Investigation of the Lack of Angiogenesis in the Formation of Lymph Node Metastases

Jeong, Han-Sin,Jones, Dennis,Liao, Shan,Wattson, Daniel A.,Cui, Cheryl H.,Duda, Dan G.,Willett, Christopher G.,Jain, Rakesh K.,Padera, Timothy P. U.S. Dept. of Health, Education, and Welfare, Publ 2015 Journal of the National Cancer Institute Vol.107 No.9

<P><B>Background:</B></P><P>To date, antiangiogenic therapy has failed to improve overall survival in cancer patients when used in the adjuvant setting (local-regional disease with no detectable systemic metastasis). The presence of lymph node metastases worsens prognosis, however their reliance on angiogenesis for growth has not been reported.</P><P><B>Methods:</B></P><P>Here, we introduce a novel chronic lymph node window (CLNW) model to facilitate new discoveries in the growth and spread of lymph node metastases. We use the CLNW in multiple models of spontaneous lymphatic metastases in mice to study the vasculature of metastatic lymph nodes (n = 9–12). We further test our results in patient samples (n = 20 colon cancer patients; n = 20 head and neck cancer patients). Finally, we test the ability of antiangiogenic therapy to inhibit metastatic growth in the CLNW. All statistical tests were two-sided.</P><P><B>Results:</B></P><P>Using the CLNW, we reveal the surprising lack of sprouting angiogenesis during metastatic growth, despite the presence of hypoxia in some lesions. Treatment with two different antiangiogenic therapies showed no effect on the growth or vascular density of lymph node metastases (day 10: untreated mean = 1.2%, 95% confidence interval [CI] = 0.7% to 1.7%; control mean = 0.7%, 95% CI = 0.1% to 1.3%; DC101 mean = 0.4%, 95% CI = 0.0% to 3.3%; sunitinib mean = 0.5%, 95% CI = 0.0% to 1.0%, analysis of variance <I>P</I> = .34). We confirmed these findings in clinical specimens, including the lack of reduction in blood vessel density in lymph node metastases in patients treated with bevacizumab (no bevacizumab group mean = 257 vessels/mm<SUP>2</SUP>, 95% CI = 149 to 365 vessels/mm<SUP>2</SUP>; bevacizumab group mean = 327 vessels/mm<SUP>2</SUP>, 95% CI = 140 to 514 vessels/mm<SUP>2</SUP>, <I>P</I> = .78).</P><P><B>Conclusion:</B></P><P>We provide preclinical and clinical evidence that sprouting angiogenesis does not occur during the growth of lymph node metastases, and thus reveals a new mechanism of treatment resistance to antiangiogenic therapy in adjuvant settings. The targets of clinically approved angiogenesis inhibitors are not active during early cancer progression in the lymph node, suggesting that inhibitors of sprouting angiogenesis as a class will not be effective in treating lymph node metastases.</P>

Endometrial fluid associated with Essure implants placed before in vitro fertilization: Considerations for patient counseling and surgical management

Sills, E Scott,Walsh, David J,Jones, Christopher A,Wood, Samuel H The Korean Society for Reproductive Medicine 2015 Clinical and Experimental Reproductive Medicine Vol.42 No.3

Essure (Bayer) received approval from the U.S. Food and Drugs Administration as a permanent non-hormonal contraceptive implant in November 2002. While the use of Essure in the management of hydrosalpinx prior to in vitro fertilization (IVF) remains off-label, it has been used specifically for this purpose since at least 2007. Although most published reports on Essure placement before IVF have been reassuring, clinical experience remains limited, and no randomized studies have demonstrated the safety or efficacy of Essure in this context. In fact, no published guidelines deal with patient selection or counseling regarding the Essure procedure specifically in the context of IVF. Although Essure is an irreversible birth control option, some patients request the surgical removal of the implants for various reasons. While these patients could eventually undergo hysterectomy, at present no standardized technique exists for simple Essure removal with conservation of the uterus. This article emphasizes new aspects of the Essure procedure, as we describe the first known association between the placement of Essure implants and the subsequent development of fluid within the uterine cavity, which resolved after the surgical removal of both devices.

