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In today's episode of OncLive On Air®, Jonathan Trent, MD, PhD, and Neeta Somaiah, MD, sat down to discuss the evolving role of circulating tumor DNA (ctDNA) testing in gastrointestinal stromal tumors (GIST), as well as the importance of identifying both initial drivers of disease and secondary resistance mechanisms when approaching frontline treatment selection and overall therapeutic sequencing.Trent is a professor of medicine, associate director of Clinical Research, and director of the Sarcoma Medical Research Program at the University of Miami Miller School of Medicine, in Florida. Somaiah is a professor and chair of the Department of Sarcoma Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.Drs Trent and Somaiah began their discussion by highlighting the rarity of GIST, underscoring the importance of evaluation at specialized sarcoma centers and comprehensive molecular testing to identify driver alterations.Somaiah then reviewed the molecular landscape of GIST, noting that approximately 70% to 80% of tumors harbor activating mutations in the KIT gene, while additional cases involve rarer alterations such as BRAF or NTRK fusions. Of note, resistance to imatinib (Gleevec) frequently emerges through secondary mutations in KIT exons 13 or 17, which can influence sensitivity to subsequent TKIs.ctDNA testing may help detect these resistance mechanisms, particularly at progression or when tissue is limited, enabling clinicians to refine sequencing strategies, both experts explained. They also discussed how mutation-informed approaches may guide treatment selection, including emerging strategies such as combining sunitinib (Sutent) with bezuclastinib to address resistant clones involving KIT exon 13 or 17 alterations.This content is a production of OncLive; this OncLive On Air podcast episode is supported by funding, however, content is produced and independently developed by OncLive.
Today on The Gist, Global Reach CEO Mickey Bergman discusses the high-stakes world of international hostage negotiation. He details the emotional intelligence required to deal with foreign officials and clarifies the behind-the-scenes realities of securing the release of Americans like Paul Whelan, Trevor Reed, and Brittney Griner. Plus, Mike opens the show by analyzing the Republican-backed SAVE Act. He argues the proof-of-citizenship voting bill is purely a messaging tactic with no chance of passing the Senate, and points out that many of the voters most likely to lack ready access to a birth certificate actually favor Donald Trump. Produced by Corey Wara Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
Today on The Gist, historic double Oscar-nominated director Geeta Gandbhir joins the show to discuss her Netflix documentary feature, The Perfect Neighbor. She breaks down the tragic murder of AJ Owens by her neighbor Susan Lorincz, explaining how Florida's "Stand Your Ground" laws, racial bias, and easy access to firearms enabled a deadly escalation. Gandbhir also explores the ethical complexities of using raw police body cam and Ring doorbell footage to document the community's grief without re-traumatizing the victim's family. Plus, why Defense Secretary Pete Hegseth is acting like a media critic instead of fighting an actual war. And in the Spiel, Donald Trump's repeated attempts to unlawfully install loyalist U.S. Attorneys keep getting smacked down by federal judges—proving the Constitution's guardrails are made of steel, not hanging by a thread. Produced by Corey Wara Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
Mike Pesca is one of our very favorite guests — on any number of topics. His book, Upon Further Review: The Greatest What-Ifs in Sports History, is a whole series of earth-shattering, hypothetical, what-if questions (and posited answers to said earth-shattering, hypothetical, what-if questions): What if a blimp full of money had exploded over world track headquarters in 1952? What if Nixon had been good at football? What if Bobby Fischer had received proper psychiatric help? What if the Dodgers hadn’t left Brooklyn? What if basketball rims were smaller than basketballs? What if the 1999 U.S. women’s national soccer team had lost the Women’s World Cup? And yes: What if the Olympics had never dropped tug of war? It goes on and on. Pesca joins us for the hour. GUESTS: Will Leitch: Contributing editor at New York magazine, founder of Deadspin, and a whole bunch of other things Mike Pesca: Host of The Gist and the author of Upon Further Review Louisa Thomas: Staff writer at The New Yorker and the author of Louisa: The Extraordinary Life of Mrs. Adams The Colin McEnroe Show is available as a podcast on Apple Podcasts, Spotify, Amazon Music, TuneIn, Listen Notes, or wherever you get your podcasts. Subscribe and never miss an episode! Subscribe to The Noseletter, an email compendium of merriment, secrets, and ancient wisdom brought to you by The Colin McEnroe Show. Join the conversation on Facebook and Twitter. Colin McEnroe, Carlos Mejia, and Chion Wolf contributed to this show, which originally aired June 7, 2018.Support the show: http://www.wnpr.org/donateSee omnystudio.com/listener for privacy information.
Today on The Gist, bestselling author Nir Eyal joins the show to discuss his new book, Beyond Belief: The Science-Backed Way to Stop Limiting Yourself and Achieve Extraordinary Results. He explains how the lead singer of Sofi Tukker cured her chronic neuroplastic pain by "throwing ass," why vision boards and manifesting actually ruin your chances of success, and why the placebo effect is getting statistically stronger every year. They also break down the critical difference between facts, faith, and beliefs—and why treating our beliefs as immutable truths is tearing society apart. Plus, Mike gives it to you straight. A geographical rundown of the world's most important, and underrated, straits. Interested in Nir's book? geni.us/beyondbelief Free belief change guide is here: nirandfar.com/belief-change Bonus content and the 30-Day Belief Transformation Journal is here: nirandfar.com/beyond-belief Produced by Corey Wara Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
Today on The Gist, Princeton PhD researcher Elizabeth Tsurkov joins the show to share her harrowing experience of being kidnapped and held hostage in Iraq for over 900 days by the Iranian-backed militia Kataib Hezbollah. She details the brutal realities of her captivity, how she used her intellect to outsmart her captors by leaving hidden "breadcrumbs" for intelligence agencies in forced confession videos, and the bizarre reality of being ordered to write geopolitical analysis for the militants. She also provides a rare, firsthand look at how the proxy group reacted in real-time to the October 7th attacks and the subsequent regional fallout. Plus, the differing approaches of the Trump and Biden administrations to hostage recovery. Produced by Corey Wara Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
