Influences of total laparoscopic hysterectomy according to body mass index (underweight, normal weight, overweight, or obese)

Study Objective: The aim of this study is to evaluate the effect of body mass index (BMI) on laparoscopic hysterectomy outcomes. Design: This was retrospective study. Setting: Minoh City Hospital, Japan. Materials and Methods: Between January 1, 2014, and June 30, 2017, 183 patients underwent total laparoscopic hysterectomy (TLH) at our institution. Intervention: Patients who underwent TLH were grouped according to BMI, as follows: underweight group (BMI <18.5 kg/m2), normal-weight group (18.5 ≤BMI <25 kg/m2), overweight group (25 ≤BMI <30 kg/m2), and obese group (BMI ≥30 kg/m2). Measurements and Main Results: Information on patients' clinical characteristics and surgical results were collected retrospectively by medical record review. The severity of complications was graded according to the Clavien–Dindo classification. We assessed clinical characteristics, surgical results, and the perioperative complications in each BMI group. Surgical results included operation time, nonsurgical operating room time estimated blood loss, uterine weight, and postoperative hospital stay. Compared with the normal-weight group, the obese group had significantly more complications (P = 0.012) and longer operation time (P = 0.04). The underweight and overweight groups did not have significantly different surgical results than the normal-weight group. Conclusion: Underweight and overweight patients had no significant differences in surgical results, compared with patients of normal weight. Obese patients had significantly longer operation times and more perioperative complications than patients with normal weight. Laparoscopic hysterectomy has burdens and risks for obese patients. Our results suggest that appropriate weight control may decrease the risk of surgery for obese patients

Gastric-Type Adenocarcinoma of the Uterine Cervix Associated with Poor Response to Definitive Radiotherapy

We aimed to evaluate the response to definitive radiotherapy (RT) for cervical cancer based on histological subtypes and investigate prognostic factors in adenocarcinoma (AC). Of the 396 patients treated with definitive RT between January, 2010 and July, 2020, 327 patients met the inclusion criteria, including 275 with squamous cell carcinoma (SCC) and 52 with AC restaged based on the 2018 International Federation of Gynecology and Obstetrics staging system. Patient characteristics, response to RT, and prognoses of SCC and AC were evaluated. The complete response (CR) rates were 92.4% and 53.8% for SCC and AC, respectively (p p p p p < 0.05). Definitive RT for cervical cancer was significantly less effective for AC than for SCC. GAS was the only independent prognostic factor associated with non-CR in AC

Interleukin 6 receptor is an independent prognostic factor and a potential therapeutic target of ovarian cancer.

Ovarian cancer remains the most lethal gynecologic cancer and new targeted molecular therapies against this miserable disease continue to be challenging. In this study, we analyzed the expressional patterns of Interleukin-6 (IL-6) and its receptor (IL-6R) expression in ovarian cancer tissues, evaluated the impact of these expressions on clinical outcomes of patients, and found that a high-level of IL-6R expression but not IL-6 expression in cancer cells is an independent prognostic factor. In in vitro analyses using ovarian cell lines, while six (RMUG-S, RMG-1, OVISE, A2780, SKOV3ip1 and OVCAR-3) of seven overexpressed IL-6R compared with a primary normal ovarian surface epithelium, only two (RMG-1, OVISE) of seven cell lines overexpressed IL-6, suggesting that IL-6/IL-6R signaling exerts in a paracrine manner in certain types of ovarian cancer cells. Ovarian cancer ascites were collected from patients, and we found that primary CD11b+CD14+ cells, which were predominantly M2-polarized macrophages, are the major source of IL-6 production in an ovarian cancer microenvironment. When CD11b+CD14+ cells were co-cultured with cancer cells, both the invasion and the proliferation of cancer cells were robustly promoted and these promotions were almost completely inhibited by pretreatment with anti-IL-6R antibody (tocilizumab). The data presented herein suggest a rationale for anti-IL-6/IL-6R therapy to suppress the peritoneal spread of ovarian cancer, and represent evidence of the therapeutic potential of anti-IL-6R therapy for ovarian cancer treatment

Immunohistochemical analyses of IL-6 in high-grade serous ovarian cancer tissues.

<p>Serial sections of stage III high-grade serous ovarian cancer tissues were immunostained with anti-IL-6 antibody (A, C) and anti-CD-68 antibody (B, D). IL-6 was strongly expressed in stroma, while cancer cells little expressed IL-6. (A, B) Sections from a 56 year-old female with stage IIIC high-grade serous ovarian cancer. (C, D) sections from a 63 year-old female with stage IIIC high-grade serous ovarian cancer. CD68 staining identified macrophages. Arrows indicate macrophages. Arrowheads indicate ovarian cancer cells. Original magnification, x100 (upper panels), and x400 (bottom panels). Black bar; 200 μm, red bar; 50 μm.</p

Proposed paracrine mechanism.

