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.

Incisional Small-Bowel Strangulation after a Caesarean Section: A Case Report.

Background and Objectives: Every surgical procedure has the possible risk of complications, and caesarean sections (CSs) are no exception. As CS rates are increasing worldwide, being familiar with rare but possible complications has become extremely important. Case report: We present a case of 25-year-old nulliparous patient who came to our hospital with twin pregnancy for a scheduled induction of labour. An urgent CS was performed due to labour dystocia. On the second postoperative day, the patient started to complain about pain in the epigastrium, but initially showed no signs of bowel obstruction, passing gas, and stools, and could tolerate oral intake. After a thorough examination, an early postoperative complication-small-bowel strangulation at the incision site-was diagnosed. Small bowels protruded in between sutured rectus abdominis muscle causing a strangulation which led to re-laparotomy. During the surgery, there was no necrosis of intestines, bowel resection was not needed, and abdominal wall repair was performed. After re-laparotomy, the patient recovered with no further complications. Conclusions: Although there are discussions about CS techniques, most guidelines recommend leaving rectus muscle unsutured. This case demonstrates a complication which most likely could have been avoided if the rectus muscle had not been re-approximated.

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.

Dysregulation of Peripheral Blood Mononuclear Cells and Immune-Related Proteins during the Early Post-Operative Immune Response in Ovarian Cancer Patients.

Surgical treatment is a cornerstone of ovarian cancer (OC) therapy and exerts a substantial influence on the immune system. Immune responses also play a pivotal and intricate role in OC progression. The aim of this study was to investigate the dynamics of immune-related protein expression and the activity of peripheral blood mononuclear cells (PBMCs) in OC patients, both before surgery and during the early postoperative phase. The study cohort comprised 23 OC patients and 20 non-cancer controls. A comprehensive analysis of PBMCs revealed significant pre-operative downregulation in the mRNA expression of multiple immune-related proteins, including interleukins, PD-1, PD-L1, and HO-1. This was followed by further dysregulation during the first 5 post-operative days. Although most serum interleukin concentrations showed only minor changes, a distinct increase in IL-6 and HO-1 levels was observed post-operatively. Reduced metabolic and phagocytic activity and increased production of reactive oxygen species (ROS) were observed on day 1 post-surgery. These findings suggest a shift towards immune tolerance during the early post-operative phase of OC, potentially creating a window for treatment. Further research into post-operative PBMC activity could lead to the development of new or improved treatment strategies for OC.

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.

Transcutaneous Electric Nerve Stimulation Reduces Pathological Sensation of Mesh One Week after Open Inguinal Hernia Surgery: Follow-Up Results from a Randomized, Double Blind and Placebo-Controlled Trial.

Background and Objectives: Quality of life (QoL) and chronic pain are important outcomes following hernia surgery. The long-term effects of Transcutaneous Electric Nerve Stimulation (TENS) on postoperative recovery are not well known. In this trial we investigated the role of TENS on QoL and on the incidence of chronic pain following inguinal hernia repair with mesh. Materials and Methods: A total of 80 male patients with elective primary unilateral hernia Lichtenstein repair were randomly allocated to receive TENS or a placebo-TENS procedure. The TENS group received conventional TENS twice a day on the first and second postoperative days. The intensity was set at 0-0.5 mA in the placebo-TENS group. General and hernia-specific QoL, as well as the incidence of chronic pain were assessed using SF-36v2 and the Carolinas comfort scale. Results: Less sensation of mesh was reported by the TENS group patients one week after surgery. At this time point, the mean sensation score was 6.07 ± 8.88 in the TENS group and 14.08 ± 16.67 in the placebo-TENS group (p = 0.029). Although at two days and one week postoperatively, TENS group patients tended to have less pain, less movement restrictions and better overall hernia-specific QoL, the differences were not statistically significant. At 6 months postoperatively, no incidence of chronic pain was found in either the placebo-TENS or TENS group. Conclusions: Conventional TENS applied in the early postoperative period following inguinal hernia repair with mesh was found to reduce mesh-related foreign body sensation one week after surgery. Promising results were also found for other QoL domains.

Cesarean Scar Thickness Decreases during Pregnancy: A Prospective Longitudinal Study.

