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Photography Class Travels to Turkey
Editor's note: WCC photography instructor Terry Abrams led a trip to Turkey by his Digital Photography Abroad class in May. The following is a first-person account of the trip by Mike Wilkinson, a student.
May 19: Departure
On a warm Michigan morning, the group gathered at Detroit Metro Airport for the 11:00am flight. Unfortunately, it was delayed for an hour due to maintenance issues, and then we had to sit on the runway for about three hours. Thanks, Delta! We arrived at JFK in New York and had missed our flight to Turkey. Things weren't starting very well. Thankfully, Terry Abrams, our group leader, was able to work with the Delta staff in New York and the travel agency that booked our trip, and we were able to avoid staying in New York. We were placed on a flight just a few hours later on Turkish Airlines, which was definitely an upgrade from Delta.
May 20: Day 1
A brief 10-hour flight later, we landed in Istanbul sometime in the afternoon (local time), which is seven hours ahead of Eastern Standard Time.
The group loaded onto a tour bus, met our tour guide, Yucel, and departed Istanbul. We headed east through the city across the Bosphorus Strait and into the continent of Asia (Turkey is about 95 percent in Asia and 5 percent in Europe). Immediately, I noticed how prosperous and modern it was. I was seeing shades of other metropolitan cities such as New York and London; lots of construction going on, lots of commerce. There were residences everywhere on the Asian side. Also, I noticed that there were Turkish flags on many of the shops and residences. As I would soon discover, the people here have a great sense of national pride. I was only able to see all this from the bus as it crawled through the rush hour traffic of Istanbul, but we would return in about a week to discover more. We traveled through rolling hills and arrived at our hotel in Ankara around midnight—or 5:00pm according to my body clock!
May 21: Day 2
We woke up early to hit a few sites in Ankara, the capital city of Turkey. They included the Museum of Anatolian Civilizations, where we had a look at some of the oldest artifacts in the world and received a commentary on the history of Turkey, which goes back hundreds of thousands of years before the birth of Christ. Then we went to the Mausoleum of Ataturk, where the tomb of Ataturk (Turkey's version of George Washington, as our guide noted) was inside a temple.
After a good lunch on the road to Cappadocia, the topography varied greatly in a very short time. From flat plains to rolling hills to amazing vistas, the landscape had much to offer. We stopped at Tuz Lake, one of the largest salt lakes in the world. A short drive later, we attended a religious ceremony where we watched something known as the "Whirling Dervishes," which was a unique experience. We arrived at our hotel later for a buffet dinner (I would soon see that most of our meals were buffet style), including some very nice Turkish dessert. With a full belly, it was time to go off to process all of my photos and use the Internet for the first time in almost three days.
May 22: Day 3
At 1:00am I woke up to what I think were screeching tires and then five gunshots. I peeked out my fifth-story window, but didn't see anything. I had noticed a wedding party going on that evening, so I hoped there may have just been some people partying a bit too much….
I woke up again just a few hours later—at 4:00am—for our hot air balloon ride. The balloon company picked us up and took us to their base station, where we were treated with much-needed coffee and some Turkish biscuits, too. We split into two vehicles and left for the launch point. The balloons were rolled out and filled with air, then our group got inside of a large basket. After some minor instruction on what to do if the landing were to go awry, we were off. It was extremely smooth and very quiet, save for the loud blast of fire into the balloon. The view was stunning, to say the least. Our pilot masterfully guided us over, around, and even through some of the valleys, controlling our altitude with incredible skill, bringing us within inches of the rock face before gently ascending over it.
We were treated to a champagne toast when we landed, and had a little fun with the balloon workers before heading back to our hotel before breakfast, as it was only 8:00am at this point!
Feeling rather rejuvenated from the amazing morning, we set off on the bus to visit some sites around Cappadocia. First we stopped at the Three Beauties rock formations for some photos, and then made a few more stops to walk around the hills and get up close to some of the unique rock formations. One stop was at the underground city of Derinkuye, where a small system of very small caves had been preserved, and many more were still being excavated. This was not a place for the claustrophobic.
Our last stop before the hotel was at a pottery-making place called Chez Galip, I think. A Turkish man who looked like Albert Einstein and had some odd obsession with women's hair gave us a demonstration on how they make pottery by hand.
May 23: Day 4
We left our hotel early once again and stopped first at the Sultan Han, where we had a talk about how to capture high-dynamic-range photos. Then we had a little free time to explore. On the drive things were really becoming scenic, with snow-covered mountaintops stretching into the sky.
After a good lunch with arguably the best lentil soup in the world, we toured an ancient Roman theater in Aspendos. I'd seen pictures of this sort of ruin before, but to actually be there was quite an experience. It's amazing how preserved it still was, even after almost 1,900 years. We then traveled to an archeological site called Perge, which was a large area filled with many ancient columns and fallen structures, with lizards and turtles scurrying about.
Something I had noticed while hiking around with 30 pounds of camera gear was that the temperature changed very quickly as the sun came out from behind the clouds. It easily would go from the low 60s to the high 70s within minutes. In Michigan, some say that if you don't like the weather, wait five minutes. It was exactly the same in Turkey.
The hotel we stayed at in Antalya was certainly a little posh, and the foreign tourists who were there definitely weren't the conservative type; lots of revealing attire and pop music. Since Turkey is a predominantly Muslim country, I was not expecting this. But I quickly saw how popular Turkey was as a vacation destination.
May 24: Day 5
I woke up after about five hours of sleep to grab some breakfast and hit the road. Speaking of breakfast, many of the breakfast and lunch places had wonderful fresh fruit, vegetables, and cheeses. There were fresh apricots, peaches, tomatoes, and greens, all in abundance and I'm sure sourced from nearby areas.
Our drive from Antalya took us west along the Mediterranean, and what an amazing drive it was: crisp green waters on our left, and tall mountains on our right for most of the drive. It reminded me of those high-speed chase scenes from James Bond movies where they go speeding around the twisting roads across the immaculate countryside. Riding in a large tour bus was almost like the same thing.
We made our way to a dock area, where we piled onto a small boat to discover the ruins of an ancient city both above and below the water. The boat ride was really fantastic, as the weather was sunny and hot but the air on the Mediterranean was cool and refreshing. Taking a boat ride was pretty relaxing, too. I made sure to take some time out and put the camera down to just enjoy myself for a moment and take in the environment.
We then drove to the ruins of Myra, where there was an amphitheater with many tourists about, mostly Russian and French. I enjoyed a short hike around and took some photographs. Before grabbing some spicy lamb kabobs for lunch, we made another brief photo stop at the St. Nicholas Church. St. Nicholas was the Bishop of Myra in the third century, and is the source of some of the legends of Santa Claus.
After driving back through the mountainside for about four hours, we checked in at our hotel in Pammukale. I washed up and set some photos to download, then grabbed a quick dinner. The sun had already set so I wasn't able to shoot a time-lapse like I had in other cities, but another opportunity presented itself when a small group of us decided to make our way into the nearby town to walk through the market. At night, we walked about 20 minutes to get into an area where there was about a half mile of restaurants and markets. I took some photos here and there, had some ice cream, and practiced speaking what little Turkish I had picked up with some of the shopkeepers.
I arrived at the meet-up point early so I started chatting with a cafe owner named Mustafar, who spoke good English. We sat down with some tea and talked about politics, culture, travel, and other things. I actually found it quite refreshing to do this, and I get the sense that he did as well. I get the feeling that Americans are stereotyped as being from a snobby, self-centered culture. And I think that's pretty accurate for the most part. I hoped that small displays of politeness and curiosity in another culture could help dispel this, even if it's just with a person or two I met on the trip.
The culture in Turkey, and in other similar areas, shows a certain openness that at first made me wary, thinking that shop owners were just trying to make a buck or that maybe people were teasing me for being an obvious tourist with a large camera. I found the reality to be that many locals just wanted to socialize. This concept has taken me a little while to figure out and get used to, but now that I have, I feel much better in public areas. Whether it's to practice English or hear about what the USA is like, or to simply ask if we are enjoying Turkey and what sights we have seen, many of the locals showed a genuine curiosity and a friendly, outgoing manner.
May 25: Day 6
Another 6:00am wake-up call. Breakfast was rather anemic, which was too bad since the first stop we made was at the Hierapolis, a huge ruins area where I must have hiked at least three or four miles with all of my camera gear. I started by going down to the travertines, where calcium carbonate limestone sparkled white with natural springs pouring cyan water over it. People were allowed to walk through these, so I waded all the way down and up them to take photos and video. It was like something out of a music video—really, really spectacular.
By the time I finished doing that I only had so much time to look at any of the many places this particular site had to offer. I made my way a bit more than a mile out to look at some ruins, and was getting absolutely cooked by the hot sun in the cloudless sky. I had to hustle to get back to the bus without going to look at another amphitheater and other ruins, but I felt that I was successful in my image capture either way. A tasty pistachio ice cream bar hit the spot as I waited for the others to return to the bus.
We drove for a while and grabbed a great lunch, then went to the ancient city ruins of Aphrodisias. Many sculptures, a small white marble amphitheater, and a large stadium were just amazing to behold. A storm was moving in while we walked round the site, threatening rain, but it never materialized. But it did make for some interesting clouds in some of my photos.
