Aerobic vaginitis is associated with carbonic anhydrase IX in cervical intraepithelial neoplasia.

The aim of this study was to analyze the association between vaginal microbiota, carbonic anhydrase IX (CAIX) and histological findings of cervical intraepithelial neoplasia (CIN). The study included 132 females, among them 66 were diagnosed with high-grade intraepithelial lesion (CIN2, CIN3, and cancer), 14 with low-grade disease, and 52 assigned to the control group. An interview focused on the behavior risk factors, together with vaginal fluid pH measurement, wet mount microscopy, detection of Chlamydia trachomatis, and Trichomonas vaginalis were performed. After colposcopy, high-grade abnormalities were detected via direct biopsies and treated with conization procedure. Conuses were immuno-stained with CAIX antibody. The histological findings were CIN1 (n = 14), and CIN2+ (included CIN2 (n = 10), CIN3 (n = 49), and cancer (n = 7; squamous cell carcinomas)). Prevalence of bacterial vaginosis (BV) was similar between the groups. Moderate or severe aerobic vaginitis (msAV) was diagnosed more often among CIN2+ (53.0%) than CIN1 (21.4%). Moderate or strong immunostaining of CAIX (msCAIX) was not detected among CIN1 cases. Thus, msAV was prevalent in CAIX non-stained group (p = 0.049) among CIN2 patients. Co-location of msAV and msCAIX was found in CIN3. Regression model revealed that msAV associated with high-grade cervical intraepithelial neoplasia independently from smoking and the number of partners.

Expression of Inflammation Depending on the Stage of Cervical Cancer.

Background and Objectives: Cervical cancer (CC) remains a major public health problem, ranking as the fourth most common cause of cancer incidence and mortality in women globally. The development of CC is believed to be closely related to chronic inflammation. Thus, we aimed to evaluate the expression of systemic inflammation in patients with CC and to determine the threshold prognostic value of the systemic inflammation markers for CC and its advanced stage. Materials and Methods: 182 participants were recruited: 94 histology-proven patient with CC and 88 healthy women with NILM confirmed by liquid-based cytology test. The pre-treatment serum concentrations of cytokines, including IFN-ß, IFN-γ, IL-1ß, IL-2, IL-6, IL-10, IL-12p70, LCN2, TREM-1, and TNF-α, were determined for all study patients. Results: The odds ratio (OR) of having IL-6 concentration >17.4 pg/mL in the CC group compared to control patients was 11.4 (95% CI: 4.897-26.684); that of having TREM-1 concentration >355.6 pg/mL was 5.9 (95% CI: 2.257-15.767); and that of having LCN2 concentration >23,721.5 pg/mL was 3.4 (95% CI: 1.455-8.166). The odds ratio (OR) of having IL-6 concentration >28.7 pg/mL in advanced-stage CC (III-IV stage) compared to early-stage CC (I-II stage) was 2.921 (95% CI: 1.06-8.045), and that of having LCN2 concentration >25,640.0 pg/mL was 4.815 (95% CI: 1.78-13.026). Conclusions: The pre-treatment serum inflammation markers IL-6, TREM-1, and LCN2 at specified levels could be used as predictors of cervical cancer, and IL-6 and LCN2 as predictors of an increased chance of advanced-stage (III-IV stages) cervical cancer. Patients with cervical cancer had expressed systemic inflammation, and expression of inflammation elevated the chance of having CC and advanced-stage disease.

Laparoscopic sentinel lymph node mapping with indocyanine green in endometrial cancer: surgeon's learning curve (cumulative sum analysis).

