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Two things happen with perennial certainty each year in our country. It's that time of the year again when countless students wait with bated breath for the much anticipated high school and twelfth board results to-be-announced. And it's that time when meteorologists get busy predicting the advent of the south west monsoons spelling relief from a sultry summer. Both these phenomenon bespeak of new beginnings in terms of growth for the country.
A total of 14,29,478 students appeared for the Maharashtra Board class XII examinations of 2017. Of these 12,79,406 cleared this basic examination that sends them onward ahead for further studies in areas of their choice. Matriculates is the revered term used to refer to these final year high school students who are now ready to blaze forth in the new found world of higher learning.
Passing the matriculation examinations opens the portals to an academic world – Pure Sciences, Humanities, Commerce, Medicine, Engineering, and Computer Sciences and so on. The avenues are open-ended and really endless in today's modern world. Matriculation is the formal process that allows one to enter a university with students getting enrolled in different fields of study. This rite of passage then sees the careful nurturance and paving of way for the development of human resources for the country at large. Education clearly plays a crucial role in creating the scientific temper of our land.
Scientific temper is a way of life and this is the time when the growing educated population is getting groomed for the social processes, to think and act with conviction, courage and knowledge. Scientific temper may also be described as an attitude which involves the application of reasoning, logic and good sense. Herein are sown the seeds of fairness, equality and democracy.
It was Jawaharlal Nehru who first used the phrase in 1946 in this sense. He goes on to give a detailed explanation in his famous book 'Discovery of India": "What is needed is the scientific approach, the adventurous and yet critical temper of science, the search for truth and new knowledge, the refusal to accept anything without testing and trial, the capacity to change previous conclusions in the face of new evidence, the reliance on observed fact and not on pre-conceived theory, the hard discipline of the mind—all this is necessary, not merely for the application of science but for life itself and the solution of its many problems."
And so, just as we implant knowledge in the young minds of our pubescent citizenry, it is also the time to sow the seeds in the ground for them to grow, flourish, and bear fruit. Monsoons are a boon for this, our land of tillers and the very foundation of our economy, contrary to what one may imagine. Our food security really rests on the monsoons. The Indian monsoon is the most prominent of the world's monsoon systems, and one on which is based the entire agricultural economy of the country.
Because the land and its cultivation depend entirely on monsoon rains it becomes absolutely necessary to invest in quantitative long-range weather forecasts. It's an area of operations that we still need to perfect. We need to be on top of the situation and move on from fathoming predictions through clues that appear prior to the months leading up to the big rains. We need to have a weather perfect forecast that ought to be released to the farmers. Forecasts need to be clearly refined so that agriculturists can positively correlate them for cultivation.
Truly, this last day of May 2017 has us believing that June is the month for new beginnings for us in India. The billowing clouds and stirring wind speeds already give indications of the onset of the great monsoons. Smiling graduating matriculates splashed on newspapers augur the scientific temper Nehru bespoke, long years back. We stand on the verge of an academic universe of our making and an agricultural revival that will spell rural development.
"Faith is the bird that feels the light and sings when the dawn is still dark"- Rabindranath Tagore


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Mathew T. Williams
August 9, 2012
On July 20th, 2012 James Holmes committed an act of alleged maniacal and lethal aggression towards a group of movie patrons. 12 dead, 59 injured…America was shocked.
Politicians ran to heat the debate of gun control, but something different happened… It fell on deaf ears. America opted for the red pill.
We no longer have closed eyes in dreams fed to us by the powers that be. The only true defense against a methodical madman, immediate retaliation!
Hey, you can huddle up in the fetal position and beg for your life. You can run into jams of crowded people who reacted the same. Or you can be prepared.
Let's talk.
Let's examine some informative details the mainstream media purposely avoids telling you.
– Colorado is a state which has Concealed Carry Licensing. Only the state government can issue an order for a location to be off limits to licensed carry. It is described to the letter of the law as government building and makes no mention of commercial or residential locations. C.R.S. 29-11.7-103
– The Century Movie theater (owned by Cine-mark of Plano, TX) has a nationwide "gun free" policy. Widely known to the awakened as "Kill Zones." Since when did corporate policies super cede state law?
– The theater did not provide proper security to its patrons. Especially if it were to demand they come stripped of their rights.
– One well trained man or woman could have stopped the shooter and saved so many lives. We don't shoot to kill, we shoot so others may live.
We cannot un-invent the gun. To conceive that we can ensure that they will be placed in the right hands at all times is just foolish.
The answer is to accept it as a tool. Not much different than what you would find in your garage or shop. It is the person who wields it that is to be in question.
How do we eliminate this infection of lunatics that go on rampages? Where is our new drug of immunity? New laws? Banned weapons? No.
There is no way to make it go away. You cannot cure evil. It is the inherent curse of man and will forever follow us. Our forefathers knew this when they founded our nation, so much so they saw it fit to instill constitutional rights to ensure we as free Americans can bear arms.
So what can you do to stand your ground? Well there are two different types of shooters: those that have and those that have not. However the solution is the same.
Bring your wallet.
A quality handgun can be had from as low as $300. Go to your local gun shop and ask questions regarding your rights to own and carry a handgun for self defense.
Ask to see different models until you find your pistol. Remember, the comfort you have with your gun's grip will be the developing foundation of your marksmanship abilities.
Find a Certified Firearms Instructor. You will be surprised to find out what you don't know. These individuals or groups are also excellent resources for local or state weapons laws.
In particular, for the new shooter, they can train you from the ground up in a relatively short time frame.
Follow four simple safety rules and be able to operate using combinations of them:
1. ALL firearms are considered loaded until both visually and physically checked.
2. NEVER point a firearm at anything you are not willing to destroy.
3. NEVER place your finger on the trigger until you are on target.
4. ALWAYS be aware of your target and its surroundings.
From the layout provided of the theater itself, and the description as to how James Holmes engaged the crowd, those in the front rows were the immediate attack.
After that he lobbed chemical canisters to the rearward upper level areas. Then he marched up the left side sweeping the audience. In this instance, an unarmed victim has little to no choice but to fight or flee.
Those that fled bottle-necked the exits. Those trapped in the center seating areas had nowhere to go. They suffered the brunt of the attack.
How do you survive a theater style shooting? Well if you're unarmed you're at the mercy of your attacker for at least 5 minutes until the police arrive. Avoid any seating that places obstacles (people or objects) between you and your exit. If you are next to the attacker, you do have the choice of utilizing force to attempt to subdue him, but this is almost as risky as running.
For those of you that choose to exercise your rights it's a whole different approach. In this instance, if you were anywhere but the front row, you would have time to draw your weapon and fire. Being that this nut job had body armor on, one shot is not going to do it.
You will also need a weapon of 9mm or greater. Preferably a .40, .45 or .357. With a firm grip you will need to fire into both chest and head (Mozambique drill) consecutively while you approach the threat. Your approach speed should be determined by steadiness, not haste. Feel free to step on the unarmed if need be; they are probably used to it, and frankly, you are saving their lives.
Once you have reached the assailant, try to assess his movement, especially in the hands. You are now at point blank range with your would-be killer. If he moves finish him. Remember once you draw your weapon and fire off that first round, there is no turning back. Get into the fight! Your job is to stop, control or neutralize the threat.
In this and many other mass shooting incidents, with all the vivacious level of carnage that comes with them, only lethal force can ensure your safety and the safety of others.
There are over 70 million gun owners that killed no one yesterday. To fight for your life and the life of your loved ones is not a super human trait. It's your duty!
– The Gunfighter's Prayer
Lord, lord make me fast and accurate.
Let my aim be true and my hand faster
than those who wish to harm me and mine.
Let not my last thought be,
"If only I had my gun",
and lord…
If today is truly the day you are to call me home…
Let me die in a pile of brass
This article first appeared on the Planet.Infowars.com Social Network.
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subset: commoncrawl


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While growing up in India, I did not get a chance to see or try a number of fruits. One of those was apricots. I do remember having dried apricots but not fresh ones so when I saw them here, I was quite excited. I did buy a box of fresh apricots though I was not sure if we will use it up. I was then tempted to bake something with it and chose to make a cake. It is more a breakfast cake as they can be quite filling and ofcourse quite nutritious. If you like cakes sweet, then add more sugar. I quite liked the cake and think I will make it often, although may use tinned apricots rest of the year.
5-6 apricots, cut into slices
¾ cup all purpose flour
¾ cup wholewheat flour
2 teaspoons baking powder
½ teaspoon soda bicarbonate
¾ cup orange juice with pulp (juice from two oranges)
¼ cup yogurt
1/3 cup margarine/butter/oil
½ cup sugar
2 teaspoon vinegar
2 tablespoon mixed peel
2 tablespoon black currants or any other dried fruit of choice
3-4 tablespoon water
Whisk together the orange juice, sugar, oil/butter/margarine and sift together baking powder, soda bicarbonate, flours and add to the orange juice mixture
Add vinegar and mix lightly
Line a cake tin with baking paper and arrange chopped apricots on the bottom
Pour the cake batter into the tin and tap gently about ten minutes
Bake in a preheated oven at 180degC for 30-40 minutes, until skewer inserted in centre comes out clean
Cool in tin for five minutes then transfer to cooling rack and cool completely


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Friday, July 22
Tempo celebrates its six-year anniversary with Rudy Currence
The Mantras with The Werks free show! at Neighborhood Theatre
Primal Chaos: Top Down Productions celebrates Wobble Factory! at Marigny
Christmas in July at Strike City
Lady Ga Ga's very own DJ and producer - DJ White Shadow at Suite
Saturday, July 23
Rickmond Media Christmas in July fundraiser at Sunset Club
2011 Independence South American party at On The Roxx Southend
Candy Land party at Mez and Kazba
Petra's Got Talent Semifinals Part 2
Radok Fest at Tremont Music Hall
There's no need to sugar-coat. Sweetness is in the air at Mez and Kazba during its special Candy Land Party, presented by dbraun Promotions, Elevate Lifestyle and Charlotte Seen, this Saturday, July 23. Models will be covered in confectionery and edible attire during a fashion show set to stimulate the sweet tooth. Folks attending should dress in their candy-themed best for blending in with the delicious decor, as well as for a chance at winning a $500 VIP table. Let the game begin. 10 p.m.-2 a.m. Mez and Kazba at EpiCentre, 210 E. Trade St. www.mezcharlotte.com.