We left that site and drove for a short while and stopped in a small village to be greeted by a group of children. They could say a few things in English, but really just wanted to have their pictures taken and act like, well, kids. Our guide treated us to some tea at a cafe, and then we made our way to our next hotel. Another evening of downloading and processing images, then off to bed.
May 26: Day 7
We were allowed to sleep in until 7:00am today! After breakfast we stopped at a local carpet shop, where we were given a demonstration on how their women hand make carpets with wool, cotton, and silk. The silk was particularly impressive, as it was removed from caterpillar cocoons in a warm vat of water, and it was very durable. Some of the rugs, depending on the number of knots per square inch, could take anywhere from two months to a year to make, especially for larger pieces that were made of silk and required upwards of 300 knots per square inch. After a demonstration of the making of these carpets, we were treated to tea and raki (a Turkish liquor) and then allowed to shop. I was actually looking to purchase a carpet, so the salesmen were extremely interested in making friends with me to get a good sale. My purchase was expensive, but I negotiated a pretty good price.
Our next stop was at the top of a small mountain at the House of the Virgin Mary. We then drove for a lunch stop where several women did all of the cooking in a regular-looking kitchen. The food was excellent. We even met a younger woman who worked there and actually lives in Rochester, Mich. She is teaching classes at a Whole Foods store in Rochester and even writing a book on Turkish cooking. What a small world!
We then drove a while and made it to Ephesus. Yucel gave us a verbal history on the site before letting us wander to take photographs. Of particular interest were the two-story library and a large amphitheater that was still being worked on, but had been used recently to host concerts by artists like Sting and Eric Clapton.
The group returned to the hotel a little bit earlier than usual, so we made the most of our time by going for a swim in the Aegean Sea and hanging out by the pool for a few hours before having dinner and getting back to work on our images. It was nice to have some down time from work to relax a bit.
May 27: Day 8
We enjoyed a nice six-hour drive through Izmir and arrived at Bursa. We toured the Green Mosque, which was unfortunately undergoing some restoration. We also checked out the Silk Market, an area with many scarves and fabrics made of silk, among other goods. We made one last stop in the Grand Mosque for a few photos and then left for our next hotel, which was a very nice four-star resort. It had a terrace pool and a good view, so we made some nice photos of the setting sun that evening.
May 28: Day 9
We left Bursa for the coast, and drove the tour bus right onto a large ferry to be carried over the Bosphorus. We hit land and entered Istanbul again. We drove down to the Grand Bazaar, where we got lost (figuratively) among the massive number of small shops and vendors selling crafts, food, spices, clothes, silk, and anything else people might buy. It was a bit dizzying, and while not as intense as the souks in Morocco, it would have been easy to get lost in there. After the bazaar, we went on a cruise along the Bosphorus Sea, guided with a commentary from Yucel about the different sites on both the Asian and European coasts. Unfortunately, the weather was overcast and a little rainy, so this was not nearly as memorable as the boat ride a few days prior on the Mediterranean.
We poked into another mosque before entering another market area, this one specializing in spices and herbs. After about an hour of wandering around there, we went to our hotel. The real eye opener about Istanbul came that evening, when a small group set out and walked into the Taksim Square area. We just walked around the main street, which was lined with modern stores. Even though it was just one small part of the city, it was clearly bustling with people, and the city had a lot of energy. Live music, 3D video projection advertisements, and people crowding the streets well after 11:00pm showed me that this was really a departure from the village-like areas and very modern.
May 29: Day 10
On this day the group traveled by foot to several amazing places. First was the Hippodrome Square, where there was the large Egyptian Obelisk. Then we simply turned around 180 degrees to be in awe of the epic Blue Mosque. The interior was massive, and decorated with spectacular wall tiles and designs. We then walked to the Topkapi Palace, which housed the Crown Jewels and had a lovely garden area to walk around in. Before we left the area, we went to Haghia Sophia, which was a church but is now considered a museum. The museum was huge on the inside, and the design of its architecture and painting was breathtaking.
After lunch it was time for a much-needed nap, as all of the long days and road trips were starting to catch up with me. In the evening a small group once again ventured out to Taksim Square. We were greeted with even more activity up and down the streets, including a big gathering of spirited football (soccer) fans celebrating with songs and cheering because of a soccer match that had happened earlier.
May 30: Day 11
I got to sleep in! I took my laptop to breakfast so that I could research how to spend my afternoon/evening, and ended up deciding to make my way back to the Sultanhamet area, where I planned to try and get a good sunset time-lapse over the Blue Mosque.
The group left around 11:00am for the Turkish Cultural Foundation, a sponsor for our trip, where we were treated to an interesting art history lecture and some light lunch. We then made our way to Arif Asci's home studio. Arif is a world-renowned photographer and documentarian. He spoke of stories from his past projects and showed us some of his photos. It was really inspiring to see the work of another visual artist, and to hear about how he came to be a part of certain projects.
After the talk, I had free time so I made my way to the top of the Galata Tower. From there I was able to take some nice panoramic photos of the city in all directions, with the minarets of all of the mosques poking into the sky. I made my way back to the hotel to reload my camera gear, then set off for the rail station near Taksim Square. I took a couple of rail lines to the Blue Mosque area, and after hiking around for a while I found the Ferman Hotel. I walked right in, went to the top, and took several hundred photos for a great time-lapse that included the setting sun. I spoke to a couple from Canada and a gentleman from Germany on my way back. I regrouped with everyone at the hotel, where we shared stories and photos, ready to begin our long journey home.
Mike Wilkinson works at WCC, and went on the trip to improve his photography skills and document the experiences of the other students who participated. A video he shot documenting the trip will be available on WCC's YouTube channel at a later date.


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by Bryan Jackson, university communications
HILTON HEAD, S.C. - For the first time, Georgia College & State University has won the coveted Peach Belt Conference (PBC) Commissioner's Cup, recognizing it as the overall top athletic program in the conference. GCSU edged out Armstrong Atlantic State University for the honor.
"Winning the Commissioner's Cup is proof that you can have excellence in the classroom as well as on the field," said GCSU President Dorothy Leland. "Not only did Georgia College lead the conference in athletics, it also led the conference in the number of students recognized for their academic success."
Georgia College won the Commissioner's Cup with a total of 72 points, for a rating of .758. Second place Armstrong Atlantic State earned 62.5 points, for a .735 rating. The winner is determined by calculating the number of points possible to each school, given the number of sports they participate in, divided by the number of points earned during the year.
"The Georgia College Bobcats had an exceptionally strong year, thanks to the strong leadership of our coaching staff and the outstanding performance of our student-athletes," said GCSU Athletic Director Jud Damon. "Nine of our 10 teams made appearances in NCAA tournaments this season, and six of our seven team sports finished with winning records."
The Bobcats won the men's tennis regular-season championship and finished in the top three in women's soccer, baseball, softball and golf and were in the top half of the PBC standings in all 10 of their intercollegiate programs.
Georgia College also saw 30 of its student-athletes named to PBC Academic All-Conference teams during the 2008-2009 season. Soccer had the most with nine, while men's basketball got three of the five spots on the first team, and men's golf got three of the five total slots on their all-conference team.
To be eligible for the academic all-conference team, a student-athlete must be either a starter or significant contributor, have achieved a 3.20 cumulative grade point average and completed at least one academic year at the university.
Other recent PBC honors for Georgia College included:
o GCSU had 110 student-athletes make the 2007-08 Peach Belt Honor Roll (earning a 3.0 or better GPA for the school year), the most of any school in the conference.
o Men's Basketball won the first PBC Team Sportsmanship Award in men's basketball;
o GCSU won Coach of the Year honors in both men's basketball and men's tennis;
"It's been a great year for our Bobcats," President Leland said.
Visit www.GCSUBobcats.com to nominate your favorite former Bobcats and Colonials to the GCSU Athletics Hall of Fame. The GCSU Department of Athletics sponsors 10 varsity athletic programs at the NCAA Division II level. As a Division II program, GCSU prides itself on balancing the life of the student-athlete, evidenced by the Bobcats' multiple appearances in post-season competition as well as documented academic success and community-service involvement. Sign up at Twitter.com username GCSUSID for up-to-the-minute reports.

subset: commoncrawl


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Testosterone can be given as a shot in the muscle, usually every 2 to 3 weeks. This is not the same as medicines you give as a shot in the penis.
Testosterone can also be given as a patch that is placed on the skin and changed every day. Or it can be used as a gel that is applied daily to the skin.
These medicines can be used to treat men who have high
prolactin levels, which can reduce the amount of testosterone produced by the
body and may lead to problems such as infertility or erection problems.
Bromocriptine and cabergoline are taken by mouth.
Replacing testosterone, if it is low,
may increase a man's sexual desire, or libido.
Bromocriptine and
cabergoline help to lower the amount of prolactin in the body. In some men, a
noncancerous tumor on the pituitary gland causes the gland to produce too much
Testosterone may be prescribed for
men who have low testosterone levels. It is not recommended for men with
testosterone levels in the low part of the normal range.
