Clinicopathological characteristics of endometrial carcinomas according to DNA mismatch repair protein status.

DNA mismatch repair protein deficiency (MMRd) in endometrial carcinoma is associated with the risk of Lynch syndrome and response to immune checkpoint inhibitors. It is also related to microsatellite instability and corresponds to a molecular subtype of endometrial tumor with an unclear prognosis. Here, we evaluated the clinicopathological characteristics and prognosis of 312 consecutive endometrial carcinoma cases submitted to complete surgical staging at a single institution. We compared MMRd and mismatch repair protein-proficient (MMRp) tumors and examined the effects of the MMR protein loss type (MLH1/PMS2 vs. MSH2/MSH6) and influence of L1CAM and p53 expression. The median follow-up period was 54.5 (range, 0-120.5) months. No difference was observed between MMRd [n = 166 (37.2%)] and MMRp [n = 196 (62.8%)] cases in terms of age, body mass index, FIGO stage, tumor grade, tumor size, depth of myometrial infiltration, or lymph node metastasis. More MMRd than MMRp tumors had endometrioid histology (87.9% vs. 75.5%) and despite MMRd had more lymphovascular space invasion (LVSI; 27.2% vs. 16.9%), they presented fewer recurrences and no difference in lymph node metastasis and disease-related death. Relative to those with MLH1/MSH6 loss, tumors with MSH2/MSH6 loss were diagnosed at earlier FIGO stages, were smaller, and had less ≥50% myometrial invasion, LVSI and lymph node metastasis. Outcomes, however, did not differ between these groups. L1CAM positivity and mutation-type p53 expression were more common in MMRp than in MMRd tumors and did not differ between the MLH1/PMS2 and MSH2/MSH6 loss groups. In the entire cohort, L1CAM and mutation p53 expression were associated with worse prognosis, but only non-endometrioid histology, FIGO stage III/IV, and deep myometrial infiltration were significant predictors. In the subgroup of endometrioid carcinomas, only FIGO stage III/IV was associated with poor outcomes. The risk of lymph node metastasis was associated with tumor size, non-endometrioid histology, and multifocal LVSI. For MMRd tumors, only tumor size and myometrial invasion depth were predictive of lymph node involvement. In our cohort, MMRd tumors were associated with greater recurrence-free, but not overall, survival. The precise identification of MMRd status, present in a substantial proportion of endometrial cancer cases, is a challenge to be overcome for proper patient management. MMRd status serves as a marker for Lynch syndrome, and a significant number of these tumors are high risk and candidate to immunotherapy.

Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma: Results of the Compassionate Use or the Expanded Access Program in Spain.

Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1-10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1-28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1-5.1) and 14.47 months (95% CI, 7.91-21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7-13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies.

Cardiovascular Screening Practices and Statin Prescription Habits in Patients with Psoriasis among Dermatologists, Rheumatologists and Primary Care Physicians.

Patients with psoriasis have a higher prevalence of cardiovascular risk factors. This study evaluated cardiovascular screening practices and statin prescribing habits among dermatologists, rheumatologists and primary care physicians (PCPs) through an online questionnaire, which was distributed through the Spanish scientific societies of the above-mentioned specialties. A total of 299 physicians (103 dermatologists, 94 rheumatologists and 102 PCPs) responded to the questionnaire. Of these, 74.6% reported screening for smoking, 37.8% for hypertension, 80.3% for dyslipidaemia, and 79.6% for diabetes mellitus. Notably, only 28.4% performed global screening, defined as screening for smoking, hypertension, dyslipidaemia, and diabetes mellitus by the same physician, and 24.4% reported calculating 10-year cardiovascular disease (CVD) risk, probably reflecting a lack of comprehensive cardiovascular risk assessment in these patients. This study also identified unmet needs for awareness of cardiovascular comorbidities in psoriasis and corresponding screening and treatment recommendations among PCPs. Of PCPs, 61.2% reported not being aware of the association between psoriasis and CVD and/or not being aware of its screening recommendations, and 67.6% did not consider psoriasis as a risk-enhancing factor when deciding on statin prescription. Thirteen dermatologists (12.6%) and 35 rheumatologists (37.2%) reported prescribing statins. Among those who do not prescribe, 49.7% would be willing to start their prescription.

Functional non-parametric mixed effects models for cytotoxicity assessment and clustering.

