The Predictive Role of Serum Lipid Levels, p53 and ki-67, According to Molecular Subtypes in Breast Cancer: A Randomized Clinical Study.

Dyslipidemia is a component of metabolic syndrome, having an important role in the carcinogenesis of different tumor types, such as prostate, ovarian, or renal cancer. The number of studies on the predictive potential of the different components of the lipid profile with a predictive potential in breast cancer is quite low. The evaluation of the lipid profile was carried out for the 142 patients who benefited from neoadjuvant therapy (NAC) in order to identify a potential predictive biomarker. The serological sample collection was performed sequentially according to a standardized protocol, pre-NAC, post-NAC and 6 months post-NAC after a 6-h pre-collection fast. We also investigated in the general group the presence or absence of the p53 mutation (TP53) and of the mitotic index ki-67, respectively, in relation to the molecular subtypes. The menopausal status, tumor size, family history, grading, Ki-67, p53 and LN metastases have a predictive nature regarding overall survival (OS) (p < 0.05), while for disease free survival (DFS), only tumor size, tumor grading, Ki-67 > 14, and p53+ are of predictive nature. The genetic and molecular analysis carried out in our group indicates that 71.67% have a Ki-67 score higher than 14%, and 39% of the patients have the positive P53 mutation. The multivariate analysis in the case of patients included in the TNBC subtype showed that the increased tumor volume (p = 0.002) and increased level of HDL (p = 0.004) represent predictive factors for the tumor response rate to NAC. High HDL-C levels before NAC and increased LDL-C levels after NAC were associated with the better treatment response in ER-positive and HER2+ breast cancer patients. Increased HDL-C values and tumor volume represent predictive factors as to the response rate to NAC in the case of patients included in the TNBC subtype. Regarding the ER+ and HER2+ subtypes, increased levels of HDL-C pre-NAC and increased levels of LDL-C post-NAC were associated with a better therapeutic response rate. Tumor grading, Ki-67, p53, and LN metastases have a predictive nature for OS, while tumor size, tumor grading, and Ki-67 > 14, and p53+ are predictive for DFS.

Unselective Measurement of Tumor-to-Stroma Proportion in Colon Cancer at the Invasion Front-An Elusive Prognostic Factor: Original Patient Data and Review of the Literature.

The tumor-to-stroma ratio is a highly debated prognostic factor in the management of several solid tumors and there is no universal agreement on its practicality. In our study, we proposed confirming or dismissing the hypothesis that a simple measurement of stroma quantity is an easy-to-use and strong prognostic tool. We have included 74 consecutive patients with colorectal cancer who underwent primary curative abdominal surgery. The tumors have been grouped into stroma-poor (stroma < 10%), medium-stroma (between 10 and 50%) and stroma-rich (over 50%). The proportion of tumor stroma ranged from 5% to 70% with a median of 25%. Very few, only 6.8% of patients, had stroma-rich tumors, 4% had stroma-poor tumors and 89.2% had tumors with a medium quantity of stroma. The proportion of stroma, at any cut-off, had no statistically significant influence on the disease-specific survival. This can be explained by the low proportion of stroma-rich tumors in our patient group and the inverse correlation between stroma proportion and tumor grade. The real-life proportion of stroma-rich tumors and the complex nature of the stroma-tumor interaction has to be further elucidated.

VRAM Flap for Pelvic Floor Reconstruction after Pelvic Exenteration and Abdominoperineal Excision.

Due to the still large number of patients diagnosed with pelvic neoplasms (colorectal, gynecological, and urological) in advanced stages right from the initial diagnosis, surgery represents the mainstay of treatment, often implying wide, eventually multi-organ resections in order to achieve negative surgical margins. Perineal wound morbidity, particularly in extralevator abominoperineal excision, leads to complications and local infection rates of up to 40%. Strategies to reduce postoperative wound complications are being pursued to address this issue. The VRAM flap remains the gold standard for autologous reconstruction after pelvic oncological resection; it was initially designed for abdominal wall defects and later expanded for large pelvic tissue defects. The flap's application is based on its physical characteristics, including abundant tissue and a generous skin paddle, which effectively obliterates dead space after exenterations. The generous skin paddle offers good cosmetic and functional outcomes at the recipient site. This article describes the case of a patient histopathologically diagnosed with stage IIIA squamous cell carcinoma of the uterine cervix who received multimodal onco-surgical treatment. The surgical mainstay of this treatment is pelvic exenteration. Pelvic reconstruction after this major surgery was performed using a vertical flap with the rectus abdominis.

