Interstitial Fluid Sphingosine-1-Phosphate in Murine Mammary Gland and Cancer and Human Breast Tissue and Cancer Determined by Novel Methods.

The tumor microenvironment is a determining factor for cancer biology and progression. Sphingosine-1-phosphate (S1P), produced by sphingosine kinases (SphKs), is a bioactive lipid mediator that regulates processes important for cancer progression. Despite its critical roles, the levels of S1P in interstitial fluid (IF), an important component of the tumor microenvironment, have never previously been measured due to a lack of efficient methods for collecting and quantifying IF. The purpose of this study is to clarify the levels of S1P in the IF from murine mammary glands and its tumors utilizing our novel methods. We developed an improved centrifugation method to collect IF. Sphingolipids in IF, blood, and tissue samples were measured by mass spectrometry. In mice with a deletion of SphK1, but not SphK2, levels of S1P in IF from the mammary glands were greatly attenuated. Levels of S1P in IF from mammary tumors were reduced when tumor growth was suppressed by oral administration of FTY720/fingolimod. Importantly, sphingosine, dihydro-sphingosine, and S1P levels, but not dihydro-S1P, were significantly higher in human breast tumor tissue IF than in the normal breast tissue IF. To our knowledge, this is the first reported S1P IF measurement in murine normal mammary glands and mammary tumors, as well as in human patients with breast cancer. S1P tumor IF measurement illuminates new aspects of the role of S1P in the tumor microenvironment.

The role of margin status and reexcision in local recurrence following breast conservation surgery.

INTRODUCTION: Breast conservation surgery (BCS) results in survival equal to mastectomy for early-stage breast cancer. Ipsilateral breast tumor recurrence (IBTR) after BCS is thought to be related to margin status. At our institution, reexcision is performed only if tumor is at inked margin or with extensive disease close to multiple margins. The purpose of this study was to determine rates of reexcision and recurrences among BCS patients using this policy. METHODS: We performed an institutional review board-approved retrospective analysis of BCS patients who underwent surgery between January 2001 and June 2005. We identified patients who had a second breast excision within 8 weeks of the first, and those patients with an IBTR. Clinical and pathologic features of patients' tumors were reviewed. RESULTS: We identified 543 patients who underwent BCS, 84 patients (15.5 %) underwent reexcision for margin status. The crude IBTR rate was 3.4 %, and the 5-year local recurrence-free survival of the reexcised group was 90.6 % compared with 97.4 % in the non-reexcised group (p = 0.0097). Of the 64 reexcision patients, 6 (9.4 %) had an IBTR versus 12 (2.6 %) of the 459 non-reexcised patients (p = 0.0151). DISCUSSION: Our reexcision rate is low compared with other reports. This results from a policy that defines "no tumor on ink" as an adequate margin for BCS, and the use of selective irradiation boosts based on margins assessed by our pathologists. Our local recurrence rate compares favorably with those seen in other studies while minimizing the need for additional operations. A higher IBTR rate after reexcision likely reflects tumor biology.

Intestinal Co-infection of Tuberculosis and CMV can Cause Massive Lower GI Bleeding in a Patient with HIV.

Tuberculosis (TB) and HIV are considered pandemic by the World Health Organization (WHO). It has been reported that HIV infection is one of the major risk factors for the development of TB, increasing the incidence by up to 1,000 times, but it often has an atypical presentation. The incidence of extrapulmonary TB is increasing, largely among HIV patients. The diagnosis of intestinal TB is a challenge because of its chronic and nonspecific presentation which often mimics other diseases, and requires a high clinical suspicion to timely diagnose. Massive lower gastrointestinal bleeding due to intestinal TB was once an uncommon complication of TB, but recent reports indicate an increased incidence especially in developing countries. We suspect that co-infection with cytomegalovirus colitis contributes to the massive hemorrhage from intestinal TB. Surgical intervention is the recommended management for intestinal TB complicated by lower gastrointestinal bleeding. Accordingly, it is important for HIV patients to be screened and treated for TB to prevent this complication. Although the diagnosis is a challenge, it is important to consider intestinal TB as a cause of gastrointestinal bleeding in the HIV positive patients.

Comparing video games and laparoscopic simulators in the development of laparoscopic skills in surgical residents.

INTRODUCTION: The video game industry has become increasingly popular over recent years, offering photorealistic simulations of various scenarios while requiring motor, visual, and cognitive coordination. Video game players outperform nonplayers on different visual tasks and are faster and more accurate on laparoscopic simulators. The same qualities found in video game players are highly desired in surgeons. Our investigation aims to evaluate the effect of video game play on the development of fine motor and visual skills. Specifically, we plan to examine if handheld video devices offer the same improvement in laparoscopic skill as traditional simulators, with less cost and more accessibility. METHODS: We performed an Institutional Review Board-approved study, including categorical surgical residents and preliminary interns at our institution. The residents were randomly assigned to 1 of 3 study arms, including a traditional laparoscopic simulator, XBOX 360 gaming console, or Nintendo DS handheld gaming system. After an introduction survey and baseline timed test using a laparoscopic surgery box trainer, residents were given 6 weeks to practice on their respective consoles. At the conclusion of the study, the residents were tested again on the simulator and completed a final survey. RESULTS: A total of 31 residents were included in the study, representing equal distribution of each class level. The XBOX 360 group spent more time on their console weekly (6 hours per week) compared with the simulator (2 hours per week), and Nintendo groups (3 hours per week). There was a significant difference in the improvement of the tested time among the 3 groups, with the XBOX 360 group showing the greatest improvement (p = 0.052). The residents in the laparoscopic simulator arm (n = 11) improved 4.6 seconds, the XBOX group (n = 10) improved 17.7 seconds, and the Nintendo DS group (n = 10) improved 11.8 seconds. Residents who played more than 10 hours of video games weekly had the fastest times on the simulator both before and after testing (p = 0.05). Most residents stated that playing the video games helped to ease stress over the 6 weeks and cooperative play promoted better relationships among colleagues. CONCLUSIONS: Studies have shown that residents who engage in video games have better visual, spatial, and motor coordination. We showed that over 6 weeks, residents who played video games improved in their laparoscopic skills more than those who practiced on laparoscopic simulators. The accessibility of gaming systems is 1 of the most essential factors making these tools a good resource for residents. Handheld games are especially easy to use and offer a readily available means to improve visuospatial and motor abilities.

A cause of unbearably painful breast, diffuse dermal angiomatosis.

Diffuse dermal angiomatosis is a rare disorder, considered to be a variant of reactive cutaneous angioendotheliomatosis. The patients commonly present with severe intractable breast pain and characteristic reticular violaceous erythematous plaques with central ulcerations. Histologically, there is infiltration of the recticular dermis by endothelial cells due to excess vascular proliferation. Herein, we report a patient who presented with unbearable bilateral breast pain with characteristic "reticular vascular marking" of her breasts, who was diagnosed with diffuse dermal angiomatosis. We were able to successfully treat our patient with a tapered isoretinoin regimen.