A multitude of natural and synthetic chemicals are present in our environment.Through the study of a compound's cytotoxicity, researchers can carefully set regulations regarding how much of a certain chemical in the ambient environment is tolerable. In the past, research has focused on point measurements such as the LD50. Instead, we consider entire time-dependent cellular response curves through the application of functional mixed effects models. We identify differences in such curves corresponding to the chemical's mode of action-i.e. how the compound attacks human cells. Through such analysis, we identify curve features to be used for cluster analysis via application of both k-means and self organizing maps. The data is analyzed by making use of functional principal components as a data driven basis and separately by considering B-splines for identifying local-time features. Our analysis can be used to drastically speed up future cytotoxicity research.

Role of systematic pelvic and para-aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy cycles for high-grade serous ovarian carcinoma.

INTRODUCTION: We analyzed the role of systematic pelvic and para-aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy (NACT) cycles for advanced high-grade serous ovarian carcinoma. MATERIALS AND METHODS: We retrospectively reviewed patients with advanced ovarian carcinoma who underwent NACT with carboplatin-paclitaxel between 2008 and 2016. Patients were included only if they had FIGO IIIC-IVB high-grade serous carcinoma with clinically negative lymph nodes after six NACT cycles (carboplatin-paclitaxel) and underwent complete or near complete cytoreduction. Patients with partial lymphadenectomy or bulky nodes were excluded. Patients who underwent systematic pelvic and aortic lymphadenectomy and those who did not undergo lymph node dissection were compared. Progression-free and overall survivals were analyzed using the Kaplan-Meier method. RESULTS: Totally, 132 patients with FIGO IIIC-IVB epithelial ovarian carcinoma were surgically treated after NACT. Sixty patients were included (39 and 21 in the lymphadenectomy and nonlymphadenectomy group, respectively); 40% had suspicious lymph nodes before NACT. Patient characteristics, blood transfusion numbers, and complication incidence were similar between the groups. In the lymphadenectomy group, 12 patients (30.8%) had histologically positive lymph nodes and the surgical time was longer (229 vs. 164 min). The median overall survival in the lymphadenectomy and nonlymphadenectomy groups, respectively, was 56.7 (95% CI 43.4-70.1) and 61.2 (21.4-101.0) months (p = 0.934); the corresponding disease-free survival was 8.1 (6.2-10.1) and 8.3 (5.1-11.6) months (p = 0.878). Six patients exclusively presented with lymph node recurrence. CONCLUSIONS: Systematic lymphadenectomy after six NACT cycles may have no influence on survival.

A survey of deep learning models in medical therapeutic areas.

Artificial intelligence is a broad field that comprises a wide range of techniques, where deep learning is presently the one with the most impact. Moreover, the medical field is an area where data both complex and massive and the importance of the decisions made by doctors make it one of the fields in which deep learning techniques can have the greatest impact. A systematic review following the Cochrane recommendations with a multidisciplinary team comprised of physicians, research methodologists and computer scientists has been conducted. This survey aims to identify the main therapeutic areas and the deep learning models used for diagnosis and treatment tasks. The most relevant databases included were MedLine, Embase, Cochrane Central, Astrophysics Data System, Europe PubMed Central, Web of Science and Science Direct. An inclusion and exclusion criteria were defined and applied in the first and second peer review screening. A set of quality criteria was developed to select the papers obtained after the second screening. Finally, 126 studies from the initial 3493 papers were selected and 64 were described. Results show that the number of publications on deep learning in medicine is increasing every year. Also, convolutional neural networks are the most widely used models and the most developed area is oncology where they are used mainly for image analysis.

Randomised multicentre clinical trial to evaluate voriconazole pre-emptive genotyping strategy in patients with risk of aspergillosis: vorigenipharm study protocol.