Today on The Gist, A jet-lagged yet very gracious comedian and writer Jena Friedman joins the show to discuss her new stand-up special, Motherfucker. She talks with Mike about why writing abortion jokes is harder than ever in a post-Roe reality, the challenges of making dark topics funny on her true crime series Indefensible, and the current landscape of risky political comedy. Jena also opens up about the vulnerability of tackling grief on stage after losing her mother while eight months pregnant. Produced by Corey Wara Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
In this episode, Gbemi and Toolz break down the Tyra Banks and America's Next Top Model documentary, old reality TV culture, Cardi B performing three months postpartum, why Nigerian concerts need to do better, the drama around Nigerian streamers, social media pile-ons, false accusations, and the backlash around Simi's “stop raping women'' tweet. They also get into celebrity deaths that hit hard, the dangers around travel destinations like Mexico, Tonto Dikeh's latest rebrand, relationship drama making the rounds online, and much more. Plus, there's Money Zone with Moneypoint and a fun Spin the Weekend moment with Gordon's Gin.If you enjoyed this episode, like, comment and subscribe. Drop the stories you want us to cover next in the comments.00:00 — Season 9 kickoff 02:05 — Promo shoot 04:10 — Plato food shout out 06:00 — Tyra Banks documentary 11:20 — Reality TV then vs now 15:40 — Extreme makeovers debate 18:30 — Big Brother fame pressure 21:00 — Cardi B postpartum tour 23:20 — Beyoncé concert standard 26:00 — Nigerian concerts discussion 29:10 — Celebrity deaths & healthcare costs 33:40 — Mexico cartel crisis 38:10 — World Cup travel concerns 41:20 — Nigerian streamers drama 45:50 — IShowSpeed's Africa tour 49:20 — Looking like you don't need money 52:10 — Mirabel assault story 56:40 — Simi tweets controversy 1:02:10 — Feminism & Twitter dragging 1:06:00 — Engagement bait & fake stories 1:09:20 — Cubana Chief Priest DNA saga 1:12:50 — Tonto Dikeh rebrand 1:15:30 — Money Zone By Moneypoint 1:20:40 — Nigeria, money & savings 1:25:10 — Business tools & POS tracking 1:28:30 — Street fight story 1:31:10 — OffAir Reacts: Throuple discussion 1:33:30 — Celebrity crushes 1:35:40 — Gordon's Cocktail time 1:38:00 — Gordon's Spin the Weekend (Brunch & Gist) 1:40:20 — Episode wrap-up#OffAirPodcast #GbemiAndToolz #TyraBanks #Simi #NigerianStreamers #CelebrityDrama #PopCulturePodcast
Today on The Gist, the line between free speech and harassment, and why the progressive left's blind spot for anti-Semitism turns "anti-Zionism" into a convenient excuse for abuse. Then comedian, actress, and writer Jamie Denbo joins the show to discuss reviving her beloved alt-comedy character, Beverly Ginsberg, for The Beverly Podcast. She opens up about her tenure as a writer and producer on Grey's Anatomy, revealing how the network's progressive double standards and post-October 7th hypocrisy forced her to resign. Plus, a healthy dose of "Jewish joy" and a few biting, in-character critiques of self-help gurus like Mel Robbins and Glennon Doyle. Produced by Corey Wara Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
Today on The Gist, Actress Gina Gershon joins the show to discuss her candid new memoir, Alpha Pussy: How I Survived the Valley and Learned to Love My Boobs. She shares the hilarious story of how a tequila-fueled comedy roast landed her a memorable role on Curb Your Enthusiasm, and drops actionable advice on dodging Hollywood predators, setting ironclad boundaries, and surviving the entertainment industry on her own terms. Bound, Showgirls and more are discussed. Plus, how the concept of 'imminence' is playing too literal a role in discussions of the war in Iran. And in the Spiel, the steelman answer to the question: 'What is the Trump administration's reason for going to war? Produced by Corey Wara Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
Selling your company isn't always a flex. Sometimes the bravest exit is walking away. If you're “fine” but your body is screaming, this episode is for you. In this episode of The Exit Whisperer, Carrie sits down with Roslyn McLarty, co-founder of The GIST, who left a fast-growing, funded company when burnout stopped being a vibe and started being a warning sign.We get into the unsexy truth founders don't post: the eye twitch, the dread, the “take a long weekend” advice that solves nothing, and the moment you realize it's not just hard — it's misaligned. Roslyn breaks down what burnout actually is (a chronically activated nervous system), how to tell “push through” from “get out,” and why chasing outcomes (revenue, valuation, the headline) is the fastest route to losing yourself.02:19 Meet Roslyn McLarty04:18 Building The GIST From Scratch05:08 Why Fundraising Was an Uphill Battle07:24 Role Misalignment: The Silent Burnout Trigger12:41 Hitting Burnout — And Finally Stopping19:56 The Inner Critic That Won't Shut Up20:16 How Burnout Warps Business Decisions21:22 The Emotional Whiplash of Leaving Your Company22:19 Processing Grief, Relief, and Identity Loss24:25 Finding Alignment After the Exit26:16 Rebuilding Without Burning Out Again29:50 How to Recognize and Regulate Burnout33:44 What Every Founder Needs to Hear
Willa Ford joins The Gist to reflect on her journey from early 2000s pop breakout to creative reinvention. Known for her TRL-era hit “I Wanna Be Bad,” Willa became a defining voice of turn-of-the-millennium pop culture. In this conversation, she looks back at that chapter — and shares what was happening behind the scenes.We discuss the evolution of her public identity (Mandah, Amanda, Willa Ford), navigating fame at a young age, and how trauma, resilience, and growth shaped her return to music. Her new album, Amanda, named after her birth name, marks a deeply personal reset — one rooted in healing, authorship, and perspective.This episode explores:Willa Ford's early 2000s pop career and TRL era fameThe story behind “I Wanna Be Bad”Reinvention and returning to music after years awayThe making of her new album AmandaCreativity, trauma, and redefining legacyIf you're a fan of early 2000s pop culture, TRL nostalgia, music reinvention stories, or artist interviews that go beyond the headlines, this conversation offers context and clarity. Listen! It's Vetrano: https://listenitsvetrano.com/the-gist-podcast/ Instagram: http://instagram.com/listenitsvetranoYouTube: https://www.youtube.com/@listenitsvetranoFacebook: http://facebook.com/ListenItsVetrano Hosted on Acast. See acast.com/privacy for more information.
The “Gist” of the article – Is your need to fix others about you and your need to feel important or significant.
In this episode, Chris Vetrano returns to The Gist after a break, sharing insights on the current state of pop culture, particularly the rise of reality TV. He discusses the evolution of the podcast, emphasizing a more opinionated and engaging approach to commentary. Chris teases upcoming interviews and topics, inviting listeners to join him in exploring the dynamic landscape of entertainment and nostalgia.Listen! It's Vetrano: https://listenitsvetrano.com/the-gist-podcast/ Instagram: http://instagram.com/listenitsvetranoYouTube: https://www.youtube.com/@listenitsvetranoFacebook: http://facebook.com/ListenItsVetrano Hosted on Acast. See acast.com/privacy for more information.