Bromocriptine and cabergoline may be prescribed for men with high
prolactin levels.
Blood tests are needed to find out the levels
of these hormones.
Testosterone may improve libido and has been shown to increase how often a man has sexual intercourse. But testosterone doesn't have a clear effect on erection problems. In some men, combining testosterone with sildenafil (for example, Viagra) increased the number of successful intercourse attempts and improved satisfaction with sexual intercourse.1
There is some evidence that cabergoline can increase the number of erections a man has. It may also help make your erection more firm.1
Bromocriptine may help restore sexual interest and
potency when erection problems are caused by high prolactin levels.2
All medicines have side effects. But many people don't feel the side effects, or they are able to deal with them. Ask your pharmacist about the side effects of each medicine you take. Side effects are also listed in the information that comes with your medicine.
Here are some important things to think about:
Call 911 or other emergency services right away if you have:
Call your doctor if you have:
Common side effects of this medicine include:
Call your doctor right away if you have:
See Drug Reference for a
full list of side effects. (Drug Reference is not available in all
When you are thinking about hormonal therapy
for erection problems, it is important to include your partner in your
While you are taking bromocriptine, avoid alcohol, and use extra care when
driving or operating machinery.
When using testosterone products on your skin, make sure you follow all of the instructions that come with the medicine.
Some experts are concerned that testosterone could increase the risk of prostate cancer. Your doctor may recommend regular exams and blood tests to check for problems.
Testosterone can affect your fertility. If you are trying to have a child, you may want to ask your doctor about how
this medicine can affect your chances of conceiving.
Medicine is one of the many tools your doctor has to treat a health problem. Taking medicine as your doctor suggests will improve your health and may prevent future problems. If you don't take your medicines properly, you may be putting your health (and perhaps your life) at risk.
There are many reasons why people have trouble taking their medicine. But in most cases, there is something you can do. For suggestions on how to work around common problems, see the topic Taking Medicines as Prescribed.
Follow-up care is a key part of your treatment and safety. Be sure to make and go to all appointments, and call your doctor if you are having problems. It's also a good idea to know your test results and keep a list of the medicines you take.
Complete the new medication information form (PDF)(What is a PDF document?) to help you understand this medication.
CitationsAgency for Healthcare Research and Quality (2009). Diagnosis and Treatment of Erectile Dysfunction. Evidence Report/Technology Assessment No. 171 [AHRQ Publication No. 08(09)-E016]. Rockville, MD: Agency for Healthcare Research and Quality. Also available online: http://www.ahrq.gov/downloads/pub/evidence/pdf/erectiledys/erecdys.pdf.Bella AJ, Lue TF (2008). Male sexual dysfunction. In
EA Tanagho, JW McAninch, eds., Smith's General Urology,
17th ed., pp. 589–610. New York: McGraw-Hill.
Last Revised:
October 17, 2012
Healthwise Staff
Medical Review:
E. Gregory Thompson, MD - Internal Medicine & E. Gregory Thompson, MD - Internal Medicine & Christopher G. Wood, MD, FACS - Urology, Oncology & Christopher G. Wood, MD, FACS - Urology, Oncology
This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information. Your use of this information means that you agree to the Terms of Use. How this information was developed to help you make better health decisions.
To learn more visit Healthwise.org
© 1995-2012 Healthwise, Incorporated. Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.


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For more than 20 years, Chugach has provided operations, training, management, and maintenance services for the U.S. Department of Labor Job Corps Program at the Alaska Job Corps Center in Palmer. The center is the first of its kind in Alaska, focusing on training Alaska youth. It provides full educational services for 250 Alaskans, including 24 single parents, in a residential setting. The center serves the largest geographic area with the most diverse population of any Job Corps center in the nation. It has been second-highest-ranked Job Corps center of the 22 centers located across the western United States.
- Chugach Education Services, Inc.
- Chugach Government Services, Inc.
- Chugach Training and Educational Solutions, LLC (website coming soon)
Chugach also supports Job Corps centers in Oregon, Florida, and the District of Columbia. In total, we operate four center locations comprising more than 60 individual facilities and 670,000 gross square feet and serving more than 1,000 students.
Students at Chugach Job Corps centers receive training in career skills that may include business technology; construction trades such as masonry, culinary preparation, plumbing and carpentry; service and technical industries, including HVAC and facilities maintenance; or water/wastewater certification.
Services Include:
- Outreach and admissions
- Curriculum and training
- Program operations
- Counseling
- Transportation
- Career preparation and transition
- Food service
- Safety and security
- Finance and procurement
- Facilities and property management


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This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
Incidence and Mortality
Estimated new cases and deaths from soft tissue sarcoma in the United States in 2012:[1]
Soft tissue sarcomas are malignant tumors that arise in any of the mesodermal tissues of the extremities (50%), trunk and retroperitoneum (40%), or head and neck (10%). The reported international incidence rates range from 1.8 to 5 per 100,000 per year.[2]
Risk Factors and Genetic Factors
The risk of sporadic soft tissue sarcomas is increased by prior radiation therapy and, in the case of lymphangiosarcoma, by chronic lymphedema. The chemicals Thorotrast, vinyl chloride, and arsenic are also established carcinogens for hepatic angiosarcomas.[3,4,5]
Soft tissue sarcomas occur with greater frequency in patients with the following inherited syndromes:[3,4,5]
Soft tissue sarcomas may be heterogeneous, so adequate tissue should be obtained via either core-needle or incisional biopsy for microscopic examination to determine histologic type and tumor grade. Careful planning of the initial biopsy is important to avoid compromising subsequent curative resection. Since the selection of treatment is determined by the grade of the tumor, it is essential to have a careful review of the biopsy tissue by a pathologist who is experienced in diagnosing sarcomas. Complete staging and treatment planning by a multidisciplinary team of cancer specialists is required to determine the optimal treatment for patients with this disease.
There is evidence that at least some favorable clinical outcomes may be associated with referral to a specialized sarcoma treatment center. In a population-based consecutive series of 375 soft tissue sarcoma patients in Sweden, local recurrence rates of resected tumors were higher in patients who were not referred to the specialized center: in 35 of 78 (45%) patients not referred; in 24 of 102 (24%) patients referred after initial surgery or incisional biopsy; and in 36 of 195 (18%) patients referred prior to any surgical procedure (P = .0001 for the difference between those never referred vs. those referred prior to any surgical procedure).[6][Level of evidence: 3iDii] However, there were no statistically significant differences in death from sarcoma between the groups of patients.
Prognostic Factors
The prognosis for patients with adult soft tissue sarcomas depends on several factors, including:[3,4,5,7]
Factors associated with a poorer prognosis include the following:[8]
Although low-grade tumors are usually curable by surgery alone, higher-grade sarcomas (as determined by the mitotic index and by the presence of hemorrhage and necrosis) are associated with higher local-treatment failure rates and increased metastatic potential.
Related Summaries
Note: Other PDQ summaries containing information about soft tissue sarcoma include:
Soft tissue sarcomas are classified histologically according to the soft tissue cell of origin. Additional studies, including electron microscopy, specialized immunohistochemistry, flow cytometry, cytogenetics, and tissue culture studies may allow identification of particular subtypes within the major histologic categories. For example, S100 antigen suggests neural sheath origin, cytokeratin suggests epithelioid or synovial cell origin, and factor VIII-related antigen suggests endothelial origin. Likewise, some subtypes of sarcomas have characteristic genetic markers, but these markers are not generally used in the routine clinical setting (e.g., t(X;18)(p11;q11) in synovial sarcomas and t(12;16)(q13;p11) in myxoid and round-cell sarcomas).[1,2,3]
The histologic grade reflects the metastatic potential of these tumors more accurately than the classic cellular classification listed below. Pathologists assign a grade based on the number of mitoses per high-powered field, the presence of necrosis, cellular and nuclear morphology, and the degree of cellularity; discordance among expert pathologists regarding tumor grade, and even histologic subtype, can be substantial.[4]
The World Health Organization lists the following cell types in its classification of soft tissue sarcomas:[5,6]
*It is recognized that dedifferentiated liposarcoma primarily arises in the context of deep atypical lipomatous tumor/well-differentiated liposarcoma, a sarcoma of intermediate malignancy because of the lack of metastatic capacity. **The category of fibrosarcoma can be inclusive of fibrosarcomatous differentiation in dermatofibrosarcoma protuberans. ***Cutaneous angiosarcoma may be difficult to stage using the AJCC system. (Refer to the PDQ summary on Gastrointestinal stromal tumor [GIST] summary for more information.
Staging has an important role in determining the most effective treatment for soft tissue sarcoma. Clinical staging involves magnetic resonance imaging (MRI) or computed tomography (CT) of the primary tumor area and a chest CT to look for metastasis to the lung (the most common site of distant spread). An abdominal CT scan is done in the case of retroperitoneal sarcomas because the liver may be the site of initial clinical metastasis for these tumors.
