Metastasis is the main cause of carcinoma-related death, yet we know little about how it initiates due to our inability to visualize stochastic invasion events. Classical models suggest that cells accumulate mutations that first drive formation of a primary mass, and then downregulate epithelia-specific genes to cause invasion and metastasis. Here, using transparent zebrafish epidermis to model simple epithelia, we can directly image invasion. We find that KRas-transformation, implicated in early carcinogenesis steps, directly drives cell invasion by hijacking a process epithelia normally use to promote death—cell extrusion. Cells invading by basal cell extrusion simultaneously pinch off their apical epithelial determinants, endowing new plasticity. Following invasion, cells divide, enter the bloodstream, and differentiate into stromal, neuronal-like, and other cell types. Yet, only invading KRasV12 cells deficient in p53 survive and form internal masses. Together, we demonstrate that KRas-transformation alone causes cell invasion and partial dedifferentiation, independently of mass formation.

Background: Peripherally inserted central catheters (PICC) are occasionally placed in the great saphenous vein (GSV) and anterior accessory great saphenous vein (AAGSV) in patients with inadequate upper extremity veins or contraindications to upper extremity placement. Outcomes on the placement of PICCs in these veins are limited. Objectives: This study aimed to determine technical success and safety of GSV/AAGSV PICCs. Materials and methods: This is a retrospective study that reviewed all GSV/AAGSV PICC placements between January 2011 and December 2019. A total of 29 PICC placements procedures were identified. The electronic medical record was queried for demographic, procedural, and complication data. Technical success was defined by whether the vein could be accessed and a PICC could be placed. Catheter-associated infections, dislodgement or migration, malfunction, and PICC-associated thrombosis were recorded. Results: Technical success of placement was 100%. Twenty-one (72%) catheters were placed in the GSV in the mid to upper thigh and eight (28%) were placed in the AAGSV. The median PICC dwell time was 13 days with a range of 3–155 days. PICC-associated complications occurred after 11 (37.9%) placements. Line associated infection was the most common complication (17.2%). Conclusion: Due to a high complication rate, GSV/AAGSV PICC placement should be considered only when upper extremity or cervical PICC placement is not feasible or contraindicated.

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Background Ileal pouch–anal anastomosis (IPAA) is the standard restorative procedure following proctocolectomy in patients with inflammatory bowel disease (IBD) who require colectomy. However, removal of the diseased colon does not eliminate the risk of pouch neoplasia. We aimed to assess the incidence of pouch neoplasia in IBD patients following IPAA. Methods All patients at a large tertiary center with International Classification of Diseases–Ninth Revision/International Classification of Diseases–Tenth Revision codes for IBD who underwent IPAA and had subsequent pouchoscopy were identified using a clinical notes search from January 1981 to February 2020. Relevant demographic, clinical, endoscopic, and histologic data were abstracted. Results In total, 1319 patients were included (43.9% women). Most had ulcerative colitis (95.2%). Out of 1319 patients, 10 (0.8%) developed neoplasia following IPAA. Neoplasia of the pouch was seen in 4 cases with neoplasia of the cuff or rectum seen in 5 cases. One patient had neoplasia of the prepouch, pouch, and cuff. Types of neoplasia included low-grade dysplasia (n = 7), high-grade dysplasia (n = 1), colorectal cancer (n = 1), and mucosa-associated lymphoid tissue lymphoma (n = 1). Presence of extensive colitis, primary sclerosing cholangitis, backwash ileitis, and rectal dysplasia at the time of IPAA were significantly associated with increased risk of pouch neoplasia. Conclusions The incidence of pouch neoplasia in IBD patients who have undergone IPAA is relatively low. Extensive colitis, primary sclerosing cholangitis, and backwash ileitis prior to IPAA and rectal dysplasia at the time of IPAA raise the risk of pouch neoplasia significantly. A limited surveillance program might be appropriate for patients with IPAA even with a history of colorectal neoplasia.