Background and Objectives: The aim of this study is to evaluate changes in uterine scar thickness after previous cesarean delivery longitudinally during pregnancy, and to correlate cesarean section (CS) scar myometrial thickness in the first trimester in two participants groups (CS scar with a niche and CS scar without a niche) with the low uterine segment (LUS) myometrial thickness changes between the second and third trimesters. Materials and Methods: In this prospective longitudinal study, pregnant women aged 18−41 years after at least one previous CS were included. Transvaginal sonography (TVS) was used to examine uterine scars after CS at 11−14 weeks. The CS scar niche ("defect") was defined as an indentation at the site of the CS scar with a depth of at least 2 mm in the sagittal plane. Scar myometrial thickness was measured, and scars were classified subjectively as a scar with a niche (niche group) or without a niche (non-niche group). In the CS scar niche group, RMT (distance from the serosal surface of the uterus to the apex of the niche) was measured and presented as CS scar myometrial thickness in the first trimester. The myometrial thickness at the internal cervical os was measured in the non-niche group. The full LUS and myometrial LUS thickness at 18−20 and 32−35 weeks of gestation were measured in the thinnest part of the scar area using TVS. Friedman's ANOVA test was used to analyse scar thickness during pregnancy and Mann−Whitney test to compare scar changes between CS scar niche and non-niche women groups. For a pairwise comparison in CS scar thickness measurements in the second and third trimesters, we used Wilcoxon Signed Ranks test. Results: A total of 122 eligible participants were recruited to the study during the first trimester of pregnancy. The scar niche was visible in 40.2% of cases. Uterine scar myometrial thickness decreases during pregnancy from 9.9 (IQR, 5.0−12.9) at the first trimester to 2.1 (IQR, 1.7−2.7) at the third trimester of pregnancy in the study population (p = 0.001). The myometrial CS scar thickness in the first trimester (over the niche) was thinner in the women's group with CS scar niche compared with the non-niche group (at internal cervical os) (p < 0.001). The median difference between measurements in the CS scar niche group and non-niche group between the second and third trimester was 2.4 (IQR, 0.8−3.4) and 1.1 (IQR, 0.2−2.6) (p = 0.019), respectively. Myometrial LUS thickness as percentage decreases significantly between the second and third trimester in the CS scar niche group compared to the non-niche group (U = 1225; z = −2.438; p = 0.015). Conclusions: CS scar myometrial thickness changes throughout pregnancy and the appearance of the CS scar niche was associated with a more significant decrease in LUS myometrial thickness between the second and third trimesters.

Transvaginal Sonographic Evaluation of Cesarean Section Scar Niche in Pregnancy: A Prospective Longitudinal Study.

Background and Objectives: To investigate the prevalence of a Cesarean section (CS) scar niche during pregnancy, assessed by transvaginal ultrasound imaging, and to relate scar measurements, demographic and obstetric variables to the niche evolution and final pregnancy outcome. Materials and Methods: In this prospective observational study, we used transvaginal sonography to examine the uterine scars of 122 women at 11+0-13+6, 18+0-20+6 and 32+0-35+6 weeks of gestation. A scar was defined as visible on pregnant status when the area of hypoechogenic myometrial discontinuity of the lower uterine segment was identified. The CS scar niche ("defect") was defined as an indentation at the site of the CS scar with a depth of at least 2 mm in the sagittal plane. We measured the hypoechogenic part of the CS niche in two dimensions, as myometrial thickness adjacent to the niche and the residual myometrial thickness (RMT). In the second and third trimesters of pregnancy, the full lower uterine segment (LUS) thickness and the myometrial layer thickness were measured at the thinnest part of the scar area. Two independent examiners measured CS scars in a non-selected subset of patients (n = 24). Descriptive analysis was used to assess scar visibility, and the intraclass correlation coefficient (ICC) was calculated to show the strength of absolute agreement between two examiners for scar measurements. Factors associated with the CS scar niche, including maternal age, BMI, smoking status, previous vaginal delivery, obstetrics complications and a history of previous uterine curettage, were investigated. Clinical information about pregnancy outcomes and complications was obtained from the hospital's electronic medical database. Results: The scar was visible in 77.9% of the women. Among those with a visible CS scar, the incidence of a CS scar niche was 51.6%. The intra- and interobserver agreement for CS scar niche measurements was excellent (ICC 0.98 and 0.89, respectively). Comparing subgroups of women in terms of CS scar niche (n = 49) and non-niche (n = 73), there was no statistically significant correlation between maternal age (p = 0.486), BMI (p = 0.529), gestational diabetes (p = 1.000), smoking status (p = 0.662), previous vaginal delivery after CS (p = 1.000) and niche development. Uterine scar niches were seen in 56.3% (18/48) of the women who had undergone uterine curettage, compared with 34.4% (31/74) without uterine curettage (p = 0.045). We observed an absence of correlation between the uterine scar niche at the first trimester of pregnancy and mode of delivery (p = 0.337). Two cases (4.7%) of uterine scar dehiscence were confirmed following a trial of vaginal delivery. Conclusions: Based on ultrasonography examination, the CS scar niche remained visible in half of the cases with a visible CS scar at the first trimester of pregnancy and could be reproducibly measured by a transvaginal scan. Previous uterine curettage was associated with an increased risk for uterine niche formation in a subsequent pregnancy. Uterine scar dehiscence might be potentially related to the CS scar niche.