The stage is determined by the size of the tumor, the histologic grade, and whether there is spread to lymph nodes or distant sites. Intracompartmental or extracompartmental extension of extremity sarcomas is also important for surgical decision making. For complete staging, a thorough review of all biopsy specimens (including those from the primary tumor, lymph nodes, or other suspicious lesions) is essential. CT scan of the chest is recommended for sarcomas larger than 5 cm (T2) or with moderate to poor differentiation (grades 2–4). Nodal involvement is rare, occurring in less than 3% of patients with sarcoma.[1]
Lymph node involvement in soft tissue sarcomas of adulthood is rare but is somewhat more frequent in some subtypes (e.g., rhabdomyosarcoma, vascular sarcomas, clear cell sarcomas, and epithelioid sarcomas) when they are high grade.[2] Because treatment decisions are predicated on pathology staging, patients should be staged before, and again after, any neoadjuvant therapy. The assessment of tumor grade can be affected in either direction, but more frequently decreased because of differential cellular loss related to the neoadjuvant chemotherapy or radiation.[3] Grade, which is based on cellular differentiation, mitotic rate, and extent of necrosis, should be recorded for all soft tissue sarcomas. A three-grade system (G1–G3) is preferred. (See Table 4 below).
The American Joint Committee on Cancer (AJCC) has designated staging by the four criteria of tumor size, nodal status, metastasis, and grade (TNMG).[3] The characteristic molecular markers of some sarcomas are not formally incorporated in the staging system pending further evaluation of their impact on prognosis. Recurrent sarcomas are restaged using the same system as for primary tumors with the specification that the tumor is recurrent.
Definitions of TNM and Grade
Neurovascular and bone invasion are indicators of poor prognosis, but they are not incorporated into the formal staging system.
Multimodality Approach
In most cases, a combined modality approach of preoperative radiation therapy (preRX) or postoperative radiation therapy (PORT) is used, rather than the radical surgical procedures, such as amputation, that were used in the past. It may even be possible to use surgery without PORT in selected cases. For example, a case series was reported from a specialized sarcoma treatment referral center in which 74 selected patients with primary extremity and trunk tumors 5 cm or less in size were found to have no histologic involvement of the surgical margins. The patients were observed without radiation therapy, and the estimated local recurrence rate after 10 years was 11%.[1][Level of evidence: 3iiiDiv] The role of chemotherapy is not as well defined as is the role for radiation therapy. Because of the evolving nature of the treatment options for this disease, patients should be offered the option of clinical trials when available. Information about ongoing clinical trials is available from the NCI Web site.
Role of Surgery
Surgical resection is the mainstay of therapy for soft tissue sarcomas. When feasible, wide-margin function–sparing surgical excision is the cornerstone of effective treatment for extremity tumors. This may be facilitated by soft tissue reconstructive surgery, which generally permits wider margins than those obtained when the surgical plan involves direct closure of the excision site.[2] Cutting into the tumor mass or shelling out the gross tumor along the plane of the pseudocapsule of compressed tumor cells and reactive tissue that often surrounds soft tissue sarcomas are associated with an elevated risk of local recurrence. Even high-grade soft tissue sarcomas of the extremities can usually be effectively treated while preserving the limb with combined-modality treatment consisting of preRX or PORT to reduce local recurrence. (Refer to the Role of Radiation Therapy section of this summary for more information.)
Only one small, single-institution randomized trial has directly compared amputation to limb-sparing surgery for soft tissue sarcomas of the extremities.[3] In a 2:1 randomization ratio, 27 patients with high-grade extremity sarcomas were assigned to a wide excision plus PORT (45 Gy–50 Gy to the wide local excision area, and a total of 60 Gy–70 Gy to the tumor bed over 6–7 weeks), and 16 were assigned to amputation at or above the joint proximal to the tumor. Both groups received adjuvant chemotherapy (i.e., doxorubicin, cyclophosphamide, and high-dose methotrexate). At 63 months, with a median follow-up of 56 months, there were four local recurrences in the 27 patients who underwent limb-sparing surgery and no recurrences in the 16 patients who underwent amputation P2 = .12. Overall survival (OS) rates were not statistically significantly different (actuarial 5-year survival rate, 83% vs. 88%, P2 = .99).[3][Level of evidence: 1iiA]
Local control of high-grade soft tissue sarcomas of the trunk and the head and neck can be achieved with surgery in combination with radiation therapy.[4] It may be possible to use surgery without PORT in selected cases. For example, a case series was reported from a specialized sarcoma treatment referral center in which 74 selected patients with primary extremity and trunk tumors 5 cm or less in size were found to have no histologic involvement of the surgical margins.[1] They were observed without radiation therapy, and the estimated local recurrence rate after 10 years was 11%.[1][Level of evidence: 3iiiDiv] The role of chemotherapy is not as well defined as is the role of radiation therapy. Because of the evolving nature of the treatment options for this disease, patients should be offered the option of clinical trials when available.
Effective treatment of retroperitoneal sarcomas requires removal of all gross disease while sparing adjacent viscera not invaded by tumor. The prognosis for patients with high-grade retroperitoneal sarcomas is less favorable than for patients with tumors at other sites, partly because of the difficulty in completely resecting these tumors and the dose-limiting toxicity of high-dose radiation therapy on visceral organs.[5,6,7,8]
In the setting of distant metastasis, surgery may be associated with long-term disease-free survival in patients with pulmonary metastasis and optimal underlying disease biology (i.e., patients with a limited number of metastases and slow nodule growth) who have undergone or are undergoing complete resection of the primary tumor.[9,10,11] It is not clear to what degree the favorable outcomes are attributable to the efficacy of surgery or the careful selection of patients based on factors that are associated with less-virulent disease.
Role of Radiation Therapy
Radiation plays an important role in limb-sparing therapy. Pre- and postoperative external-beam radiation therapies (EBRT), as well as brachytherapy, have been shown to decrease the risk of local recurrence. They have not been shown to increase OS but are used to avoid amputation for all but the most locally advanced tumors or for limbs seriously compromised by vascular disease, where acceptable functional preservation is not possible. In the case of EBRT, irradiation of the entire limb circumference is avoided to preserve vascular and nerve structures that are critical to function and preservation of the limb.
PORT has been tested in a single-institution randomized trial of 141 patients with extremity sarcomas who were treated with limb-sparing surgery. Patients with high-grade tumors (n = 91) also received adjuvant chemotherapy (i.e., five 28-day cycles of doxorubicin and cyclophosphamide). All patients were randomly assigned to receive radiation (45 Gy to a wide field, plus a tumor-bed boost of 18 Gy over 6–7 weeks), concurrent with chemotherapy in the case of high-grade tumors versus no radiation.[12] At up to 12 years of follow-up, there was one local recurrence in the 70 patients randomly assigned to receive radiation versus 17 recurrences in the 71 control patients (P = .0001), with similar reduction in risk of local recurrence for both high- and low-grade tumors. However, there was no difference in OS between the radiation and control groups.[12][Level of evidence: 1iiDiii] Global quality of life was similar in the two groups, but the radiation therapy group had substantially worse functional deficits resulting from reduced strength and joint motion as well as increased edema.
To limit acute toxicity with preRX, smaller fields and lower doses are generally given than is the case with PORT. PreRX has been directly compared with PORT for extremity soft tissue sarcomas in a multicenter randomized trial.[13,14,15] Designed to include 266 patients, the trial was stopped early after 190 patients had been accrued because of an increase in wound complications in the preRX group. The scheduled radiation in the preRX group was a wide field of 50 Gy in 2 Gy fractions (first phase of the trial) with an additional 16 Gy to 20 Gy to the tumor bed and a 2-cm margin (second phase of the trial) only if tumor cells were found at the surgical margins.
Patients in the PORT group were scheduled to receive radiation during both phases of the trial. The wound-complication rates were 35% versus 17% in the preRX and PORT groups, respectively (P = .01). In addition, limb function at 6 weeks after surgery was worse in the preRX group (P = .01).[13] At 5 years, the two groups had similar local control rates (93% vs. 92%) and OS (73% vs. 67%, P = .48).[14] Of the 129 patients evaluated for limb function at 21 to 27 months after surgery (n = 73 for preRX and n = 56 for PORT), limb function was similar in both groups, but there was a statistical trend for less fibrosis in the preRX group (P = .07).[15]
Brachytherapy has also been investigated as an adjuvant therapy for soft tissue sarcomas. Although it has possible advantages of convenience and less radiation to normal surrounding tissue relative to EBRT, the two treatment strategies have not been directly compared in terms of efficacy or morbidity. However, adjuvant brachytherapy has been compared to surgery without radiation.