The Value of Tumor Infiltrating Lymphocytes (TIL) for Predicting the Response to Neoadjuvant Chemotherapy (NAC) in Breast Cancer according to the Molecular Subtypes.

INTRODUCTION: The antitumor host immune response is an important factor in breast cancer, but its role is not fully established. The role of tumor infiltrating lymphocytes (TIL) as an immunological biomarker in breast cancer has been significantly explored in recent years. The number of patients treated with neoadjuvant chemotherapy (NAC) has increased and the identification of a biomarker to predict the probability of pCR (pathological complete response) is a high priority. MATERIALS AND METHODS: We evaluated 334 cases of BC treated with NAC followed by surgical resection from 2020-2022 at the Ist Clinic of Oncological Surgery, Oncological Institute "Prof Dr I Chiricuta" Cluj Napoca. Of the above, 122 cases were available for histological evaluation both in pre-NAC biopsy and post-NAC resection tissue. Evaluation of biopsy fragments and resection parts were performed using hematoxylin eosin (H&E). The TIL evaluation took place according to the recommendations of the International TIL Working Group (ITILWG). RESULTS: There was a strong association between elevated levels of pre-NAC TIL. At the same time, there is a statistically significant correlation between stromal TIL and tumor grade, the number of lymph node metastases, the molecular subtype and the number of mitoses (p < 0.005). Intratumoral TIL showed a significant correlation with tumor size, distant metastasis, molecular subtype, number of mitosis, stage and lymph node metastasis (p < 0.005). We also demonstrated that high pre-NAC STIL represents a strong predictive marker for pCR. CONCLUSION: This study reveals the role of TIL as a predictive biomarker in breast cancer not only for the well-established TNBC (triple negative breast cancer) and HER2+ (Her2 overexpressed) subtypes but also in Luminal A and B molecular subtypes. In this scenario, the evaluation of sTIL as a novel predictive and therapy-predicting factor should become a routinely performed analysis that could guide clinicians when choosing the most appropriate therapy.

The Use of Wound Infiltration for Postoperative Pain Management after Breast Cancer Surgery: A Randomized Clinical Study.

(1) Background: The present study aims to evaluate the reduction of postoperative pain in breast surgery using a series of local analgesics, which were infiltrated into the wound; (2) Methods: Envelopes containing allocation were prepared prior to the study. The patients involved were randomly assigned to the groups of local anesthesia infiltration (Group A) or normal pain management with intravenous analgesics (Group B). The random allocation sequence was generated using computer-generated random numbers. The normally distributed continuous data were expressed as the means (SD) and were assessed using the analysis of variance (ANOVA), independent-sample t-test, or paired t-test; (3) Results: The development of the postoperative pain stages was recorded using the VAS score. Therefore, for Group A, the following results were obtained: the VAS at 6 h postoperatively showed an average value of 0.63 and a maximum value of 3. The results for Group B were the following: the VAS score at 6 h postoperatively showed an average value of 4.92, a maximum of 8, and a minimum of 2; (4) Conclusions: We can confirm that there are favorable statistical indicators regarding the postoperative pain management process during the first 24-38 h after a surgical intervention for breast cancer using local infiltration of anesthetics.

Low-Cost and Reproductible Method to Obtain Mapping of Lymphatic Drainage in Patient with Early Endometrial Cancer.