Anita Overcash
Jumaane Torrence knows the importance of innovating and then sticking to your guns. Thats what hes done with his entertainment venue/nightclub Tempo, which celebrates its six year anniversary this Friday, July 22 with a show by Rudy Currence and Ida Divine.
I think the main thing we can attribute our success to is having a vision beyond the norm, Torrence explains. A lot of venues, promoters and establishments kind of piggyback what others are trying to do instead of carving a niche for themselves in the market. My goal here was to just study the market and see what was missing and try to fill a void, and in doing that create your own culture and carve a niche.
Tempos niche is based on their focus to bring in a variety of top performers and artists, instead of just opening the doors and offering drinks and a dance floor.
The club, which is 25 and up, is strict when it comes to the age requirement and their dress code, which prohibits such pieces of apparel as ball caps, jerseys and T-shirts. Torrence points out that its important for patrons to know that everyone is held to the same expectations.
Tempos success hasnt been lost on the competition, which at times has tried to copy their formula.
Thats been our challenge since the day we opened, and thats why we always try to stay ahead of the pack. There are a lot of venues that have piggybacked our concept, and most of them have failed, Torrence says. A lot of venues have opened up saying theyre going to be 25 and up, with dress requirements, and then after the first couple of months they pretty much drop all their standards and pretty much let anyone in just for an extra dollar.
While Tempos success is due in part to staying true to their original concept, Torrence still realizes how important it is to not become stale.
We dont want to change our target audience, but instead, to keep them coming back by providing new and fresh ideas for them.
I have a confession to make: The recent Penguin drama did not have a big impact on my life.
I did not join the Facebook page calling for a boycott. I didnt participate in very many conversations about the issue, either in person or online. And once I heard about the current, now previous, owners plans to open up around the corner at The Diamond, I even secretly thought it might be nice to have the crowd split between the two camps. At least then getting a table on a Friday night wouldnt be such an ordeal.
In case you dont already know the story, allow me sum up the situation.
Ten years ago, Brian Rowe and Jimmy King took over ownership of the Penguin, signing two five-year lease agreements. They redid the restaurant, which first opened in 1954. The pair built the Penguin into such a successful restaurant that it was featured on the Food Networks Diners, Drive-Ins and Dives, and it was not unusual to wait half an hour or more for a table at 10 oclock on a Thursday night.
Original owners, the Ballentine family, decided against renewing King and Rowes lease, instead offering a deal the two found unacceptable. Since the Ballentines retained ownership of both the building and the name, King and Rowe were left with, in their words, no other option but to leave and begin anew somewhere else. Thus was reborn the Diamond.
As a fan of the old Penguin, I did have some concerns that the new version would be lacking. The Ballentines made clear their plans to redo the place a bit and make it fit for franchising (read: mass consumption). Still, surely they would not tinker too much with a beloved institution.
The first thing I noticed was how much brighter it was in the new Penguin. All the better to see my fellow dining companions, who were much different than I remembered. They had all turned into well-scrubbed families and high school kids with neat haircuts and nice smiles.
I was right about one thing though: It was much easier to get a table. Granted, it was around 8:30 on a Monday night, but that would have meant a full house at the old Penguin.
Congrats go out to Raleigh's DJ Forge, who won the Red Bull's Thre3style DJ competition, held last night at Phoenix. This is the second year in a row he has taken the title.
Each DJ had a 15-minute spin session, and judging was based on choice of songs, creativity, skills and of course, the audiences response.
The vibe at this year's competition was very different from last year's, which was also held in the same venue. Being as Thursday nights are usually Phoenix's college night, the atmosphere was more about the party instead of the music. But that doesn't mean that the battling DJs didn't bring their best (even if a couple of them did look kind of nervous).
I will say, though, that I can definitely go without hearing Petey Pablo's North Carolina-praising song "Raise Up" for a while.
And I was a bit surprised that DJ Forge ended his set with Enrique's song "Hero." When he stood there, his arms crossed over his chest in triumph, as the seconds counted down to zero, I couldn't help but think, "Wow. He's really ending it like this?" It was original, to say the least. But what do I know? The crowd was loving it, and apparently, so did the judges.
Friday, July 15
Underground Events presents Underground Comedy, Art and Music at Tremont Music Hall
Retroactive Flashback Fridays at Breakfast Club
Slam Charlotte's first slam of the season at McGlohon Theatre
Ultra La Rumba Colombiana with Osvaldo Roman
Saturday, July 16
Ink Floyd Presents: God Save The Queen (City) at The Chop Shop
The Sol Kitchen presents DJ ?uestlove at RE:Public
Fans of late-night TV may only know ?uestlove as "the guy from the Roots with the big afro who plays the drums on Jimmy Fallon's show." But real music heads know that he's also a super-skilled producer (banging out tracks for folks like Erykah Badu and other notables) and a renowned crate-digging DJ who spins at clubs all over the world.
Well, the true heads will be happy to know that Mr. ?uest will be bringing his DJ skills to the Q.C. for a rare, one-night banger at RE:Public on July 16. So bring your ass. And even if you just dig looking at his big 'fro on the boob tube, you should come check him out in the flesh. $15 (in advance). 10 p.m. RE:Public, 314 N. College St., Charlotte. 704-375-0733. www.thsolkitchen.com.
Check out this video, courtesy of Rebrand Media.
You don't always like the music that you hear in the club. Well, this Thursday is your chance to help decide who THE best spinner in Charlotte really is.
Charlotte is the last stop for Red Bull's Thre3Style DJ competition. This Thursday, July 14, seven of the most wanted and begged for DJs will be spinning all in the same place and for the same reason to win the title of the City's Best DJ and get the chance to move on to the National Finals.
Local DJs competing include DJ Complete, DJ Forge (who was Charlotte's qualifier winner in 2010), Marley Carroll of Mr. Invisible, Dj Soden, DJ AHuf, DJ Scooby, DJ Red and SPCLGST.
A 15 minute spin session will include three different types of music. Judging will be based on choice of songs, creativity, skills and of course the audience's response.
Large and in charge DJ Z-Trip will not only be performing but is also one of the three judges for the contest.
The DJ who earns the title of Charlotte's best will advance to the National Finals held in Las Vegas. The overall winner of the Nationals will then move on to compete in Vancouver, British Columbia, for the Red Bull Thre3Style International Final and earn the overall champion title.
This competition isn't about what tricks you can do behind the booth it's how many hands you raise in the air and how many people get out on the dance floor.
What better place than one of the hottest clubs in Charlotte, Phoenix, to have this event. Doors open at 8 p.m. but the actual competition doesn't start till 9 p.m. $5 cover.
Find out more from watching this video.
The Deal: Dharma Lounge hosted Charlotte's Dirty Mega Party on Friday, July 8, with a high ollie contest and homemade bikini contest and I had to see what was up.
The Good: The skate contest was the first thing to catch my eye. Even though I didn't see many kids succeed at the hurdle, it was pretty entertaining to watch them crash and burn. Inside the room people were grouped together at bar tables like a high school cafeteria. I found myself in a sea of eclectic people from emo, punk, business and preppy. People were dressed grungy in torn clothes with messy uncombed hair, glammed up like a high fashion 80s model and the usual try-hards where they looked like they had stepped out of a GQ magazine. The cozy lounge area in the corner was perfect for my minute escape from the loud crowd and booming sounds coming from the DJ booth. Non-stop electric dance beats filled the room; however, I didn't see anyone actually step out and dance.
The Bad: The main reason I was so excited about going to the club was to see the homemade bikini contest. Unfortunately, it was going to be closer to the end of the night. I wasn't going to stay that long, and it seemed like the crowd agreed because I kept noticing people sneaking out.
The Verdict: Even though I had the major disappointment of not seeing the bikini contest, the bar's atmosphere itself made up for it. It's opposite from the typical Charlotte club scene with rap music that is nice to get away from sometimes. You don't see the same ol' group of trendy fashionistas and gangsta swag guys grinding to the same top 40 hits we hear all the time.
And here are some photos.
It took a minute to register.
In fact, it didnt hit me until my friend stopped to ask, Did that guy just call me a freak? Indeed, he had.
To be exact, as he passed us hed said, All these freaks around, like this kid.
We were in Uptown for the second Buskapalooza, an organized busking event put together by April Denée to raise awareness about her upcoming documentary Busk! Wed been on the street less than five minutes.
The man was with his wife. They both looked to be in their mid forties. She didnt say anything, or at least refrained until we were out of earshot.
My friend, who fronts a local punk band, has blue hair, which was enough to qualify him as a freak in this mans opinion.
Now, I know this is merely an isolated anecdote and that a middle aged guy walking around Uptown thinking anyone who looks vaguely different is inherently a freak isnt the most shocking of realizations. Yet, I cant help but feel that its more emblematic than Id like to believe.


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Warner Bros. has released the first The Good Lie trailer. Reese Witherspoon stars as an American woman who is assigned to help three Sudanese refugees (a few of the "Lost Boys of Sudan") move to the United States. Everything falls into place when "from the executive producer of The Blind Side" flashes across the screen in the middle of the trailer. Relying on the perspective of a bankable white star to tell the story of Sudanese refugees is problematic, but there is still a good story in there. Director Philippe Falardeau earned rave reviews for his last feature, Monsieur Lazhar, so I hope he finds an effective way to tell that story.
Arnold Oceng, Ger Duany, Emmanuel Jal, Nyakuoth Weil, and Corey Stoll star in the October 3 release. Brian Grazer, Ron Howard, and that Blind Side EP Molly Smith are producing. Watch the Good Lie trailer after the break.