Transcutaneous Electric Nerve Stimulation Reduces Acute Postoperative Pain and Analgesic Use After Open Inguinal Hernia Surgery: A Randomized, Double-Blind, Placebo-Controlled Trial.

In this randomized, double-blind, placebo-controlled trial, we evaluated the role of transcutaneous electrical nerve stimulation (TENS) in the multimodal treatment (nonopioid analgesics and kinesiotherapy) of postoperative pain following open inguinal hernia repair. In total, 80 males participants with elective primary unilateral hernia Lichtenstein repair were randomly allocated to receive TENS or a placebo-TENS procedure. The TENS group received local and segmental conventional TENS on the first and second postoperative days. In the placebo-TENS group, intensity was set at 0 to 0.5mA. Change of pain level at rest, when walking, when standing up from bed, pressure algometry parameters and additional analgesic use were the main outcomes. Reduction of VAS pain score and absolute and relative pain relief were observed in the TENS group following the procedures compared to the placebo-TENS group (P< .001). The pressure pain threshold and maximal tolerable pressure in the hernia side were equal before the TENS procedure in both groups (P= .84), but after the procedure, these were higher in TENS group (P< .001). Additional nonopioid analgesics requirements were lower in the TENS group on the first and second postoperative days (P< .001). TENS is a safe procedure that can reduce postoperative pain and analgesic use after open inguinal hernia repair. The study was registered in the database of clinicaltrials.gov (register number NCT03739060). PERSPECTIVE: This article presents TENS as a safe and effective nonpharmacologic intervention to reduce postoperative pain after open inguinal hernia repair. TENS could be used in daily practice as part of a multimodal postoperative pain treatment, especially for patients suffering from hyperalgesia.

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.

Stimulated upregulation of HO-1 is associated with inadequate response of gastric and ovarian cancer cell lines to hyperthermia and cisplatin treatment.

Heme oxygenase (HO)-1 is a heat shock protein induced by hyperthermia, responsible for cellular resistance to temperature. The aim of this in vitro study was to clarify the response of gastric and ovarian cancer cells to hyperthermic intraperitoneal chemotherapy, following the modulation of HO-1 expression. AGS and OVCAR-3 cells were treated with different temperature regimens, either alone or in combination with an IC50 dose of cisplatin for 1 h. Prior to treatment, HO-1 expression was silenced by short interfering RNA transfection. In OVCAR-3 cells, cisplatin increased HO-1 mRNA expression by 3.73-fold under normothermia and 2.4-fold under hyperthermia; furthermore, these factors similarly increased HO-1 protein expression levels. Exposure to cisplatin under hyperthermia reduced the viability of OVCAR-3 cells by 36% and HO-1-silencing enhanced this effect by 20%. HO-1-silencing under normothermia increased apoptotic rates in cisplatin-treated OVCAR-3 cells by 2.07-fold, and hyperthermia enhanced the effect by 3.09-fold. Semi-quantitative polymerase chain reaction (PCR) cell analysis indicated that exposure to cisplatin decreased the cell index under normothermia, and that hyperthermia boosted this effect in OVCAR-3. In AGS cells, only temperature increased cellular HO-1 levels. Silencing HO-1 in AGS cells at 37°C reduced viability by 16% and increased apoptotic rates 2.63-fold. Hyperthermia did not affect AGS viability; however, apoptosis was increased 6.84-fold. PCR analysis indicated no additional effects of hyperthermia on the AGS cell index. HO-1 is induced in cancer cells by different stressors in a variable manner. In tumors with highly inducible HO-1, prior silencing of this gene could improve the cellular response to hyperthermia and cisplatin.

Hyperthermia potentiates cisplatin cytotoxicity and negative effects on mitochondrial functions in OVCAR-3 cells.

