Szpakowski M

Cytokine secretion by decidual lymphocytes in transient hypertension of pregnancy and pre-eclampsia

BACKGROUND: Transient hypertension (TH) and preeclampsia (PE) are believed to have different pathophysiology. However, 15-25% of pregnant women initially diagnosed as having TH develop PE. To clarify the immuno-pathogenetical connections between the two syndromes, we studied the pattern of T helper cell (Th)1/Th2 cytokine balance disturbances existing inside maternal decidua in normal pregnancy (NP) and pregnancies complicated with TH and PE. METHODS: Third-trimester decidual tissue was obtained by curettage of uterine cavity during elective caesarean sections in NP (n = 11), TH (n = 17) and PE (n = 21) patients. Cell suspensions were prepared by an electromechanical dispersal method and centrifugated using a standard gradient sedimentation technique. Isolated lymphocytes were placed in medium (RPMI 1640, 10% fetal calf serum, L-glutamine, penicillin, streptomycin) and cultured for 72 h with or without mitogen phytohaemaglutinine (PHA). The enzyme-linked immunosorbent assay method was used for estimation of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12 and interferon-gamma (IFN-gamma) in culture supernatant. STATISTICAL ANALYSIS: The Kruskal-Wallis and the Mann-Whitney U tests were used (p < 0.05). RESULTS: Both spontaneous and PHA-stimulated secretion of Th2-type cytokines IL-6 and IL-10 was decreased in PE patients compared with TH and NP patients. The concentration of Th1-type cytokine IFN-gamma was increased in patients suffering both from TH and PE. CONCLUSION: On the base of decidual cytokine secretion, both PE and TH are syndromes of local Th1/Th2 cytokine balance disturbances as compared with NP, and TH seems to be an intermediate step to PE.

Ovarian cancer cells modulate human blood neutrophils response to activation in vitro.

In cancer, numerous cells of both innate and adaptive immune systems are activated. Polymorphonuclear neutrophils are potent effector cells of inflammation that are an important component of tumour development and progression. The important signalling proteins that are involved in neutrophil functions are extracellular signal‐regulated kinases 1/2 (ERK1/2). We investigated the reactive oxygen species (ROS) production, adhesive ability and CD11b/CD18 adhesion molecule expression on neutrophils isolated from peripheral blood of ovarian cancer patients and the in vitro response of these cells to stimuli and direct contact with ovarian cancer cells isolated from tumour. We found that functional activities of neutrophils isolated from patients with advanced stages of ovarian cancer (FIGO III/IV) were intensified in comparison to neutrophils isolated from healthy female volunteers. Neutrophils of cancer patients produce higher amounts of ROS in response to stimuli than those of control group. Unstimulated neutrophils of patients possess higher expression of CD11b/CD18 molecule that is accompanied by increased adhesive ability of these cells. Our results reveal that augmented functional activities of neutrophils may result from the intensification of ERK1/2 kinases phosphorylation. We found that interactions with ovarian cancer cells modulate neutrophil functions as a result of cell‐to‐cell direct contact. We conclude that ovarian cancer cells affect pro‐inflammatory activities in neutrophils via influence of signalling pathways in response to stimuli. Our results suggest the possibility that neutrophils responding to contact with cancer cells contribute to the progression and metastatic potential of tumour cells.

T lymphocyte subpopulations and lymphocyte proliferative activity in normal and pre-eclamptic pregnancy.