OBJECTIVES: To evaluate surgeons' learning curves for laparoscopic sentinel lymph node biopsy in endometrial cancer. METHODS: A prospective observational study was performed at the Oncogynecology Center, Lithuanian University of Health Sciences Hospital, from March 2018 to October 2022. Participating surgeons had no previous experience of laparoscopic sentinel lymph node biopsy with indocyanine green tracer. Cumulative sum analysis was used to create learning curves for the performance of eight surgeons, based on a specific result over a time period. Two different cumulative sum plots were made for each surgeon: successful bilateral sentinel lymph node mapping and removal of sentinel lymph node specimens containing actual lymphatic tissue. RESULTS: 190 patients were included. The overall rate of sentinel lymph node mapping was 89.5%: successful bilateral mapping was achieved in 134 (70.5%) patients, while in 36 (19%) patients sentinel lymph nodes were mapped unilaterally. The bilateral detection rate significantly improved in later study periods (from 59.3% in the first year to 85.0% in the last year; p=0.03). Analysis of the performance of the surgeons for bilateral sentinel lymph node mapping showed that the cumulative sum plot crossed the H0 limit line after 13 consecutive successful bilateral sentinel lymph node biopsies, indicating an acceptable level of competence to achieve the bilateral detection rate of at least 75%. This was accomplished by only one surgeon after 30 surgeries. Analysis of the performance of the surgeons for identification and removal of specimens containing histologically confirmed lymphatic tissue showed that the cumulative sum plots crossed the H0 limit line after six consecutive successful sentinel lymph node removals. This was accomplished by most of the surgeons (5 of 8). CONCLUSION: At least 30 procedures of indocyanine green traced laparoscopic sentinel lymph node biopsy were needed to reach an acceptable level of competence for a bilateral sentinel lymph node detection rate of at least 75%. TRIAL REGISTRATION NUMBER: ACTRN12619000979156.

Factors, associated with elevated concentration of soluble carbonic anhydrase IX in plasma of women with cervical dysplasia.

Precancerous lesions of human cervix uteri have a tendency for regression or progression. In cervical intraepithelial neoplasia grade 2 (CINII) case there is an uncertainty if a lesion will progress or regress. The carbonic anhydrase IX (CAIX) enzyme is overexpressed in cervical cancer which is more sensitive to radiotherapy. CAIX is associated with poor prognosis in solid hypoxic tumors. The aim of this study was to determine factors related to elevated soluble CAIX (s-CAIX) in high-grade intraepithelial lesion (HSIL) cases. METHODS: Patients diagnosed with HSIL (N = 77) were included into the research group whereas without HSIL (N = 72)-the control group. Concentration of the soluble CAIX (s-CAIX) in plasma was determined by the DIANA ligand-antibody-based method. C. trachomatis was detected from cervical samples by PCR. Primary outcomes were risk factors elevating s-CAIX level in HSIL group. Non-parametric statistical analysis methods were used to calculate correlations. RESULTS: The s-CAIX level in patients with HSIL was elevated among older participants (rs = 0.27, p = 0.04) and with C. trachomatis infection (p = 0.028). Among heavy smokers with HSIL, the concentration of s-CAIX was higher in older women (rs = 0.52, p = 0.005), but was not related to the age of heavy smokers' controls (τ = 0.18 p = 0.40). CONCLUSION: The concentration of s-CAIX was higher among older, heavy smoking and diagnosed with C. trachomatis patients. All these factors increased the risk for HSIL progression.

The Feasibility of Sentinel Lymph-Node, Mapped with Indocyanine Green, Biopsy in Endometrial Cancer Patients: A Prospective Study.

Background and objectives. Systematic pelvic lymphadenectomy (LND) is an essential part of lymph-node status evaluation in endometrial cancer (EC) patients to tailor the adjuvant treatment. However, it is associated with the post-operative lymphatic complications and does not improve the outcomes of the disease. Indocyanine green (ICG) mapped sentinel lymph-node biopsy (SLB) has recently been introduced into the clinical practice as an alternative for the surgical lymph-node evaluation in EC patients with the potential to decrease LND related complications. The aim of our study was to evaluate the feasibility of ICG mapped SLB in low, intermediate, and high-risk EC patients in a center with no previous experience on endoscopic SLB procedure. Materials and Methods: The prospective study was performed. 170 patients with histologically confirmed EC were included. Sentinel lymph-nodes (SLs) were mapped with ICG dye and removed ahead of the total laparoscopic hysterectomy. Low-risk patients received only SLB, while SLB and LND were performed for intermediate and high-risk patients. Results: The overall detection rate of SLs was 88.8%. Bilateral mapping was achieved in 68.2% of the patients. The overall detection rate for low-risk patients was 93.7%, 85.0% for the intermediate-risk group, and 100% for high-risk patients (p = 0.232). The most common anatomical sites of SLs were the external iliac (45.8% on the right and 46.6% on the left) and obturator regions (20.9% and 25.6%, respectively). Positive lymph-nodes were found in 8 (4.7%) patients. The sensitivity of SLB was 75.0% and negative predictive value (NPV)-97.2%. Conclusions: Even in the center with no previous experience, sentinel lymph-node biopsy using ICG mapping is feasible. However, the favorable outcomes might be associated with the learning process of newly established method.