Via Apple:
Official synopsis:
They were known simply as "The Lost Boys." Orphaned by the brutal Civil war in Sudan that began in 1983, these young victims traveled as many as a thousand miles on foot in search of safety. Fifteen years later, a humanitarian effort would bring 3600 lost boys and girls to America. In "The Good Lie," Philippe Falardeau (writer and director of the Oscar®- nominated Foreign Language film "Monsieur Lazhar") brings the story of their survival and triumph to life. Sudanese actors Arnold Oceng, Ger Duany, Emmanuel Jal, and newcomer Nyakuoth Weil, many of whom were also children of war, star alongside Academy Award® winner Reese Witherspoon and Corey Stoll.


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Aim: Vasoactive intestinal polypeptide producing neuroendocrine tumors are rare and cause severe hormonal symptoms. Patients/methods: Eighteen patients with vasoactive intestinal polypeptide producing neuroendocrine tumors were analyzed with reviews of medical records, radiology and tumor tissue specimens. Results: Twelve patients (67%) had liver metastases at diagnosis. Chemotherapy, somatostatin analogs and interferon were given as medical therapies. Streptozocin/5-fluorouracil produced an objective response in 40% of the evaluable patients. Somatostatin analogs gave a clinical/biochemical response in eight out of nine patients. Transarterial embolization of the liver and peptide receptor radionuclide therapy was given to refractory cases. Sixteen patients died during the observation period. The median overall survival from diagnosis was 102 months. Conclusion: Systemic chemotherapy and somatostatin analogs should be given in cases of advanced disease or for hormonal symptoms.
BACKGROUND: In our center, the combination of streptozocin (STZ) and 5-fluorouracil (5-FU) has been used as the first-line treatment in the majority of patients with pancreatic neuroendocrine tumors (pNETs) over the past few decades. The objective of the current study was to assess the efficacy, prognostic factors and safety of the combination of STZ and 5-FU.
PATIENTS AND METHODS: Medical records and radiological reports of 133 patients with pNETs who received the combination of STZ and 5-FU during the period 1981-2014 were retrospectively evaluated.
RESULTS: Median survival from start of treatment was 51.9 months in the whole group. In the radiologically evaluable patients (n = 100) progression-free survival was 23 months. Complete response was reached in 3 patients (3%), partial response in 25 patients (25%), 64 patients (64%) had stable disease and 8 patients (8%) had progressive disease. In a multivariate analysis, surgery of the primary tumor and having a G3 tumor were significant positive and negative prognostic factors of survival from start of treatment, respectively. Having either a G3 tumor or stage IV tumor were significant prognostic factors for shorter progression-free survival. Chemotherapy had to be discontinued in 29 patients due to side-effects, of which kidney toxicity (mainly grade 1-2) was the most frequent.
CONCLUSION: As shown in recent reports, the combination of STZ and 5-FU is effective in the treatment of pNETs in terms of survival and radiological response, and has an acceptable toxicity profile.
Insulin-like growth factor 1 (IGF-1) may influence cellular growth, differentiation and secretion.
Cryosectioned normal human adrenal glands (n = 6), cortical adenoma (n = 21), and carcinoma (n = 17) were stained immunohistochemically for IGF-1 and its receptor, and human adrenocortical cancer cells expressing the receptor were analysed for influences on proliferation.
Normal cortical parenchyma generally displayed faint IGF-1 reactivity and intracellular receptor staining. Similar labelling encompassed the adenomas, but only 6 of them were receptor reactive. IGF-1 expression was conspicuous in 11 carcinomas, and 6 of them displayed cell surface receptor reactivity. All aldosterone producing lesions were receptor antibody unreactive. Recombinant IGF-1 dose-dependently stimulated the cell proliferation, and this effect was reversed by the receptor antibody.
IGF-1 may interact with function and proliferation of the human adrenal cortex with particular reference to cortical carcinomas lacking discernible aldosterone excess.
OBJECTIVE:Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant syndrome usually caused by loss-of-function mutations in the MEN1-gene. However, a minority of patients who fulfill the criteria for MEN1 are not found to harbor MEN1-mutations. Besides, some of these individuals, present with a subtly different phenotype suggestive of sporadic disease. The aim of the present study was to investigate the genetic architecture of mutation-negative MEN1. DESIGN:Fourteen patients with a clinical diagnosis (n=13) or suspicion (n=1) of MEN1 who had negative genetic screening of the MEN1 gene were included. METHODS:Constitutional DNA from the included patients, as well as tumor DNA from six of the patients, was subjected to whole genome sequencing. Constitutional variants were filtered against population databases and somatic variants were studied under a tumor-suppressor model. RESULTS:Three patients carried pathogenic variants (two splice-site variants, one missense variant) in MEN1 that had not been detected during routine clinical sequencing, one patient carried a pathogenic variant in CASR and one patient carried a gross deletion on chromosome 1q which included the CDC73 gene. Analysis of matched tumor DNA from six patients without mutations did not detect any recurrent genes fulfilling Knudson's two-hit model. CONCLUSION:These results highlight the possibility of germline mutations being missed in routine screening, the importance of considering phenocopies in atypical or mutation-negative cases. The absence of apparent disease-causing mutations suggests that a fraction of MEN1 mutation negative MEN1 cases may be due to the chance occurrence of several endocrine tumors in one patient.
Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus.
PATIENTS AND METHODS: Patients with NETs that underwent treatment with everolimus at our Institution were identified and those with available tumour tissue were selected for further analysis. Targeted next-generation sequencing (NGS) was used to re-sequence 22 genes that were selected on the basis of documented involvement in the MTOR signalling pathway or in the tumourigenesis of gastroenterpancreatic NETs. Radiological responses were documented using Response Evaluation Criteria in Solid Tumours.
RESULTS: Six patients were identified, one had a partial response and four had stable disease. Sequencing of tumour tissue resulted in a median sequence depth of 667.1 (range=404-1301) with 1-fold coverage of 95.9-96.5% and 10-fold coverage of 87.6-92.2%. A total of 494 genetic variants were discovered, four of which were identified as pathogenic. All pathogenic variants were validated using Sanger sequencing and were found exclusively in menin 1 (MEN1) and death domain associated protein (DAXX) genes. No mutations in the MTOR pathway-related genes were observed.
CONCLUSION: Targeted NGS is a feasible method with high diagnostic yield for genetic characterization of pancreatic NETs. A potential association between mutations in NETs and response to everolimus should be investigated by future studies.
OBJECTIVES: Progranulin (PGRN) promotes cell growth and cell cycle progression in several cell types and contributes to tumorigenesis in diverse cancers. We have recently reported PGRN expression in islets and tumors developed in an MEN1 transgenic mouse. Here we sought to investigate PGRN expression and regulation after exposure to hypoxia as well as its effects on pancreatic islet cells and neuroendocrine tumors (NETs) in MEN1 mice.
METHODS: Gene and protein expression were analyzed by quantitative polymerase chain reaction, immunohistochemistry, and Western blot. We also investigated PGRN expression in samples from patients carrying pancreatic NETs associated or not with the multiple endocrine neoplasia 1 syndrome, using enzyme-linked immunosorbent assay and immunohistochemistry analysis.
RESULTS: Progranulin is upregulated in tumors and islets of the MEN1 mouse as well as in the serum of patients with pancreatic NETs associated with glucagonoma syndrome. In normal mice islets and pancreatic tumors, PGRN expression was strongly potentiated by hypoxia. Progranulin promotes cell proliferation in islet cells and βTC-6 cells, a process paralleled by activation of the mitogen-activated protein kinase signaling cascade.
CONCLUSIONS: Our findings identify PGRN as an effective inducer of pancreatic islet cell proliferation and a possible important factor for pancreatic endocrine tumor development.
INTRODUCTION: Little is known about how Pancreatic Neuroendocrine Tumors (PanNETs) evolve over time and if changes towards a more aggressive biology correlates with prognosis. The purpose of this study was to characterize changes PanNET differentiation and proliferation over time, and to correlate findings to overall survival (OS).
PATIENTS AND METHODS: In this retrospective cohort study we screened 475 PanNET patients treated at Uppsala University Hospital, Sweden. Sporadic patients with baseline and follow-up tumor samples were included. Pathology reports and available tissue sections were re-evaluated with regard to tumor histopathology and Ki-67 index.
RESULTS: Forty-six patients with 106 tumor samples (56 available for pathology re-evaluation) were included. Median Ki-67 index at diagnosis was 7% (range 1-38%), grade 1 n=8, grade 2 n=36, and grade 3 n=2. The median change in Ki-67 index (absolute value; follow-up - baseline) was +14% (range -11 to +80%). Increase in tumor grade occurred in 28 patients (63.6%), the majority from grade 1/2 to grade 3 (n=24, 54.5%). The patients with a high-grade progression had a median OS of 50.2 months compared to 115.1 months in patients without such progression (HR 3.89, 95% CI 1.91-7.94, P<0.001).
CONCLUSIONS: A longitudinal increase in Ki-67 index and increase in tumor grade were observed in a majority of PanNETs included in this study. We propose that increase in Ki-67 index and high-grade progression should be investigated further as important biomarkers in PanNET.
Biochemical signs and severity of symptoms of primary hyperparathyroidism (pHPT) differ among patients, and little is known of any coupling of clinical characteristics of nonfamilial pHPT to genetic abnormalities in the parathyroid tumors. Mutations in the recently identified MEN1 gene at chromosome 11q13 have been found in parathyroid tumors of nonfamilial pHPT. Using microsatellite analysis for loss of heterozygosity (LOH) at 11q13 and DNA sequencing of coding exons, the MEN1 gene was studied in 49 parathyroid lesions of patients with divergent symptoms, operative findings, histopathological diagnosis, and biochemical signs of nonfamilial pHPT. Allelic loss at 11q13 was detected in 13 tumors, and 6 of them demonstrated previously unrecognized somatic missense and frameshift deletion mutations of the MEN1 gene. Many of the detected mutations would most likely result in a nonfunctional menin protein, consistent with a tumor suppressor mechanism. Clinical and biochemical characteristics of HPT were apparently unrelated to the presence or absence of LOH and the MEN1 gene mutations. However, the demonstration of LOH at 11q13 and MEN1 gene mutations in small parathyroid adenomas of patients with slight hypercalcemia and normal serum PTH levels suggest that altered MEN1 gene function may also be important for the development of mild sporadic pHPT.