The purpose of this study was to assess whether any changes occur in the cellular immunity in normal and pre-eclamptic pregnancy. T lymphocyte subpopulations and the lymphocyte proliferative responses to mitogens (PHA, Con A, PWM) in the fetal calf serum were examined in normal pregnant and pre-eclamptic primiparas in the third trimester of pregnancy. In normal pregnancy the absolute and percentage numbers of CD3+ and CD4+ T cells were significantly lower and the CD4+/CD8+ ratio almost halved, in comparison with non-pregnant subjects. In the pre-eclamptic women a decreased absolute and percentage content of CD8+ T cells and increased percentage of CD3+ and CD4+ lymphocytes were found--in comparison with the normal pregnant women--which led to an almost 2.5-fold increase of the CD4+/CD8+ ratio. No disorders were found in the lymphocyte proliferative responses to mitogens in either normal or pre-eclamptic pregnancy. We conclude that despite the shifts among T lymphocyte subsets, mitogen-induced lymphocyte proliferation presents its functional stability and unchanged reactivity in normal and pre-eclamptic pregnancy.

Production of Cytokines During Interaction of Peripheral Blood Mononuclear Cells with Autologous Ovarian Cancer Cells or Benign Ovarian Tumour Cells

Cytokines produced by tumour and immune cells may play a significant role in a modulation of immune cells response against tumour. We investigated an ability of peripheral blood mononuclear cells (PBMC) of patients with early and advanced stages of ovarian cancer and from non‐cancer patients to produce various cytokines in the presence or absence of autologous ovarian cancer (OC) cells or benign ovarian tumour (BOT) cells. Activated PBMC of patients with advanced stage of cancer produced slight amount of interferon γ (IFN‐γ) and what’s more, the production of IFN‐γ was decreased in the presence of OC cells. PBMC of patients with ovarian cancer or benign ovarian tumour generated comparable amounts of interleukin 6 and 10 (IL‐6, IL‐10), and transforming growth factor β1 (TGF‐β1). PBMC of the patients with cancer produced higher amount of tumour necrosis factor α (TNF‐α) than PBMC of non‐cancer patients. We demonstrated here that the reciprocal contact of OC cells from advanced cancer with autologous PBMC altered the direction of produced cytokines and leads to the down‐regulation of IFN‐γ and TNF‐α as well as to up‐regulation of immunosuppressive (IL‐10, TGF‐β1) and pro‐inflammatory (IL‐6) cytokines production.

The interaction of HspA1A with TLR2 and TLR4 in the response of neutrophils induced by ovarian cancer cells in vitro

Inducible heat shock protein (HspA1A) promotes tumor cell growth and survival. It also interacts with effector cells of the innate immune system and affects their activity. Recently, we showed that the direct contact of ovarian cancer cells, isolated from tumor specimens, with neutrophils intensified their biological functions. Our current experiments demonstrate that the activation of neutrophils, followed by an increased production of reactive oxygen species, by cancer cells involves the interaction of HspA1A from cancer cells with Toll-like receptors 2 and 4 expressed on the neutrophils’ surface. Our data may have a practical implication for targeted anticancer therapies based, among other factors, on the inhibition of HspA1A expression in the cancer cells.

Interdisciplinary treatment of the patient with adenoid cystic carcinoma of the Bartholin's gland resulting in 15 years' survival: a case report and review of literature

Carcinoma of the Bartholins gland is very rare, comprises below 2% of Bartholins gland lesions and adenoid cystic carcinoma (ADC) is one of the most uncommon variants and accounts for 10-15% of Bartholins gland malignancies. There is no consensus on treatment of ADC of the Bartholins gland: reported cases were treated with local excision or vulvectomy with or without lymphadenectomy followed or not by radiotherapy. The survival of patients varies significantly, so we present a case of interdisciplinary treatment of ADC resulting in 15 years’ survival. The patient was initially treated with local excision, but the margins were not clear. Then vulvectomy, inguinal lymphadenectomy and adjuvant brachytherapy were performed resulting in 7 years free of the disease. Relapses were excised by abdominoperineal amputation of the rectum and distal part of the vagina with sigmoideostomy, excisions of local recurrences in vagina and metastasectomy of isolated lung metastases. The patient died manifesting multiple lung metastases 15 years after the initial diagnosis. Based on our experience and world literature, in cases of adenoid cystic carcinoma of the Bartholins gland, vulvectomy with or without lymphadenectomy should be considered as a treatment of choice and in patients with positive margin, surgery should be extended by adjuvant radiotherapy.

