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Insulin resistance in ADT for prostate cancer
Reply to Herstein et al.
Interstitial Brachytherapy
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Jianlin Yuan, Surgeon Fourth Military Medical University, Weijun Qin, Yufeng Zhao
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qinweij{at}fmmu.edu.cn Jianlin Yuan, et al.
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Dear Editor: We read the review by Michaelson et al with great interest [1]. It gives detailed complications of prostate cancer treatment and is helpful for the improvement of prostate cancer treatment. However, we would like to point out that the discussion about insulin resistance as a complication of androgen-deprivation treatment (ADT) for prostate cancer patients is inaccurate. The authors referred to insulin resistance as a complication of ADT to prostate cancer patients according to the conclusion reported by Smith and Nathan [2]. However, the defects of the study done by Smith and Nathan made their conclusion that insulin resistance occurs during ADT in prostate cancer patients questionable. First, OGTT was used for the evaluation of insulin sensitivity, which, compared with the gold standard of insulin sensitivity test, the hyperinsulinemic euglycemic clamp [3], has inevitable limitations. The gold standard could be used as in this study the number of patients observed is only 25. Second, a group of prostate cancer patients with placebo treatment paralleling that of ADT treatment for 12 weeks is necessary. This parallel-group design will give the information of changes in parameters with the development of prostate cancer and minimizes the risk of drawing an inaccurate conclusion. Third, the data for fasting insulin levels is not accordant to the test of homogeneity of variances, but student t-test was used to examine the difference. It would be noted that student t-test is unreliable when variances among groups are significantly different. Therefore, the conclusion that insulin resistance occurs in ADT patients is questionable. The study in androgen receptor knockout (ARKO) mice indicated that late-onset obesity developed but insulin sensitivity did not change significantly under androgen deficiency [4]. Impartial discussion on the cited reference rather than direct citation without analysis should be adopted in the review, and thus an accurate conclusion can be drawn. Thank you, Weijun Qin, MD, PhD (1)
(1) Urology Department, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China; (2) Center of Experimental Teaching, Fourth Military Medical University, Xi'an, Shaanxi, China Correspondence to: Jianlin Yuan and Yufeng Zhao. References: 1. Michaelson MD, Cotter SE, Gargollo PC, Zietman AL, Dahl DM, Smith MR. Management of complications of prostate cancer treatment. CA Cancer J Clin 2008;58(4):196-213. 2. Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol & Metab 2006;91(4):1305-1308. 3. Monzillo LU, Hamdy O. Evaluation of insulin sensitivity in clinical practice and in research settings. Nutr Rev 2003 Dec;61(12):397-412. 4. Yanase T, Fan W, Kyoya K, Min L, Takayanagi R, Kato S, Nawata H. Androgens and metabolic syndrome: lessons from androgen receptor knock out (ARKO) mice. J Steroid Biochem Mol Biol 2008;109(3-5):254-7. |
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Ted Gansler, MD, MBA, Editor CA: A Cancer Journal for Clinicians
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ca.edoff{at}cancer.org Ted Gansler, MD, MBA
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Thanks so much for your e-Letter notifying us of the error in answer "c" to question 7 of the CME quiz for the article Management of Complications of Prostate Cancer Treatment by Michaelson et al. [1]. Michaelson et al. correctly state, "While occurring in less than 1% of patients, formation of a rectal fistula is a serious complication". Answer "c" should have read, "is associated with a <1% risk of rectal fistula formation". I apparently misplaced the "<" in writing the quiz and apologize for any confusion or inconvenience among readers who took this quiz prior to July 25, 2008, when we corrected this oversight. Thank you as well for the additional information in your letter regarding the incidence of rectal fistula following prostate brachytherapy.
Sincerely yours, References 1. Michaelson MD, Cotter SE, Gargollo PC, et al. Management of Complications of Prostate Cancer Treatment. CA Cancer J Clin 2008;58(4):196-213. |
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Paul Herstein, MD, Radiation Oncology Group Health Cooperative, Seattle, Kent Wallner, MD, Radiation Oncology, PS VA, U of WA, Group Health Cooperative, Seattle
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herstein.p{at}ghc.org Paul Herstein, MD, et al.
