MMP7 interacts with ARF in nucleus to potentiate tumor microenvironments for prostate cancer progression in vivo.

ARF couples with TP53 in a canonical signaling pathway to activate cellular senescence for tumor suppressive function under oncogenic insults. However, the mechanisms on aberrant elevation of ARF in cancers are still poorly understood. We previously showed that ARF (p14ARF in human and p19Arf in mouse) elevation correlates with PTEN loss and stabilizes SLUG to reduce cell adhesion in prostate cancer (PCa). Here we report that ARF is essential for MMP7 expression, E-Cadherin decrease and the anchorage loss to the extracellular matrix (ECM) in PCa in vitro and in vivo. We found that Mmp7 is aberrantly elevated in cytosol and nucleus of malignant prostate tumors of Pten/Trp53 mutant mice. Interestingly, p19Arf deficiency strikingly decreases Mmp7 levels but increases E-Cadherin in Pten/Trp53/p19Arf mice. ARF knockdown markedly reduces MMP7 in human PCa cells. Conversely, tetracycline-inducible expression of ARF increases MMP7 with a decrease of E-Cadherin in PCa cells. Importantly, MMP7 physically binds ARF to show the co-localization in nucleus. Co-expression of MMP7 and ARF promotes cell migration, and MMP7 knockdown decreases wound healing in PCa cells. Furthermore, MMP7 elevation correlates with ARF expression in advanced human PCa. Our findings reveal for the first time that the crosstalk between ARF and MMP7 in nucleus contributes to ECM network in tumor microenvironments in vivo, implicating a novel therapeutic target for advanced PCa treatment.

Competence acquisition for single-incision laparoscopic cholecystectomy.

BACKGROUND AND OBJECTIVES: Within the past few years, there has been a push for an even more minimally invasive approach to biliary disease with the adoption of single-incision laparoscopic cholecystectomy. We sought to compare 4 individual surgeon experiences to define whether there exists a learning curve for performing single-incision laparoscopic cholecystectomy. METHODS: We performed a retrospective review 290 single-incision laparoscopic cholecystectomies performed by a group of general surgeons, with varying levels of experience and training, at 3 institutions between May 2008 and September 2010. The procedure times were recorded for each single-incision laparoscopic cholecystectomy, ordered chronologically for each surgeon, and subsequently plotted on a graph. The patients were also combined into cohorts of 5 and 10 cases to further evaluate for signs of improvement in operative efficiency. RESULTS: Of the 4 surgeons involved in the study, only 1 (surgeon 4, laparoscopic fellowship trained with <5 years' experience) confirmed the presence of a learning curve, reaching proficiency within the first 15 cases performed. The other surgeons had more variable procedure times, which did not show a distinct trend. When we evaluated the cases by cohorts of 5 cases, surgeon 4 had a significant difference between the first and last cohort. Increased body mass index resulted in a slightly longer operative time (P < .0063). The conversion rate to multiport laparoscopic surgery was 3.1%. CONCLUSIONS: Our results indicate that among experienced general surgeons, there does not seem to be a significant learning curve when transitioning from conventional laparoscopic cholecystectomy to single-incision laparoscopic cholecystectomy. The least experienced surgeon in the group, surgeon 4, appeared to reach proficiency after 15 cases. Greater than 5 years of experience in laparoscopic surgery appears to provide surgeons with a sufficient skill set to obviate the need for a single-incision laparoscopic cholecystectomy learning curve.

Ultrasound-guided placement of midline catheters in the surgical intensive care unit: a cost-effective proposal for timely central line removal.

