CA-125 KELIM as an Alternative Predictive Tool to Identify Which Patients Can Benefit from PARPi in High-Grade Serous Advanced Ovarian Cancer: A Retrospective Pilot Diagnostic Accuracy Study.

BRCA mutation and homologous recombination deficiency (HRD) are the criteria for the administration of PARP inhibitor (PARPi) maintenance therapy. It is known that PARPi efficacy is related to platinum sensitivity and that the latter can be demonstrated from the CA-125 elimination rate constant (KELIM). This study aims to investigate if KELIM can be another tool in the identification of patients that could be benefit from PARPi therapy. Retrospective analysis of patients with high-grade serous advanced ovarian cancer that underwent cytoreduction and was further tested for HRD status. The HRD status was tested either by myChoice HRD CDx assay or by RediScore assay. KELIM score was measured in both neoadjuvant and adjuvant settings with the online tool biomarker-kinetics.org. A total of 39 patients had available data for estimating both HRD status and KELIM score. When assuming KELIM as a binary index test with the value 1 as the cut-off point, the sensitivity was 0.86, 95% CI (0.64-0.97) and the specificity was 0.83, 95% CI (0.59-0.96). On the other hand, when assuming KELIM as a continuous index test, the area under the curve (AUC) was 81% and the optimal threshold, using the Youden index, was identified as 1.03 with a sensitivity of 85.7% and a specificity of 83.3%. KELIM score seems to be a new, cheaper, and faster tool to identify patients that can benefit from PARPi maintenance therapy.

The Use of CA-125 KELIM to Identify Which Patients Can Achieve Complete Cytoreduction after Neoadjuvant Chemotherapy in High-Grade Serous Advanced Ovarian Cancer.

(1) Background: Neoadjuvant chemotherapy followed by interval debulking surgery is used in the treatment of advanced ovarian cancer. However, no tool can safely predict if complete cytoreduction after 3-4 cycles can be achieved. This study aims to investigate if the KELIM score can be a triage tool in the identification of patients that will be ideal candidates for interval debulking surgery (IDS). (2) Methods: We retrospectively analyzed the records of patients with high-grade serous advanced ovarian cancer that were treated in the 1st Department of Obstetrics-Gynecology, 2012-2022, with neoadjuvant chemotherapy followed by IDS. Patient characteristics, oncological outcome and follow-up information were collected. The primary outcome was the association of the KELIM score with residual disease. (3) Results: 83 patients were categorized into two groups: Group A (51 patients) with favorable (≥1) and Group B (32 patients) with unfavorable (<1) KELIM scores. A statistically significant correlation between KELIM and residual disease (p < 0.05) exists, showing that patients with a favorable KELIM score can achieve a complete IDS. Furthermore, there was a statistically significant difference in overall survival (p = 0.017), but no difference was observed in progression-free survival (p = 0.13); (4) Conclusions: KELIM seems to safely triage patients after neoadjuvant chemotherapy and decide who will benefit from IDS.

In Vitro and In Vivo Effects of Docetaxel and Dasatinib in Triple-Negative Breast Cancer: A Research Study.

Introduction Triple-negative breast cancer (TNBC) comprises a heterogeneous group of tumors with a single trait in common: an evident aggressive nature with higher rates of relapse and lower overall survival in the metastatic context when compared to other subtypes of breast cancer. To date, not a single targeted therapy has been approved for the treatment of TNBC, and cytotoxic chemotherapy remains the standard treatment. In the present experimental study, we examine the effects of the chemotherapeutic docetaxel and the bcr/abl kinase inhibitor dasatinib on TNBC cell lines (in vitro) and on TNBC tumor xenograft mouse models (in vivo). Materials and methods TNBC cell lines were cultivated and treated with various concentrations of docetaxel and dasatinib (5 nM to 100 nM). Cell death and apoptosis were studied by flow cytometry. TNBC cell lines were then injected in BALB/c athymic nude mice to express the tumor in vivo. Four groups of mice were created (group A: control; group B: DOC; group C: DAS; group D: DOC + DAS) and treated, respectively, with the drugs and their combination. Tumors were obtained, maintained in a 10% formaldehyde solution, embedded in paraffin, and sent for further histological evaluation (hematoxylin-eosin staining and immune-histochemical analysis) to assess the tumor growth inhibition. Results The cytotoxic effects of docetaxel seem statistically important, with little effect on apoptosis. The effect of dasatinib in vitro and vivo is statistically important, in terms of apoptosis and tumor reduction, with little adverse effects. Conclusions TNBC is a difficult-to-treat oncologic condition, even in an experimental setting. Promising results concerning the addition of targeted therapies (dasatinib) to the conventional cytotoxic ones (docetaxel) have been shown, awaiting further evaluation.