Introduction: Endometrial cancer is the most common form of gynecological cancer in developed countries. Current recommended therapeutic management takes into account a number of factors such as: TNM stage, justification for primary surgery, desire to preserve fertility. For primary operable cases, surgical staging has become an extremely important pillar, in which the status of the pelvic lymph nodes needs to be known (1-3). Material and Method: Between August 2015 and June 2021, a multicenter prospective observational study was performed in the "Prof. Dr. I. Chiricuta" Oncological Institute Cluj Napoca, 2nd Department of Surgery of "Pius Brinzeu" County Hospital Timisoara, 1st Department of General Surgery of Arad County Hospital, 2nd Department of Obstetrics and Gynecology "Dominic Stanca" Cluj Napoca and "Dr. Carol Davila" Central Military Emergency University Hospital Bucharest, Romania with the main aim of examining the sentinel lymph node detection rate using methylene blue as a tracer. Surgeries were performed by the team of surgeons of the mentioned clinics, and patients were informed about this study and signed an informed consent form for enrollment. Results: A total of 116 cases met the inclusion criteria for this prospective study. The mean age of the included patients was 62.3 years (minimum - 38, maximum - 83). The mean body mass index was 31.8 (minimum - 19.9, maximum - 48.2). In terms of histological type of the endometrial cancer, the majority of cases were endometrioid cancer, amounting to 72.5% of the total (n=84). A considerable number of cases were of mixed type, either with clear cell carcinoma (8.6%, n=10) or mixed carcinosarcoma (17.2%, n=20). The preferred approach for surgery was laparoscopic surgery rather than traditional surgery (72% vs 28%). Another element investigated from a histological point of view is the tumour grading, the degree of differentiation of cells with anarchic development, we note that 50% (n=58) were G2. Of the 116 cases of endometrial carcinoma included in the study, in 83% of cases (n=96) methylene blue tracer injection was successful and sentinel node was identified. The SLN technique continues to be of great interest and use in surgical centers around the world. The method of detecting sentinel lymph nodes varies depending on the individual. According to literature studies, indocyanine (ICG- Indocyanine green) is the gold standard for lymph node mapping, with superior detection rates when compared to other existing versions. Another key factor to consider when selecting a sentinel node identification method is cost-effectiveness. The use of methyl blue as a marker tracer is the most cost-effective option with equivalent detection rate outcomes. Conclusions: Based on the results of our study and other studies in the literature, lymphatic mapping using methylene blue as a tracer in endometrial cancer is a cost-effective method with a favourable detection rate. With this low-cost procedure we can achieve a correct tumor staging, avoiding overtreatment. There are multiple ways to identify the sentinel node using different tracers with higher accuracy, but the objective of the study was not to make a comparison between different tracers, but to present the feasibility of lymph node mapping using methylene blue as a low cost tracer with good reproducibility, short learning curve and optimal detection rate.

Assessment of renal and hepatic dysfunction by co-exposure to toxic metals (Cd, Pb) and fluoride in people living nearby an industrial zone.

Togo's phosphate processing plant at Kpeme discharges waste, containing Cd, Pb, and fluoride, into the sea and on the soil. Heavy metals toxicity on kidneys and the liver has been studied. However, fluoride toxicity on these organs remains to be investigated. The present study deals with the variation in renal and hepatic functioning parameters due to fluoride, Cd and Pb. Totally, 350 volunteers were recruited from five different localities around this phosphate processing plant for sample collection. Cd and Pb contents in blood samples were determined by spectrophotometry and fluoride by the titanium chloride method. Biochemical parameters were measured using Biolab kits. The pollutant contents were elevated in polluted areas where ASAT, ALAT, creatinine, and urea increased, and total protein decreased. Correlation and multivariate tests showed that fluoride is related to the various pathologies mentioned. PCA revealed that phosphate processing in Togo is a source of renal and hepatic toxicity.

Immediate Breast Reconstruction in Large Ptotic Breasts Using the Inferior Based Dermal Flap. Indications and Technique.