Today on The Gist, President Trump's marathon two-hour State of the Union address with a quick quiz: Can you spot the actual presidential claim among the fakes? Then, C. Thi Nguyen joins the show to unpack the powerful psychology behind our convictions. They discuss why our limiting beliefs are exactly like our own faces (we can't see them without a mirror), how chronic neuroplastic pain can be cured by simply teaching your brain you're safe, and why the placebo effect is somehow getting stronger every single year. Produced by Corey Wara Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
On this Saturday edition of The Gist, we present "One From The Future." Mike joins Ruy Teixeira on the Liberal Patriot podcast to discuss a brewing theory regarding the mechanics of political change. They debate the utility of the "Scalpel" (technocratic, targeted cuts) versus the "Chainsaw" (the Elon Musk/DOGE approach of massive disruption). Plus, a look at why Democrats are better at mobilizing than organizing, the trap of "The Omnicause," and the re-branding of objectivity in modern journalism. Produced by Corey Wara Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
Today on The Gist, Mike breaks down Judge Richard Leon's ruling that Pete Hegseth's attempt to strip Senator Mark Kelly of his rank was absolute "horse feathers." Then, Ben Terris of New York Magazine joins to discuss his feature on the health of the President in 2026. They discuss the "talking points" held by Walter Reed doctors, the vanity behind the hand bruises, and the difficulty of assessing Trump's mental acuity when his inner circle has committed to the bit. Produced by Corey Wara Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
How To! has a new host - veteran journalist and podcaster Mike Pesca, host of The Gist, Not Even Mad, and Funny You Should Mention podcasts. It's the same great Ambie Award nominated show, covering new topics, with new experts, and Mike's signature humor. You've got questions. We find answers. We all need advice, but it's not always clear who to ask. Each week, Mike Pesca invites a listener on the show to tackle a real problem, like protecting our elderly loved ones from scammers, emigrating as a throuple, and speaking without saying "um" - all with help from world-class experts: attorneys, doctors, entrepreneurs, authors, researchers - who actually know what they're talking about. Think of it as eavesdropping on someone else's therapy session, without the co-pay or awkward silence.
Why do elites in both political parties keep misreading the public? In today's episode of The Liberal Patriot Podcast, I speak with journalist Mike Pesca to unpack the surprising voter ID consensus, the “scalpel vs. chainsaw” problem in modern politics, media tribalism, Bari Weiss and CBS, and the Democrats' struggle between moderation and resistance. Mike is an award-winning journalist and podcast host whose work spans public radio, print, and television. He is the creator and host of The Gist, the longest-running daily news podcast in history; moderator of Not Even Mad, a political debate podcast; and host of Funny You Should Mention, a co-production with the Comedy Cellar, where he conducts in-depth interviews with stand-up comedians. Are we stuck in a permanent overreaction cycle in politics—or is there still room for reform? Please listen in to find out!A transcript of this podcast is available on our website at the top of the post page. Get full access to The Liberal Patriot at www.liberalpatriot.com/subscribe
Dr. Pedro Barata and Dr. Ugwuji Maduekwe discuss the evolving treatment landscape in gastroesophageal junction and gastric cancers, including the emergence of organ preservation as a selective therapeutic goal, as well as strategies to mitigate disparities in care. Dr. Maduekwe is the senior author of the article, "Organ Preservation for Gastroesophageal Junction and Gastric Cancers: Ready for Primetime?" in the 2026 ASCO Educational Book. TRANSCRIPT Dr. Pedro Barata: Hello, and welcome to By the Book, a podcast series from ASCO that features compelling perspectives from authors and editors of the ASCO Educational Book. I'm Dr. Pedro Barata. I'm a medical oncologist at University Hospitals Seidman Cancer Center and an associate professor of medicine at Case Western Reserve University in Cleveland, Ohio. I'm also the deputy editor of the ASCO Educational Book. Gastric and gastroesophageal cancers are the fifth most common cancer worldwide and the fourth leading cause of cancer-related mortality. Over the last decade, the treatment landscape has evolved tremendously, and today, organ preservation is emerging as an attainable but still selective therapeutic goal. Today, I'm delighted to be speaking with Dr. Ugwuji Maduekwe, an associate professor of surgery and the director of regional therapies in the Division of Surgical Oncology at the Medical College of Wisconsin. Dr. Maduekwe is also the last author of a fantastic paper in the 2026 ASCO Educational Book titled "Organ Preservation for Gastroesophageal Junction and Gastric Cancers: Ready for Prime Time?" We explore these questions in our conversations today. Our full disclosures are available in the transcript of this episode as well. Welcome. Thank you for joining us today. Dr. Ugwuji Maduekwe: Thank you, Dr. Barata. I'm really, really glad to be here. Dr. Pedro Barata: There's been a lot of progress in the treatment of gastric and gastroesophageal cancers. But before we actually dive into some of the key take-home points from your paper, can you just walk us through how systemic therapy has emerged and actually allowed you to start thinking about a curative framework and really informing surgery decision-making? Dr. Ugwuji Maduekwe: Great, thank you. I'm really excited to be here and I love this topic because, I'm terrified to think of how long ago it was, but I remember in medical school, one of my formative experiences and why I got so interested in oncology was when the very first trials about imatinib were coming through, right? Looking at the effect, I remember so vividly having a lecture as a first-year or second-year medical student, and the professor saying, "This data about this particular kind of cancer is no longer accurate. They don't need bone marrow transplants anymore, they can just take a pill." And that just sounded insane. And we don't have that yet for GI malignancies. But part of what is the promise of precision oncology has always been to me that framework. That framework we have for people with CML who don't have a bone marrow transplant, they take a pill. For people with GIST. And so when we talk about gastric cancers and gastroesophageal cancers, I think the short answer is that systemic therapy has forced surgeons to rethink what "necessary" really means, right? We have the old age saying, "a chance to cut is a chance to cure." And when I started out, the conversation was simple. We diagnose the cancer, we take it out. Surgery's the default. But what's changed really over the last decade and really over the last five years is that systemic therapy has gotten good enough to do what is probably real curative work before we ever enter the operating room. So now when you see a patient whose tumor has essentially melted away on restaging, the question has to shift, right? It's no longer just, "Can I take this out?" It's "Has the biology already done the heavy lifting? Have we already given them systemic therapy, and can we prove it safely so that maybe we don't have to do what is a relatively morbid procedure?" And that shift is what has opened the door to organ preservation. Surgery doesn't disappear, but it becomes more discretionary. Necessary for the patients who need it, and within systems that can allow us to make sure that we're giving it to the right patients. Dr. Pedro Barata: Right, no, that