The aim of this study was to determine the effects of hyperthermia, cisplatin and their combination on mitochondrial functions such as glutamate dehydrogenase (GDH) activity and mitochondrial respiration rates, as well as survival of cultured ovarian adenocarcinoma OVCAR-3 cells. Cells treated for 1 h with hyperthermia (40 and 43 °C) or cisplatin (IC50) or a combination of both treatments were left for recovery at 37 °C temperature for 24 h or 48 h. The obtained results revealed that 43 °C hyperthermia potentiated effects of cisplatin treatment: combinatory treatment more strongly suppressed GDH activity and expression, mitochondrial functions, and decreased survival of OVCAR-3 cells in comparison to separate single treatments. We obtained evidence that in the OVCAR-3 cell line GDH was directly activated by hyperthermia (cisplatin eliminated this effect); however, this effect was followed by GDH inhibition after 48 h recovery. A combination of 43 °C hyperthermia with cisplatin induced stronger GDH inhibition in comparison to separate treatments, and negative effects exerted on GDH activity correlated with suppression of mitochondrial respiration with glutamate + malate. Cisplatin did not induce uncoupling of oxidative phosphorylation in OVCAR-3 cells but induced impairment of the outer mitochondrial membrane in combination with 43 °C hyperthermia. Hyperthermia (43 °C) potentiated cytotoxicity of cisplatin in an OVCAR-3 cell line.

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.

Narrow line between benefit and harm: Additivity of hyperthermia to cisplatin cytotoxicity in different gastrointestinal cancer cells.

AIM: To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells. METHODS: AGS (gastric cancer cell line), Caco-2 (colon cancer cell line) and T3M4 (pancreatic cancer cell line) were treated by cisplatin and different temperature setting (37 °C to 45 °C) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin. RESULTS: AGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 °C to 41 °C in neither cancer cell line. However, a temperature of 43 °C enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 °C by 30%, 20%, and 18% in AGS, Caco-2, and T3M4 cells, respectively. CONCLUSION: In addition to cisplatin, hyperthermia up to 43 °C does not affect the viability of cancer cells in a synergistic manner.

Response of OVCAR-3 Cells to Cisplatin and Hyperthermia: Does Hyperthermia Really Matter?

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) is proposed as a promising treatment method, but fundamental information about the contribution of hyperthermia to intraperitoneal chemotherapy is lacking. The purpose of this study was to investigate the cytotoxic effect of hyperthermia and cisplatin on OVCAR-3 cells in vitro. MATERIALS AND METHODS: Imitating the typical clinical conditions of HIPEC, OVCAR-3 cells were exposed to hyperthermia and cisplatin for 1 h. MTT viability test, flow cytometric analysis, and real-time cell and isobologram analysis were performed. RESULTS: Hyperthermia up to 42°C did not significantly increase the effect of cisplatin regarding the viability and apoptosis of OVCAR-3 cells. Moreover, an antagonistic effect of hyperthermia and cisplatin was revealed. CONCLUSION: Our investigation of OVCAR-3 cells critically disputes the benefit of hyperthermia in ovarian cancer treatment. Further in vitro and in vivo research is essential for better understanding of the mechanisms of action of hyperthermia and its role in the treatment of epithelial ovarian cancer.

Upregulation of cugbp2 increases response of pancreatic cancer cells to chemotherapy.

PURPOSE: Altered expression and/or function of ribosomal RNA (rRNA)-binding proteins CUGBP2/CELF2 might influence post-transcriptional regulation of the HO-1- and COX-2-mediated cytoprotective pathways and represents an important therapeutic target. The aim of this study was to assess the effects of CUGBP2-mediated post-transcriptional regulation of COX-2 and HO-1 in pancreatic cancer cells in regard of response to gemcitabine (GEM) treatment. METHODS: Expression of CUGBP2, COX-2, and HO-1 was evaluated using qRT-PCR and Western blot methods. Cell viability after treatment with GEM and/or curcumin and siCUGBP2 was evaluated using MTT and crystal violet tests. RNA immunoprecipitation analysis was used to confirm COX-2 and HO-1 post-transcriptional regulation by CUGBP2 protein. RESULTS: CUGBP2 expression at the messenger RNA (mRNA) level was 2.2-fold lower (p = 0.007), but HO-1 and COX-2 expression was increased 6.9- (p = 0.023) and 2.3- (p = 0.046) fold in pancreatic cancer tissues. The median survival of patients with low CUGBP2 expression from the lowest tercile was 13.8 months. The median survival of patients in terciles of middle and high CUGBP2 expression levels was 21.9 month (p = 0.123). Induction of CUGBP2 expression by curcumin resulted in the downregulation of HO-1 and COX-2 and strongly sensitized tumor cells to GEM treatment. However, CUGBP2 silencing upregulated HO-1 and COX-2 protein expression and had a high effect on cells viability. CONCLUSION: Decreased activity of CUGBP2 could be associated with high chemoresistance and early dissemination of pancreatic cancer through the HO-1- and COX-2-mediated cytoprotective and carcinogenesis pathways. Curcumin significantly increased the effectiveness of GEM treatment in vitro via the CUGBP2-mediated post-transcriptional regulation pathway.