IL-6 597A/G (rs1800797) and 174G/C (rs1800795) Gene Polymorphisms in the Development of Cervical Cancer in Lithuanian Women.

Our study aimed to evaluate the distribution of genotypes and allele frequencies of IL-6 597A/G (rs1800797) and 174G/C (rs1800795) polymorphisms in HPV infected and uninfected healthy women and cervical cancer patients. A PCR based Multiplex HPV genotyping test kit was used for in vitro detection and differentiation of high risk HPV genotypes. Genotyping of two polymorphisms, IL-6 597A/G (rs1800797) and 174G/C (rs1800795), was performed using the KASP genotyping assay kit. Cervical cancer patients were more likely to be HPV positive than control patients. Allele C of IL-6 rs1800795 was associated with a higher risk of cervical cancer by 2.26-fold and genotype CC by 5.37-fold. Genotype CC of IL-6 rs1800795 was more frequent in the HPV positive group compared with the HPV negative group (p = 0.002). Allele G of IL-6 rs1800797 was more frequently found in women with HPV16/HPV18 compared to other HPV types (p = 0.045). Women with AA genotypes of IL-6 rs1800797 were less frequently infected with HPV16/HPV18 compared to other HPV types (p = 0.045). The major finding of the study is the significant association of C allele and CC genotype of IL-6 1800795 gene with cervical cancer in the Lithuanian population. Genotype CC of IL-6 rs1800795 has a significant association with HPV infection as well.

Performance of the IOTA ADNEX Model on Selected Group of Patients with Borderline Ovarian Tumours.

Background and objectives: ultrasound is considered to be the primary tool for preoperative assessment of ovarian masses; however, the discrimination of borderline ovarian tumours (BOTs) is challenging, and depends highly on the experience of the sonographer. The Assessment of Different NEoplasias in the adneXa (ADNEX) model is considered to be a valuable diagnostic tool for preoperative assessment of ovarian masses; however, its performance for BOTs has not been widely studied, due to the low prevalence of these tumours. The aim of this study was to evaluate the performance of ADNEX model for preoperative diagnosis of BOTs. Methods: retrospective analysis of preoperative ultrasound datasets of patients diagnosed with BOTs on the final histology after performed surgery was done at a tertiary oncogynaecology centre during the period of 2012-2018. Results: 85 patients were included in the study. The performance of ADNEX model based on absolute risk (AR) improved with the selection of a more inclusive cut-off value, varying from 47 (60.3%) correctly classified cases of BOTs, with the selected cut-off of 20%, up to 67 (85.9%) correctly classified cases of BOTs with the cut-off value of 3%. When relative risk (RR) was used to classify the tumours, 59 (75.6%) cases were identified correctly. Forty (70.2%) cases of serous and 16 (72.7%) cases of mucinous BOTs were identified when AR with a 10% cut-off value was applied, compared to 44 (77.2%) and 15 (68.2%) cases of serous and mucinous BOTs, correctly classified by RR. The addition of Ca125 improved the performance of ADNEX model for all BOTs in general, and for different subtypes of BOTs. However, the differences were insignificant. Conclusions: The International Ovarian Tumour Analysis (IOTA) ADNEX model performs well in discriminating BOTs from other ovarian tumours irrespective of the subtype. The calculation based on RR or AR with the cut-off value of at least 10% should be used when evaluating for BOTs.

Circulating inflammatory markers in cervical cancer patients and healthy controls.