makes total sense. And going back to the outcomes that you get with these systemic therapies, I mean, big efforts to find effective regimens or cocktails of therapies that allow us to go to what we call "complete response," right? Pathologic complete response, or clinical complete response, or even molecular complete response. We're having these conversations across different tumors, hematologic malignancies as well as solid tumors, right? I certainly have those conversations in the GU arena as well. So, when we think of pathologic CRs for GI malignancies, right? If I were to summarize the data, and please correct me if I'm wrong, because I'm not an expert in this area, the traditional perioperative chemo gives you pCRs, pathologic complete response, in the single digits. But then when you start getting smarter at identifying biologically distinct tumors such as microsatellite instability, for instance, now you start talking about pCRs over 50%. In other words, half of the patients' cancer goes away, it melts down by offering, in this case, immunotherapy as a backbone of that neoadjuvant. But first of all, this shift, right, from going from these traditional, "not smart" chemotherapy approaches to kind of biologically-driven approaches, and how important is pCR in the context of "Do I really need surgery afterwards?" Dr. Ugwuji Maduekwe: That's really the crux of the entire conversation, right? We can't proceed and we wouldn't be able to have the conversation about whether organ preservation is even plausible if we hadn't been seeing these rates of pathologic complete response. If there's no viable tumor left at resection, did surgery add something? Are we sure? The challenge before this was how frequently that happened. And then the next one is, as you've already raised, "Can we figure that out without operating?" In the traditional perioperative chemo era, pathologic complete response was relatively rare, like maybe one in twenty patients. When we go to more modern regimens like FLOT, it got closer to one in six. When you add immunotherapy in recent trials like MATTERHORN, it's nearly triple that rate. And it's worth noting here, I'm a health services-health disparities researcher, so we'll just pause here and note that those all sound great, but these landmark trials have significant representation gaps that limit and should inform how confidently we generalize these findings. But back to what you just said, right, the real inflection point is MSI-high disease where, with neoadjuvant dual-checkpoint blockade, trials like NEONIPIGAS and INFINITY show pCR rates that are approaching 50% to 60%. That's not incremental progress, that's a whole new different biological reality. What does that mean? If we're saying that 50% to 60% of the people we take to the OR at the time of surgery will end up having no viable tumor, man, did we need to do a really big surgery? But the problem right now is the gold standard, I think we would mostly agree, the gold standard is pathologic complete response, and we only know that after surgery. I currently tell my patients, right, because I don't want them to be like, "Wait, we did this whole thing." I'm like, "We're going to do this surgery, and my hope is that we're going to do the surgery and there will be no cancer left in your stomach after we take out your stomach." And they're like, "But we took out my stomach and you're saying it's a good thing that there's no cancer." And yes, right now that is true because it's a measure of the efficacy of their systemic therapy. It's a measure of the biology of the disease. But should we be acting on this non-operatively? To do that, we have to find a surrogate. And the surrogate that we have to figure out is complete clinical response. And that's where we have issues with the stomach. In esophageal cancer, the preSANO protocol, which we'll talk about a little bit, validated a structured clinical response evaluation. People got really high-quality endoscopies with bite-on biopsies. They got endoscopic ultrasounds. They got fine-needle aspirations and PET-CT, and adding all of those things together, the miss rate for substantial residual disease was about 10% to 15%. That's a number we can work with. In the stomach, it's a lot more difficult anatomically just given the shape of people's stomachs. There's fibrosis, there's ulceration. A fair number of stomach and GEJ cancers have diffuse histology which makes it difficult to localize and they also have submucosal spread. Those all conceal residual disease. I had a recent case where I scoped the patient during the case, and this person had had a 4 cm ulcer prior to surgery, and I scoped and there was nothing visible. And I was elated. And on the final pathology they had a 7 cm tumor still in place. It was just all submucosal. That's the problem. I'm not a gastroenterologist, but I would have said this was a great clinical response, but because it's gastric, there was a fair amount of submucosal disease that was still there. And our imaging loses accuracy after treatment. So the gap between what looks clean clinically and what's actually there pathologically remains very wide. So I think that's why we're trying to figure it out and make it cleaner. And outside of biomarker-selected settings like MSI-high disease, in general, I'm going to skip to the end and our upshot for the paper, which is that organ preservation, I would say for gastric cancer particularly, should remain investigational. I think we're at the point where the biology is increasingly favorable, but our means of measurement is not there yet. Dr. Pedro Barata: Gotcha. So, this is a perfect segue because you did mention the SANO, just to spell it out, "Surgery As Needed for Oesophageal" trial, so SANO, perfect, I love the abbreviation. It's really catchy. It's fantastic, it's actually a well-put-together perspective effort or program applying to patients. And can you tell us how was that put together and how does that work out for patients? Dr. Ugwuji Maduekwe: Yeah, I think for those of us in the GI space, we have SANO and then we also have the OPRA for rectum. SANO for the upper GI is what takes organ preservation from theory to something that's clinically credible. The trial asked a very simple question. If a patient with a GEJ adenocarcinoma or esophageal adenocarcinoma achieved what was felt to be a clinical complete response after chemoradiation, would they actually benefit from immediate surgery? And the question was, "Can you safely observe?" And the answer was 'yes'. You could safely observe, but only if you do it right. And what does that mean? At two years, survival with active surveillance was not inferior to those who received an immediate esophagectomy. And those patients had a better early quality of life. Makes sense, right? Your quality of life with an esophagectomy versus not is going to be different. That matters a lot when you consider what the long-term metabolic and functional consequences of an esophagectomy are. The weight loss, nutritional deficiencies that can persist for years. But SANO worked because it was very, very disciplined and not permissive. You mentioned rigor. They were very elegant in their approach and there was a fair amount of rigor. So there were two main principles. The first was that surveillance was front-loaded and intentional. So they had endoscopies with biopsies and imaging every three to four months in the first year and then they progressively spaced it out with explicit criteria for what constituted failure. And then salvage surgery was pre-planned. So, the return-to-surgery pathway was already rehearsed ahead of time. If disease reappeared, take the patient to the OR within weeks. Not sit, figure out what that means, think about it a little bit and debate next steps. They were very clear about what the plan was going