In a single-institution trial, 164 patients with sarcomas of the extremity or superficial trunk were randomly assigned during surgery, if all gross tumor could be excised, to receive an iridium-192 implant (delivering 42 Gy–45 Gy over 4–6 days; 78 patients) or to a control arm of no radiation (86 patients).[16,17] Some of the patients with high-grade tumors received adjuvant doxorubicin-based chemotherapy if they were thought to be at a high risk for metastasis (34 patients in each study arm). With a median follow-up of 76 months, the 5-year actuarial local recurrence rates were 18% and 31% in the brachytherapy and control arms, respectively (P = .04). This difference was limited to patients with high-grade tumors. There was no discernible difference in sarcoma-specific survival rates between the brachytherapy and control arms (84% and 81%, respectively; P = .65), and there was no difference in the high tumor-grade group.[16][Level of evidence: 1iiDiii] The rates of clinically important wound complications (e.g., need for operative revision or repeated seroma drainage, wound separation, large hematomas, or purulent infection) were 24% and 14% in the radiation and control arms, respectively (P = .13); wound reoperation rates were 10% and 0%, respectively (P = .006).[17]
Intensity-modulated radiation therapy (IMRT) has been used to deliver preRX or PORT to patients with extremity soft tissue sarcomas in an effort to spare the femur, joints, and selected other normal tissues from the full prescription dose and to maintain local control while potentially reducing radiation therapy-related morbidity. Initial single-institution reports suggest that high rates of local control with some reduction in morbidity are possible with this technique.[18,19]
In some tumors of the extremities or trunk, surgery alone can be performed without the use of radiation. Evidence for this approach is limited to single-institution, relatively small, case series [1,20,21] or analysis of outcomes in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) tumor registry.[22] However, these comparisons suffer from low statistical power and differential evaluability rates that could have introduced bias.[1] Patient selection factors may vary among surgeons. In general, this approach is considered in patients with low-grade tumors of the extremity or superficial trunk that are less than or equal to 5 cm in diameter (T1) and have microscopically negative surgical margins; long-term local tumor control is about 90% in such patients.[23]
On occasion, surgical excision cannot be performed in the initial management of soft tissue sarcomas because the morbidity would be unacceptable or nearby critical organs make complete resection impossible. In such circumstances, radiation has been used as the primary therapy.[24] However, this must be considered a treatment of last resort. Experience is limited to retrospective case series from single centers.[24][Level of evidence 3iiiDiv]
Role of Adjuvant or Neoadjuvant Chemotherapy for Clinically Localized Tumors
The role of adjuvant chemotherapy is not completely clear. The investigation of its use falls into two categories or generations—pre- and postifosfamide regimens. In discussions with a patient, any potential benefits should be considered in the context of the short- and long-term toxicities of the chemotherapy.
First-generation trials (preifosfamide)
Several prospective, randomized trials were unable to determine conclusively whether doxorubicin-based adjuvant chemotherapy benefits adults with resectable soft tissue sarcomas. The majority of these studies accrued small numbers of patients and did not demonstrate a metastasis-free survival or an OS benefit for adjuvant chemotherapy.[4] A small study of adjuvant chemotherapy showed a positive effect on both disease-free survival (DFS) and OS in patients treated with postoperative chemotherapy.[25] There was wide interstudy variability among the reported trials, including differences in therapeutic regimens, drug doses, sample size, tumor site, and histologic grade.
A quantitative meta-analysis of updated data from 1,568 individual patients in 14 trials of doxorubicin-based adjuvant therapy showed an absolute benefit from adjuvant therapy of 6% for local relapse-free interval (95% confidence interval [CI], 1%–10%), 10% for distant relapse-free interval (95% CI, 5%–15%), and 10% for recurrence-free survival (95% CI, 5%–15%). A statistically significant OS benefit at 10 years was not detected: absolute difference 4% (95% CI, -1%–+9%).[26,27][Level of evidence: 1iiDii] However, only a small proportion of patients in this meta-analysis were treated with ifosfamide, an agent with demonstrated activity against soft tissue sarcoma. In addition, a subset analysis suggested that patients with sarcomas of the extremities may have benefited from adjuvant chemotherapy (hazard ratio [HR] for death, 0.8, P = .029), but there was no clear evidence that patients with extremity sarcomas had outcomes that were statistically significantly different from the outcomes of patients with tumors at other sites (P = .58).[27]
Second-generation trials (postifosfamide)
Subsequent chemotherapy trials were performed using anthracycline and ifosfamide combinations in patients who primarily had extremity or truncal soft tissue sarcomas. The data are conflicting, and the issue is still not settled. In a small feasibility study, 59 patients with high-risk soft tissue sarcomas, 58 of whom had an extremity or trunk as the primary site, underwent primary resection plus PORT and were randomly assigned to observation versus a dose-dense regimen of six 14-day courses of ifosfamide, dacarbazine (DTIC), and doxorubicin (IFADIC regimen) with granulocyte colony-stimulating factor (G-CSF) bone marrow support and mesna uroprotection.[28] There were no statistically significant differences in OS or relapse-free survival (RFS), but the study was severely underpowered.
In a second trial performed by the Italian National Council for Research, high-risk patients were treated with local therapy (i.e., wide resection plus preRX or PORT, or amputation as clinically necessary) and were then randomly assigned to observation versus five 21-day cycles of 4-epidoxorubicin (epirubicin) plus ifosfamide (with mesna and G-CSF).[25,29] Based on power calculations, the planned study size was 190 patients, but the trial was stopped after 104 patients had been entered because an interim analysis revealed a statistically significant (P = .001) difference in DFS favoring the chemotherapy arm. By the time of the initial peer-reviewed report of the study, the DFS still favored the chemotherapy group (median DFS of 48 months vs. 16 months), but the P value had risen to .04.[25]
Although there was no difference in metastasis-free survival at the time of the report, there was an improvement in median OS (75 months vs. 46 months, P = .03). However, at the follow-up report (at a median of 89.6 months in a range of 56–119 months), OS differences were no longer statistically significant (58.5% vs. 43.1% [P = .07]). The DFS difference had also lost statistical significance (47.2% vs. 16.0% [P = .09).[29] In summary, the trial was underpowered because it was stopped early, and the early promising results that led to stopping the trial diminished as the trial matured.
In a third, underpowered, single-center trial, 88 patients with high-risk soft tissue sarcomas (64 of whom had extremity or truncal primary tumors) underwent surgery (with or without radiation) and were then randomly assigned to receive four 21-day cycles of chemotherapy (epirubicin [n = 26] or epirubicin plus ifosfamide [n = 19]) versus no adjuvant chemotherapy (n = 43).[30] The trial was closed prematurely because of a slow accrual rate. After a median follow-up of 94 months, the 5-year DFS in the chemotherapy and control arms was 69% versus 44%, respectively (P = .01); the 5-year OS rates were 72% versus 47% (P = .06). All of the benefit associated with chemotherapy appeared restricted to the 19 patients who received epirubicin plus ifosfamide.
In yet another underpowered trial, 137 patients with high-risk soft tissue sarcomas (93% with extremity or truncal primary tumors) who met the eligibility criteria were randomly assigned to undergo surgical resection (with or without radiation) or to receive three preoperative 21-day cycles of doxorubicin plus ifosfamide.[31] This multicenter European Organization for Research and Treatment of Cancer trial (EORTC-62874) was closed because of slow accrual and results that were not promising enough to continue. With a median follow-up of 7.3 years, the 5-year DFS in the surgery alone and chemotherapy plus surgery arms was 52% and 56%, respectively (P = .35); and OS was 64% and 65%, respectively (P = .22).
These last four trials have been combined with the 14 first-generation trials in a trial-level meta-analysis.[32] Of the 18 randomized trials of patients with resectable soft tissue sarcomas, five trials used a combination of doxorubicin (50–90 mg/m2 per cycle) plus ifosfamide (1500–5000 mg/m2 per cycle). The remaining 13 trials used doxorubicin (50–70 mg/m2 per cycle) alone or with other drugs. The absolute risk reduction in local recurrence rates associated with any chemotherapy added to local therapy was 4 percentage points (95% CI, 0%–7%), and it was 5 percentage points (95% CI, 1%–12%) when ifosfamide was combined with doxorubicin. The absolute reduction in overall mortality was 6 percentage points with any chemotherapy (95% CI, 2%–11%; [i.e., a reduction from 46%–40%]), 11 percentage points for doxorubicin plus ifosfamide (95% CI, 3%–19%; [i.e., a reduction from 41%–30%]), and 5 percentage points for doxorubicin without ifosfamide.[32][Level of evidence: 1iiA]
An additional multicenter randomized trial (EORTC-62931 [NCT00002641]), the largest trial reported to date using adjuvant doxorubicin (75 mg/m2) plus ifosfamide (5000 mg/m2), was subsequently published in abstract form and was not included in the above meta-analysis.[33] The results differed from those reported in the meta-analysis.[32] After local therapy, 351 patients were randomly assigned to five 21-day cycles of adjuvant therapy versus observation. The trial was stopped for futility because the 5-year RFS was 52% in both arms. OS was 64% in the chemotherapy arm versus 69% in the observation arm. In a subsequent abstract, the EORTC investigators reported a combined analysis of this trial and their previous trial (EORTC-62771) [34] of adjuvant cyclophosphamide plus doxorubicin plus DTIC (CYVADIC), representing the two largest trials of adjuvant therapy for adult soft tissue sarcoma in the literature.[35] The combined analysis showed no improvement in either RFS or OS associated with adjuvant chemotherapy.[35][Level of evidence: 1iiA]
In summary, the impact of adjuvant chemotherapy on survival is not clear but is likely to be small in absolute magnitude. Therefore, in discussions with a patient, any potential benefits should be considered in the context of the short- and long-term toxicities of the chemotherapy.