Hyperparathyroidism affects most patients with multiple endocrine neoplasia type 1 (MEN 1). This study investigates expression of the candidate MEN1 gene phospholipase C beta 3 (PLC beta 3) and expression and function of a putative calcium sensing protein (CAS) in hyperparathyroidism of MEN 1.
In 31 parathyroid glands from 17 patients with MEN 1, CAS distribution was studied immunohistochemically and parallel sections were explored for PLC beta 3 mRNA expression by in situ hybridization. Enzymatically dispersed parathyroid cells were analyzed for cytoplasmic calcium concentrations [Ca2+]i and parathyroid hormone (PTH) release.
All glands exhibited a heterogeneously reduced CAS immunoreactivity, especially meager in nodularly assembled parathyroid cells. Calcium regulated [Ca2+]i and PTH release tended to be more deranged in the glands possessing the lowest immunostaining. Parathyroid PLC beta 3 invariably was homogeneously expressed, and this included even MEN 1 patients with reduced PLC beta 3 expression in endocrine pancreatic tumors.
The findings support variable calcium insensitivity of [Ca2+]i and PTH release in hyperparathyroidism of MEN 1, apparently coupled to heterogeneously reduced CAS expression. For clarification of the role of PLC beta 3 in MEN 1 parathyroid tumorigenesis further study of this protein is required.
Parents of children recently diagnosed with cancer can experience severe psychosocial distress. Experiential avoidance has been defined as the tendency to avoid or escape from certain private experiences (e.g., thoughts, feelings, memories) or contexts that elicit them (Hayes et al., 1996). This construct has been shown to be linked to distress in several populations and has received increased interest as a target for intervention. The purpose of this study was to investigate the relationship between traumatic stress, experiential avoidance, and depression in parents of children recently diagnosed with cancer. It was hypothesized that experiential avoidance would account for the relationship between traumatic stress and depression.
48 parents (33 mothers and 15 fathers) of children recently diagnosed with cancer and who participated in the screening/pre-assessment of a RCT of a psychosocial intervention were included in the current cross-sectional study. The mean (SD) of months since the child's diagnosis was 3.5 (1.8). Parents provided self-report of demographic characteristics, general anxiety, traumatic stress, experiential avoidance, and depression.
Hierarchical regression was used with depression as dependent variable. In step 1 demographic variables and general anxiety was entered (∆R2 = .57, p < .001). In step 2 traumatic stress was added resulting in a significant increase in explained variance (∆R2 = .04, p < .05, β for traumatic stress = 0.39, p < .05). In step 3 experiential avoidance was added resulting in a significant increase in explained variance (∆R2 = .06, p < .05, β for experiential avoidance = 0.35, p < .05). Furthermore, traumatic stress was no longer a significant predictor of depression (β = 0.15, p = 40). Total R2 in the final model was .68. Mediation analysis (Preacher & Hayes, 2008) confirmed a significant indirect effect from traumatic stress to depression via experiential avoidance (estimate = 0.21, bootstrap 95% CI = 0.03-0.38).
The current results suggest that experiential avoidance accounts for the relationship between traumatic stress and depression in parents of children recently diagnosed with cancer. Experiential avoidance could be a potential target in psychosocial interventions for this group.
Endocrine pancreatic tumors are neuroendocrine neoplasms with malignant potential and give rise to varied clinical syndromes due to excessive secretion of multiple hormones. In this study 22 endocrine pancreatic tumors and 11 carcinoid tumors were examined for the expression of CD44 using a monoclonal antibody. CD44 gene activity of 11 endocrine pancreatic tumor tissues and five carcinoid tumor tissues was also studied by amplifying messenger RNA with the polymerase chain reaction followed by electrophoresis and blot hybridization. Strong immunoreactivity was detected on all gastrinomas examined (P < 0.001), and in two non-functioning endocrine pancreatic tumors. Such immunoreactivity was not observed in other subtypes of endocrine pancreatic tumors. In the normal human pancreas, the acinar portion and ductal epithelial cells stained strongly positive but pancreatic islet cells did not show any significant immunostaining. Furthermore, in endocrine pancreatic tumors with metastatic disease, CD44-positive tumors had a tendency to metastasize to lymph nodes (P = 0.005), as compared with CD44-negative tumors which were locally invasive or metastasized to the liver. Although, in this limited material and short follow-up, we were not able to show any statistical significance, patients with CD44-negative endocrine pancreatic tumors had prolonged survival time compared with patients with CD44-positive tumors (73% versus 59% at 5 years; P = 0.7). Of 10 carcinoid tumors examined, all three foregut carcinoids and one midgut carcinoid stained strongly positive, whereas all other midgut carcinoids were negative. Analysis of CD44 splice variants showed that in all five gastrinomas there was overproduction of alternatively spliced larger molecular variants as compared with other types of endocrine pancreatic tumors and carcinoid tumors. The band pattern from one case of carcinoid tumor with a fulminant clinical course was similar to that of gastrinomas, whereas other carcinoid tumors expressed the epithelial form of CD44. The earlier identified splice variants which confer metastatic behavior on a pancreatic tumor cell line were not expressed in neuroendocrine tumors. Our data indicate that CD44 expression in endocrine pancreatic tumors correlates with the ability to give rise to lymph node metastases and may play a vital role in determining the fate of metastasizing cells. Moreover, because gastrin is not detectable in the normal human pancreas, the pancreatic ductal cell positivity for CD44 strengthened the ductal origin concept of gastrinomas. The band pattern of CD44 splice variants suggests that the previously described splice variants conferring metastatic behavior do not accompany metastatic activity of neuroendocrine tumors.
Vascular therapeutic targeting requires thorough evaluation of the mechanisms activated in the specific context of each particular tumor type. We highlight structural, molecular, and functional microvascular aberrations contributing to development and maintenance of pancreatic neuroendocrine tumors (NETs), with special reference to multiple endocrine neoplasia 1 (MEN1) syndrome, using a Men1 mouse model. Tissue samples were analyzed by immunofluorescence to detect vessel density and pericyte distribution within the endocrine pancreas; expression of angiogenic factors was assessed by immunohistochemistry and quantitative real-time PCR in isolated islets and adenomas cultured under normoxic or hypoxic conditions. The increased vascular density of pancreatic NETs developed in Men1 mice was paralleled by an early and extensive redistribution of pericytes within endocrine tissue. These morphological alterations are supported by, and in some cases preceded by, fine-tuned variations in expression of several angiogenic regulators and are further potentiated by hypoxia. By combining two novel ex vivo and in vivo single-islet and tumor perfusion techniques, we demonstrated that both vascular reactivity and blood perfusion of tumor arterioles are significantly altered in response to glucose and L-nitro-arginine methyl ester. Our findings unravel multiple potential molecular and physiological targets differentially activated in the endocrine pancreas of Men1 mice and highlight the need for in-depth functional studies to fully understand the contribution of each component to development of pancreatic NETs in MEN1 syndrome.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder with a high penetrance characterized by tumors of the parathyroid glands, the endocrine pancreas, and the anterior pituitary. The MEN1 gene, a putative tumor suppressor gene, has been mapped to a 3- to 8-cM region in chromosome 11q13 but it remains elusive as yet. We have combined the efforts and resources from four laboratories to form the European Consortium on MEN1 with the aims of establishing the genetic and the physical maps of 11q13 and of further narrowing the MEN1 region. A 5-Mb integrated map of the region was established by fluorescence in situ hybridization on both metaphase chromosomes and DNA fibers, by hybridization to DNA from somatic cell hybrids containing various parts of human chromosome 11, by long-range restriction mapping, and by characterization of YACs and cosmids. Polymorphic markers were positioned and ordered by physical mapping and genetic linkage in 86 MEN1 families with 452 affected individuals. Two critical recombinants identified in two affected cases placed the MEN1 gene in an approximately 2-Mb region around PYGM, flanked by D11S1883 and D11S449.
Adrenocortical carcinoma (ACC) and pheochromocytoma and paraganglioma (PPGL) are defined by clinicopathological criteria and can be further sub-divided based on different molecular features. Whether differences between these molecular subgroups are significant enough to re-challenge their current clinicopathological classification is currently unknown. It is also not fully understood to which other cancers ACC and PPGL show similarity to. To address these questions, we included recent RNA-Seq data from the Cancer Genome Atlas (TCGA) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) datasets. Two bioinformatics pipelines were used for unsupervised clustering and principal components analysis. Results were validated using consensus clustering model and interpreted according to previous pan-cancer experiments. Two datasets consisting of 3319 tumors from 35 disease categories were studied. Consistent with the current classification, ACCs clustered as a homogenous group in a pan-cancer context. It also clustered close to neural crest derived tumors, including gliomas, neuroblastomas, pancreatic neuroendocrine tumors, and PPGLs. Contrary, some PPGLs mixed with pancreatic neuroendocrine tumors or neuroblastomas. Thus, our unbiased gene-expression analysis of PPGL did not overlap with their current clinicopathological classification. These results emphasize some importances of the shared embryological origin of these tumors, all either related or close to neural crest tumors, and opens for investigation of a complementary categorization based on gene-expression features.
This review aims to provide clinicians and researchers with a condensed update on the most important studies in the field during 2017. We present the academic output measured by active clinical trials and peer-reviewed published manuscripts. The most important and contributory manuscripts were summarized for each diagnostic entity, with a particular focus on manuscripts that describe translational research that have the potential to improve clinical care. Finally, we highlight the importance of collaborations in adrenal tumor research, which allowed for these recent advances and provide structures for future success in this scientific field.