There is increasing evidence that host inflammatory responses play an important role in the development and progression of cancers. There are some data that cancer is associated not only with inflammation at the site of the lesion, but also with dysregulations of the host overall systemic immune response. In the case of cervical cancer, inflammation is an important factor associated with the development, progression, and potential metastasis of the disease. What is unclear still in the potential for modifications of host responses to human papillomaviruses (HPV) - a known causative agent of CC, that could be induced by cigarette smoking. In particular, it remains to be determined how the inflammation induced by HPV infection could impact on CC incidence/severity. In this prospective study, serum levels of 10 cytokines were evaluated using Multiplex and ELISA assays. The samples were the sera of 43 CC patients and 60 healthy (NILM) controls. All outcomes were evaluated in relation to host HPV and to their smoking status. The results in indicated that serum sTREM-1, TNFα, IFNß, IL-1ß, and IL-6 levels were significantly increased in CC (HPV+) patients compared to healthy NILM controls. A similar trend was observed for IL-10 and IL-2 levels. Within the two groups, differences in cytokine levels between smokers and never smokers were not remarkable. The findings here support the hypothesized role of systemic inflammation in the pathophysiology of CC.

Associations among Serum Lipocalin-2 Concentration, Human Papilloma Virus and Clinical Stage of Cervical Cancer.

Background and objective: Lipocalin 2 (LCN2) has an oncogenic role in promoting tumorigenesis through enhancing tumor cell proliferation and the metastatic potential. The aim of our study was to determine whether serum LCN2 could serve as a diagnostic marker of cervical cancer (CC) and to evaluate the correlation between its serum concentration, the clinical stage of the cancer and Human Papilloma Virus HPV infections in women. Materials and methods: A total of 33 women with histologically proven cervical cancer (CC), 9 women with high- grade cervical intraepithelial neoplasia (HSIL) and 48 healthy women (NILM) were involved in the study. A concentration of LCN2 was assayed with the Magnetic LuminexR Assay multiplex kit. An HPV genotyping kit was used for the detection and differentiation of 15 high-risk (HR) HPV types in the liquid-based cytology medium (LBCM) and the tissue biopsy. Results: The majority (84.8%) of the women were infected by HPV16 in the CC group, and there was no woman with HPV16 in the control group (P < 0.01). Several types of HR HPV were found more often in the LBCM compared to in the tissue biopsy (P = 0.044). HPV16 was more frequently detected in the tissue biopsy than the LBCM (P < 0.05). The LCN2 level was higher in HPV-positive than in HPV-negative women (P = 0.029). The LCN2 concentration was significantly higher in women with stage IV than those with stage I CC (P = 0.021). Conclusions: Many HR HPV types, together with HPV16/18, can colonize the vagina and cervix, but often HPV16 alone penetrates into the tissue and causes CC. The serum LCN2 concentration was found to be associated not only with HR HPV infection, irrespective of the degree of cervical intraepithelial changes, but also with advanced clinical CC stage. LCN2 could be used to identify patients with advanced disease, who require a more aggressive treatment.

Prevalence of human papillomavirus types 16, 18, and 45 in women with cervical intraepithelial changes: associations with colposcopic and histological findings.

The aim of the study was to determine the prevalence of human papillomavirus (HPV) types 16, 18, and 45 in women with cervical intraepithelial changes caused by high-risk HPV in relation to colposcopic and histological findings. MATERIAL AND METHODS. A prospective study of 393 women with cervical cytologic changes confirmed by the Papanicolaou test was undertaken from April 3, 2006, to April 3, 2007. The Hybrid Capture 2 assay was performed. HPV-positive women underwent genotyping for types 16, 18, and 45. Colposcopy and biopsy were performed in 317 (80.7%) and 249 women (63.4%), respectively. The results were analyzed by age groups. RESULTS. Of all the women with cervical intraepithelial changes, 59% were positive for HR HPV, and 62% were positive for HPV types 16, 18, and 45. HPV types 16, 18, and 45 were detected in 54.8% of women with ASC-US/AGUS/ASC-H, 50.0% of women with LSIL, and 75.6% of women with HSIL. After confirmation of any histological and colposcopic changes, HPV types 16, 18, and 45 were detected in 68.0% and 69.0% of women, respectively. Moreover, 84.2% of the women with HSIL and high-grade colposcopic changes, and 78.5% of the women with HSIL and CIN 2/CIN 2-3/CIN 3/carcinoma in situ were positive for HPV types 16, 18, and 45. The sensitivity of the Papanicolaou test together with the Hybrid Capture 2 test compared with the Papanicolaou test together with the HPV 16/18/45 test diagnosing CIN 2+ changes did not differ (96.7% vs. 97.1%), but the specificity was higher (40.3% vs. 8.0%). CONCLUSIONS. The majority of the cytologic, colposcopic, and histological changes were caused by HPV types 16, 18, and 45. Despite the high prevalence of HPV types 16, 18, and 45, testing for these genotypes together with the Papanicolaou test did not improve the diagnosis of high-grade cervical intraepithelial lesions.