Introduction: Achieving good aesthetic outcomes during immediate reconstruction in women with large ptotic breast presents a unique challenge for the reconstructive surgeon. We present our paradigm regarding immediate reconstruction in patients with large ptotic breasts, using the inferiorly based dermal flap. Materials and Methods: Ten patients with large ptotic breasts underwent mastectomy and immediate implant reconstruction at the "Prof. Dr. I. Chiricuta" Institute of Oncology. The mastectomy was carried out using a Wise pattern skin resection with preservation of a dermal flap at the lower pole of the breast. The flap was sutured to the pectoralis major muscle and completed the subpectoral pocket created for the implant. Results: The reconstruction was done bilaterally in three cases with a total number of 13 reconstructed breasts. Of these 11 required dermal flaps. All reconstructions were completed successfully and there were no implant losses. Four breasts (36%) developed superficial necrosis of the tip of the mastectomy flaps at the T junction. Conclusion: The dermal flap technique is safe, versatile and reliable. It is used in a wide array of reconstructive scenarios as it provides the surgeon with an excellent alternative to more costly and unreliable methods.

Malignant phyllodes tumors of the breast associating malignancy of both mesenchymal and epithelial components (invasive or in situ ductal carcinoma).

Phyllodes tumors of the breast are biphasic tumors consisting from an epithelial component and a mesenchymal component. Usually, the mesenchymal component of the tumor is the one who dictates the malignancy of the biphasic proliferation. Presence of the malignancy of the both, epithelial [under the form of invasive carcinoma or ductal carcinoma in situ (DCIS)] and mesenchymal components is very rare. Most of the data available from the literature refers to single case presentations. This paper presents the experience of Prof. Dr. Ion Chiricuta Oncological Institute (IOCN), Cluj-Napoca, Romania, with the malignant phyllodes tumors with both epithelial and mesenchymal components showing malignancy. Over two decades (1999-2018), four cases of malignant phyllodes tumors with concomitant epithelial and mesenchymal malignancy were found and presented as a case series. Two out of four cases were malignant phyllodes tumors harboring invasive breast carcinomas (one case with associated DCIS and one case of pure invasive carcinoma) and two cases were malignant phyllodes tumors with the epithelial component showing DCIS. Average follow-up period was 67 months (from 39 to 132 months) with a disease-free survival of 58 months.

Institutional results of OncoOVARIAN Dx - a novel algorithm for the preoperative evaluation of adnexal masses.

PURPOSE: The purpose of this study was to evaluate the predictive performance of OncoOVARIAN Dx algorithm, which takes into account tumor markers (beta HCG, CA 19.9, CEA, AFP, CA 125, HE4), general biochemistry and clinical data (age, menopause, comorbidities) in patients scheduled for surgical removal of a suspicious adnexal tumor in comparison with the Risk of Malignancy Algorithm (ROMA) model. METHODS: Consecutive women diagnosed with an adnexal tumor mass and scheduled for surgical intervention at a single tertiary cancer between October 2018 - June 2019 were enrolled. Preoperative values of tumor markers and general biochemistry (ASAT, ALAT, GGT, total bilirubin, creatinine) were determined. Following surgery with adequate surgical staging, a definite pathological diagnosis was made and used as reference. RESULTS: A total of 50 patients were selected, including 20 benign, 5 borderline and 25 malignant epithelial ovarian cancer (EOC) cases on final pathology. Borderline tumors comprised 3 serous and 2 mucinous FIGO stage I cases. Malignant tumors included 17 high grade serous, 4 endometrioid and 4 mucinous types, FIGO stage IA-IIIC. The two models demonstrated very good correlation (Phi 0.78, p<0.001). The sensibility (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) of OncoOVARIAN Dx versus ROMA model were 76.66% vs. 60%, 95% vs. 100%, 95.83% vs. 100%, 73.07% vs. 62.5%, respectively. In postmenopausal patients higher Se (85.71%), Sp (100%) and PPV (100%) were observed for OncoOVARIAN Dx. CONCLUSIONS: OncoOVARIAN Dx model demonstrated higher Se and NPV compared to ROMA and could be a useful marker in the preoperative management of adnexal masses; however larger studies are warranted to validate and further refine this algorithm.

Cardiovascular dysfunction and oxidative stress following human contamination by fluoride along with environmental xenobiotics (Cd & Pb) in the phosphate treatment area of Togo, West Africa.