to be. So they've given us this blueprint for, like, watching people safely. I think what's remarkable is that if you don't do that, if you don't have that infrastructure, then organ preservation isn't really careful. It's really hopeful. And that's what I really liked about the SANO trial, aside from, I agree, the name is pretty cool. Dr. Pedro Barata: Yeah, no, that's a fantastic point. And that description is spot on. I am thinking as we go through this, where can this be adopted, right? Because, not surprisingly, patients are telling you they're doing a lot better, right, when you don't get the esophagus out or the stomach out. I mean, that makes total sense. So the question is, you know, how do you see those issues related to the logistics, right? Getting the multi-disciplinary team, getting the different assessments of CR. I guess PETs, a lot of people are getting access to imaging these days. How close do you think this is, this kind of program, to be implemented? And maybe I would assume it might need to be validated in different settings, right, including the community. How close or how far do you think you see that being applied out there versus continuing to be a niche program, watch and wait program, in dedicated academic centers? Dr. Ugwuji Maduekwe: I love this question. So I said at the top of this, I'm a health equity/health disparities researcher, and this is where I worry the most. I love the science of this. I'm really excited about the science. I'm very optimistic. I don't think this is a question of "if," I think it's a question of "when." We are going to get to a point where these conversations will be very, very reasonable and will be options. One of the things I worry about is: who is it going to be an option for? Organ preservation is not just a treatment choice, and I think what you're pointing out very rightly is it's a systems-level intervention. Look at what we just said for SANO. Someone needs to be able to do advanced endoscopy, get the patients back. We have to have the time and space to come back every three to four months. We have to do molecular testing. There needs to be multi-disciplinary review. There needs to be intensive surveillance, and you need to have rapid access to salvage surgery. Where is that infrastructure? In this country, it's mostly in academic centers. I think about the panel we had at ASCO GI, which was fantastic. And as we were having the conversation, you know, we set it up as a debate. So folks were debating either pro-surveillance or pro-surgery. But both groups, both people, were presenting outcomes based on their centers. And it was folks who were fantastic. Dr. Molena, for example, from Memorial Sloan Kettering was talking about their outcomes in esophagectomies [during our session at GI26], but they do hundreds of these cases there per year. What's the reality in this country? 70% to 80% to 90%, depending on which data you look at, of the gastrectomies in the United States occur at low-volume hospitals. Most of the patients at those hospitals are disproportionately uninsured or on government insurance, have lower income and from racial and ethnic minority groups. So if we diffuse organ preservations without the system to support it, we're going to create a two-tiered system of care where whether you have the ability to preserve your organs, to preserve bodily integrity, depends on where you live and where you're treated. The other piece of this is the biomarker testing gap. One of the things that, as you pointed out at the beginning, that's really exciting is for MSI-high tumors. Those are the patients that are most likely to benefit from immunotherapy-based organ preservation. But here's the problem. If the patient isn't tested at time of initial diagnosis before they ever see me as a surgeon, the door to organ preservation is closed before it's ever open. And testing access remains very inconsistent across academic networks. And then there's the financial toxicity piece where, for gastrectomy, pancreatectomy, I do peritoneal malignancies, more than half of those patients experience significant financial toxicity related to their cancer treatment. We're now proposing adding at least two years, that's the preliminary information, right? It's probably going to be longer. At least a couple of years of surveillance visits, repeated endoscopies, immunotherapy costs. How are we going to support patients through that? We're going to have to think about setting up navigation support, geographic solutions, what financial counseling looks like. My patient for clinic yesterday was driving to see me, and they were talking about how they were sliding because it was snowing. And they were sliding for the entire three-hour drive down here. Are we going to tell people like that that they need to drive down to, right, I work at a high-volume center, they're going to need to come here every three months, come rain or snow, to get scoped as opposed to the one-time having a surgery and not needing to have the scopes as frequently? My concern, like I said, I'm an optimist, I think it is going to work. I think we're going to figure out how to make it work. I'm worried about whether when we deploy it, we widen the already existing disparities. Dr. Pedro Barata: Gotcha, and that's a fantastic summary. And as I'm thinking also of what we've been talking in other solid tumors, which one of the following do you think is going to evolve first? So we are starting to use more MRD-based assays, which are based on blood test, whether it's a tumor-informed ctDNA or non-informed. We are also trying to get around or trying to get more information response to systemic therapies out of RNA-seq through gene expression signatures, or development of novel therapeutics which also can help you there. Which one of these areas you think you're going to help this SANO-like approach move forward, or you actually think it's actually all of the above, which makes it even more complicated perhaps? Dr. Ugwuji Maduekwe: I think it's going to be all of the above for a couple of reasons. I would say if I had to pick just one right now, I think ctDNA is probably the most promising and potentially the missing piece that can help us close the gap between clinical and pathologic response. If you achieve clinical complete response and your ctDNA is negative, so you have clinical and molecular evidence of clearance, maybe that's a low-risk patient for surveillance. If you have clinical complete response but your ctDNA remains positive, I would say you have occult molecular disease and we probably need intensified therapy, closer monitoring, not observation. I think the INFINITY trial is already incorporating ctDNA into its algorithm, so we'll know. I don't think we're at the point where it alone can drive surgical decisions. I think it's going to be a good complement to clinical response evaluation, not a replacement. The issue of where I think it's probably going to be multi-dimensional is the evidence base: who are we testing? Like, what is the diversity, what is the ancestral diversity of these databases that we're using for all of these tests? How do we know that ctDNA levels and RNA-seq expression arrays are the same across different ancestral groups, across different disease types? So I think it's probably going to be an amalgam and we're going to have to figure out some sort of algorithm to help us define it based on the patient characteristics. Like, I think it's probably different, some of this stuff is going to be a little bit different depending on where in the stomach the cancer is. And it's going to be a little bit more difficult to figure out if you have a complete clinical response in the antrum and closer to the pylorus, for example. That might be a little bit more difficult. So maybe the threshold for defining what a clinical complete response needs to be is higher because the therapeutic approach there is not quite as onerous as for something at the GE-junction. Dr. Pedro Barata: Wonderful. And I'm sure AI, whether it's digitization of the pathology from the biopsies and putting all this together, probably might play a role as well in the future. Dr. Maduekwe, it's been fantastic. Thank you so much for sharing your insights with us and also congrats again for the really well-done review published. For our listeners, thank you for staying with us. Thank you for your time. We will post a link to this fantastic article we discussed today in the transcript of this episode. And of course, please join us again next month on the By the Book Podcast for more insights on key advances and innovations that are shaping modern oncology. Thank you, everyone. Dr. Ugwuji Maduekwe: Thank you. Thank you for having me. Watch the ASCO GI26 session: Organ Preservation for Gastroesophageal and Gastric Cancers: Ready for Primetime? Disclaimer: The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions. Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement. Follow today's speakers: Dr. Pedro Barata @PBarataMD Dr. Ugwuji Maduekwe @umaduekwemd Follow ASCO on social media: @ASCO on X (formerly Twitter) ASCO on Bluesky ASCO on Facebook ASCO on LinkedIn Disclosures: Dr. Pedro Barata: Stock and Other Ownership Interests: Luminate Medical Honoraria: UroToday Consulting or Advisory Role: Bayer, BMS, Pfizer, EMD Serono, Eisai, Caris Life Sciences, AstraZeneca, Exelixis, AVEO, Merck, Ipson, Astellas Medivation, Novartis, Dendreon Speakers' Bureau: AstraZeneca, Merck, Caris Life Sciences, Bayer, Pfizer/Astellas Research Funding (Inst.): Exelixis, Blue Earth, AVEO, Pfizer, Merck Dr. Ugwuji Maduekwe: Leadership: Medica Health Research Funding: Cigna
Today on the Gist, contextualizing Donald Trump's "wrong and crazy" proposal to nationalize elections, arguing that while the rhetoric is alarming, the Constitution makes it impossible to execute. Then Conor Heffernan, author of When Fitness Went Global, joins the show to discuss the history of "physical culture," explaining why he lifts heavy stones in graveyards and how the first fitness influencer, Eugen Sandow, shifted the world from functional strength to pure aesthetics—while selling a few bogus dumbbells along the way. And in the Spiel, Mike analyzes the recent FBI raid in Georgia, arguing that Trump's attempt to weaponize the DOJ to prove a stolen election will likely backfire by highlighting his biggest political liability. Produced by Corey Wara Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
During an appearance on The Gist with Mike Pesca, we discussed the curious backstory of, you guessed it, the word gist. X: @lexiconvalleyFacebook: facebook.com/LexiconValleyWebsite: booksmartstudios.com/LexiconValley Learn more about your ad choices. Visit megaphone.fm/adchoices
Former EuroLeague standout James Gist joins The Benas Podcast to talk honestly about life after pro basketball, chasing the NBA dream, and preparing for basketball retirement.Drafted by the San Antonio Spurs and stashed in Europe, James built a high-level career with elite clubs like Partizan and Panathinaikos, winning titles across Europe. He shares what it was like balancing NBA aspirations while fully committing to a professional career overseas — and why mentorship played a key role in his development.James also opens up about his transition into coaching high school players, passing on lessons from his career, and helping the next generation prepare for life both on and off the court. This episode offers valuable insight for players and coaches thinking about retirement and what comes next after basketball.Topics:00:00 Intro1:00 Rookie in Europe & mentorship9:55 NBA dreams19:10 Fan bases & Cultures33:20 Euro coaching vs US coaching40:20 ProBallers.com45:15 Retirement Process & Identity52:15 Next Generation Mindset1:01:40 Unlearning habits1:05:15 New realizations as a coach1:16:10 ATOs
Huge if true...it's a new episode of Confessions with Alexei Toliopoulos & Mish Wittrup. And live shows are happening too...so have a look below... Sammy's live special: watch here Full video: watch here Follow Mish: here Follow Alexei: here Follow Sammy on instagram & threads: here Follow Confessions: here See omnystudio.com/listener for privacy information.
Today on The Gist, Mike explains why he won't be watching Netflix's Skyscraper Live, arguing that Alex Honnold's latest stunt is an "attractive nuisance" that plays on our darkest voyeuristic instincts rather than the Olympic ideal. Then, New York Times reporter Kenneth Vogel joins the show to discuss his book Devil's Advocates. He breaks down the "sh*tbag business" of foreign lobbying, covering Paul Manafort's pioneering work with dictators, Rudy Giuliani's "security consulting" hustle, and the very real legal exposure facing Hunter Biden. Produced by Corey Wara Coordinated by Lya Yanne Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
Today on The Gist, a look at Donald Trump's plan to cap credit card interest rates at 10%—a populist move that might actually rob the poor to pay for the rich man's travel perks. Then, former CIA analyst and The Rest Is Classified co-host David McCloskey discusses his new novel, The Persian. He explains how real-world Mossad operations inside Iran are so "insane" they don't even need to be exaggerated for fiction, from remote-controlled machine guns to the devastating pager attack that crippled Hezbollah's command and control. He also breaks down the "unlikely but plausible" tradecraft used in the Israel-Iran shadow war and why the U.S. organizational and legal structure wouldn't—or couldn't—pull off the same stunts. Produced by Corey Wara Coordinated by Lya Yanne Video and Social Media by Geoff Craig Do you have questions or comments, or just want to say hello? Email us at thegist@mikepesca.com For full Pesca content and updates, check out our website at https://www.mikepesca.com/ For ad-free content or to become a Pesca Plus subscriber, check out https://subscribe.mikepesca.com/ For Mike's daily takes on Substack, subscribe to The Gist List https://mikepesca.substack.com/ Follow us on Social Media: YouTube https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Instagram https://www.instagram.com/pescagist/ X https://x.com/pescami TikTok https://www.tiktok.com/@pescagist To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist
Send us a textIn this episode, we discuss an approach to gastrointestinal stromal tumor, with a focus on its physiology, work-up, and management. Written by: Dr. Lotus Alphonsus. Reviewed by: Dr. Gary May. Support the show
We're back from the holiday break! (Sort of.) This interview with the inimitable Mike Pesca was recorded on Boxing Day and released right away to paying subscribers. Now it's available to everyone. Host of The Gist and author of the newsletters Pesca Profundities and The Gist List, Mike has turned the humble "bonus segment" into a multi-level rmarketing scheme multi-tiered pricing philosophy. How does he do it? We'll find out! We also talk about the hardest part of the creator economy (discovery), the incentives that reward martyrdom and outrage, and, most of all, Mike's December 26 Substack post No One's Nice To Bari Weiss. The CBS News editor-in-chief has been all over the headlines this past week after spiking delaying a 60 Minutes segment on CECOT, the notorious El Salvador terrorist prison, that was on the cusp of airing. Is it because the segment needed to "move beyond the forty-yard lines?" Or is something else going on? Also: a discussion on a mega-viral Compact article about systemic discrimination against white millennial men, a cry against Hamilton erasure, and why my lack of grip strength is more than made up for by my alarmingly hyperextensive fingers.