Classical radical hysterectomy and nerve-sparing radical hysterectomy in the treatment of cervical cancer

Aim of the study To compare Piver III radical hysterectomy (RH) with nerve-sparing radical hysterectomy (NSRH) for cervical cancer patients in terms of postoperative physiology of pelvic autonomic nerves and perioperative complications. Material and methods Seventy-three consecutive patients with invasive cervical cancer underwent RH (53 cases) or NSRH (20 cases) from 2001 to 2012 at the Department of Gynecology and Gynecologic Oncology of Polish Mothers Memorial Hospital – Research Institute in Łódź. Results Compared with patients treated with RH, patients who underwent NSRH presented no significant difference in terms of operative time (146 vs. 143 minutes, p > 0.05), blood loss and hospital stay (9.2 vs. 7.5 days, p > 0.05). A positive surgical margin was found in 6 cases of RH. No serious surgical complications were found in the NSRH group, while there were 4 cases in the RH group. Conclusions Nerve-sparing radical hysterectomy is safe and feasible surgical management for cervical cancer patients, which should improve the physiology of the pelvic autonomic nerve system postoperatively. The technique is relatively new and its oncologic efficiency has not been fully established yet, moreover it requires sophisticated anatomical knowledge and high operative skills.

Vaginal hysterectomy vs. laparoscopically assisted vaginal hysterectomy in women with symptomatic uterine leiomyomas: a retrospective study.

Introduction Uterine leiomyomas are the most common benign tumors of the female reproductive system. Although the majority of myomas are asymptomatic, some patients have symptoms or signs of varying degrees and require a hysterectomy. The aim of the study The aim of the study was to compare the clinical results of two minimally invasive hysterectomy techniques: vaginal hysterectomy (VH) and laparoscopically assisted vaginal hysterectomy (LAVH). Material and methods A retrospective, observational study was performed at a tertiary care center: the Gynecology and Gynecologic Oncology Department, Polish Mothers Memorial Hospital Research Institute. The study period was from January 2003 to December 2012. A total of 159 women underwent either vaginal hysterectomy (VH, n = 120) or laparoscopically assisted vaginal hysterectomy (LAVH, n = 39) for symptomatic uterine myomas. Outcome measures, including past medical history, blood loss, major complications, operating time and discharge time were assessed and compared between the studied groups. Statistical analysis was performed using Student t-test, U-Mann Whitney test, χ2 test and Yates‘χ2 test. P < 0.05 was considered statistically significant. Results There were no differences in patients’ mean age. Parity was significantly higher in the VH group (VH 1.9 ± 0.7 vs. LAVH 1.5 ± 0.8; p = 0.008). No difference was found in the mean ± standard deviation (SD) uterine volume between vaginal hysterectomy and LAVH groups (179 ± 89 vs. 199 ± 88 cm3), respectively. The mean operative time was significantly longer for the LAVH group (83 ± 29 vs. 131 ± 30 min; p = 0.0001). The intraoperative blood loss (VH 1.3 ± 1.1 vs. LAVH 1.4 ± 0.9 g/dl; p = 0.2) and the rate of intra- and postoperative complications were similar in both groups studied. The mean discharge time was longer for LAVH than for VH (VH 4.2 ± 1.2 vs. LAVH 5.3 ± 1.3 days, p = 0.0001). Conclusions Laparoscopically assisted vaginal hysterectomy and VH are safe hysterectomy techniques for women with the myomatous uterus. Concerning the LAVH, the abdominal-pelvic exploration and the ability to perform adnexectomy safely represent the major advantages comparing with VH. Vaginal hysterectomy had a shorter operating time and the mild blood loss making it a suitable method of hysterectomy for cases in which the shortest duration of surgery and anesthesia is preferable.