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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2007.08.055 Byline: Thomas J. Herzog (a), Bradley J. Monk (b) Keywords: cervical adenocarcinoma; cervical cancer; cervical screening; HPV; vaccine Abstract: Widespread use of the Papanicolaou test for the screening of cervical cancers has lead to a significant decline in overall incidence and mortality rates over the past 3 decades. When different histologic types of cervical cancers are considered and trends are reexamined, it becomes apparent that observed declines are reflective of squamous cell carcinomas predominantly; the rates for adenocarcinomas continue to rise. This rise in incidence may be due to the greater difficulty in screening for glandular precursor lesions that often arise high within the endocervical canal. Reducing the incidence and mortality rates that are associated with adenocarcinomas can be accomplished by using improved screening techniques and large-scale implementation of cervical cancer vaccines that target the predominant oncogenic human papillomavirus types that are associated with adenocarcinoma. Author Affiliation: (a) Columbia University, Irving Comprehensive Cancer Center, New York Presbyterian Hospital, New York, NY (b) Department of Gynecologic Oncology, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, CA Article History: Received 15 May 2007; Accepted 22 August 2007

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2006.01.039 Byline: Thomas J. Herzog (a), Robert L. Coleman (b), James P. Guerrieri (c), Kathie Gabriel (d), Wei Du (d), Lee Techner (d), John G. Fort (d), Bruce Wallin (d) Abstract: The purpose of this study was to investigate the safety and efficacy of alvimopan, a novel peripherally acting mu-opioid receptor antagonist, in patients who undergo simple total abdominal hysterectomy. Author Affiliation: (a) Columbia University, New York, NY (b) The University of Texas, M.D. Anderson Cancer Center, Houston, TX (c) Mentor, OH (d) Adolor Corporation, Exton, PA Article History: Received 21 September 2005; Revised 15 December 2005; Accepted 12 January 2006 Article Note: (footnote) Supported by Adolor Corporation (Exton, PA) and GlaxoSmithKline (Philadelphia, PA).

The safety and efficacy of alvimopan, a novel peripherally acting mu-opioid receptor antagonist, in patients who undergo simple total abdominal hysterectomy are investigated. Alvimopan has a safety profile that is similar to that of placebo and it has provided an improved lower gastrointestinal recovery in women who undergo simple total abdominal hysterectomy.

Byline: Thomas J. Herzog, Todd K. Horiuchi, Sybilann Williams, H.Marvin Camel, David G. Mutch Keywords: Granulocyte-macrophage colony-stimulating factor; gynecologic malignancies Abstract: OBJECTIVE: In spite of increased expression of granulocyte-macrophage colony-stimulating factor surface receptors on solid tumors, the growth modulatory effects of granulocyte-macrophage colony-stimulating factor have not been well defined in gynecologic malignancies. We assessed the in vitro growth effects of granulocyte-macrophage colony-stimulating factor on such cell lines. STUDY DESIGN: By use of a chromium 51 incorporation assay the in vitro growth effects of granulocyte-macrophage colony-stimulating factor on 12 cell lines derived from human malignancies were measured. RESULTS: No growth stimulatory or inhibitory effect was mediated by granulocyte-macrophage colony-stimulating factor on six cell lines, whereas three lines showed consistent but not statistically significant dose-dependent growth stimulation. There was, however, a statistically significant increase in growth of short duration in three other cell lines at clinically relevant doses of granulocyte-macrophage colony-stimulating factor. Fluorometric cell cycle analysis demonstrated no change in cell-cycle distribution. CONCLUSION: Within this in vitro system, stimulation of gynecologic malignancies in patients receiving granulocyte-macrophage colony-stimulating factor for mitigation of the myelosuppressive effects of cytotoxic chemotherapy does not appear to be widespread nor sustained beyond 48 hours. (AM J OBSTET GYNECOL 1996;174:161-8.) Author Affiliation: St. Louis, Missouri Article History: Received 11 October 1994; Revised 10 April 1995; Accepted 3 May 1995 Article Note: (footnote) [star] From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine., [star][star] Supported in part by an American Cancer Society Research Career Development Award (D.G.M.)., a Reprint requests: Thomas J. Herzog, MD, Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine, 4911 Barnes Hospital Plaza, St. Louis, MO 63110., aa 0002-9378/96 $5.00 + 0 6/1/66027