Isolated aberrant right cysticohepatic duct injury during laparoscopic cholecystectomy: Evaluation and treatment challenges of a severe postoperative complication associated with an extremely rare anatomical variant.

A typical bile duct branching patterns represent one of the major causes of bile duct injury (BDI) during laparoscopic cholecystectomy (LC). The most common classified variations of bile duct branching, involve the right posterior sectoral duct (RPSD) and its joining with the right anterior or left hepatic duct. Variant bile duct anatomy can rarely be extremely complex and unclassified. This report describes an extremely rare case of an isolated injury to an aberrant right hepatic duct formed by the joining of ducts from segments V, VII, and VIII draining into the cystic duct (cysticohepatic duct) during LC, associated with an inferior RPSD opening to left hepatic duct. Detailed evaluation of both endoscopic and magnetic cholangiograms established the diagnosis. Bile duct injury was subsequently managed surgically by a demanding Roux-en-Y hepaticojejunostomy. This extremely rare case aims to serve as a useful reminder of the consistent inconsistency of biliary anatomy, alerting surgeons to beware of variant bile duct branching patterns during open or LC that constitute a dreadful pitfall for severe and life-threatening bile duct injuries.

Medical practice in the ancient Asclepeion in Kos island.

Asclepius was called "a great doctor for every disease". Asclepius was born in Trikala, Thessaly, in the middle of Greece, where the first Asclepeion was established. Patients coming to the Asclepeia were first taking cleaning baths and then entered the main Asclepeion, where they were examined by priests-therapists and were accommodated in certain areas-rooms of the Asclepeion. Inscriptions found in marble plaques describe treatment of some diseases and the sum of money paid for every treatment. These were the first medical records and fees in ancient Greece. Patients were considered as a unique psychosomatic entity. Patients followed many instructions in order to relax and rest, submitted daily baths, exercises, massages, entertainment attending theatrical or poetic or athletic races, reading special books, promenades, special diets or were kept fasting and were instructed to take many kinds of medicine per os, suppositories, ointments, eye drops etc. The main diseases treated in the Asclepeia were: chronic neuropsychological disorders, skin diseases and chronic lung diseases. Other diseases gynaecological, ophthalmic and surgical were also treated. Today, like in the ancient Asclepeia, the psychology of patients is important and certain preparatory drugs are administered before the actual main treatment of surgery or of some psychic disorders. In Aalborg, Denmark, a large prototype medical university hospital, is scheduled to be built in an area of 350acres within the next 15 years. The psychosomatic dogma and principals of a "green building" will be well respected. The Asclepeion of the island of Kos, where as we know Hippocrates was born, was built on the 5th century B.C. and functioned till the 4th century A.D. and had three floors. The Asclepeion had many dedications, of which many parts of the human body in marble: an ear, a damaged penis and two breasts. Surgical tools were also found and are now exhibited in the Dion Museum. After the 4th century A.D. the Asclepeion was destructed and/or destroyed by religious groups, more earthquakes, conflagrations, the Saint John's Knights of Jerusalem and the Turks. Recent excavations in the area in order to find and restore the old Asclepeion started in 1902. Now Asclepeion is partly restored. In conclusion, it is suggested that Hippocratic medicine, as practiced in the Asclepeion of the island of Kos, using psychosomatic means of treatment in a green natural environment was effective for many diseases at that time but also inspired modern medicine and as an example a large university institution is now under constructions based on the above ideals.