Mike Pesca digs into the vault for two 2017 interviews exploring the "ground game" of the New York stand-up scene and the "ad hominem screech" of early outrage culture. Dan Soder discusses his transition from a hard-drinking youth to a maturity fueled by caffeine and cannabis, admitting that his iconic Russian accent bit remains the "Free Bird" closer he can't quite escape. Meanwhile, Moshe Kasher dissects the launch of his series Problematic and the shallowing of the American brain, arguing that a comedian's primary duty is the "primacy of laughter" rather than social activism. Along the way: why Arizona rain smells like "hot nails" and how lighting a cigarette at night acts as a lighthouse for the mentally ill. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Rosebud Baker explains why motherhood is the most political act of her life and how she handles breastfeeding pressure by claiming she's "raising her daughter autistic" with formula and vaccines. The SNL writer joins Mike Pesca to discuss her transition from the "joke-heavy" homework of her first special to the conversational honesty of Motherlode, while detailing her process of churning out 50 headlines a day for Weekend Update. Along the way: the "embarrassing" ego of Elon Musk's comedy crusade, the legacy of her grandfather James Baker, and the dolphin-riding photo that finally convinced her comedian husband to get a hair transplant. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Comedian Robby Hoffman explains why she treats complaining as "enjoying"—and why her Depression-era instincts make her shakier during good times than disasters. Her approach to stand-up is visceral rather than cerebral: she doesn't remember the bit about the woman closing the airplane bathroom door, she replays the movie and watches her body operate on its own. Along the way: memories of growing up with nine siblings in Montreal poverty, where conflict wasn't optional ("we didn't get to not know anything"), the nightstand intervention that changed her brother Schnaer's life, and why she keeps a crisp $100 bill in her wallet like Depression-era insurance. Plus, the greatest taxonomy of social fakery ever delivered by a lesbian comedian—a warning that "being offended isn't that bad" and people who put "kind" in their Twitter bios are statistically suspect. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Oxford-educated archaeology student turned freestyle sensation Chris Turner joins Mike Pesca to explain how his "British period" of deadpan one-liners evolved into the show-stopping rap flow that now defines his Comedy Cellar sets. Turner discusses the "evolutionary advantage" of not knowing the rules of hip hop as a ten-year-old in Manchester—a blissful ignorance that convinced him freestyling was just "making up a story"—and how he uses those same instincts to neutralize hecklers today. Along the way: a masterclass in the "tennis match" of flow state, the absurdity of 50 Cent's car-based fax machine, and a spontaneous freestyle that weaves together Jerry Springer, RFK Jr., and the "Antilles heel" of Hispaniola. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Michelle Buteau explains why she is the "achievable Beyonce" for government workers and how her history editing grim news footage at WNBC led her to a record-breaking comedy career. Her new special, A Beautiful Mind, marks her as the first woman of color to headline Radio City Music Hall—a feat she attributes to the same grit that carried her through five years of IVF and "weird needles" at TSA. Along the way: the "dangerous" trend of punching down in comedy, the specific anxiety of visiting a Bronx reptile sanctuary while high on an edible, and the culture shock of a Dutch husband who still defends the practicality of wooden clogs. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Actor and comedian T.J. Miller explains why a traumatic brain injury is his improvisational "cheat code"—and how a 2010 surgery for an arteriovenous malformation (AVM) in his right frontal lobe fueled a career of manic chaos. Miller discusses the "invisible disability" of brain surgery and the high-stakes gamble of a 10% fatality rate. Along the way: a tour of city mottos, from the low-bar honesty of Toledo to the bizarre promise that Auburn, Washington is "more than you imagined." Plus, a look at the "Bulgarian" financial ecosystem of Fort Wayne, Indiana, where a three-bedroom house costs $485 a month. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Mike unlocks two interviews from the vault featuring comics who navigate the cultural minefield with very different styles. First, Sarah Silverman discusses her evolution from "arrogant ignoramus" character comedy to earnest podcasting, reflecting on her blackface controversy, her embrace of the "Bernie bro" label, and why she believes being wrong never feels shitty if you're willing to learn. Then, Kyle Kinane joins to talk about his special Loose in Chicago, the specific pain of being a Cubs fan (pre-World Series win), and his low-stakes conspiracy theories about Trader Joe's parking lots. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
In this special holiday week episode, Mike sits down with comedian Alex Edelman, fresh off a Tony Award for his show Just For Us and a spot on the Time 100 list. They discuss the "liquid dynamics" of a Comedy Cellar audience, the art of bombing while testing new material, and why jokes about the Israel-Gaza conflict are the hardest tightrope in comedy right now. Edelman explains why comedy thrives in doubt rather than certainty, how he uses "invisible pillars" to structure a narrative, and why he believes a joke should be "conversant with the moment, not beholden to it." Plus, Mike offers a critique of the mockumentary format glut in modern sitcoms. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
In this special Christmas Day edition, Mike gives the gift of Roy Wood Jr., a comedian who embodies the "profundities in punchlines" ethos. Wood joins to discuss his CNN show Have I Got News for You, his upbringing as the son of a pioneering radio journalist, and the central thesis of his comedy: that in a fractured world, people prioritize dopamine over truth. They debate whether political comedy has devolved into mere applause lines, why comedians are the new op-ed writers, and the delicate art of crafting a joke about police reform that actually lands with everyone. Plus, Mike explains why you need a "Christmas Eve" song if you want your novelty hit to last. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
In a special Christmas Eve edition, Mike brings you a "gift" from the comedy vault: an interview with the brilliantly off-kilter Django Gold. A veteran of The Late Show with Stephen Colbert and The Onion, Gold discusses his YouTube special Bag of Tricks and his commitment to playing a paranoid, morose character on stage—a persona he claims is "closer to who I really am" than any bubbly crowd-pleaser. They dissect the mechanics of anti-humor, the joy of "uncomfortable staring," and why Gold believes the best comedy leaves the audience "a little dimly lit." Plus, Mike muses on the specific genius of "Christmas Eve" songs versus generic holiday tracks. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
"Who will buy my smelly panties?" A woman realizes that it would be a waste to just wash them. A married man in an open relationship wishes his wife would be as affectionate as his lovers. On the Magnum, it's everybody's favorite guy who knows things about sports...Mike Pesca! (Host and creator of The Gist, the longest running daily news and analysis podcast, and the author of Upon Further Review: The Greatest What-Ifs In Sports History.) Dan and Mike go over the particulars of the steamy Canadian show "Heated Rivalry" to determine how closely it hews to the sport called "hockey." And, a gay man is tempted to sleep with guys who are in monogamous relationships. He wants to be a "gay's gay"- a good upstanding gay. Not some home-wrecking gay. But he also would very much like to sleep with these lads...will Dan advise him to listen to the angel or the devil on his shoulder? This episode is brought to you by Squarespace. They make it easy to build a website or blog. Give it a whirl at Squarespace.com/Savage and if you want to buy it, use the code Savage for a 10% off your first purchase. This episode is brought to you by Feeld, a dating app where the open-minded can meet the like-minded. Download Feeld on the App Store or Google Play. This episode is brought to you by Mars Men- supplements that support healthy levels of testosterone. For a limited time, Lovecast listeners get 60% off for life AND 2 free gifts when you use the code Savage at MenGoToMars.com. Dan Savage is a sex-advice columnist, podcaster, author, and creator of the It Gets Better Project. From ethical non-monogamy to unethical non-monogamy, cuckolding to crossdressing and with a dose of progressive politics, Dan Savage is a cultural force for sex positivity, when we most need it.