INTRODUCTION: Invasive aspergillosis is the most important cause of morbidity and mortality in patients with haematological diseases. At present, voriconazole is the first-line treatment for invasive fungal disease. The pharmacokinetic interindividual variability of voriconazole depends on genetic factors. CYP450 is involved in 70%-75% of total metabolism of voriconazole, mainly CYP3A4 and CYP2C19, with the remaining 25%-30% of metabolism conducted by monooxygenase flavins. CYP2C19 single nucleotide polymorphisms could explain 50%-55% of variability in voriconazole metabolism. MATERIALS AND METHODS: The main objective is to compare efficiency of pre-emptive voriconazole genotyping with routine practice. The primary outcome is serum voriconazole on the fifth day within the therapeutic range. The secondary outcome is the combined variables of therapeutic failure and adverse events within 90 days of first administration, associated with voriconazole. A total of 146 patients at risk of invasive aspergillosis who will potentially receive voriconazole will be recruited, and CYP2C19 will be genotyped. If the patient ultimately receives voriconazole, they will be randomised (1:1 experimental/control). In the experimental arm, patients will receive a dose according to a pharmacogenetic algorithm, including CYP2C19 genotype and clinical and demographic information. In the control arm, patients will receive a dose according to clinical practice guidelines. In addition, a Spanish National Healthcare System (NHS) point-of-view cost-effectiveness evaluation will be performed. Direct cost calculations for each arm will be performed. CONCLUSION: This trial will provide information about the viability and cost-effectiveness of the implementation of a pre-emptive voriconazole genotyping strategy in the Spanish NHS. ETHICS AND DISSEMINATION: A Spanish version of this protocol has been evaluated and approved by the La Paz University Hospital Ethics Committee and the Spanish Agency of Medicines and Medical Devices. Trial results will be submitted for publication in an open peer-reviewed medical speciality-specific publication. TRIAL REGISTRATION NUMBER: Eudra-CT: 2019-000376-41 and NCT04238884; Pre-results.

Ten years of experience with endometrial cancer treatment in a single Brazilian institution: Patient characteristics and outcomes.

Few reports have described the clinical and prognostic characteristics of endometrial cancer, which is increasing worldwide, in large patient series in Brazil. Our objective was to analyze the clinicopathological characteristics, prognostic factors, and outcomes of patients with endometrial cancer treated and followed at a tertiary Brazilian institution over a 10-year period.This retrospective study included 703 patients diagnosed with endometrial cancer who were treated at a public academic tertiary hospital between 2008 and 2018. The following parameters were analyzed: age at diagnosis, race, body mass index, serum CA125 level before treatment; histological type and grade, and surgical stage. Outcomes were reported relative to histological type, surgical staging, serum CA125, lymph-vascular space involvement (LVSI), and lymph-node metastasis. The median patient age at diagnosis was 63 (range, 27-93) years (6.4% were <50 years). Minimally invasive surgeries were performed in 523 patients (74.4%). Regarding histological grade, 468 patients (66.5%) had low-grade endometrioid histology and 449 patients (63.9%) had stage I tumors. Tumors exceeded 2.0 cm in 601 patients (85.5%). Lymphadenectomy was performed in 551 cases (78.4%). LVSI was present in 208 of the patients' tumors (29.5%). Ninety-three patients (13.2%) had recurrent tumors and 97 (13.7%) died from their malignant disease. The robust prognostic value of FIGO stage and lymph node status were confirmed. Other important survival predictors were histological grade and LVSI [overall survival: hazard ratio (HR) = 3.75, p < 0.001 and HR = 2.01, p = 0.001; recurrence: HR = 2.49, p = 0.004 and HR = 3.22, p = 0.001, respectively). Disease-free (p = 0.087) and overall survival (p = 0.368) did not differ significantly between patients with stage II and III disease. These results indicate that prognostic role of cervical involvement should be explored further. This study reports the characteristics and outcomes of endometrial cancer in a large population from a single institution, with systematic surgical staging, a predominance of minimally invasive procedures, and well-documented outcomes. Prognostic factors in the present study population were generally similar to those in other countries, though our patients' tumors were larger than in studies elsewhere due to later diagnosis. Our unexpected finding of similar prognoses of stage II and III patients raises questions about the prognostic value of cervical involvement and possible differences between carcinomas originating in the lower uterine segment versus those originating in the body and fundus. The present findings can be used to guide public policies aimed at improving the diagnosis and treatment of endometrial cancer in Brazil and other similar countries.

Cardiophrenic lymph node resection in cytoreduction for primary advanced or recurrent epithelial ovarian carcinoma: a cohort study.