<p>CD11b⁺CD14⁺ cells, which are predominantly macrophages, are one of the major sources of IL-6 production in an ovarian tumor microenvironment and promoted ovarian cancer invasion, proliferation and angiogenesis.</p

Expression of IL-6 and IL-6R in ovarian cancer cell lines.

<p>Real-time RT-PCR of IL-6 (A) and IL-6R (B). Total RNA was collected from seven different ovarian cancer cell lines using TRIzol and subjected to real-time RT-PCR. The 2^-ΔΔCT method was used to calculate the relative abundance with respect to GAPDH expression. Relative fold differences with respect to primary ovarian surface epithelium (OSE) are presented. (C) Western Blot. Cell lysates from seven ovarian cancer cells were resolved by SDS-PAGE and immunoblotted with an antibody against IL-6 and IL-6R. β-Actin was used as a loading control. (D) RT-PCR. RNA was collected and the expressions of full-length IL-6R (IL-6R) and soluble IL-6R (sIL-6R) expression in ovarian cancer cell lines were examined. PCR conditions were as described in Material and Methods. (E) ELISA assay of sIL-6R. Seven ovarian cancer cells (1 x 10⁵ each) were plated onto 24-well plates and cultured with 1 ml of serum-free medium for 72 h. Conditioned media were collected and the concentration of human sIL-6R was measured by ELISA. Experiments were repeated three times. n.d.; not detected. (F) Western Blot. Exogenous treatment of IL-6 activates IL-6/IL-6R signaling in ovarian cancer cell lines. SKOV3ip1 cells were stimulated with IL-6 (100 ng/mL) for 30 minutes with or without pretreatment using ranti-IL-6R antibody (1–100 μg/ml) non-immune IgG as control. Cell lysates were collected and equal amount of cell lysates (30 μg) was resolved by 10% SDS-PAGE and immunoblotted with anti–phosphorylated STAT3 (p-STAT3) antibody and anti–phosphorylated p44/42 MAPK (p-ERK1/2) antibody. The membranes were stripped and rehybridized with antibodies detecting the total forms of the protein. Blots are representative of three experiments.</p

Characteristics of the patients whose ascites were collected and used for analyses.

<p>Characteristics of the patients whose ascites were collected and used for analyses.</p

Characteristics of the patients (n = 94).

<p>Characteristics of the patients (n = 94).</p

CD11b⁺CD14⁺ cells from ovarian cancer ascites promote ovarian cancer cell invasion and proliferation <i>via</i> producing IL-6.

<p>(A) The protocol of isolation of CD11b^-, CD11b⁺CD14^- and CD11b⁺CD14⁺ cells using magnetic-activated cell sorting (MACS) technology (Miltenyi Biotech). ELISA assay of IL-6 (B) and sIL-6R (C). 1 x 10⁵ of SKOV3ip1 cells and primary cells indicated in the figure were plated onto 6-well plates and cultured with 2 ml of serum-free medium for 72 h. Conditioned media were collected and the concentrations of human IL-6 (B) as well as sIL-6R (C) were measured by ELISA. Experiments were repeated three times and values are means (±SD) of triplicates. (D) Matrigel invasion assay. 1 x 10⁵ SKOV3ip1 cells were placed on the upper chamber with the same number of primary cells indicated in the figure seeded on the bottom chamber as a chemoattractant, and were allowed to invade for 72 h. The relative number of invading cells when no cells were plated on the bottom chamber was set as 1.0. (E) Anti-IL-6R antibody inhibited ovarian cancer cell invasion induced by CD11b⁺CD14⁺ cells. In this experiment, the co-culture experiment in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118080#pone.0118080.g004" target="_blank">Fig. 4D</a> was repeated with the addition of the 10 μg/ml of anti-IL-6R antibody or non-immune IgG in the bottom chamber. Representative pictures of transwells are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118080#pone.0118080.g004" target="_blank">Fig. 4D</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118080#pone.0118080.g004" target="_blank">4E</a> (<i>bottom</i>). (F) In vitro cell proliferation assay. 1 x 10⁴ SKOV3ip1 cells were plated in 24-well plates. Thereafter, polycarbonate filters with 1-μm pores were placed onto 24-well plates and the same number of primary cells indicated in the figure were seeded as a stimulant and cells were cultured for 72 h. Cell proliferation was expressed as the ratio of the number of viable cells. (G) Anti-IL-6R antibody inhibited ovarian cancer cell proliferation induced by CD11b⁺CD14⁺ cells. In this experiment, the co-culture experiment in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118080#pone.0118080.g004" target="_blank">Fig. 4F</a> was repeated with the addition of the 10 μg/μl of anti-IL-6R antibody or non-immune IgG in the upper chamber. Experiments were repeated three times and values are means ± SD of triplicates. n.s.; not significant, n.d.; not detected, *; P < 0.05, **; P < 0.01.</p

Multivariate analysis for progression free survival of the patients.

<p>HR, hazard ratio;</p><p>95% CI, 95% confidence interval.</p><p>Multivariate analysis for progression free survival of the patients.</p