In Togo, the phosphate ore mill discharges waste containing xenobiotics like cadmium, lead and fluoride. If the role of heavy metals in the appearance of pathologies is known, the role of fluoride remains to be studied alongside xenobiotics. This study tested the hypothesis that the toxicity of fluoride contributes, along with heavy metals, to physiological dysfunction. In this process, we have studied the variation in the parameters of cardiovascular functioning, depending on the level of human contamination by fluoride and xenobiotics. The concentration of Cd and Pb in blood samples were determined by AAS and fluoride by titanium-chloride method. Lipid peroxidation, the total antioxidant potential of collected blood samples and the parameters of cardiovascular dysfunction were also measured. Cd, Pb and F contents and lipid peroxidation were found to be significantly elevated in polluted areas than control zone as well as total cholesterol, LDL and triglyceride. HDL and antioxidant potential of blood decreased in the polluted areas. Correlation tests showed that fluoride levels are related to variations in the bio-indicators of high blood pressure and oxidative stress (R varied from 0.354 to 0.907). Togo phosphate treatment leads to human contamination with fluoride, along with Cd and Pb, increasing the risk of cardiovascular dysfunction and oxidative stress.

Synthesis, characterization and application of gelatin-carboxymethyl cellulose blend films for preservation of cherry tomatoes and grapes.

In the present study, gelatin-carboxymethyl cellulose blend film was synthesized, characterized and applied for the first time to preserve cherry tomatoes (Solanum lycopersicum var. cerasiforme) and grapes (Vitis vinifera). Gelatin (Gel) film forming solution was incorporated with carboxymethyl cellulose (CMC) at three volume per volume (Gel:CMC) ratios, namely 75:25, 50:50 and 25:75. CMC treatment has improved the transparency, tensile strength (TS), elongation at break (EAB), water vapor permeability and oxygen permeability of gelatin films. A pronounced effect was obtained for 25Gel:75CMC film. The TS and EAB values were increased from 25.98 MPa and 2.34% (100Gel:0CMC) to 37.54 MPa and 4.41% (25Gel:75CMC), respectively. A significant improvement in antimicrobial property of gelatin films against two food pathogens, namely Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was obtained in the presence of CMC. The effectiveness of gelatin-CMC blend films to extend the shelf life of agricultural products was evaluated in a 14-day preservation study. The gelatin-CMC films were successfully controlled the weight loss and browning index of the fruits up to 50.41% and 31.34%, respectively. Overall, gelatin-CMC film is an environmental friendly film for food preservation.

Electro-Fenton process for implementation of acid black liquor waste treatment.

In this work, an eco-friendly solution for the remediation of wastewater generated in the lignin recovery process from eco-industrial paper mill has been proposed in their way towards a more circular economy strategy. Thus, the application of the electro-Fenton process for the degradation of the non-recovered lignin and other organic compounds form a scarcely studied acid black liquor waste (ABLW) was successfully performed. This treatment was able to operate in a range of COD loads (0.5-19.5mgO2·L-1) showing high degradation values of the ABLW determined by the abatement of color, total phenolic content and COD. Then, the optimization of the working conditions for the design of a sustainable treatment system with optimum efficiency was carried out using a response surface methodology. The experiment carried out in the calculated optimal conditions for the electro-Fenton degradation process (current intensity 132.5mA, catalyst dosage of 0.10mM, and temperature 40°C) showed a COD removal of 74.82% and current efficiency 77.79%, close to the theoretical value predicted by the model 73.12% and 77.06%, respectively. In addition, the identification of the final products permitted to confirm the mineralization efficiency.

Improvement of recovery parameters using patient-controlled epidural analgesia after oncological surgery. A prospective, randomized single center study.