OBJECTIVES: To evaluate the clinical outcomes of epithelial ovarian carcinoma patients who underwent cardiophrenic lymph node resection. METHODS: We retrospectively reviewed the records of all surgically treated patients with advanced epithelial ovarian carcinoma (stages IIIC-IV) who underwent cardiophrenic lymph node resection between 2002 and 2018. Only those in whom cardiophrenic lymph node involvement was the only detectable extra-abdominal disease were included. Patients with suspected cardiophrenic lymph node metastasis on staging images underwent a transdiaphragmatic incision to access the para-cardiac space after complete abdominal cytoreduction achievement. Data on disease-free survival, overall survival, and surgical procedures performed concurrently with cardiophrenic lymph node resection were collected. RESULTS: Of the total 456 patients, 29 underwent cardiophrenic lymph node resection; of these, 24 patients met the inclusion criteria. Twenty-two, one, and one patients had high grade serous epithelial ovarian carcinoma, low grade epithelial ovarian carcinoma, and ovarian carcinosarcoma, respectively. Ten patients had recurrent disease (recurrence group). Fourteen patients underwent cytoreduction during primary treatment (primary debulking group); four underwent cytoreduction after neoadjuvant chemotherapy. Cardiophrenic lymph node resection was performed on the right side in 19 patients, left side in three, and bilaterally in two. The average procedural duration was 28 minutes, with minimal blood loss and no severe complications. Twenty-one patients had cardiophrenic lymph node positivity. The median disease-free intervals were 17 and 12 months in the recurrent and primary debulking surgery groups, respectively. The mediastinum was the first recurrence site in 10 patients. Five patients developed brain metastases. Five patients had an overall survival beyond 50 months. CONCLUSIONS: Although rare, the cardiophrenic lymph nodes may be a site of metastasis of ovarian cancer. Although their presence might indicate future recurrence, some patients may achieve long-term survival. Resection should be considered in cases of suspicious involvement to confirm extra-abdominal disease and achieve complete cytoreduction.

L1 Cell Adhesion Molecule (L1CAM) expression in endometrioid endometrial carcinomas: A possible pre-operative surrogate of lymph vascular space invasion.

BACKGROUND: Risk stratification of endometrial carcinomas is primarily based on surgical staging that requires extensive retroperitoneal lymph node dissection. One of the most powerful predictor of lymph node involvement is the lymph vascular space invasion (LVSI). The objective of this study was to determine the potential of L1 Cell Adhesion Molecule (L1CAM) to predict LVSI and its association with other risk factors in endometrioid endometrial carcinomas. MATERIALS AND METHODS: We studied 47 consecutive patients aged 37-88 (61.34±10.52). Twenty-three patients (48.9%) were submitted to complete surgical staging. Nine patients (19.1%) underwent surgical staging without para-aortic dissection. Seven (14.9%) were submitted to hysterectomy with no lymph node dissection. Eight patients (17.0%) only had the biopsy material for analysis. The 32 patients submitted to lymphadenectomy were staged according to the FIGO system and classified among the risk categories of the ESMO-ESGO-ESTRO guidelines. The following histological characteristics were analyzed: tumor size (mm), depth of myometrial infiltration, presence of microcystic, elongated, and fragmented (MELF) pattern of myoinvasion, and lymph vascular space invasion (LVSI). Immunohistochemical analyses of mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, p53, and L1CAM were performed in formalin-fixed paraffin embedded whole tumor tissue sections. RESULTS: LVSI was identified in 26/41 (63,4%) of the cases. L1CAM was positive in 8/47 (17%) cases, all of them positive for LVSI and within the high-risk category of ESMO-ESGO-ESTRO. L1CAM-positive cases were associated with high histological grade and p53 aberrant immunohistochemical profile. Besides, it showed a trend to larger tumors, greater depth of myometrial infiltration, and with a higher frequency of the MELF pattern of myoinvasion. LVSI was also associated with FIGO stage, tumor size, depth of myometrial infiltration, and tumor grade. CONCLUSIONS: L1CAM is highly associated with LVSI and could be used as a pre-operative predictor of lymph node involvement in endometrioid endometrial carcinomas.

Stochastic dynamics and survival analysis of a cell population model with random perturbations.

We consider a model based on the logistic equation and linear kinetics to study the effect of toxicants with various initial concentrations on a cell population. To account for parameter uncertainties, in our model the coefficients of the linear and the quadratic terms of the logistic equation are affected by noise. We show that the stochastic model has a unique positive solution and we find conditions for extinction and persistence of the cell population. In case of persistence we find the stationary distribution. The analytical results are confirmed by Monte Carlo simulations.