Role of regional hyperthermia
The use of regional hyperthermia to enhance the local effects of systemic chemotherapy in the neoadjuvant and adjuvant setting is under investigation. In a multicenter phase III trial, 341 patients with high-risk (tumor ≥5 cm, grade 2–3, and deep to fascia) soft tissue sarcomas (149 extremity tumors and 192 nonextremity tumors) were randomly allocated to receive four 21-day cycles of chemotherapy (etoposide 125 mg/m2 on days 1 and 4; ifosfamide 1500 mg/m2 on days 1–4; doxorubicin 50 mg/m2 on day 1) with or without regional hyperthermia both before and after local therapy.[36] Approximately 11% of the patients were being treated for recurrent tumors. The regional hyperthermia was designed to produce tumor temperatures of 42°C for 60 minutes and was given on days 1 and 4 of each chemotherapy cycle. After the first four cycles of chemotherapy, definitive surgical excision of the tumor was performed, if possible, followed by radiation therapy, if indicated (i.e., a 52.7 Gy median dose delivered), and then the last four cycles of chemotherapy plus or minus hyperthermia. Three of the nine treatment centers with particular expertise in hyperthermia treated 91% of the patients in the trial.
The median duration of follow-up was 34 months. Local progression occurred in 56 patients in the hyperthermia group and 76 patients in the control group. The relative HR for local progression or death was 0.58 (95% CI, 0.41–0.84), with an absolute difference at 2 years of 15% (76% vs. 61%; 95% CI of the difference 6–26). The decreased risk of local progression or death was seen in both extremity and nonextremity tumors. However, hyperthermia had no effect on distant failure rates nor was there a statistically significant effect on OS (HR, .88, 95% CI, 0.64–1.21; P = .43).[36][Level of evidence: 1iiDiii] There was a higher rate of grade 3 to 4 leucopenia in the hyperthermia group: 77.6% versus 63.5% (P = .005). Since a large proportion of the patients were treated at centers with special expertise, there is no certainty that the finding can be generalized to apply to other settings.
Role of isolated limb perfusion
Isolated limb perfusion is under investigation as a means to deliver high doses of chemotherapy and permit limb salvage in unresectable primary or recurrent extremity soft tissue sarcomas that would otherwise require amputation, in the opinion of the surgeon.[37,38] Common drugs used in the procedure are TNF-alpha, melphalan, and interferon-gamma. Experience is limited to case series with response rates and reported avoidance of amputation as the outcome.[37,38][Level of evidence 3iiiDiv] The technique requires specialized expertise to avoid severe local and systemic toxicity including systemic effects of TNF-alpha. The technique has not been directly compared to standard approaches with combined systemic and local therapy.
Role of chemotherapy for advanced disease
Doxorubicin is a mainstay of systemic therapy in the management of locally advanced and metastatic soft tissue sarcoma. Pegylated liposomal encapsulated doxorubicin is a formulation of doxorubicin designed to prolong the half-life of circulating doxorubicin and slow the release of active drug.[39] The changed pharmacokinetics result in less myelosuppression and possibly less cardiotoxic effects, but there is a substantial incidence of hypersensitivity-like reactions and hand-foot syndrome. Its clinical activity relative to unencapsulated doxorubicin is not clear.[39][Level of evidence 3iiiDiv] Other drugs that are thought to have clinical activity as single agents are ifosfamide, epirubicin, gemcitabine, and paclitaxel.[40,41,42,43][Level of Evidence 3iiiDiv] Their clinical activity relative to single-agent doxorubicin is not clear, and they are not known to have superior activity.
There is controversy about the clinical benefit of adding other drugs to doxorubicin as a single agent. A systematic evidence review and meta-analysis conducted by the Cochrane Collaboration summarized the eight randomized trials reported from 1976 to 1995.[44] No additional randomized trials had been reported or were known to be in progress between 1995 and the 2002 literature search. Single-agent doxorubicin had been compared with a variety of doxorubicin-containing combinations that included vincristine, vindesine, cyclophosphamide, streptozotocin, mitomycin-C, cisplatin, and/or ifosfamide. Combination regimens consistently caused more nausea and hematologic toxicity. However, the better response rates associated with combination therapy were marginal and depended on the statistical model used (fixed effects model ORresp = 1.29; 95% CI, 1.03–1.60, P = .03; random effects model ORresp = 1.26; 95% CI, 0.96–1.67, P = .10) There was no statistically significant difference in the 1- (ORmortality = 0.87; 95% CI, 0.73–1.05, P = .14) or 2-year mortality rates (ORmortality = 0.84; 95% CI, 0.67–1.06, P = .13).
These results were very similar even when the analyses were restricted to the four trials that used DTIC and/or ifosfamide as part of the combination regimen with doxorubicin agents that were postulated to have greater activity than the others tested. A subsequent meta-analysis of all three published randomized trials of chemotherapy regimens that contained ifosfamide versus those that did not came to similar conclusions: tumor response rates were better when the regimen included ifosfamide (RRresp = 1.52; 95% CI, 1.11–2.08), but mortality at 1 year was not (RRmortality = 0.98; 95% CI, 0.85–1.13).[45][Level of evidence: 1iiDiv]. Therefore, response rate was a poor surrogate for OS. Quality-of-life outcomes were not reported in any of the above-mentioned randomized trials, but toxicity was worse when agents were added to doxorubicin.
Refer to the Treatment Option Overview section of this summary for a more detailed discussion of the roles of surgery and radiation therapy.
Low-grade soft tissue sarcomas have little metastatic potential, but they have a propensity to recur locally. Accordingly, surgical excision with negative tissue margins of 1 cm to 2 cm or larger in all directions is the treatment of choice for patients with these early-stage sarcomas.[1,2,3] The Mohs surgical technique may be considered as an alternative to wide surgical excision for the very rare, small, well-differentiated primary sarcomas of the skin when cosmetic results are considered to be important, as margins can be assured with minimal normal tissue removal.[4]
Carefully executed high-dose radiation therapy using a shrinking-field technique may be beneficial for unresectable tumors or for resectable tumors in which a high likelihood of residual disease is thought to be present when margins are judged to be inadequate, and when wider resection would require either an amputation or the removal of a vital organ.[5] Because of the low metastatic potential of these tumors, chemotherapy is usually not given.[6,7]
Standard treatment options:
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Refer to the Treatment Option Overview section of this summary for a more detailed discussion of the roles of surgery, radiation therapy, and chemotherapy.
High-grade localized soft tissue sarcomas have an increased potential for local recurrence and metastasis. For sarcomas of the extremities, local control comparable to that obtained with amputation may be achieved with limb-sparing surgery that involves wide local excision in combination with preoperative radiation therapy (preRX) or postoperative radiation therapy (PORT).
Complete surgical resection is often difficult for sarcomas of the retroperitoneum because of their large size before detection and anatomical location.[1,2] As opposed to soft tissue sarcomas of the extremities, local recurrence is the most common cause of death in patients with retroperitoneal soft tissue sarcomas. Complete surgical resection (i.e., removal of the entire gross tumor) is the most important factor in preventing local recurrence and, in many instances, requires resection of adjacent viscera.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II adult soft tissue sarcoma and stage III adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Regional lymph node involvement by soft tissue sarcomas of adulthood is very infrequent. However, sarcoma types that more commonly spread to lymph nodes include high-grade rhabdomyosarcoma, vascular sarcomas, and epithelioid sarcomas.[1]
Refer to the Treatment Option Overview section of this summary for a more detailed discussion of the roles of surgery, radiation therapy, and chemotherapy.
In the setting of lung metastasis, resection of metastatic tumors may be associated with long-term disease-free survival in patients selected for optimal underlying disease biology (i.e., patients with a limited number of metastases and slow tumor growth).[1,2,3] It is not clear to what degree the favorable outcomes are attributable to the efficacy of surgery or to careful selection of patients based upon factors that are associated with less-virulent disease.[1,2,3] The value of resection of hepatic metastases is unclear.
As noted in the Treatment Option Overview section above, doxorubicin is the standard systemic therapy in the management of metastatic sarcomas.[4,5] Other drugs that are felt to have clinical activity as single agents are ifosfamide, epirubicin, gemcitabine, and paclitaxel.[6,7,8,9] Their clinical activity relative to single-agent doxorubicin is not clear, and they are not known to have superior activity. There is controversy about whether adding drugs to doxorubicin offers clinical benefit beyond what is achieved by doxorubicin as a single agent. For older patients to avoid severe toxicity, sequential use of single agents may be the preferred strategy for palliation.
Standard treatment options
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Treatment of patients with recurrent soft tissue sarcoma depends on the type of initial presentation and treatment. Patients who develop a local recurrence often can be treated by local therapy: surgical excision plus radiation therapy after previous minimal therapy or amputation after previous aggressive treatment.[1,2,3,4,5,6,7] Resection of limited pulmonary metastases may be associated with favorable disease-free survival.[8,9,10][Level of evidence 3iiiDiv] However, the contribution of selection factors, such as low tumor burden, slow tumor growth, and long disease-free interval, to these favorable outcomes is not known.
