James Lipton, the actor-turned-teacher and interviewer of actors, has died at the age of 93. According to his wife, Kedakai Mercedes Lipton, the cause of death was bladder cancer.
Lipton, who hosted the Emmy-winning Bravo show "Inside the Actor's Studio" for 23 years, was known for his extensive pre-interview preparation (notated on a large stack of blue note cards) and sympathetic attitude. He also centered his questions on the craft of the artist and not on gossip. The formula worked well, as he was often able to win the trust of his famous guests who then revealed intimate and sometimes unexpected things about themselves. Among the over 300 guests he interviewed were Hollywood stars including Paul Newman, Alec Baldwin, Sally Field, and Meryl Streep, directors Sidney Lumet and Francis Ford Coppola, and comedians Robin Williams, Dave Chappelle, and Will Farrell (who did an infamous impersonation of Lipton on "Saturday Night Live").
The show was filmed in front of an audience which consisted of students of the . It often went on for several hours, which was edited down to 1 hour for the TV series. The format came full circle, when one of those former students, , was himself interviewed by Lipton.
At the end of each interview, Lipton asked his guest a series of 10 questions (originated by French television personality ). The last question was always: "If heaven exists, what would you like to hear God say when you arrive at the pearly gates?" In a 2012 , Lipton, an atheist, gave his own answer to the question: "You see, Jim? You were wrong. I exist ... But you may come in anyway."
Bladder Cancer
Bladder cancer is the sixth most common cancer in the United States after lung cancer, prostate cancer, breast cancer, colon cancer, and lymphoma. It is the third most common cancer in men and the eleventh most common cancer in women. Of the roughly 70,000 new cases annually, about 53,000 are in men and about 18,000 are in women. Of the roughly 15,000 annual deaths, more than 10,000 are in men and fewer than 5,000 are in women. The reasons for this disparity between the sexes are not well understood.
According to the national SEER registry, 2020 will see an estimated 81,400 new cases and 17,980 deaths from bladder cancer.
Histopathology
Under normal conditions, the bladder, the lower part of the kidneys (the renal pelvises), the ureters, and the proximal urethra are lined with a specialized mucous membrane referred to as transitional epithelium (also called urothelium). Most cancers that form in these tissues are transitional cell carcinomas. These tumors can be either low- or high-grade.
- Low-grade bladder cancer often recurs in the bladder after treatment but rarely invades the muscular wall of the bladder or spreads to other parts of the body. Patients rarely die from low-grade bladder cancer.
- High-grade bladder cancer commonly recurs in the bladder and has a strong tendency to invade the muscular wall of the bladder and spread to other parts of the body. High-grade bladder cancer is treated more aggressively than low-grade bladder cancer and is much more likely to result in death. Almost all deaths from bladder cancer result from high-grade disease.
Bladder cancer is also divided into muscle-invasive and nonmuscle-invasive disease, based on invasion of the muscularis propria (also referred to as the detrusor muscle), which is the thick muscle deep in the bladder wall. Muscle-invasive disease (MIBC) is much more likely to spread to other parts of the body and is generally treated by either removing the bladder or treating the bladder with radiation and chemotherapy. Nonmuscle-invasive disease (NMIBC) can often be treated by removing the tumor(s) via a transurethral approach. Sometimes chemotherapy or other treatments are introduced into the bladder with a catheter to help fight the cancer. NMIBC is the most common type of bladder cancer.
Risk Factors
Increasing age is the most important risk factor for most cancers. In addition, there is strong evidence linking exposure to carcinogens to bladder cancer. The most common risk factor for bladder cancer in the United States is cigarette smoking. It is estimated that up to half of all bladder cancers are caused by cigarette smoking and that smoking increases a person's risk of bladder cancer two to four times above baseline risk.
Certain occupational exposures have also been linked to bladder cancer, and higher rates of bladder cancer have been reported in textile dye and rubber tire industries; among painters; leather workers; shoemakers; and aluminum-, iron-, and steelworkers. Specific chemicals linked to bladder carcinogenesis include beta-naphthylamine, 4-aminobiphenyl, and benzidine. Although these chemicals are now generally banned in Western countries, many other chemicals still in use are also suspected of causing bladder cancer.
Genetics also play a role in bladder cancer. Somatic mutations in the , , , and genes are common in bladder cancers. Each of these genes plays a critical role in regulating gene activity and cell growth. Additionally, deletions of part or all of chromosome 9 are commonly found in bladder cancer, particularly in NMIBC.
Clinical Features
Bladder cancer typically presents with gross or microscopic hematuria. Less commonly, patients may complain of urinary frequency, nocturia, and dysuria, symptoms that are more common in patients with carcinoma in situ. Patients with upper urinary tract urothelial carcinomas may present with pain resulting from obstruction by the tumor.
Treatment
NMIBC
Treatment of NMIBCs (Ta, Tis, T1) is based on risk stratification. Essentially all patients are initially treated with a transurethral resection of the bladder tumor followed by a single immediate instillation of intravesical chemotherapy (mitomycin C is typically used in the United States).
Subsequent therapy after the treatment above is based on risk and typically consists of one of the following:
- Surveillance for relapse or recurrence (typically used for tumors with low risk of recurrence or progression).
- A minimum of 1 year of intravesical treatments with BCG (Bacille Calmette-Guérin) plus surveillance for relapse (typically used for tumors at intermediate or high risk of progression to muscle-invasive disease).
- Additional intravesical chemotherapy (typically used for tumors with a high risk of recurrence but low risk of progression to muscle-invasive disease).
Muscle-Invasive and Metastatic Bladder Cancer
Standard treatment for patients with MIBCs whose goal is cure is either neoadjuvant multiagent cisplatin-based chemotherapy followed by radical cystectomy and urinary diversion or radiation therapy with concomitant chemotherapy. Other treatment approaches include the following:
- Radical cystectomy followed by multiagent cisplatin-based chemotherapy.
- Radical cystectomy without perioperative chemotherapy.
- Radiation therapy without concomitant chemotherapy.
- Partial cystectomy with or without perioperative chemotherapy.
In May 2016, the FDA approved a breakthrough immunotherapy for locally advanced or metastatic urothelial carcinoma, (Tecentriq), a drug that inhibits the PD-1/PD-L1 receptor interaction. Since that time, two additional treatments have been approved:
- (Balversa) is a targeted therapy, used for patients whose tumors have particular alterations in one of the four genes encoding fibroblast growth factor receptors.
- (Padcev) is an antibody-drug conjugate. The antibody component is directed against nectin-4, a cell adhesion molecule highly expressed on urothelial cancer cells. The drug component is a microtubule inhibitor known as MMAE (monomethyl auristatin E) that inhibits cell division by blocking polymerization of tubulin. MMAE is released once the antibody-drug conjugate is internalized.
Additional drugs are currently undergoing .
Sources: ,
Michele R. Berman, MD, and Mark S. Boguski, MD, PhD, are a wife and husband team of physicians who have trained and taught at some of the top medical schools in the country, including Harvard, Johns Hopkins, and Washington University in St. Louis. Their mission is both a journalistic and educational one: to report on common diseases affecting uncommon people and summarize the evidence-based medicine behind the headlines.