Introduction of robotic surgery for endometrial cancer into a Brazilian cancer service: a randomized trial evaluating perioperative clinical outcomes and costs.

OBJECTIVE: The purpose of this study was to evaluate the clinical outcome and costs after the implementation of robotic surgery in the treatment of endometrial cancer, compared to the traditional laparoscopic approach. METHODS: In this prospective randomized study from 2015 to 2017, eighty-nine patients with endometrial carcinoma that was clinically restricted to the uterus were randomized in robotic surgery (44 cases) and traditional laparoscopic surgery (45 cases). We compared the number of retrieved lymph nodes, total time of surgery, time of each surgical step, blood loss, length of hospital stay, major and minor complications, conversion rates and costs. RESULTS: The ages of the patients ranged from 47 to 69 years. The median body mass index was 31.1 (21.4-54.2) in the robotic surgery arm and 31.6 (22.9-58.6) in the traditional laparoscopic arm. The median tumor sizes were 4.0 (1.5-10.0) cm and 4.0 (0.0-9.0) cm in the robotic and traditional laparoscopic surgery groups, respectively. The median total numbers of lymph nodes retrieved were 19 (3-61) and 20 (4-34) in the robotic and traditional laparoscopic surgery arms, respectively. The median total duration of the whole procedure was 319.5 (170-520) minutes in the robotic surgery arm and 248 (85-465) minutes in the traditional laparoscopic arm. Eight major complications were registered in each group. The total cost was 41% higher for robotic surgery than for traditional laparoscopic surgery. CONCLUSIONS: Robotic surgery for endometrial cancer presented equivalent perioperative morbidity to that of traditional laparoscopic surgery. The duration and total cost of robotic surgery were higher than those of traditional laparoscopic surgery.

Advanced Atherosclerosis with Leriche Syndrome, in a Patient with Carney Complex.

Carney complex (CNC) is a rare autosomal dominant syndrome. Spotty skin pigmentation is the major clinical manifestation of CNC, followed by cardiac myxomas, benign tumors that usually present with features from the classical triad of obstructive cardiac, embolic and non-specific constitutional symptoms (NCS). NCS are caused by the overproduction of interleukin-6 (IL-6), a pro-inflammatory cytokine which mediates the induction of intercellular adhesion molecule 1 (ICAM-1) and promotes endothelial dysfunction and atherosclerosis. Thus, myxomas may be directly linked to an increased risk of atherosclerotic events. We report here a case of a 74-year-old woman with left atrial myxoma, skin pigmentary abnormalities, thyroid disorder and extensive atherosclerosis, with non-embolic occlusion of infrarenal abdominal aorta.

Introduction of robotic surgery for endometrial cancer into a Brazilian cancer service: a randomized trial evaluating perioperative clinical outcomes and costs

OBJECTIVE: The purpose of this study was to evaluate the clinical outcome and costs after the implementation of robotic surgery in the treatment of endometrial cancer, compared to the traditional laparoscopic approach. METHODS: In this prospective randomized study from 2015 to 2017, eighty-nine patients with endometrial carcinoma that was clinically restricted to the uterus were randomized in robotic surgery (44 cases) and traditional laparoscopic surgery (45 cases). We compared the number of retrieved lymph nodes, total time of surgery, time of each surgical step, blood loss, length of hospital stay, major and minor complications, conversion rates and costs. RESULTS: The ages of the patients ranged from 47 to 69 years. The median body mass index was 31.1 (21.4-54.2) in the robotic surgery arm and 31.6 (22.9-58.6) in the traditional laparoscopic arm. The median tumor sizes were 4.0 (1.5-10.0) cm and 4.0 (0.0-9.0) cm in the robotic and traditional laparoscopic surgery groups, respectively. The median total numbers of lymph nodes retrieved were 19 (3-61) and 20 (4-34) in the robotic and traditional laparoscopic surgery arms, respectively. The median total duration of the whole procedure was 319.5 (170-520) minutes in the robotic surgery arm and 248 (85-465) minutes in the traditional laparoscopic arm. Eight major complications were registered in each group. The total cost was 41% higher for robotic surgery than for traditional laparoscopic surgery. CONCLUSIONS: Robotic surgery for endometrial cancer presented equivalent perioperative morbidity to that of traditional laparoscopic surgery. The duration and total cost of robotic surgery were higher than those of traditional laparoscopic surgery.