BACKGROUND: The early removal of central intravenous (IV) catheters, as a means of reducing the incidence of central line-associated blood stream infections (CLABSI), remains a major health care initiative. However, attaining IV access in the surgical intensive care unit (SICU) can be quite difficult. We report the success of a novel, resident-driven program for the placement of ultrasound-guided midline catheters in critically ill patients. MATERIALS AND METHODS: A prospective pilot study of 31 subjects admitted to the SICU from June to December 2011 was performed. Intermediate-length (20 cm) midline catheters were placed by trained housestaff, under ultrasound guidance, into the basilic or cephalic veins. Procedural details including time to cannulation, complications, and costs were recorded. RESULTS: Successful placement was achieved in 96.8% (n = 30), with a mean follow-up of 9.8 ± 5.6 (range 2-21) days. An average of 1.3 ± 0.7 (range 1-4) attempts with a median of 13.0 ± 14.5 (range 0.5-68) minutes was required for successful venous cannulation. The most common site was the basilic vein (n = 23). Only minor complications were encountered; three catheters leaked at the insertion site and one patient developed phlebitis. No CLABSI occurred. The total procedure cost was $87 per catheter for the SICU team compared with $1500 per catheter when performed by an interventional radiologist. During the study period, a total of 283 central line days were avoided with an estimated cost savings of $13,614. CONCLUSIONS: Ultrasound-guided midline catheters placed by the housestaff are a cost-effective alternative for patients in the SICU with difficult IV access. Successful placement can help facilitate early central line removal and thus may reduce CLABSI rates.

Robotic vs. laparoscopic colorectal surgery: an institutional experience.

BACKGROUND: Robotic colorectal surgery is gaining interest in general and colorectal surgery. The use of the da Vinci(®) Robotic system has been postulated to improve outcomes, primarily by increasing the dexterity and facility with which complex dissections can be performed. We report a large, single institution, comparative study of laparoscopic and robotic colectomies, attempting to better elucidate the benefits of robotic surgery in patients with colorectal disease. METHODS: We conducted a retrospective review of 171 patients who underwent robotic and laparoscopic colectomies (79 and 92, respectively) at our institution between November 2004 and November 2009. Patients in both groups had well-matched preoperative parameters. All cases were further subdivided by their anatomical location into right-sided and left-sided colectomy, and analysis was performed within these two subgroups. Perioperative outcomes reported include operative time, operative blood loss, time to return of bowel function, time to discontinuation of patient controlled analgesia, length of stay, and intraoperative or postoperative complications. RESULTS: Our results indicate that there is no statistical difference in length of stay, time to return of bowel function, and time to discontinuation of patient-controlled analgesia between robotic and laparoscopic left and right colectomies. Interestingly, the total procedure time difference between the laparoscopic and robotic colectomies was much smaller than previously published accounts (mean 140 min vs. 135 min for right colectomy; mean 168 min vs. 203 min for left colectomy). CONCLUSIONS: Our study is one of the largest reviews of robotic colorectal surgery to date. We believe that our results further demonstrate the equivalence of robotic surgery to laparoscopic surgery in colorectal procedures. Future research should focus on surgeon-specific variables, such as comfort, ergonomics, distractibility, and ease of use, as other ways to potentially distinguish robotic from laparoscopic colorectal surgery.

Dual pathology in a patient with right lower quadrant pain.

Meckel diverticula are remnants of the omphalomesenteric duct. They have 2% incidence in the general population, are usually asymptomatic, and tend to be diagnosed incidentally. The generally held principle had been that asymptomatic cases do not require resection, as exemplified by a 2008 systematic review of over 200 studies. However, a recent series reported an increased risk of malignancies, and recommended mandatory resection. We present a case of Meckel diverticulitis with concurrent infiltrative appendiceal carcinoid in a patient with right lower quadrant pain.

Ectopic pancreas: a diagnostic dilemma.

An ectopic pancreas is defined as pancreatic tissue lacking vascular or anatomic communication with the normal body of the pancreas. It is rarely symptomatic as it is found incidentally at laparotomy most of the time. Despite advances in diagnostic modalities, it still remains a challenge to the clinician to differentiate it from a neoplasm. It is prudent to differentiate it from neoplastic etiologies, as simple surgical excision can potentially be curative. We discuss the presentation, diagnosis, and treatment of an interesting case of ectopic pancreas presenting as a gastric antral tumor.