PURPOSE: The aim of this study was to compare patient-controlled epidural analgesia (PCEA) versus conventional opioid intravenous (IV) infusion after gastrointestinal cancer surgery regarding several post-surgery parameters of recovery. METHODS: One hundred and one patients were prospectively randomized to receive either thoracic/lumbar PCEA (PCEA group) or the standard analgesia technique used in our hospital, conventional IV infusion of morphine (IVMO group) after gastrointestinal cancer surgery. Pain intensity, time of mobilization and bowel function recovery were analyzed post-surgery. We also evaluated postoperative complications and length of Postoperative-Intermediate Intensive Care Unit (PI-ICU) stay and hospital stay. RESULTS: Pain intensity was significantly less in the PCEA group in comparison with the IVMO Group at awakening 2, 8, 24, 30 and 48 hours after surgery (p <0.001, p <0.001, p <0.001, p = 0.043, p = 0.036, and p = 0.029, respectively). The latency to bedside mobilization, walking, first postoperative flatus and apparition of first stool were significantly faster (1.74 versus 2.26 days, 3.06 versus 3.78 days, 2.1 versus 3.14 days and 3.73 versus 5.28 days, respectively) in the PCEA group than in the IVMO group (p <0.001, p <0.001, p <0.001, and p <0.001, respectively). The incidence of nausea/vomiting was significantly lower in the PCEA group in comparison with the IVMO group (p = 0.001). Surgical-associated complications were significantly lower in the IVMO Group than in the PCEA group (p = 0.023). Length of PI-ICU stay was similar in the two groups but length of hospital stay was significantly shorter in PCEA group (4 versus 5 days p = 0.2849, 9 versus 12 days; p <0.001). CONCLUSIONS: PCEA provides better postoperative pain control, improves postoperative recovery after gastrointestinal cancer surgery compared with conventional intravenous morphine infusion. Therefore, it is more acceptable than conventional pain management.

Electrokinetic-Fenton technology for the remediation of hydrocarbons historically polluted sites.

The feasibility of the electrokinetic-Fenton technology coupled with surfactants in the treatment of real historically hydrocarbons polluted soils has been studied. The characterisation of these soils from Spain and Romania was performed and identified as diesel and diesel-motor oil spillages, respectively. Moreover, the ageing of the spillages produced by the soil contamination was estimated showing the historical pollution of the sites (around 11 and 20 years for Romanian and Spanish soils, respectively). An ex-situ electrochemical treatment was performed to evaluate the adequacy of surfactants for the degradation of the hydrocarbons present in the soils. It was found an enhancement in the solubilisation and removal of TPHs with percentages increasing from 25.7 to 81.8% by the presence of Tween 80 for Spanish soil and from 15.1% to 71.6% for Triton X100 in Romanian soil. Therefore, the viability of coupling enhanced electrokinetic and Fenton remediation was evaluated through a simulated in-situ treatment at laboratory scale. The results demonstrated that the addition of the selected surfactants improved the solubilisation of the hydrocarbons and influenced the electroosmotic flow with a slight decrease. The efficiency of the treatment increased for both considered soil samples and a significant degradation level of the hydrocarbons compounds was observed. Buffering of pH coupled with the addition of a complexing agent showed to be important in the treatment process, facilitating the conditions for the degradation reactions that take place into the soil matrix. The results demonstrated the effectiveness of the selected techniques for remediation of the investigated soils.

The influence of omega-3 polyunsaturated fatty acids (omega-3 pufa) on lactobacilli adhesion to the intestinal mucosa and on immunity in gnotobiotic piglets.

The effect of application of omega-3 polyunsaturated fatty acids (omega-3 PUFA) on intestinal colonization by Lactobacillus paracasei and on cellular immunity has been investigated in gnotobiotic pigs. The administration of polyunsaturated fatty acids positively affected the adhesion of Lactobacillus paracasei to the jejunal mucosa of gnotobiotic piglets. When compared to the control group, the number of Lactobacillus paracasei adhering to the jejunal mucosa was by 12% higher in piglets of the experimental group (5.10 log 10/cm2 vs. 4.55 log 10/cm2). The respective counts of Lactobacillus paracasei adhering to the ileal and colonic mucosa of 28 day old gnotobiotic piglets reached 4.45 and 5.05 log 10/cm2 in group C and 4.44 and 4.95 log 10/cm2 in group E. Omega-3 PUFA supplementation increased the phagocytic activity of neutrophils by almost 100% on day 28 of life as well as the subpopulations of lymphocytes (CD8) in the peripheral blood of germ-free piglets on day 21 of life. Our results indicate that the action of probiotics in the gut may be modulated by dietary PUFA. The stimulatory effect of PUFA upon adhesion of lactobacilli could be used for enhancing the effectiveness of probiotics in inhibiting digestive tract pathogens.