A novel model to estimate lymph node metastasis in endometrial cancer patients.

OBJECTIVES:: To evaluate the postoperative pathological characteristics of hysterectomy specimens, preoperative cancer antigen (CA)-125 levels and imaging modalities in patients with endometrial cancer and to build a risk matrix model to identify and recruit patients for retroperitoneal lymphadenectomy. METHODS:: A total of 405 patients undergoing surgical treatment for endometrial cancer were retrospectively reviewed and analyzed. Clinical (age and body mass index), laboratory (CA-125), radiological (lymph node evaluation), and pathological (tumour size, grade, lymphovascular space invasion, lymph node metastasis, and myometrial invasion) parameters were used to test the ability to predict lymph node metastasis. Four parameters were selected by logistic regression to create a risk matrix for nodal metastasis. RESULTS:: Of the 405 patients, 236 (58.3%) underwent complete pelvic and para-aortic lymphadenectomy, 96 (23.7%) underwent nodal sampling, and 73 (18%) had no surgical lymph node assessment. The parameters predicting nodal involvement obtained through logistic regression were myometrial infiltration >50%, lymphovascular space involvement, pelvic lymph node involvement by imaging, and a CA-125 value >21.5 U/mL. According to our risk matrix, the absence of these four parameters implied a risk of lymph node metastasis of 2.7%, whereas in the presence of all four parameters the risk was 82.3%. CONCLUSION:: Patients without deep myometrial invasion and lymphovascular space involvement on the final pathological examination and with normal CA-125 values and lymph node radiological examinations have a relatively low risk of lymph node involvement. This risk assessment matrix may be able to refer patients with high-risk parameters necessitating lymphadenectomy and to decide the risks and benefits of lymphadenectomy.

Modeling and simulation for toxicity assessment.

The effect of various toxicants on growth/death and morphology of human cells is investigated using the xCELLigence Real-Time Cell Analysis High Troughput in vitro assay. The cell index is measured as a proxy for the number of cells, and for each test substance in each cell line, time-dependent concentration response curves (TCRCs) are generated. In this paper we propose a mathematical model to study the effect of toxicants with various initial concentrations on the cell index. This model is based on the logistic equation and linear kinetics. We consider a three dimensional system of differential equations with variables corresponding to the cell index, the intracellular concentration of toxicant, and the extracellular concentration of toxicant. To efficiently estimate the model's parameters, we design an Expectation Maximization algorithm. The model is validated by showing that it accurately represents the information provided by the TCRCs recorded after the experiments. Using stability analysis and numerical simulations, we determine the lowest concentration of toxin that can kill the cells. This information can be used to better design experimental studies for cytotoxicity profiling assessment.

A novel model to estimate lymph node metastasis in endometrial cancer patients

OBJECTIVES: To evaluate the postoperative pathological characteristics of hysterectomy specimens, preoperative cancer antigen (CA)-125 levels and imaging modalities in patients with endometrial cancer and to build a risk matrix model to identify and recruit patients for retroperitoneal lymphadenectomy. METHODS: A total of 405 patients undergoing surgical treatment for endometrial cancer were retrospectively reviewed and analyzed. Clinical (age and body mass index), laboratory (CA-125), radiological (lymph node evaluation), and pathological (tumour size, grade, lymphovascular space invasion, lymph node metastasis, and myometrial invasion) parameters were used to test the ability to predict lymph node metastasis. Four parameters were selected by logistic regression to create a risk matrix for nodal metastasis. RESULTS: Of the 405 patients, 236 (58.3%) underwent complete pelvic and para-aortic lymphadenectomy, 96 (23.7%) underwent nodal sampling, and 73 (18%) had no surgical lymph node assessment. The parameters predicting nodal involvement obtained through logistic regression were myometrial infiltration >50%, lymphovascular space involvement, pelvic lymph node involvement by imaging, and a CA-125 value >21.5 U/mL. According to our risk matrix, the absence of these four parameters implied a risk of lymph node metastasis of 2.7%, whereas in the presence of all four parameters the risk was 82.3%. CONCLUSION: Patients without deep myometrial invasion and lymphovascular space involvement on the final pathological examination and with normal CA-125 values and lymph node radiological examinations have a relatively low risk of lymph node involvement. This risk assessment matrix may be able to refer patients with high-risk parameters necessitating lymphadenectomy and to decide the risks and benefits of lymphadenectomy.