Pheochromocytoma and paraganglioma (PPGL) can be divided into at least four molecular subgroups. Whether such categorizations are independent factors for prognosis or metastatic disease is unknown. We performed a systematic review and individual patient meta-analysis aiming to estimate if driver mutation status can predict metastatic disease and survival. Driver mutations were used to categorize patients according to three different molecular systems: two subgroups (SDHB mutated or wild type), three subgroups (pseudohypoxia, kinase signaling or Wnt/unknown) and four subgroups (tricarboxylic acid cycle, VHL/EPAS1, kinase signaling or Wnt/unknown). Twenty-one studies and 703 patients were analyzed. Multivariate models for association with metastasis showed correlation with SDHB mutation (OR 5.68 (95% CI 1.79-18.06)) as well as norepinephrine (OR 3.01 (95% CI 1.02-8.79)) and dopa mine (OR 6.39 (95% CI 1.62-25.24)) but not to PPGL location. Other molecular systems were not associated with metastasis. In multivariate models for association with survival, age (HR 1.04 (95% CI 1.02-1.06)) and metastases (HR 6.13 (95% CI 2.86-13.13)) but neither paraganglioma nor SDHB mutation remained significant. Other molecular subgroups did not correlate with survival. We conclude that molecular categorization accordingly to SDHB provided independent information on the risk of metastasis. Driver mutations status did not correlate independently with survival. These data may ultimately be used to guide current and future risk stratification of PPGL.
Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms, arising from neuroendocrine cells that are dispersed throughout the body. Around 20% of NETs occur in the context of a genetic syndrome. Today there are at least ten recognized NET syndromes. This includes the classical syndromes: multiple endocrine neoplasias types 1 and 2, and von Hippel-Lindau and neurofibromatosis type 1. Additional susceptibility genes associated with a smaller fraction of NETs have also been identified. Recognizing genetic susceptibility has proved essential both to provide genetic counseling and to give the best preventive care. In this review we will also discuss the knowledge of somatic genetic alterations in NETs. At least 24 genes have been implicated as drivers of neuroendocrine tumorigenesis, and the overall rates of genomic instability are relatively low. Genetic intra-tumoral, as well as inter-tumoral heterogeneity in the same patient, have also been identified. Together these data point towards the common pathways in NET evolution, separating early from late disease drivers. Although knowledge of specific mutations in NETs has limited impact on actual patient management, we predict that in the near future genomic profiling of tumors will be included in the clinical arsenal for diagnostics, prognostics and therapeutic decisions.
Better prognostic markers are needed for pancreatic endocrine tumors. Survivin is an apoptosis inhibitor that is suggested to have a negative prognostic impact in several tumor types. Contradictory data exist, especially regarding the significance of a nuclear versus cytoplasmic location of survivin. The prognostic relevance of nuclear and cytoplasmic survivin expression in pancreatic endocrine tumors-controlled for the tumor Ki-67 index, World Health Organization classification, and TNM stage-was investigated.
A total of 111 patients treated at a tertiary referral center were retrospectively evaluated. Clinical data were gathered from medical records. Immunohistochemistry for survivin and Ki-67 was performed on paraffin-embedded tissue. Univariate and multivariate Cox analyses were performed.
Patients with tumors that had <5% survivin-positive nuclei had a mean survival of 225 months [95% confidence interval (CI) 168-281]. The corresponding figure for patients with 5 to 50% survivin-positive tumor cell nuclei was 101 months [95% CI 61-140; hazard ratio (HR) 2.4; P < 0.01) and with >50% survivin-positive nuclei 47 months (95% CI 24-71; HR 4.9; P < 0.001). Nuclear survivin expression in >50% of the tumor cells was an independent marker of a poor prognosis (HR 5.7; P < 0.01). Cytoplasmic survivin was not a significant prognostic factor in the multivariate analysis (HR 0.94; P = 0.90).
High expression of nuclear survivin is a significant marker of a poor prognosis in patients with a pancreatic endocrine tumor.
Expression of ghrelin has been reported in pancreatic endocrine tumours, but data on ghrelin receptor protein expression are lacking. The aim of this study was to examine the ghrelin receptor, as well as ghrelin, in a selected series of these tumours, including multiple endocrine neoplasia 1 (MEN1) associated tumours, and to correlate data with clinical features including body mass index.
Immunohistochemical detection of ghrelin and its receptor was performed on frozen tissue from 31 tumours: 9 MEN1 and 22 sporadic. Twenty tumours were analysed by quantitative PCR. Plasma ghrelin was assessed in 26 patients.
Twenty-one (68%) of 31 tumours showed immunoreactivity for ghrelin (8/9 MEN1) and 19/20 expressed ghrelin mRNA. Ghrelin receptor protein was detected in 21/30 (70%) tumours (4/8 MEN1), and mRNA was detected in all analysed tumours. Insulinomas had significantly higher levels of receptor mRNA than other tumours. Five patients had elevated plasma ghrelin (> 2 SD above the control group mean). No significant difference in mean plasma ghrelin levels was found between patients (908 ± 569 ng/l) and controls (952 ± 164 ng/l). Mean BMI was 24·3 kg/m2. There was no association between ghrelin or receptor expression and survival.
We report the first immunohistochemical data on expression of the ghrelin receptor in pancreatic endocrine tumours: 70% of tumours in our material. Concomitant ghrelin and receptor expression was seen in 50% of tumours, indicating an autocrine loop. Ghrelin was expressed in 68% of tumours (8/9 MEN1). Despite frequent ghrelin expression, elevated circulating ghrelin is rare in these patients.
Expression of the neuroendocrine marker synaptic vesicle protein 2 (SV2) has been reported in a few cases of gastrointestinal stromal tumors (GISTs). The goal of the present study was to assess the relevance of this finding and identify a possible hormone production in these tumors. We chose to study the orexigen ghrelin and its receptor, since these patients are seldom cachexic, even in advanced disease stages. We investigated ghrelin expression by means of immunohistochemistry on frozen or paraffin-embedded sections from 22 GISTs from a well-characterized patient material. Expression of the growth hormone secretagogue receptor, the ghrelin receptor, was investigated in a subset of lesions. In six tumors, mRNA levels of ghrelin, the ghrelin receptor, and SV2 were analyzed by real-time quantitative PCR. Totally 17 out of 22 tumors showed immunoreactivity for ghrelin. Five out of ten tumors were immunoreactive for the ghrelin receptor, and all of these co-expressed ghrelin. All tumors expressed ghrelin, ghrelin receptor, and SV2 mRNA. GISTs frequently express SV2, ghrelin, and its receptor, indicating the presence of autocrine/paracrine loops.
Unequivocal pathologic markers for the prognosis of pancreatic endocrine tumors are often lacking. Suggestions for prognostic guidance include the WHO classification. Recently, a tumor-node-metastasis (TNM) staging system was proposed. We evaluate this system, as well as assess other potential prognostic factors such as tumor Ki67, size, endocrine syndrome, heredity, body mass index (BMI), and plasma chromogranin A, in a large patient material treated at a single institution.
A total of 324 patients with pancreatic endocrine tumor, consecutively diagnosed and treated at a tertiary referral center, were retrospectively evaluated. Median follow-up was 54 months (range, 1-423 months). Patient and tumor data were extracted from medical records. Univariate and multivariate analyses were done to recognize factors of prognostic value.
The median overall survival was 99 months (95% confidence interval, 81-117). Five- and 10-year survival rates were 64% and 44%, respectively. In univariate analysis, TNM stage, radical surgery, WHO classification, nonfunctioning tumor, Ki67 ≥2%, chromogranin A ≥3 times the upper normal limit, BMI <20 kg/m2, sporadic tumor, tumor size, and referral from our primary uptake area had a significant prognostic effect. In multivariate analysis, TNM stage, WHO classification, radical surgery, and Ki67 ≥2% retained their significance. Having a nonfunctioning tumor was not an independent marker of poor prognosis and neither was heredity.
The recently suggested TNM staging system emerged as a useful clinical tool.
Purpose: A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors. Experimental Design: Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m2) for 5 days every 4 weeks. Patients had previously received a mean of 2.4 antitumoral medical regimens. Tumor response was evaluated radiologically according to the Response Evaluation Criteria in Solid Tumors every 3 months on an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was also assessed. The expression of 06-methylguanine DNA methyltransferase, an enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry (n = 23) and compared with response to temozolomide. Results: Median overall time to progression was 7 months (95% confidence interval, 3-10). Radiologic response was seen in 14% of patients and stable disease in 53%. Side effects were mainly hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer Institute toxicity criteria). Ten patients had tumors with 06-methylguanine DNA methyltransferase immunoreactivity in <10% of nuclei, whereas four patients showed radiologic responses. Conclusions: Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses.
Patients with neuroendocrine gastrointestinal tumors usually present with inoperable metastatic disease and severe hormonal symptoms. Specific chemotherapy, interferon-alpha (IFN), and somatostatin analogs are established therapies for these patients, but all of them eventually fail. Hepatic arterial embolization can provide reduction of both hormonal symptoms and tumor burden in these patients.
Between 1981 and 1995, a total of 55 liver embolizations with gel foam powder were performed on 41 patients with histopathologically verified neuroendocrine tumors; 29 had carcinoid tumors and 12 had endocrine pancreatic tumors (EPTs). All patients had received medical treatment, including chemotherapy (n = 18), IFN (n = 31), and octreotide (n = 19), and were experiencing treatment failure when liver embolization was performed at a median of 37 months after diagnosis of liver metastases. Medical treatment was continued after embolization.
An overall objective response was noted in 15 of 29 patients with carcinoid tumors (52%). The median duration of effect was 12 months in patients with midgut carcinoid tumors. An overall objective response was observed in 6 of 12 patients with EPTs (50%), with a median duration of effect of 10 months. Adverse events were observed, and, in agreement with earlier reports, the rate of serious complications was 10%. Survival analyses showed a median survival of 80 months and a 5-year survival rate of 60% from the performance of embolization on patients with midgut carcinoid tumors, whereas for patients with EPTs the median survival from embolization was only 20 months.
Liver embolizations performed relatively late in the clinical course in our series appeared to be as effective as "early" embolizations in other series of patients with carcinoid tumors. The results for those with EPTs were poorer, and earlier embolizations may result in better outcomes for these patients. Considering the morbidity associated with the procedure, it is imperative to select patients according to extent of liver involvement, severity of carcinoid heart disease, and somatostatin receptor status.