Contraceptive failure after hysteroscopic sterilization: Analysis of clinical and demographic data from 103 unplanned pregnancies

( E. Scott Sills ),( Xiang Li ),( Christopher A. Jones ),( Samuel H. Wood ) 대한산부인과학회 2015 Obstetrics & Gynecology Science Vol.58 No.6

Objective This investigation examined data on unplanned pregnancies following hysteroscopic sterilization (HS). Methods A confidential questionnaire was used to collect data from women with medically confirmed pregnancy (n=103) registered after undergoing HS. Results Mean (±SD) patient age and body mass index (BMI) were 29.5±4.6 years and 27.7±6.1 kg/m2, respectively. Peak pregnancy incidence was reported at 10 months after HS, although <3% of unplanned pregnancies occurred within the first three months following HS. Mean (±SD) interval between HS and pregnancy was 19.6±14.9 (range, 2 to 84) months. Patients age ≥30 years and BMI <25 reported conception after HS somewhat sooner than younger patients, although the differences in time to pregnancy were not significant (P=0.24 and 0.09, respectively). The recommended post-HS hysterosalpingogram (to confirm proper placement and bilateral tubal occlusion) was obtained by 66% (68/103) of respondents. Conclusion This report is the first to provide patient-derived data on contraceptive failures after HS. While adherence to backup contraception 3 months after HS can be poor, many unintended pregnancies with HS occur long after the interval when alternate contraceptive is required. Many patients who obtain HS appear to ignore the manufacturer’s guidance regarding the post-procedure hysterosalpingogram to confirm proper device placement, although limited insurance coverage likely contributes to this problem. The greatest number of unplanned pregnancies occurred 10 months after HS, but some unplanned pregnancies were reported up to 7 years later. Age, BMI, or surgical history are unlikely to predict contraceptive failure with HS. Further follow-up studies are planned to capture additional data on this issue.

Role of the Wada test and functional magnetic resonance imaging in preoperative mapping of language and memory: two atypical cases

Połczyń,ska, Monika M.,Benjamin, Christopher F.A.,Moseley, Brian D.,Walshaw, Patricia,Eliashiv, Dawn,Vigil, Celia,Jones, Michael,Bookheimer, Susan Y. Informa UK (TaylorFrancis) 2015 Neurocase Vol.21 No.6

Analysis of surgeries performed after hysteroscopic sterilization as tabulated from 3,803 Essure patient experiences

E. Scott Sills,Xiang Li,Samuel H. Wood,Christopher A. Jones 대한산부인과학회 2017 Obstetrics & Gynecology Science Vol.60 No.3

ObjectiveAlthough previous research has suggested that risk for reoperation among hysteroscopic sterilization (HS) patients is more than ten times higher than for patients undergoing standard laparoscopic tubal ligation, little has been reported about these subsequent procedures. MethodsThis descriptive cohort study used a confidential online questionnaire to gather data from women (n=3,803) who volunteered information on HS followed by device removal surgery performed due to new symptoms developing after Essure placement. ResultsIn this sample, mean age was 35.6 years and women undergoing hysterectomy after HS comprised 64.9% (n=2,468). Median interval between HS and hysterectomy was 3.7 (interquartile range, 3.9) years and mean age at hysterectomy was 36.3 years. Some patients (n=1,035) sought removal of HS devices and fallopian tubes only, while other miscellaneous gynecological procedures were also occasionally performed for Essure-associated symptoms. When data from all patients who had any post-Essure surgery besides hysterectomy were aggregated (e.g., device removal + “other” cases, n=1,335) and compared to those cases undergoing hysterectomy, mean age was significantly lower than for the hysterectomy group (34.4 vs. 36.3 years, respectively; P<0.01); uterus-conserving surgeries were also typically performed significantly earlier than hysterectomy (P<0.01). ConclusionThis investigation is the first to characterize specific gynecological operations after Essure, and suggests that the predominant surgical answer to HS complaints is hysterectomy for many women. Dissatisfaction with HS may represent an important indication for hysterectomy and additional study is needed to quantify this phenomenon.