Referral pattern, management, and long-term results of laparoscopic bile duct injuries: a case series of 44 patients.

BACKGROUND AND OBJECTIVE: The incidence of bile duct injuries (BDIs) after laparoscopic cholecystectomy (LC) is higher than after open cholecystectomy, and the management of these lesions is still controversial. This study analyzed diagnostic and management strategies as well as long-term outcomes after BDI. MATERIAL AND METHODS: A prospective database of patients with BDIs at the Clinic of Surgery was maintained during the 8-year period (2000-2007). The long-term results were evaluated during 2008-2010, after 36- to 120-month follow-up (median, 84 months). RESULTS: In our series, 21 patients (48%) presented with minor and 23 (52%) with major BDIs. The overall incidence of BDIs was 0.24%. In 92% of cases in the minor BDI group, endoscopic stenting resulted in a good outcome. Major BDIs were treated by immediate, early, or delayed surgery depending on the timeliness of diagnosis and presence of biliary sepsis and/or cholangitis. The mean estimated time to failure after the initial treatment in the minor BDI group was significantly longer when compared with the major BDI group (114.3 vs. 81.8 months, log-rank test P=0.048). The hazard ratio of initial treatment failure after major versus minor BDIs was 6.06 (95% CI, 1.01-17.59). The mean estimated time to develop a biliary stricture after immediate, early, and delayed reconstructions was not different (P>0.05 in pairwise comparisons by log-rank test). CONCLUSIONS: Minor BDIs are best served by endoscopy, while surgical repair may be an efficient option when injury is diagnosed intraoperatively. The timing of reconstruction after major BDIs does not portend a different outcome; consequently, every attempt to achieve infection control should be warranted. Referral to a tertiary care center should be encouraged to facilitate a proper classification of preoperative injuries and multidisciplinary approach.

Blockade of leukocyte haptokinesis and haptotaxis by ketoprofen, diclofenac and SC-560.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAID) represent a one of the most widely used anti-inflammatory substances. Their anti-inflammatory effects are mainly based on inhibition of cyclooxygenase. The potential direct effect of NSAID on leukocyte migration was poorly investigated. Using time-lapse microscopy and 96-well fluorescence-based assay, we studied the effect of three different NSAID, ketoprofen, diclofenac and SC-560, on leukocyte haptokinesis and haptotaxis in vivo and in vitro. RESULTS: NSAID induced an immediate inhibiting effect on leukocyte migration both in vitro and in vivo. This effect was dose-dependent and was not restricted to a specific type of leukocytes. The inhibition of leukocyte migration by NSAID was partially re-stored after removal of inhibiting agent. Only complete blockade of leukocyte migration was accompanied by a strong reduction of [Ca(2+)]i. CONCLUSIONS: NSAID strongly supress leukocyte migration. The results of the present study may have important clinical implications since blockade of leukocyte migration can be achieved after topical application of NSAID.

Colonic intussusception caused by colonic lipoma: a case report.

Intussusception is a pediatric condition that rarely presents in adults. Colonic lipomas 4 cm and more in diameter can cause colonic intussusception leading to emergency operation. Surgical resection of the involved segment must be the procedure of choice. We report a case of colonic intussusception caused by colonic lipoma in an adult. The patient underwent operation, and histopathological examination of the specimen confirmed the diagnosis of colonic submucosal lipoma.

Facial skin metastasis of colorectal cancer: a case report.

INTRODUCTION: Liver and lungs are common locations of distant metastases of colorectal cancer. Skin metastases of colorectal cancer are very rare, and facial lesions are extremely uncommon. CASE PRESENTATION: An anterior resection of the rectum was performed for rectal cancer T3N0M0G3. A small ulcer on the upper lip developed 3.5 years after primary operation. Metastasis of adenocarcinoma was confirmed histologically, and local excision was performed. At the same time, a solitary metastasis in the right lung was diagnosed, and the right lower lobectomy was performed. No other metastasis or local recurrences were observed during the next 7 months. CONCLUSION: Skin metastases in the face from colorectal cancer are very rare and may indicate tumour relapse several years after primary resection. These patients have a worse prognosis.