A prospective study has been performed on 84 patients with endocrine pancreatic tumours evaluated at the Medical Department in Uppsala. Available information concerning the patients' presenting symptoms, age at diagnosis, clinical syndrome, tumour location, location of metastases, diagnostic radiology, biochemical and histopathological findings has been analysed. Our results indicate that most patients initially show rather vague and non-specific symptoms, with dyspepsia and pain being the most frequent presenting features. The median delay between appearance of the first symptom and diagnosis was 2 years; the delay was 3 5 months in sporadic cases and 14.5 months in familial cases. In spite of improvements in diagnostic methods, the median age at diagnosis (53 years) has not been reduced, and most patients are encountered when the tumour has reached an advanced stage. There is a need for a method of screening patients with still uncharacteristic abdominalsymptoms for a neuroendocrine tumour. The presence of elevated levels of plasma chromogranin in all patients with a proven tumour suggests that such possibilities exist, and the use of this biochemical marker in the future might reduce the age at diagnosis and thus improve the likelihood of cure and survival of patients with endocrine pancreatic tumours.
A prospective study was performed on 84 patients with neuroendocrine pancreatic tumors. Fifty-nine (70%) had malignant tumors and received causal medical treatment. Streptozotocin in combination with 5-fluorouracil or doxorubicin was used as first-line treatment and produced overall objective responses in 20 of 44 (45%) patients with a median duration of response of 27.5 months. Thirty-two patients who failed on chemotherapy subsequently received interferon treatment and 20 (63%) responded objectively with a median duration of 20.5 months. Octreotide, third-line treatment in 14 patients, produced objective responses in four patients (28%) (median duration of response, 16 months). The median survival from diagnosis in malignant cases was 6.7 years. Even if none of the current medical therapies are curative for patients with malignant endocrine pancreatic tumors, a prolonged survival would be observed during the last decade. Since the age at diagnosis has not been dramatically reduced despite improvements in diagnostic methods, the prolonged survival might be attributed to causal medical treatment.
Positron emission tomography is an in vivo tracer and imaging technique that utilizes short-lived positron emitting radionuclides (11C, 15O, 13N, 18F) with half-lives ranging between 2 min and 2 hours. These radionuclides are interesting from the labelling viewpoint since they are natural constituents of most biologically active compounds. The short half-life is an advantage with regard to the irradiation dose to the patient but it is also a limitation since it requires the production of these radionuclides in close vicinity to the positron emission tomography camera.
Many neuroendocrine tumors (NETs) have a tendency to metastasize to the liver. In case of limited number of metastases, liver surgery or radiofrequency ablation (RFA) may result in apparently total clearance of metastases. However, it is not clear whether such therapy will provide symptom reduction or increased survival.
Seventy-three patients with foregut (n=6) or midgut carcinoids (n=37) or endocrine pancreatic tumors (n=28), and two patients with NETs without discernable origin were studied. Symptoms were evaluated using a Symptom Severity Score. Liver surgery was performed in 42 operations and RFA on 205 lesions.
Apparently total clearance of liver metastases was attained in 1 of 6 patients with foregut carcinoids, 15 of 37 with midgut carcinoids, and 13 of 28 with EPT. Symptom improvement was noted in 12 of 17 (70.6%) patients with carcinoid syndrome, and 75% also reduced their 5-HIAA and P-CgA by at least 50%. Patients with nonfunctioning EPT generally had no improvement of symptoms after surgical/RFA liver treatment, but eight patients had functioning EPT, and four of these reduced their biochemical markers by at least 50%. NETs with higher Ki67 index tended to recur more often. Complications occurred in 9 of 45 open surgery procedures, and in 8 of 203 RFA procedures.
Treatment of liver metastases is successful in midgut carcinoid patients with limited liver metastases. Patients with foregut carcinoid and EPTs recur more often, possibly related to higher Ki67 index, and treatment of liver lesions less often reduces symptoms. Liver resections and RFA may be safely performed, and RFA is associated with few complications.
Adrenocortical carcinoma is a rare cancer that has a poor response to cytotoxic treatment.
We randomly assigned 304 patients with advanced adrenocortical carcinoma to receive mitotane plus either a combination of etoposide (100 mg per square meter of body-surface area on days 2 to 4), doxorubicin (40 mg per square meter on day 1), and cisplatin (40 mg per square meter on days 3 and 4) (EDP) every 4 weeks or streptozocin (streptozotocin) (1 g on days 1 to 5 in cycle 1; 2 g on day 1 in subsequent cycles) every 3 weeks. Patients with disease progression received the alternative regimen as second-line therapy. The primary end point was overall survival.
For first-line therapy, patients in the EDP-mitotane group had a significantly higher response rate than those in the streptozocin-mitotane group (23.2% vs. 9.2%, P<0.001) and longer median progression-free survival (5.0 months vs. 2.1 months; hazard ratio, 0.55; 95% confidence interval [CI], 0.43 to 0.69; P<0.001); there was no significant between-group difference in overall survival (14.8 months and 12.0 months, respectively; hazard ratio, 0.79; 95% CI, 0.61 to 1.02; P=0.07). Among the 185 patients who received the alternative regimen as second-line therapy, the median duration of progression-free survival was 5.6 months in the EDP-mitotane group and 2.2 months in the streptozocin-mitotane group. Patients who did not receive the alternative second-line therapy had better overall survival with first-line EDP plus mitotane (17.1 month) than with streptozocin plus mitotane (4.7 months). Rates of serious adverse events did not differ significantly between treatments.
Rates of response and progression-free survival were significantly better with EDP plus mitotane than with streptozocin plus mitotane as first-line therapy, with similar rates of toxic events, although there was no significant difference in overall survival.
A recent study using comparative mapping analysis suggests that the proximal segment of mouse chromosome 19 contains the mouse homologs of the human multiple endocrine neoplasia type 1 (MEN1) flanking markers proximal to the locus. We have recently shown that phospholipase C-beta 3 (PLCB3) is a candidate gene for the MEN1 syndrome. In the present investigation we used fluorescence in situ hybridization with a genomic DNA clone for mouse Plcb3, and mapped the locus to chromosome region 19B. This is in agreement with the comparative mapping of the MEN1 flanking markers in mouse.
Recently the multiple endocrine neoplasia type 1 (MEN-1) tumor suppressor gene was cloned. MEN-1 encodes a nuclear protein, called menin, of hitherto unknown function. In order to investigate the biological function of menin we employed the yeast two-hybrid system to identify menin-interacting proteins. Here we report that menin functions as a transcriptional repressor through interaction with the transcription factor JunD. The interaction is mediated via the N-terminal transcription activation domain of JunD, and the C-terminal part of menin. In transient co-transfection experiments, expression of menin leads to specific repression of JunD transcriptional activity, which is dependent on the integrity of the menin C-terminal region. C-Terminal truncations of the protein not only abolish repression, but increase JunD transcriptional activity, implying the existence of a functional domain separate from the JunD-binding region. Menin-mediated repression is relieved by the histone deacetylase inhibitor trichostatin A, indicating that deacetylation of histones is an essential component of this repression mechanism, as has recently been demonstrated for the retinoblastoma protein. Missense, in-frame deletions, frameshift and nonsense mutations lead to inactivation of menin or possibly to truncated proteins. This would result in loss of repression of menin/JunD target genes, as well as non-target genes through indirect mechanisms, deregulation of cellular growth control and endocrine tumorigenesis.
Among 33 patients with endocrine pancreatic tumors due to multiple endocrine neoplasia type 1 (MEN-1), 19 (58%) patients had hypergastrinemia, 7 (21%) patients had hyperinsulinism, and 7 (21%) patients had clinically non-functioning lesions. At least one gross tumor was found in all patients undergoing pancreatic surgery, including those with negative localization studies prior to operation. The patients also had additional macroscopic tumors as well as numerous microadenomas, and the lesions frequently were positive for immunostaining with multiple hormones, mainly pancreatic polypeptide, insulin, glucagon, and somatostatin. Duodenal endocrine lesions were found in 4 of 5 investigated patients and stained with gastrin and somatostatin antibodies. Distal, mainly subtotal pancreatic resection, was performed in 18 patients, eventually combined with caput tumor enucleation or duodenotomy, while a few patients underwent only tumor enucleation or a Whipple procedure. The long-term outcome of operation was most favorable in patients with hyperinsulinism; only 1 patient had clinical recurrence. Patients with hypergastrinemia experienced only transitory lowering of serum gastrin values after pancreatic surgery and 47% of them had or developed metastases. Such tumor spread was seen in 57% of the patients with non-functioning lesions. Nine patients died from progressive tumor disease during follow-up. Consistent with previous studies, we found that surgery is indicated in MEN-1 patients with hyperinsulinism even if a lesion is not visualized by radiology. In addition, these indications should be extended to also include patients with only biochemical markers of disease, including elevations of gastrin, as these indicate the presence of gross tumors.
The only cure for patients with pulmonary carcinoids is surgery. In the present paper, we report the results of medical treatment of patients with metastatic tumors, their circulating hormone markers, and immunohistochemical profile of the tumors. PATIENTS AND
The response to systemic antitumoral treatment was studied in 31 patients with metastatic pulmonary carcinoids. Median survival from treatment start was 25 months. Alpha-interferon treatment has resulted in stable disease in 4 of 27 patients (median duration 15 months), while 23 patients showed progressive disease. Somatostatin analogues given as single drug treatment resulted in progressive disease. Streptozotocin and 5-fluorouracil resulted in progressive disease in seven of seven patients. Stable disease was obtained for 8 and 10 months respectively in two of two patients treated with streptozotocin + doxorubicin. Two of eight patients treated with cisplatinum + etoposide showed a significant decrease in tumor size lasting six and eight months respectively, and one displayed stable disease for seven months. Elevation of plasma chromogranin A was seen in 93%.