There is no standard chemotherapy for recurrent soft tissue sarcomas that have progressed after doxorubicin as a single agent or in combination with other agents that have clinical activity, such as ifosfamide, epirubicin, gemcitabine, and paclitaxel. Any of these agents not previously administered to the patient may be used sequentially at the time of recurrence or progression.[11,12,13,14][Level of Evidence 3iiiDiv] Given that none of these agents has been shown to increase overall survival in this setting, clinical trials are an appropriate option.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent adult soft tissue sarcoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Editorial changes were made to this summary.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of adult soft tissue sarcoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Adult Soft Tissue Sarcoma Treatment are:
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Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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National Cancer Institute: PDQ® Adult Soft Tissue Sarcoma Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://cancer.gov/cancertopics/pdq/treatment/adult-soft-tissue-sarcoma/HealthProfessional. Accessed <MM/DD/YYYY>.
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Pigmented Acrylic Ink
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Acid-free, archival quality pigmented acrylic inks are available in rich, vivid colors. Inks are waterproof and lightfast. Ideal for calligraphy, drawing, painting, stamping, airbrush, and more. 12 ml (0.50 oz.) plastic jars.
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Can Speedball pigmented opaque white ink be reconstituted if dried out?- Asked by Merrill on 08-May-14
Once these Pigmented Acrylic Inks dry they become permanent and waterproof. May try adding an acrylic medium or thinner, but this may change the consistency of the inks.- Answered by MisterArt on 09-May-14
Can these acrylic (or any acrylic) inks be used with Speedball steel brushes?- Asked by Karen LoCicero on 05-Aug-13
If you clean them immediately, and you can thin them with a bit of water if it seems too thick for the steel brush tool to handle.- Answered by MisterArt on 06-Aug-13
Can I thin Speedball gold pigmented acrylic ink?- Asked by jwhody on 26-Jun-13
A lot of inks just plain spoil if they are sitting for a long time, similar to milk souring. You could attempt to thin it (with water, since acrylic is water-based) and see if it helps.- Answered by MisterArt on 26-Jun-13
Does the Speedball Super pigmented gold ink show up on dark paper?- Asked by Kara on 18-Jun-13
Upon asking the people at Speedball this question, they told me it will show up on dark paper, but you may have to put on a second coat. We do have a marker that's called the Pilot gold and silver pens that are actually paint in a pen. We have them by Sharpie, as well (Sharpie paint pens). These will work on black paper, really opaque, but you may be wanting to brush it on, or use it in a pen of your own. Another trick some artists use is to mix gold gouache with a little water, to make an ink like consistency, and that is very opaque. A friend who was a calligrapher did this with her calligraphy pens.- Answered by MisterArt on 18-Jun-13
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Hawkins Jazz Collective at the Owl Shop
March 13 @ 9:00 pm - 11:30 pm
|Recurring Event (See all)
An event every week that begins at 9:00pm on Wednesday, repeating until December 18, 2019
The Hawkins Jazz Collective performs every Wednesday evening from 9:00 pm to midnight at the Owl Shop in downtown New Haven. This is hard driving straight ahead jazz that represents the best of the post bop era. FREE.
The Owl Shop is located at 268 College Street, New Haven, CT 06510.
Photo by Craig S. O'Connell


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Bring on the Bronx
CLEARWATER, Fla. — One final blog entry for 2008 Spring Training. After this, it's off to bed for a quick bit of sleep before I get up in a few hours to catch a flight back to Toronto. Come Saturday night, I'll be in the Big Apple gearing up for Opening Day.
Spring didn't go exactly as the Jays would've hoped. Losing Casey Janssen (torn labrum) was a big blow to the pitching staff, having Scott Rolen (broken finger) possibly sidelined until May hurt the lineup and B.J. Ryan (coming back from Tommy John) wasn't able to meet his goal of breaking camp with the club.
The offense didn't look fantastic, but Vernon Wells, Lyle Overbay and Aaron Hill jump out as guys who did look great at the plate this spring. In Grapefruit League play, Toronto finished 11-16, but it's worth noting that in 1992 and 1993 (the Jays' two World Series title seasons) the team posted 13-18 and 11-19 spring marks, respectively.
"You can throw our record out the window," Jays manager John Gibbons said on Thursday. "I think you can do that. We saw a lot of good things. We're banged up more than we would've hoped, that's for sure, but overall I saw a lot of good individual things, though our record doesn't indicate that."
So Toronto heads north with a slightly bruised roster, but as of right now, the injuries — aside from Janssen's — don't appear to be major blows. It's possible that Ryan is back by mid April, which would be a boost to the bullpen, and in a perfect world, Rolen could be back in April, too (seems unlikely, though).
The only real question mark I see right now, besides the obvious wait-and-see with the offense, is a lack of depth behind the starting rotation. Roy Halladay, A.J. Burnett, Dustin McGowan, Shaun Marcum and Jesse Litsch are a formidable five, but the depth chart is rather thin behind that group. Toronto is one pitching injury away from uncertainty and the Jays are pinning a lot of hopes on repeat showings from the M&M boys and Litsch, as well as full seasons from Doc and A.J.
This should be an interesting year for the Jays. They look like a club that could either seriously contend for a playoff spot or just float to another near .500 finish. One thing is for sure, if the Jays get off to a slow start, there could be some decision-makers who find themselves on the hot seat pretty quick. But let's not put the cart ahead of the horse — as pitching coach Brad Arnsberg loves to say. Let's just get this thing rolling. Enough of this spring stuff…
Catch up with you from Yankee Stadium in a few days. So long, Florida.
15 Comments
Nice post, Jordan. I think as far as the starting rotation goes, there is more cause for optimism than there was last year. Litsch is pitching well enough not to lose a turn, and if someone goes down, we still have 4 guys that can go every 5 days. The way our minor leaguers pitched this Spring, there are several guys that could step in to the #5 spot. Compare that to last year when we had 3 openings to fill.
This is interesting: Buck Coats is on the team, and Stewart is not. Is this goodbye day for Stew?
Agreed, our rotation has enough top end talent that I feel they could lose a man for a little while and still hold out. To me Halladay, Burnett and McGowan are 1a,1b, and 1c. Plus I really like the way Marcum handles himself he is underrated. I look how much Ian Kennedy is hyped by the Yankee's and he doesn't do anything that Marcum can't do.
They have David Purcy and Gustavo Chacin waiting, both of them could fill in quite nicely. This team is much more capable of battling through a FEW injuries this year, than last. I have a feeling it's going to show in the standings.
There is depth behind the rotation it's just not proven depth. If the rotation stays healty into atleast June we would be in a better position to fill holes with Chacin or possibly Purcy being ready. Early injuries to any of the top four would make it very tough to fill the rotation adequately.
From opening day this team needs some good fortune and to avoid further injuries. Wells looks to be back, Hill is going to be an allstar this year and should hit second in my opinion (but he won't). Stairs with his reborn short swing will have another big year as will Rios. I expect Overbay to have a good year, back to his 06 numbers would be nice.
The question marks are… Thomas!!! Zaun/Barajas and now Rolen.
All in all this team should be fun to watch, and with some good fortune, LOOK OUT!
One thing that will help us through an early injury, rmatty, is the excellent bullpen. The other 4 will have to eat innings to keep the pen from getting gassed, and we will have to put runs on the board, but there is plenty of help for whoever gets the call.
We all know watching Thomas in April is like watching paint dry, but he gets better as the season goes along. I hope Rios isn't swinging for the fences. He is such a good hitter, he should do what comes naturally, and take the power as it comes. Zaun isn't hitting well right now, but Barajas is, and Scutaro is doing an excellent job at third.
We may not have an A-Rod or a Papi, but our whole lineup hits well, with no soft spots, and we should wear out a lot of pitchers.
Granted our pen is a definite strong point and they will be heavily relied upon in the seasons first month as starters get stretched into higher pitch counts but they wouldn't be able to make up the loss of one of our top 4 starters. They NEED to remain healthy for us to contend unless of course someone in the minors steps up like M&M or Litsch did last year. I don't see that guy at the moment, maybe Purcy but he is inconsistant as of now. Hopefully we won't need to search for that diamond in the rough this year and we roll out the same 5 all year… Wouldn't that be nice… Unlikely but nice.
Thomas has proven throughout his career that he is a slow starter… but this guy gets slower by the hour. Why wouldn't he hire (with his 9mil salary) a pitcher to throw to him on the offseaon so he can "set his timing" as Frank likes to say. Start earlier so you are actually READY for opening day. You can't bench him when he stinks because he needs to see pitching to "set his timing" so Gibbons is basically stuck with him and his slow starts. We all remember last years 8 game skid which basically dug a hole too deep to climb out of, especially in this division and Frank was front and center of that slump. In this division you can be out of the race by the time mid May rolls around… Even if Frank lights it up he can't make up 10 games by himself.