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Ted Gansler, MD, MBA Editor CA: A Cancer Journal for Clinicians 250 Williams Street NW Atlanta, GA
M. Dror Michaelson, MD Dear Drs Gansler and Michaelson, We read CA regularly and appreciate the breadth and quality of the reviews it provides. We find the quizzes helpful in reinforcing the main points made in the articles. However, we would like to call your attention to an inaccuracy in a current quiz: Management of Complications of Prostate Cancer Treatment, M Dror Michaelson, et al, Volume 58, Number 4, July/August 2008. The authors appropriately refer to rectal fistula as a "rare complication" of interstitial brachytherapy of the prostate (page 204, legend to Figure 3). Later they state, without providing a reference: "While occurring in less than 1% of patients, formation of a rectal fistula is a serious complication" (page 205).
Unfortunately, in the quiz associated with this article, they present the following question and maintain that "c" is the correct answer: Four series have been reported pertaining to rectal fistula incidence after interstitial brachytherapy (BT) with 125I or 103Pd, with or without external beam. (July 1994 - June 1999, U of Virginia) 765 patients received outpatient BT. Of the 754 patients with follow up, 640 patients received BT monotherapy, 69 patients received BT monotherapy as a boost after EBRT, and 45 patients received BT as salvage therapy. Seven rectal fistulas developed in 754 patients (1%) between 9 months and 12 months after treatment. Among patients who underwent salvage BT, 4 of 45 patients (8.8%) developed rectal fistulas. All six patients who developed fistulas in the context of combination BT/EBRT or salvage BT had biopsy of an anterior rectal lesion overlying the prostate [1]. (Jan 1997 - October 2002, Brigham and Women's Hospital and West Roxbury Veteran's Administration Hospital) 7 rectal-urethral fistulas developed from roughly 700 (1%) patients treated with prostate brachytherapy. Symptoms occurred at a mean of 27.3 months after brachytherapy. Previous TURP (28 %) and pelvic irradiation or external beam radiation therapy (14%) were not associated with increased risk of rectal-urethral fistula [2]. (September 1998 - October 2001, Seattle and West Virginia) 503 patients were treated with BT alone and had a minimum of 24 months of follow up. Rectal fistulas occurred in 2 patients (0.4%); both had received moderate rectal radiation doses and extensive intervention for rectal bleeding [3]. (1995 - 2003, Leeds, UK) 1455 patients were treated with prostate BT with or without external beam, including patients treated for salvage, at a single UK centre with at least 2 years of follow up. Recto-urethral fistula was identified in 3 (0.2%) patients, occurring at 19-27 months following BT. All these patients had BT monotherapy and had been investigated with endoscopy and low rectal biopsy [4]. Taken as a whole, these series suggest a declining incidence with improving dosimetry and implant technique (Figure 1). They also implicate invasive instrumentation of the irradiated rectum as causal in the development of fistulas. We believe the incidence of fistulization today is likely to be just a fraction of 1%, particularly if prostate and rectal doses are monitored carefully and post-implant intervention in the rectum is kept to an absolute minimum. Given the dread nature of this complication, a 1% risk of fistula might dissuade physicians from offering this treatment, and discourage patients from choosing it. At 0.2 to 0.4 percent fistula risk, brachytherapy may be perceived as substantially less frightening. 1. Theodorescu D, Gillenwater JY, Koutrouvelis PG. Prostatourethral-rectal fistula after prostate brachytherapy. Cancer 2000;89(10):2085-2091. 2. Shah SA, Cima RR, Benoit E, Breen EL, Bleday R. Rectal complications after prostate brachytherapy. Dis Colon Rectum 2004;47(9):1487-1492. Epub 2004 Aug 12. 3. Tran A, Wallner K, Merrick G, et al. Rectal fistulas after prostate brachytherapy. Int J Radiat Oncol Biol Phys 2005;63(1):150-154. 4. Shakespeare D, Mitchell DM, Carey BM, et al. Recto-urethral fistula following brachytherapy for localized prostate cancer. Colorectal Dis 2007;9(4):328-331.
Kent Wallner, MD
Paul Herstein, MD |
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