The results of systemic antitumoral treatment of pulmonary carcinoids with distant metastases are generally discouraging. Chemotherapy with cisplatinum + etoposide, or doxorubicin combined with streptozotocin or paclitaxel may be of value. Alpha-interferon and octreotide offer efficient symptomatic relief, but stabilizes tumor growth in merely 15% of the cases. Plasma chromogranin A is the most frequently elevated tumor marker.
To report our experience of liver embolization with trisacryl gelatin microspheres (Embospheretrade mark) in patients with metastatic neuroendocrine tumors.
Fifteen patients underwent selective embolization of the right or left hepatic artery with Embosphere. One lobe was embolized in seven patients and both lobes, on separate occasions, in eight patients. Seven patients had midgut carcinoids, two had lung carcinoids, one suffered from a thymic carcinoid, and five had endocrine pancreatic tumors. Eight patients suffered from endocrine symptoms, seven of whom had carcinoid syndrome and one WDHA (watery diarrhea, hypokalemia, achlorhydria) syndrome.
Partial radiological response was seen after eight embolizations (in six different patients), stable disease was observed after 13 embolizations (after three of these, necroses occurred), while radiological progression was noted after only two embolizations. Only two patients experienced a biochemical response. Clinical improvement of carcinoid syndrome was observed after five embolizations. There were no major complications. Fever >38 degrees C was seen after all but four embolizations, and urinary tract infections were diagnosed after eight embolizations.
Selective hepatic artery embolization with Embosphere particles is a safe treatment for patients with metastatic neuroendocrine tumors and may lead to partial radiological response as well as symptomatic improvement of disabling endocrine symptoms.
In a substantial proportion of cases with endocrine malignant disease the primary lesion cannot be localised and the pathologist hesitates upon the origin of the tumour. Well differentiated neuroendocrine carcinomas of the small bowel can usually be identified by the strong serotonin immunoreactivity, but foregut carcinoids may also stain positive for serotonin and the differential diagnosis between the various foregut tumours may be difficult. We examined if immunostaining for gastrin-releasing-peptide (GRP) may aid in establishing the origin of an unknown neuroendocrine tumour. Tumour tissue from 79 patients (27 lung carcinoids, 4 thymic carcinoids, 4 gastric neuroendocrine tumours, 17 pancreatic well differentiated neuroendocrine carcinomas, 1 duodenal well differentiated neuroendocrine tumour and 26 well differentiated neuroendocrine carcinomas of the small bowel) were immunostained with antibodies against GRP and serotonin. Positive staining for GRP was found in 12/27 lung carcinoids. All other tumour types were consistently GRP-negative (p?<?0.0001). We conclude that immunostaining for GRP may aid in defining the origin of the tumour, and that GRP-immunoreactivity increases the suspicion of a lung carcinoid.
BACKGROUND: Type 1 gastric carcinoids are associated with hypergastrinaemia and chronic atrophic gastritis, type 2 occur in patients with multiple endocrine neoplasia type 1 combined with Zollinger-Ellison syndrome, and type 3 lack any relation to hypergastrinaemia. Type 1 tumours are usually benign whereas type 3 are highly malignant. AIMS: To identify possible tumour markers in patients with gastric carcinoids. PATIENTS/METHOD: Nine patients with type 1, one with type 2, and five with type 3 were evaluated with regard to symptoms, hormone profile, and prognosis. RESULTS: Plasma chromogranin A was increased in all patients but was higher (p < 0.01) in those with type 3 than those with type 1 carcinoids. All patients with type 3 carcinoids died from metastatic disease, but none of the type 1 patients died as a result of their tumours. One type 1 patient with a solitary liver metastasis received interferon alpha and octreotide treatment. Nine months later, the metastasis was no longer detectable. She is still alive eight years after diagnosis, without recurrent disease. This represents the only reported case of foregut carcinoid with an unresectable liver metastasis that seems to be have been cured by biotherapy. CONCLUSIONS: Plasma chromogranin A appears to be a valuable tumour marker for all types of gastric carcinoid. Combination therapy with interferon alpha and octreotide may be beneficial in patients with metastasising type 1 gastric carcinoids.
Tumor tissues from 43 patients with typical bronchial carcinoids have been immunostained with monoclonal antibodies (mAbs) against the standard form (CD44s) and the splice variants v4, v5, v6, v7, v7-8, v9 and v10 of the adhesion molecule CD44. The staining results were correlated with clinical data. Ten patients (23%) had regional lymph node metastases at diagnosis. Distant metastases have occurred in 12% of the patients; 9% died during the observation period of median 65 months (14-325). Positive staining for CD44s was correlated with decreased risk for distant metastases and disease related death. All patients with distant metastases were v6-negative. Patients with CD44v7-8-positive tumors had decreased risk for distant metastases, but the differences in mortality did not reach statistical significance. CD44v9 correlated significantly with decreased risk for distant metastases and death. The remaining CD44 variants (v4, v5 and v10) did not correlate significantly with clinical outcome. Our results confirm earlier observations that typical bronchial carcinoids are potentially malignant. However, positive staining for CD44s, v7-8 and v9 seems to be associated with a more favorable outcome, and may be taken into consideration in prognostic evaluation.


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07 July 2020 - Events
In my first Blog "Lowering the bar in Barder" I discussed the case of Mr Critchell, who having lost his father within a month of the drawing of the Court order, found the terms of his divorce settlement altered by the court so as to remove his charge against the family home on the basis that he no longer needed the money, now or in the future.
I explained within that Blog the circumstances in which one can consider applying for a variation of an order on Barder principles, and concluded by questioning whether there would be much judicial appetite for running such arguments in big money cases. I was wrong. On 11 June 2015, the High Court handed down its decision in the case of WA v Executors of the Estate of HA & Others. This was without doubt a very big money case.
WA v HA
In WA v HA, the court considered the wife's appeal against an order for financial provision made by Deputy District Judge McHardy, by consent, in November 2014. The award provided £17m to the husband. Although there had been a pre-nuptial agreement in the case, both parties accepted that it was not a relevant factor in the negotiations which led to the agreement being reached at the time. The sum was to be paid in two instalments of £8.67m, the first of which the wife paid within fourteen days of the order. The second was to follow.
Tragically, the husband committed suicide less than a month after the order was made. At some point between the order being made and the husband's death, and unbeknown to the wife, he had made a new will. He had also in the interim used some of his settlement to purchase a home for his elderly mother (who up until that time had been living in the grounds of the family estate). The will provided that the entirety of the husband's estate would be left to his three brothers, on the condition that they did not give any of the money to his former-wife. Surprisingly, no financial provision was made for the parties' three minor children.
The wife, who was described by the judge as being "fabulously wealthy", sought for the entirety of the money to be repaid to her and for the order to be set aside. She argued that the proximity of the husband's death invalidated the consent order, as the order was based upon his future financial needs, which were no longer a necessary consideration. The husband's estate resisted the wife's application on the basis that the husband's death was foreseeable at the time of the original order.
The Court found that the tests in Barder had been met and reduced the total award to £5m. A repayment of £3.67 was payable to the wife from the husband's estate, and the second tranche was set aside.
In reaching its conclusion, the Court paused to consider the following: was the husband's death foreseen/foreseeable? If not, was his award a sharing award or a needs based award?
It is fundamental that, in order to get a potential Barder case off the ground, " a new event must have occurred since the making of the order which invalidates the basis, or fundamental assumption, upon which the order was made….". This has been translated by case-law to mean that the event in question must be "unforeseen" and "unforeseeable" (i.e. more than a theoretical possibility) at the time the order was made.
On the facts of this case, the wife claimed that the husband's suicide was entirely unforeseen by her, because despite evidence of his state of mind showing that he might present a suicide risk during the proceedings, at the time the order was made 3 months later, the medical evidence was much more positive and found that he was no longer a danger to himself.
Objective or subjective test?
The Court agreed with the wife; it accepted that the wife did not foresee his suicide and also that it was unforeseeable; but unforeseeable by whom? What the Court did not clarify is the extent to which each limb (foresight and foreseeability) are objective or subjective tests. Almost certainly the event cannot have been foreseen by the spouse, but did it also have to be unforeseeable by her, or unforeseeable generally (i.e. by any reasonable bystander)? Given the decision in S v S (Ancillary Relief: Consent Order) [2002] in which the Court found (emphasis added) "it must still be unforeseeable in the sense that it was not envisaged and could not reasonably have been envisaged at the time…". it must surely have to be objectively unforeseeable (i.e. by the Court).
It begs the question of what the Court would do if the event was unforeseen by, and unforeseeable to, the wife in question, but would have been foreseeable to any reasonable individual and the Court. Presumably the order would still stand, irrespective of what she had thought (or not thought). Perhaps that is less surprising in cases of court-imposed settlements, but ostensibly less fair to the innocent spouse who had not thought X could happen, whilst everyone else did. With increasing numbers of spouses representing themselves in financial remedy proceedings, there is potentially greater scope for unfairness when the financially weaker party, with perhaps less financial acumen and no solicitor, does a deal not really knowing what is or is not foreseeable with regard to her husband's company, assets or remuneration.
Needs and Sharing
The position is now definitive: an order can be overturned under Barder principles if it made provision for needs, but not if it was a "sharing" order.
The difficulty is how one unpicks what component of an order constitutes "needs" and what forms part of "sharing", if any. If there is a consent order, as in this case, quite often the way in which the financial provision is structured is not articulated in correspondence or on the face of the order. Many judgments are obscure when it comes to explaining in any great detail how the Judge reached the figure he or she did.
Here it was held that the husband's claim was "primarily needs-based". The Court noted, but seemingly did not give great weight to the fact, that there had been no exchange of budgets or property particulars. The real focus was on the fact that the majority of the assets in the case were gifted/inherited, and therefore the logical conclusion was that the award was primarily driven by needs. However, once the Court had determined that the order was based on needs, and hence could be challenged under Barder, as part of its assessment of what the revised sum should be, it dealt first with sharing!