Thomas Chatterton Williams joins to discuss his new book, The Summer of Our Discontent: The Age of Certainty and the Demise of Discourse. He argues that the racial reckoning of 2020 was not an inevitable tide of history but a perfect storm of pandemic isolation, polarizing politics, and institutional failure. TCW dissects how mainstream institutions—from the New York Times to the Philadelphia Inquirer—abandoned objectivity for "moral clarity," and how misinformation about cases like Jacob Blake fueled a cycle of violence in Kenosha. Mike and Thomas debate whether the Left's introspection is necessary to defeat the "worse" impulses of the MAGA Right, or if it just alienates the base. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Quico Toro joins to discuss Charlatans: How Grifters, Swindlers, and Hucksters Bamboozle the Media, the Markets, and the Masses, distinguishing the "parasitic" nature of the charlatan from the hit-and-run tactics of the scammer. He traces the lineage of the grift from the official alchemists of 16th-century Venice to the upsell tactics of Trump University, arguing that loneliness and the internet have created a "target-rich environment" for swindlers. Then, a pivot to the environment: Mike and Quico debate whether the "green halo" around solar and wind constitutes its own form of elite misinformation, and why the villainization of nuclear energy—and the partisanship of climate policy—has stalled real progress. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
In light of the recent tragedy, Mike unlocks a 2016 interview with the late Rob Reiner. It is a conversation that now plays differently: Reiner discusses his film Being Charlie, which was written by his son Nick Reiner—the man now arrested in connection with his death. Mike reflects on the director's legacy, the eerie prescience of their discussion on addiction and family, and the President's disparagement of the deceased. Then, The Spiel turns to the Compact magazine essay by Jacob Savage on the "vanishing" white male in cultural industries. Mike parses the statistics—from Ivy League hiring to MacArthur Grants—to ask if the corrective pendulum has swung too far. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Comedian Jay Jurden explains why nine years of theater training is his "superpower" on the stand-up stage—and why he treats every punchline like a line of dialogue rather than a personal diary entry. His new special, Yes Ma'am, argues that physical specificity (from "rolling a wheelchair into affordable housing" to Marjorie Taylor Greene's hooves) is what separates a 300-level performer from a novice looking at their shoes. Along the way: memories of growing up in Canton, Mississippi, where movie sets for A Time to Kill. Plus, the greatest college football analogy ever delivered by a gay comedian—a warning against "scrambling" for viral crowd work instead of sticking to the designed play. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Neuroscientist Nicholas Wright explains why big powers "lose" wars they dominate on the kill ratio—and why counterinsurgencies (Vietnam, Afghanistan, maybe Iraq) reliably punish the side with less at stake. His new book, Warhead: How the Brain Shapes War and War Shapes the Brain, argues that identity, surprise, and revenge are ancient brain features, while metacognition—the mind watching itself—can be the thin guardrail against strategic self-harm. Along the way: post-1945 German polling as a reminder that political "reconstruction" happens on a years-long timetable, not on an American attention span. Plus, a Trump "warrior dividend" of $1,776 per service member—tariffs funding patriotism, one numerology check at a time. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Clyburn discusses The First Eight: A Personal History of the Pioneering Black Congressmen Who Shaped a Nation, explaining how Reconstruction-era Black lawmakers navigated power, compromise, and backlash—and why their choices still resonate. He reflects on faith as action, not rhetoric, and on history as a guide rather than a museum piece. Plus: Maryland lawmakers override Gov. Wes Moore's veto of a reparations study, and The Spiel turns to a new report on how white men have been squeezed out of cultural institutions—and what that shift means. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Russian journalist in exile Mikhail Zygar traces an information system so sealed even Gorbachev couldn't get the facts in The Dark Side of the Earth: Russia's Short-Lived Victory Over Totalitarianism. He draws a straight psychological line from late-Soviet overload to our current tech-firehose, arguing humans don't change much; institutions do (and the Soviet Union didn't have many worthy of the name). Plus: a quote-counting tour through Chris Whipple's Vanity Fair Susie Wiles interviews: "an alcoholic's personality," "conspiracy theorist," "ketamine user," "right-wing absolute zealot." Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Data journalist Chris Dalla Riva brings charts, facts, and plenty of fight to Uncharted Territory: What Numbers Tell Us About the Biggest Hit Songs and Ourselves, a tour through every Billboard Hot 100 #1 and the strange incentives that pick our "popular." They debate whether streaming makes the charts more accurate or just more boring—why Christmas songs now squat in the Top 10, why covers almost always slow songs down, and what the early "wilderness years" of the Hot 100 were missing. There's also a detour into the power of platform kings (hello, Sean Parker) and how a playlist can turn "Royals" into destiny. Plus: Trump's ghoulish Rob Reiner post, a reminder of Reiner's unreal directing run, and a weekend that managed to be both pointless and ugly. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
In this special Saturday edition, Mike sits down with Daniel Oppenheimer of Eminent Americans to tackle a high-stakes question: Who is worthy of the Fresh Air throne? They dissect the craft of interviewing, critique the "unprepared celebrity" podcast trend, and evaluate potential successors ranging from Colin McEnroe to Jon Ronson. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Shadi Hamid joins to discuss his new book, The Case for American Power, arguing that progressives' retreat from global engagement is a mistake. He contends that while the Left often views U.S. hegemony as intrinsically immoral—citing the legacy of Iraq and the tragedy in Gaza—the alternative of withdrawal often leads to greater atrocities, such as the unchecked devastation in Syria. Hamid makes the case that moral righteousness without power is toothless, and that ceding the global stage to bad actors or rival superpowers creates a more dangerous world. Plus, Mike critiques the Sunday show trend of grilling Treasury Secretary Scott Bessent on the price of bananas and Tonka trucks, arguing that "gotcha" questions about specific items ignore the reality of inflation as a composite number. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
Anthony Weiner and John Ketcham break down a Congress being flayed by its own fringes, where the "crazies" sometimes deliver the sharpest institutional critiques. They then assess Pete Hegseth and the possible release video of a lethal Caribbean boat strike, the challenges reshaping New York politics, and what it really means to govern a city you once nearly ran. Goat Grinders takes on Waymo running over a dog , taxing pet food and fare-evasion crackdowns. Produced by Corey Wara Email us at thegist@mikepesca.com To advertise on the show, contact ad-sales@libsyn.com or visit https://advertising.libsyn.com/TheGist Subscribe to The Gist: https://subscribe.mikepesca.com/ Subscribe to The Gist Youtube Page: https://www.youtube.com/channel/UC4_bh0wHgk2YfpKf4rg40_g Subscribe to The Gist Instagram Page: GIST INSTAGRAM Follow The Gist List at: Pesca Profundities | Mike Pesca | Substack
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