Long-term results of high-dose-rate brachytherapy and external-beam radiotherapy in the primary treatment of endometrial cancer.

In this report we update our long-term follow-up results of the prospective study whose aim was to evaluate the efficacy of high-dose-rate (HDR) brachytherapy in combination with external-beam radiotherapy (EBRT) in the treatment of medically inoperable endometrial cancer. Between 1995 and 1998, 29 patients with stages I-III medically inoperable carcinoma of endometrium were treated with definitive irradiation. All patients underwent combined intracavitary HDR brachytherapy and EBRT. The EBRT dose was 50 Gy with midline shield from 16 Gy. The HDR brachytherapy dose was 50 Gy, delivered in 5 fractions in a weekly schedule. Overall survival (OS) at 5 and 10 years was 48.3% and 20.7%, respectively. Disease-specific survival (DSS) at 5 and 10 years was 73.5% and 67.9%, respectively. The 10-year DSS rate was 73.5% for all stages, 85.7% for Stage I disease, 71.4% for Stage II, and 16.7% for stage III disease. Late Grade 1-2 radiation complications were observed in 4 patients (13.8%). Our long-term follow-up confirms that HDR brachytherapy with EBRT appears to be an effective and safe treatment for stage I and II medically inoperable endometrial cancer.

Lichen sclerosus et atrophicus in pediatric and adult male patients with congenital and acquired phimosis.

Lichen sclerosus et atrophicus is a chronic inflammatory sclerotic and atrophic disease of unknown cause that predominantly affects male and female genital skin. This study was designed to evaluate histological characteristics of congenital and acquired phimoses among pediatric (n=60) and adult (n=60) male patients who were admitted for circumcision to the Clinics of Urology and Pediatric Surgery of Kaunas University of Medicine Hospital between 2000 and 2003 and to determine the rate of lichen sclerosus et atrophicus and other histological diagnoses among them. This study demonstrates that 45.1% of congenital and 62.3% of acquired phimoses show histological signs of lichen sclerosus et atrophicus. The rate of lichen sclerosus et atrophicus was statistically significantly higher among patients with acquired than congenital phimosis. Boys with acquired narrowing of prepuce were statistically significantly 3.9 times more likely to develop lichen sclerosus et atrophicus than those with congenital phimosis. There were no statistically significant differences between rates of lichen sclerosus et atrophicus and other dermatological diagnoses among pediatric and adult male patients if the type of phimosis (acquired or congenital) was considered. Histological features of lichen sclerosus et atrophicus and other histological diagnoses in boys and men with phimosis were detected with equal frequency irrespective the age of the subjects. The rate of lichen sclerosus et atrophicus was similar among all boys (56.7%) and men (53.3%) treated for phimosis. Only the type of phimosis had a statistically significant influence on the rate of lichen sclerosus et atrophicus and other histological diagnoses.

Fetal middle cerebral artery Doppler velocimetry in cases of rhesus alloimmunization.

OBJECTIVE: To assess fetal middle cerebral artery (MCA) peak systolic velocity (PSV) in cases of rhesus alloimmunization and to establish whether MCA-PSV is valid for the prediction of fetal anemia. METHODS: The study population included 157 pregnant women diagnosed with rhesus alloimmunization. MCA-PSV measurements were obtained within 3 days of blood sampling for estimation of hemoglobin concentration either at delivery or cordocentesis by the same operator and by means of the same ultrasound machine using techniques described previously. To evaluate the measurements of the MCA-PSV as the multiples of median (MoM) for gestation we used original nomograms for various gestational ages derived from a group of 273 normal fetuses between 22 and 40 weeks of gestation, not at risk for anemia. Receiver-operator characteristic (ROC) curves were employed to evaluate the relation of the sensitivity (the true positive rate) and the false positive rate (100% specificity) of different threshold values of the MCA-PSV. RESULTS: The sensitivity of the MCA-PSV was 94.4% in the case of the subgroup of fetuses with severe anemia. The sensitivity of the MCA-PSV test decreased in less anemic fetuses and was 77.3% in the subgroup with moderate anemia and 32% in the subgroup with mild anemia. According to ROC curves, we selected the optimal MCA-PSV threshold values of 1.15, 1.44, and 1.53 MoM for the prediction of mild, moderate, and severe anemia, respectively. CONCLUSIONS: MCA-PSV is a significant Doppler index valid for the prediction of moderate and severe fetal anemia.