Although there had been a pre-marital agreement excluding sharing, this did not prevent the Court from making an award for £5m, entirely based on the husband being able to "share" in the value of the family home/estate. When it came to the consideration of the husband's "needs", the Court found that this would have included provision to house the husband's mother (although it is unclear whether the Court would have reached the same conclusion had the wife not willingly taken that responsibility on previously), as well as the husband's ability to enable him to make bequests. Although the £5m figure for sharing was seen as "exceeding his reasonable needs modestly", the Court did not see that as a reason to reduce the award. It "simply seems right" as per Mr Justice Moor.
So where do we end up? We have a case where the settlement was overturned on the basis that it was calculated primarily by reference to needs, only to be replaced with an order primarily calculated by reference to sharing. One wonders whether the outcome would have been different had the husband (a) left his assets to his children (notwithstanding the fact that they were generously provided for by the wife); (b) not had an elderly mother who needed support; © not made it clear that he had a desire to make charitable bequests; and (d) had a less wealthy wife. Surely £5m is an extraordinary sum for one's needs, if their life expectancy is only 1 month, however generously assessed.
This case also brings interestingly to the fore the question of capital support for elderly parents and the ability to make charitable donations when assessing one's needs. Perhaps such provisions need to be included in budgets, in cases where there is plenty of money to go around.
Nasim v Nasim
Some two months later, on 5 August 2015, the High Court was faced with yet another application under the Barder principles, but founded on an entirely new and once could say "unforeseeable" use of the test.
The case of Mr and Mrs Nasim provides a particularly interesting application of the Barder principles. The High Court granted the husband permission to appeal an order made in November 2014. Following a fifteen-year marriage, divorce proceedings were issued in 2013, which were followed by financial remedy proceedings. The order in November 2014 awarded approximately 70% of the net proceeds of sale of the former matrimonial home (worth c. £290,000) to the wife. The Court's primary reason for the unequal division was the parties' intention that the two children of the marriage (aged 13 and 10 at the time) would spend 70% of their time staying with their mother rendering her housing needs greater than that of their father. The second factor was that the husband had secure employment and a greater mortgage borrowing capacity. Not an altogether surprising result, one would say, when the mother was the primary carer and it was a moderate assets case.
A mere matter of weeks after Deputy District Judge Butler gave his judgment, there was an "incident" (little is said about this in the judgment) between Mrs Nasim and their eldest daughter, following which Mrs Nasim was prosecuted. Thereafter, the children were no longer willing to see their mother, and moved in with their father.
The High Court reasoned that, were it not for the first instance Judge's understanding that the children would be spending less time staying with their father, he would have awarded the husband an equal share of the proceeds of the former matrimonial home, rather than a mere 30%. The change in residence was sufficient to invalidate the basis upon which the Judge had ordered an unequal division of the proceeds of sale. Seemingly this was unforeseen and unforeseeable. The fact that the wife had since undergone an Islamic ceremony of marriage with a man, and an English civil marriage with yet another man was completely irrelevant to the question of whether to allow the appeal and that in itself was not a Barder event. Whether it will be for the judge dealing with the matter under re-determination is another question.
Barder to the test
This case deploys quite an original use of the principle in Barder. Undoubtedly, few practitioners would advise clients to rely on Barder if a child was to leave home. Will it now be possible to rely on Barder if a child goes to boarding school (and is no longer primarily at home)? Possibly not if it was foreseeable and had previously been discussed between the parents. And what of the teenager who no longer gets on with mum and moves out; can dad recoup some of his capital?
It rather seems that the Barder principles are being tested more and more frequently in the Court room and new and ingenious ways of applying them are being deployed. Has the bar in Barder been lowered? Perhaps not, but we have learnt one lesson; the creativity of legal counsel cannot be underestimated!


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Race 11: Round of South Carolina
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Race 11: Round of South Carolina
- Spoiler:
- Reject of the Race: Lycoia
Moore blew up on the pace lap, Lareau and Delgado were both the worst type of moving chicanes, Plissken blew up under yellow, Woodard drove like a fool, and a debutant outdrive every other Lycoia representative in the field! Were it not for Kard, I would have lumped Lenard in here too!
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Catbag wrote:If there were no insanity, it would be necessary to invent it.
Anon wrote:Yeah, but what if Ann Coulter tried bath salts?
Re: Race 11: Round of South Carolina
- Spoiler:
- Delgado Not Interested in Hearing Complaints After First DDE Double Points Night
Tom Delgado & Brandon Lareau came under a ton of fire after the Round of Darlington this evening for being moving chicanes, but the co-owner of DeGarmo-Delgado Enterprises refused to have any of it after both he and Lareau came home with points finishes. A pit reporter came down to the #37 box and tried to get Delgado's thoughts, and that's where the fun started.
"I get it, it's the last lap and the leader's gotta get by. Should have gotten by me sooner. I am not in the business of laying down and dying for people, never have and never will. I'm racing Tony (Durbin) for position and more prize money for the team, and you expect me to just lay down, die, and forget it? <censored> that, and <censored> you. This team needs all the money it can get and it needs the best finishes it can get...and don't get me wrong, I like Leonid! I always have! He's a real man's man, and I expect the two of us to be talking really loudly later. However, and no disrespect intended towards Tony either, but when Tony's in front, it's brilliant driving. When I'm trying to maximize my finishing position and our prize money, it's wrong. This is why I retired two years ago. Can't stand the <censored> "politics over racing" mindset around here!" An infuriated Delgado said after his 16th place finish. We later found out that Delgado was angry because he felt that Roderick's inability to get to him sooner and get by took away from what was a very good night for his team.
If we learned anything from tonight, we learned that while Tom Delgado at nearly 40 years old may not be the driver he was a few years ago as far as ability goes, he may be more intense than ever. That's a scary thought for his ASCC driver's championship rivals going forward towards the end of the 2014 calendar year.
Last edited by Magus978 on Thu Aug 06, 2015 1:08 pm; edited 1 time in total
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Re: Race 11: Round of South Carolina
- Spoiler:
- Ben Atkins left irate after Round of South Carolina
It wasn't a long race for Atkins at Darlington Speedway. In fact, it only lasted about 55 laps for the British driver, who was caught up in the second caution of the day after Axel Andersson forced a three wide move on Team EFR teammates Ian Cooper and Scott Bates, leaving Atkins nowhere to go. Atkins was running inside the top 25, one lap down at the time.
"It's stupid that you have the hard working guys in underpowered rides trying to earn 20th while you have wankers like Andersson and Griffith out there in competitive rides wrecking people" said Atkins, "It's a bunch of BS that they think it's okay to go out there and wreck people because they have a better car. Did you see how Devereux was driving today? Swerving into people and putting cars in the wall because they didn't move over in a split second. He's up there with Griffith on the list of self righteous dickheads in the field."
Late in the race, Anthony Griffith was put into the wall and out of the race by Greg Woodard, and when that happened, Atkins was seen cheering in his garage stall. After the wreck, Atkins continued a streak of races with no points, which has not been broken since the Karjala Grand Prix this season.
cowabunga it is
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Re: Race 11: Round of South Carolina
- Spoiler:
- A tough night for Kazeyama and Maximus
Darlington left its mark on a lot of drivers, Azuma Kazeyama was no exception, after dropping out from two incidents on track, it left the Japanese Driver irritated, after contact with Zelda Ashby and Cameron Taylor that brought out the first yellow, he was tagged from behind by the 39 of Brandon Lareau in retaliation for a incident earlier which lead to his cut tire.
Kazeyama would attempt to continue on but by mid way through the race the car was put behind the wall.
"This race sums up our team's season as a whole." Kazeyama replied, "Mackay night got compromised because Devereux was his typical impatient self, and Lareau decided that under yellow was a good time to develop a attitude about a earlier incident. We tried to solider on but the car just started falling apart there and we couldn't finish with it."
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Re: Race 11: Round of South Carolina
- Spoiler:
- Webster Solid in TMMCS Debut
After running in the Karjala Consolation Race several months ago, Zack Webster made his long-awaited TM Master Cup Series debut in the Round of South Carolina at the Darlington Speedway for Power Steering Inc. After settling in solidly in the top 15 at the start of the race, Webster found himself one lap down after a wild and confusing caution period. Webster continued to fight, and at one point he found himself leading the way for PSI before being passed late by teammate Greg Woodard. Webster was able to bring the car home with a respectable 13th place finish.
Webster was very upbeat in his comments after the race.
"I've got to start by thanking the guys over at PSI. They gave me a great piece for this debut. The car was the best on the short run--we weren't as solid as we wanted to be on the long run. I think the first goal for me as a driver was to go out there and enjoy the experience of racing in a TMMCS points race. That's a pretty simple goal to accomplish with the kind of cars that PSI puts out to drive. I thought another realistic goal was to maybe get inside the back part of the top 20 and maybe score a couple of points. 13th place and 14 points certainly exceeded my expectations quite a bit."
"It was pretty amazing to be able to carry the flag for PSI for a small portion of the race there at the end. I didn't quite have the car or the experience to keep Greg from catching me, but it sure was a lot of fun to be able to lead the PSI drivers for a small stint at the end of the race. I'm proud of the effort we put forth on this entire #32 SuperCharged Energy team, and I'm looking forward to being back in that car hopefully sometime soon."
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Management Team
Steve W. Bergstrom
Dan C. Campbell
Matthew W. Rowland
Tom L. Brock
William B. Mathews
William B. Mathews,
General Counsel and Vice President of Legal Affairs
Mr. Mathews has served as Secretary and Vice President of Legal Affairs of our general partner since November 2009 and General Counsel of our general partner since March 2011. Prior to our formation, he served as Vice President, General Counsel and Secretary of Foothills Energy Ventures, LLC from December 2006 to November 2009, as well as a director from August 2009 to November 2009. Prior to Foothills, Mr. Mathews served as Assistant General Counsel for ONEOK Partners, L.P., Northern Border Partners, L.P. and Bear Paw Energy, LLC from July 2001 to December 2006 and, previous to that, as Vice President and General Counsel of Duke Energy Field Services (now DCP Midstream, LLC) until 2000, having joined a predecessor company in 1985. He received a J.D. from the University of Denver and a B.S. in Civil Engineering from the University of Colorado.