BACKGROUNDIbrutinib, an irreversible Bruton tyrosine kinase inhibitor, has been associated with an increased risk of bleeding. There is a paucity of data on the risk of bleeding in patients on ibrutinib undergoing dermatologic surgery.OBJECTIVETo determine the frequency of bleeding complications associated with ibrutinib in patients undergoing dermatologic surgery.MATERIALS AND METHODSA retrospective, single-center, case–control study of patients on ibrutinib undergoing skin surgery between January 2013 and March 2020 compared with sex, disease, and age-matched control patients undergoing cutaneous surgeries.RESULTSA total of 75 surgeries performed on 37 case patients and 116 surgeries performed on 64 control patients were included. Ibrutinib was associated with a statistically significant increased rate of bleeding events (6/75 [8%] vs 1/116 [0.8%], p-value = .02). Compared with ibrutinib patients who did not have a bleeding event, those on ibrutinib who suffered bleeding were all men, older (mean age 82.7 vs 73.0, p-value= .01), and had lower mean platelet counts (104.0 vs 150.5 K/μL, p-value = .03).CONCLUSIONIbrutinib may be associated with increased risk of bleeding in patients with hematologic malignancies, particularly older men with lower platelet levels and on multiple anticoagulants. Transient discontinuation of ibrutinib should be considered for dermatologic surgeries.

BACKGROUND Dermatologic surgeons are faced with a dilemma when counseling actively smoking patients who require dermatologic surgery: recommend total cessation of all nicotine that is associated with extremely high rates of cessation failure or recommend nicotine replacement therapy (NRT). OBJECTIVE To determine the safety of NRT in dermatologic surgery. MATERIALS AND METHODS PubMed was queried: [(nicotine OR electronic cigarettes) AND (flap OR wound healing)]. RESULTS Smoking tobacco is detrimental to wound healing, supported by ample evidence (1A). Perioperative smoking cessation reduces risk (1B). Basic science demonstrates both a benefit and detriment of nicotine depending on the factor studied (2A). Human studies suggest no detrimental effect of nicotine on perioperative complications (1B). Nicotine may be detrimental to flaps, but evidence is limited to basic science (2A). CONCLUSION Dermatologists should consider recommending nicotine replacement for smokers in the perioperative period. Evidence is lacking to determine safety in flaps. It is presumed based on animal studies that nicotine has a negative effect on flaps; however, it is likely less than tobacco. Weighing the risk of cessation failure without nicotine replacement versus nicotine replacement after flap is challenging. Electronic cigarettes should be discouraged as a means of NRT.

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PURPOSE Fibrin sheaths are a significant cause of dialysis catheter dysfunction. This study aimed to determine the role of anticoagulation, antiplatelet medications, and other factors in delaying fibrin sheath formation. METHODS An institutional review board-approved retrospective review of all patients treated for tunneled dialysis catheter fibrin sheaths from January 2014 to January 2020 was undertaken. All catheters were symmetric tipped, 14.5 F in diameter, and placed via the internal jugular vein. Seventy patients with venographically confirmed fibrin sheaths that developed after de novo catheter placement were identified. Recurrent fibrin sheaths were excluded. The impact of anticoagulation and antiplatelet therapy, as well as statin therapy, catheter side (right or left), hematocrit, platelet count, prothrombin time (PT), and international normalized ratio (INR), on the time to fibrin sheath formation was determined. RESULTS Patients on anticoagulation had a longer median catheter implantation time of 109.2 days (interquartile range (IQR): 29.3-178.5 days) compared to 80.7 days (IQR: 28.0-168.6 days) among patients not on anticoagulation. Catheter dwell time among patients taking antiplatelet therapy was 86.0 days (IQR: 31.5-160.7 days) versus 74.4 days (IQR: 27.5-202.4 days) for patients not on antiplatelet medication. Patients taking statins versus those not taking statins had median catheter dwell times of 97.5 days (IQR: 27.5-138.5 days) and 62.4 days (IQR: 29.9-259.6 days), respectively. Time to fibrin sheath formation was not significantly associated with hematocrit ( P = .16), platelet count (0.12), PT ( P = .51), or INR ( P = .74). CONCLUSION Anticoagulation has no significant benefit in delaying sheath formation in patients with tunneled dialysis catheters. Hematologic and coagulation parameters at the time of catheter placement were also not associated with catheter dwell time.