Byline: Edward R. Kost, Thomas J. Herzog, Lisa M. Adler, Sybilann Williams, David G. Mutch Keywords: Tumor necrosis factor receptor; ovarian cancer Abstract: OBJECTIVE: Our purpose was to define the expression of tumor necrosis factor receptors on ovarian cancer cells and determine what role these receptors play in tumor necrosis factor-[alpha] - mediated cytolysis. STUDY DESIGN: Cell surface expression of tumor necrosis factor-[alpha] receptors was determined on ovarian cancer cell lines Caov-3, SK-OV-3, NIH : OVCAR-3, and A2780 by a tumor necrosis factor-[alpha] binding assay that used iodine 125 - labeled tumor necrosis factor-[alpha]. Monoclonal antibodies specific for the 55 to 60 kd (TR60) and 75 to 80 kd (TR80) tumor necrosis factor receptors were used to determine the relative density of each receptor type. To elucidate which receptor(s) was responsible for mediating the signal for cytolysis, 24-hour MTT cytolytic assays that used tumor necrosis factor-[alpha] and emetine were performed in the presence or absence of receptor-specific monoclonal antibodies. RESULTS: The four ovarian cell lines expressed a similar number of surface receptors, 4500 to 7000 per cell, had similar dissociation constants, 0.3 to 0.6 nmol/L, and expressed predominately the TR60 receptor subtype. Receptor function studies showed that the presence of the monoclonal antibody to the TR60 receptor completely inhibited tumor necrosis factor-[alpha] - mediated cytolysis, whereas the monoclonal antibody to the TR80 receptor only partially blocked cytolysis. CONCLUSIONS: Ovarian cancer cell lines express both tumor necrosis factor receptors, with the TR60 receptor being the dominant subtype. Tumor necrosis factor-[alpha] - mediated cytolysis appears to be dependent on the presence of a functional TR60 receptor. The TR80 receptor does not appear requisite for cytolysis; however, a complementary role cannot be excluded. Manipulation of tumor necrosis factor receptor subtypes on ovarian cancer cells may enhance the cytotoxic effects, thus improving the therapeutic efficacy of tumor necrosis factor-[alpha]. (AM J OBSTET GYNECOL 1996;174:145-53.) Author Affiliation: St. Louis, Missouri Article History: Received 1 November 1994; Revised 18 April 1995; Accepted 21 April 1995 Article Note: (footnote) [star] From the Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Washington University School of Medicine., [star][star] Reprint requests: Edward R. Kost, MD, Washington University School of Medicine, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, 4911 Barnes Hospital Plaza, St. Louis, MO 63110., a 0002-9378/96 $5.00 + 0 6/1/65848

Background. Paclitaxel (Taxol, Bristol-Myers Squibb, Princeton, NJ) is a promising drug for the treatment of ovarian cancer. Exposure times and dose-response relationships should be explored to optimize future clinical applications of this drug. Methods. The cytotoxic effects of paclitaxel on four human ovarian cancer cell lines (Caov-3, SK-OV-3, NIH: OVCAR-3, and A2780) were analyzed using chromium-51 release assays and tetrazolium-based colorimetric assays. Cells were exposed to paclitaxel for 4 and 24 hours at concentrations ranging from [10.sup.-10] [-10.sup.-4] M. Two paclitaxel preparations were compared: paclitaxel in DMSO and paclitaxel in cremophor EL, the carrier used in pharmacologic preparations. Cell cycle analysis compared cells exposed to [10.sup.-5] M paclitaxel in dimethyl sulfoxide for 4 hours to those exposed for a hours. Results. No difference in cell proliferation was demonstrated after 4 hours of treatment when compared with a hours of treatment with paclitaxel in dimethyl sulfoxide at 24,48 and 72 hours after treatment in any of the cell lines tested, over all concentrations tested. When paclitaxel in cremophor was used, there was a significant decrease in cell proliferation only at [10.sup.-4] M of paclitaxel. Similar results were seen with [10.sup.-4] M equivalent concentration of the carrier alone. A cell cycle shift to G2/M was the same after 4 or 24 hours of exposure when assessed at a hours. Conclusions. A dose escalation from [10.sup.-10] to [10.sup.-4] M of paclitaxel in dimethyl sulfoxide did not inhibit cell proliferation significantly in any of these cell lines. Moreover, shorter exposure times did not appear to alter the cellular response to paclitaxel. Consequently, administration of smaller dosages over shorter time periods may not compromise the cytotoxic effect of this agent. Clinical studies must be performed to validate these observations. Cancer 1994;74:1891-8.

A retrospective review is undertaken to evaluate the feasibility and morbidity of cytoreductive surgery in the elderly. The results indicate that optimal cytoreduction to a largest tumor diameter of