Puerperal Clostridium perfringens sepsis in a patient with granulocytopenia.

We present a lethal case of fulminant puerperal sepsis with massive hemolysis after cesarean section in a patient with intermittent granulocytopenia.

[Disseminated ovarian, bone, and bone marrow metastases from gastric cancer]. / Kiausidziu, kaulu ir kaulu ciulpu metastazes sergant isplitusiu skrandzio veziu.

The main cause of death in patients with gastric cancer is disease dissemination. It is not clear why gastric cancer metastasizes to different organs. Early detection and destruction of circulating malignant cells before developing metastases may markedly improve survival of these patients. Krukenberg tumors (metastases of non-gynecological origin in the ovaries) usually are circular cell carcinomas of gastric cancer. Bone metastases of gastric cancer are rare, but if they are diagnosed, patients survive only 2-5 months on the average. Disseminated bone marrow metastases from gastric cancer do not always show the sudden course of the disease, but hematological complications are signs of poor prognosis. Hematological paraneoplastic disorders can be miscellaneous: they usually manifest as anemia of various origin, as leucocytosis in half of the patients, as leukemoid reactions in one-third of the patients, and as hemolysis and thrombocytopenia in half of the patients (often with disseminated intravascular coagulation). Currently, chemotherapy is the most effective treatment for outspread gastric cancer. Unfortunately, there is no exclusively effective scheme for treatment. Lymph node metastases are more sensitive to chemotherapy than primary gastric cancer, while in contrary, hepatic metastases are less sensitive than primary gastric cancer. This article includes a literature review and a rare case of gastric cancer.

[Surgical treatment of advanced epithelial ovarian cancer]. / Chirurginis isplitusio epitelinio kiausidziu vezio gydymas.

Primary cytoreductive surgery remains the standard care in advanced ovarian cancer. Optimal cytoreductive surgery is defined as a residual tumor load less than 1 cm. after operation. The randomized clinical trials showed that interval debulking surgery improved survival in patients who did not undergo optimal primary debulking surgery. The retrospective trials have suggested that the outcome for patients treated with neoadjuvant chemotherapy followed by interval debulking surgery is the same as for patients treated with primary debulking surgery followed by adjuvant chemotherapy. The neoadjuvant chemotherapy should not to be used for clinical practice until the randomized clinical trial carried out by Gynecological Cancer Group of the European Organization for Research and Treatment of Cancer and National Cancer Institute of Canada answers this question. There are no data from randomized trials to show the survival advantage in patients who received second-look operation as compared to those who did not.

Prevalence of Chlamydia trachomatis, Chlamydia psittaci and Chlamydia pneumoniae antibodies in blood donors and attendees of STD clinics.

OBJECTIVE: To estimate the prevalence of Chlamydia trachomatis, C. psittaci and C. pneumoniae antibodies in sera from altogether 931 blood donors, patients with symptoms of urethritis, assumed salpingitis and sexually acquired reactive arthritis (SARA), and women with fertility problems. METHODS: IgG antibodies to C. trachomatis, C. psittaci and C. pneumoniae were determined by microimmunofluorescence (MIF) tests. All patients were also tested for genital C. trachomatis infection using direct immunofluorescence (DIF) tests. RESULTS: The DIF-positive cases had a significantly (p < 0.0001) higher prevalence of C. trachomatis antibodies than the DIF negatives, i.e. 88.5% versus 14% in men with urethritis, 94.3% versus 36.4% in women with salpingitis, 66.7% versus 16.7% in SARA patients and 90.6% versus 20.8% in women with fertility problems. Antibody reactivity to all three chlamydial species was found significantly (p < 0.0001) more often in the patient groups and in those with a DIF-confirmed genital C. trachomatis infection than in blood donors. CONCLUSIONS: Presence of serum antibodies to C. trachomatis is tightly associated with the presence of chlamydiae in the genital tract, which also influences the cross-reactivities occurring in the MIF tests between chlamydial species.