native esophagogastric junction and after Nissen fundoplication in two swine. The EUS characteristics of a properly performed fundoplication were determined. Subsequently, complications of Nissen fundoplication were created, and EUS was performed on each. The EUS criteria of each mechanism of failure were defined. RESULTS: EUS provided sufficient axial resolution to distinguish the esophagus, the fundoplication, and the surrounding hiatal structures within a single image. US of the native esophagogastric junction discerned the length of intra-abdominal esophagus, esophagogastric junction, crura, and anterior hiatus, and, thus, the point of entry into the abdominal cavity. EUS of Nissen fundoplication revealed a 5-layered pattern in a 360 degree configuration. These layers represent the following: (1) the esophageal wall, (2) the space between the esophagus and the fundoplication, (3) the inner gastric wall of the fundoplication, (4) the gastric lumen, and (5) the outer gastric wall of the fundoplication. A slipped repair was identified by the presence of an echogenic gastric serosa within the fundoplication. A tight fundoplication results in attenuation of the gastric walls, thickening of the esophageal wall, and loss of the 5-layer pattern secondary to obliteration of the potential spaces of the gastric lumen. Dehiscence of the fundoplication was evidenced by a less than 360 degree 5-layer pattern. CONCLUSIONS: EUS of hiatal anatomic relationships is feasible and provides detailed information regarding the integrity and the position of a Nissen fundoplication. EUS may enable a precise determination of the anatomic causes of failure after antireflux surgery.

Endoscopic appraisal of the gastroesophageal valve after antireflux surgery.

OBJECTIVES: Little consensus exists regarding the endoscopic assessment of the esophagogastric junction after antireflux surgery. The purpose of this report is to characterize the gastroesophageal valve appearance unique to each type of antireflux procedure and to introduce an endoscopic lexicon by which to describe this anatomic region. METHODS: Endoscopic images were obtained from patients who had undergone any one of the following procedures: Nissen, Collis-Nissen, Toupet, and Dor fundoplications and Hill repair. Images were excluded if patients had any symptoms of heartburn, regurgitation, dysphagia, chest pain, or gas bloat or if they were using antisecretory medication. Seven photographs per operation type were evaluated by experienced surgeons and gastroenterologists tasked with describing defining characteristics of each procedure. RESULTS: Ten valve criteria were developed to uniquely identify and quantify the ideal endoscopic appearance of each procedure. Illustrations were created to clearly depict those traits. CONCLUSIONS: Using 10 gastroesophageal valve criteria, the key components of a successful functional repair of the esophagogastric junction were defined. These criteria can be employed when evaluating upper gastrointestinal complaints after antireflux surgery and may ultimately serve as a dependable outcome measure.