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2010.01.059 Byline: Thomas J. Herzog (a), Thomas C. Krivak (b), Amanda Nickles Fader (c), Robert L. Coleman (d) Keywords: chemotherapy drug response marker; in vitro chemosensitivity testing; ovarian cancer; platinum-based chemotherapy Abstract: We sought to determine the association between tumor responses in vitro to platinum therapy by using the ChemoFx drug response marker and overall survival (OS) after first-line platinum-based chemotherapy in patients with advanced-stage primary ovarian cancer (POC). Author Affiliation: (a) Irving Comprehensive Cancer Center, New York-Presbyterian Hospital, Columbia University College of Physicians and Surgeons, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, New York, NY (b) Magee-Women's Hospital, University of Pittsburgh Medical Center, Pittsburgh, PA (c) Greater Baltimore Medical Center/Johns Hopkins Medical Institutions, Baltimore, MD (d) Department of Gynecologic Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX Article History: Received 9 June 2009; Revised 12 August 2009; Accepted 20 January 2010 Article Note: (footnote) This study was supported by Precision Therapeutics Inc, Pittsburgh, PA., Dr Krivak is a member of the speaker's bureau of Precision Therapeutics Inc. Drs Coleman and Herzog have served as consultants for Precision Therapeutics Inc., Cite this article as: Herzog TJ, Krivak TC, Fader AN, et al. Chemosensitivity testing with ChemoFx and overall survival in primary ovarian cancer. Am J Obstet Gynecol 2010;203:68.e1-6.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2009.12.016 Byline: G. Reza Jalali (a), Thomas J. Herzog (b), Bruce Dziura (c), Robert Walat (a), Michael W. Kilpatrick (a) Keywords: 3q gain; cervical cancer; cervical intraepithelial neoplasia; LSIL; negative predictive value Abstract: The chromosome 3q26 region is a biomarker for cervical cancer. Women with low-grade squamous intraepithelial lesions (LSIL) currently are referred for immediate colposcopy. The objective of this study was to determine the negative predictive value of the 3q26 amplification test for the persistence or regression of LSIL. Author Affiliation: (a) Ikonisys Inc, New Haven, CT (b) Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, College of Physicians and Surgeons, Columbia University, New York, NY (c) New England Pathology Associates, Mercy Medical Center, Springfield, MA Article History: Received 7 July 2009; Revised 14 October 2009; Accepted 15 December 2009 Article Note: (footnote) Authorship and contribution to the article is limited to the 5 authors indicated. There was no outside funding or technical assistance with the production of this article., Cite this article as: Jalali GR, Herzog TJ, Dziura B, et al. Amplification of the chromosome 3q26 region shows high negative predictive value for nonmalignant transformation of LSIL cytology. Am J Obstet Gynecol 2010;202:581.e1-5.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ajog.2009.06.015 Byline: Nisha Bansal (a), Thomas J. Herzog (a)(c), Richard E. Shaw (d), William M. Burke (a)(c), Israel Deutsch (b)(c), Jason D. Wright (a)(c) Keywords: cervical cancer; radiation; radical hysterectomy; SEER Abstract: We compared survival for women with early-stage cervical cancer who were treated with primary radiation or radical hysterectomy. Author Affiliation: (a) Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, NY (b) Department of Radiation Oncology, Columbia University College of Physicians and Surgeons, New York, NY (c) Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY (d) California Pacific Medical Center, San Francisco, CA Article History: Received 6 April 2009; Revised 18 May 2009; Accepted 5 June 2009 Article Note: (footnote) Cite this article as: Bansal N, Herzog TJ, Shaw RE, et al. Primary therapy for early-stage cervical cancer: radical hysterectomy vs radiation. Am J Obstet Gynecol 2009;201:485.e1-9. , Authorship and contribution to the article is limited to the 6 authors indicated. There was no outside funding or technical assistance with the production of this article.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2009.06.002 Byline: Thomas J. Herzog (a)(b), Nicanor I. Barrena Medel (c)(d) Abstract: This article has been removed: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article was withdrawn after being released to press but before final printing. Author Affiliation: (a) Division of Gynecologic Oncology, New York-Presbyterian Hospital/Columbia University Medical Center, New York, New York, USA (b) Department of Clinical Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York, USA (c) Columbia University Medical Center, New York, New York, USA (d) Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital Sotero del Rio, Santiago, Chile

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjmed.2009.06.002 Byline: Thomas J. Herzog (a)(b), Nicanor I. Barrena Medel (c)(d) Keywords: Adenocarcinoma; Cervical cancer; Human papillomavirus; Prophylactic vaccine; Squamous cell carcinoma Abstract: The 2 most common forms of cervical cancer are squamous cell carcinoma (SCC), arising from epithelial cells, and adenocarcinoma (AC), which arises from glandular cells. The substantial decline in overall cervical cancer incidence observed in the United States over the past half century primarily reflects declines in the incidence of SCC, which account for the large majority of cervical cancer cases. By contrast, there has been an increase in AC incidence in recent decades. Although cervical screening is effective in detecting SCC, glandular cytopathology is often overlooked, leading to later diagnoses of AC and poorer prognoses. Differences in etiology between SCC and AC include variation in the distribution of human papillomavirus (HPV) types present in respective neoplasias. HPV infection is a necessary cause of cervical cancer, and recently developed prophylactic HPV vaccines may be effective in reducing infection from common HPV types implicated in AC as well as SCC. This article reviews the etiology and progression of cervical cancer from epithelial and glandular origins, discusses the HPV types involved, and addresses primary and secondary forms of cervical cancer prevention. Author Affiliation: (a) Division of Gynecologic Oncology, New York-Presbyterian Hospital/Columbia University Medical Center, New York, New York, USA (b) Department of Clinical Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons, New York, New York, USA (c) Columbia University Medical Center, New York, New York, USA (d) Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital Sotero del Rio, Santiago, Chile Article Note: (footnote) Statement of author disclosure: Please see the Author Disclosures section at the end of this article.