Don't forget that in the normal scheme of things, the #5 guy only goes about 3 times a month. There are not too many teams that can run their 5 guys in order like the jays can. In the unlikely event that somebody goes down, you could call on John Parish or Chacin. You get 3-4 innings the first start, 5 in start #2, and 6-7 for the rest. The way the pen is pitching, you could probably have 1 guy take up the slack, because the next day you have The Doc to give everybody a rest. The situation isn't as good as nobody hurt, but we should still be able to win half the games with the #5 starter, which is pretty good.
As for Thomas, he didn't lose those 8 games all by himself. There were a bunch of guys that weren't producing. If we could figure out how to get everybody out of the gate with a hot bat, we would be sitting in the dugout, not blogging.
The Jays need to be winnng more consistently this year.
By that I mean not just beating BOS and NYY when they have the chance, but also the likes of the Rays (esp in Tropicana field) and the Rangers. How many times in the last 2 seasons that we saw the Jays won 3 out of 4 at home against a team like BOS or NYY, then went to TB and lost 2 out of 3?
Losing streak should not be a big problem with out starting rotation. It is getting on a winning run that is important. The Jays will always be pretenders if they keep on alternating wins and losses, they need winning streak of more than 5 games (through the rotation once) or just a good 15-4 run to put them into contention this yr.
I was not blaming Thomas for the 8 game skid, simply pointing out that his slow start certainly didn't help the situation. We need him hitting in April the way he hits in September!!!
So let's say that after the first 8 weeks of the season we find ourselves in 4th, behind the usual suspects and a Rays' team playing up to its potential. How do things play out? Do we hold the course? Fire the manager? Fire the genreal manager? Do we unload Bernett/Rolens/etc. for draft picks at the trade deadline? In other words, if this is a pivotal year for the organization, and I believe most of us would agree it is, what should the plan be if things go south. Assuming, of course, we are not willing to accept the party line" "we have a great team on paper, but injuries…"
I'm excited ! I think this is a great team. Scutaro is a perfectly fine stopgap for Rolen, he was practically a regular in Oakland last year so he's not your normal backup.
I don't know why people worry about Thomas, he was terrible last spring, april and may. And there is really no reason not to think he wont be again this year. The dudes old, he takes time to warm up, and become better able to tell the difference between the cataracts and the baseball.
Unload Rolen ???
Ha, if it was only that easy ! The JP was the last person the cardinals called. They tried to get rid of him and no luck.
For better or worse Rolen is a Bluejays for the next 3.
Burnett, IF healthy is one difference maker the Jays have that we could def flip at the deadline for something quality. Especially if he's healthy at the deadline that means he's raking it and opting out for sure.
Im hoping he is ! And Boston pitching is ravaged by injuries and they become desperate enough to trade us Jed Lowrie !!!
I can't see who they would "unload" if the team struggles or is out of the picture mid season. They have two many guys they can't move and two many guys no one would give up anything for. If they struggle its Gibbons or JP that have to answer because thats how it works. I can't see this team if healthy having problems staying in the race. Depth has never been better (maybe before Rolen and Jansen got hurt) on this team.
If Thomas is old and needs more time to get ready, he should then start getting ready earlier… It is simply that easy!!! We need him to be our best hitter since that is his sole job on this team, from start to finish.
I agree that the jays are one starter injury away from disaster. There are no adequate replacements at AAA . Chacin, Purcey and Banks are not major league ready. To be prepared for this I wish JP would sign Claudio Vargas. He's a proven starter and has a lot of potential that Arnsberg could help him with.
Burt: I think you should wait 8 months before you start worrying about stuff like that. I realize you like the doom and gloom, but we might as well start the season with a little optimism….
Whoops, meant 8 "weeks", not "months"….
Hem: I agree with you. I am actually not a doom and gloom guy. However, after 15 years of unfounded optimism and doom and gloom, as you call it, I am not ready to jump on the bandwagon just to watch people fall off when things go south. My point is simply this: you are either a pretender or a contender and there is no in between. The AL east is just too tough for pretenders. If we do not have superior talent, we need to take steps to get some. If we already have talent, great! Let's go for it. But we cannot stay competitive with the other teams that are improving, via savvy drafting, if we do not have a plan for when things go wrong. It seems to me that there is very little difference between the Jays and the leafs over the last 15 years. Short on talent, long on excuses. I'm just saying, let's get it right so that in another 15 years we are not where we are now!


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What is the BodyHoliday?
Set on a secluded cove of white sand beach at the edge of the Caribbean Sea, surrounded by tropical gardens and rainforest, BodyHoliday Saint Lucia is the ultimate getaway for body and mind. Recognised as one of the finest destination resorts and centre of well-being, there couldn't be a more idyllic corner of the world to escape to. But what makes this vacation truly idyllic is it's designed by you.
Here, you are encouraged to do as much or as little as you like. At this all-inclusive luxury resort dedicated to well-being, there are any number of ways to soothe the senses and restore the spirit. Based on a philosophy of relaxation, restorative beauty, exercise and diet, BodyHoliday offers every possibility. The renowned Wellness Centre, voted one of the world's best spas by Condé Nast Traveler, caters to every need with an indulgent array of time-honoured body treatments as well as state-of-the-art therapies, while BodyHoliday's five-star restaurants satisfy every taste with menus that feature locally-sourced foods and ingredients fresh from the resort's own organic garden. Then, there is the endless list of activities on land and sea–from yoga sessions and fitness classes, scuba diving, sailing, tennis and golf to more exotic adventures including biking the coastline, hiking the mountains or abseiling a river gorge. However you design it, BodyHoliday can be a hive of activity or a haven of peace and serenity.
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Home » THE RISING
+ Dan OFarrell And The Difference Engine + Strangeways + Tyler Collins
Age restriction 14+
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"The Rising are fronted by Tommy Overington. He′s a star, and he means it! Great tunes and a great band" Alan Mcgee – Creation Records
The Rising are a 6 piece psychedelic pop/ rock n roll band from Southampton
This autumn, The Rising return with their much anticipated second studio album "Are You Ready To Fly?"
It was recorded at the legendary Rockfield Studios in Monmouth, Wales and was engineered by Welsh experimental musician Tim Lewis (Thighpaulsandra) who has played keyboards for Julian Cope and Spiritualized amongst others during his illustrious career.
The group started recording the follow-up to their 2013 self-titled debut album in October 2014 at Liam Watson's Toe Rag Studios in London, but decamped to Rockfield in October 2015, when they began to explore different sounds and genres - namely psychedelic pop - which they sought to introduce alongside their existing brand of 60's influenced rock n roll. Along with the growing number of personnel in the band and the limited recording options available at the analogue-only Toe Rag, it became difficult to continue the project there. A move to a more contemporary digital recording studio was needed and after whittling down their shortlist of potential locations, the band decided on Rockfield.
Due to the album being totally self-funded, The Rising have had to constantly keep busy in between recording sessions by selling out local gigs in their hometown of Southampton as well as playing shows up and down the country. During this time they have also appeared at The Isle Of Wight Festival, Victorious Festival, Common People and Bestival before finally finishing the album in June 2018.
"Are You Ready To Fly?" sees the band experiment with new ideas and influences, which adds a fresh dynamic and a real sense of evolution to their sound, without straying too far away from the nucleus of their eponymous release which won the band an impressive fanbase.
The Rising celebrated the release of their new album by selling out a special album launch show at The Joiners in Southampton on Friday 9th November - the day of the album's release. They then signed off 2018 in style by supporting Shaun Ryder's Black Grape on their winter tour at The Engine Rooms in Southampton on Friday 30th November.
Plus support from
Tyler Collins Strangeways Dan O'Farrell And The Difference Engine


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Also found in: Dictionary, Thesaurus, Financial, Acronyms, Encyclopedia, Wikipedia.
An individual who has lawfully received possession of a Commercial Paper, such as a check, and who is entitled to payment on such instrument.
A holder is distinguishable from a holder in due course since, in addition to possession of the instrument, the latter takes it for value, in Good Faith, and in the absence of any notice that there is any claim against it or that it is overdue or has been dishonored, which means that payment of it has been refused.
n. a general term for anyone in possession of property, but usually referring to anyone holding a promissory note, check, bond or other paper, either handed to the holder (delivery) or signed over by endorsement, for which he/she/it is entitled to receive payment as stated in the document. (See: check, bill of exchange, promissory note, bona fide purchaser, endorsement, holder in due course)
holdernoun endorsee, individual in possession, keeper, owner, payee, person in possession, possessor, receiver, recipient
Associated concepts: bona fide holder, holder for value, holder in due course, holder in good faith, holder of a lien, joint holder, legal holder, license holder, negotiable instruuents, original holder, policyholder, property holder, stockholder
See also: bearer, catchall, coffer, depository, receiver, recipient, tenant
holdera payee or indorsee in possession ofa bill of exchange or promissory note.
HOLDER. The holder of a bill of exchange is the person who is legally in the possession of it, either by endorsement or delivery, or both, and entitled to receive payment either from the drawee or acceptor, and is considered as an assignee. 4 Dall. 53. And one who endorses a promissory note for collection, as an agent, will be considered the holder for the purpose of transmitting notices. 2 Hall, R. 112; 6 How. U. S. 248; 20 John. 372. Vide Bill of Exchange.