Georgios C. Zografos

Background: Evidence regarding EUS-guided intratumoral phosphorus-32 (P-32) microparticle implantation for locally advanced pancreatic cancer (LAPC) remains limited. This prospective pilot study evaluated its technical feasibility, preliminary safety, and early disease-control outcomes when administered in combination with gemcitabine plus nab-paclitaxel. Methods: Seventeen patients with unresectable LAPC underwent EUS-guided intratumoral P-32 microparticle implantation through a 22-gauge fine-needle aspiration needle during the fourth week of systemic chemotherapy. Intratumoral distribution was assessed using Bremsstrahlung SPECT/CT. Tumour response was evaluated according to RECIST version 1.1, and treatment-emergent adverse events were graded according to CTCAE version 4.0. The main secondary endpoint was local disease control rate at approximately 16 weeks (LDCR16w). All analyses were descriptive. Results: Implantation was technically successful in all 17 patients (100.0%; exact 95% CI, 80.5–100.0%), and SPECT/CT confirmed intratumoral distribution in every case. No implantation-related procedural complications were recorded (0/17; exact 95% CI, 0.0–19.5%). At approximately 16 weeks, CT assessment was available for 16 patients: seven had a partial response and nine had stable disease. The LDCR16w was 16/16 among evaluable patients (100.0%; exact 95% CI, 79.4–100.0%) and 16/17 in the all-treated analysis (94.1%; exact 95% CI, 71.3–99.9%). A reduction in CA19-9 of at least 50% was observed in 13/16 evaluable patients. Four patients underwent subsequent R0 resection (4/17, 23.5%; exact 95% CI, 6.8–49.9%). Adverse events were predominantly grade 1–2; one grade 3 abdominal pain event and no grade 4–5 events were recorded. Only three deaths occurred during a median OS follow-up of 15.6 months, making survival estimates exploratory and statistically immature. Conclusions: In this small, single-center pilot cohort of highly selected patients, EUS-guided intratumoral P-32 microparticle implantation combined with gemcitabine plus nab-paclitaxel was technically feasible and provided preliminary safety information. Because of the absence of a chemotherapy-only comparator, the small sample size, and the limited follow-up, the radiographic, biomarker, resection, and survival outcomes cannot be attributed specifically to P-32 implantation and should be considered descriptive and hypothesis-generating. Larger controlled studies with longer follow-up are required to determine clinical efficacy.

Background Severe obesity is associated with hormonal imbalances, hyperandrogenism, and insulin resistance, all of which adversely affect reproductive physiology. Metabolic and bariatric surgery (MBS) produces durable weight loss and metabolic improvement, but its effects on ovarian reserve markers and reproductive hormones in women of reproductive age remain incompletely characterized. Objective To prospectively evaluate the impact of laparoscopic sleeve gastrectomy on obesity indices, reproductive hormones, ovarian reserve markers, and insulin resistance over 12 months in women with severe obesity. Methods Thirty-two women with severe obesity (BMI > 40 kg/m²) undergoing laparoscopic sleeve gastrectomy were assessed at three time points: baseline (2–4 weeks before surgery, prior to the standard pre-operative very-low-calorie diet), 6 months, and 12 months post-operatively. Anthropometric, reproductive-hormone (anti-Müllerian hormone [AMH], antral follicle count [AFC], follicle-stimulating hormone [FSH], luteinizing hormone [LH], estradiol, sex hormone-binding globulin [SHBG], total testosterone, calculated free androgen index [FAI]), and metabolic (HOMA-IR) parameters were measured. Non-parametric tests (Wilcoxon signed-rank, Spearman correlation) were applied. Results BMI decreased from 42.38 ± 1.41 to 25.65 ± 0.34 kg/m² at 12 months (p < 0.001). AMH declined from 3.13 ± 0.17 to 2.24 ± 0.44 ng/mL; AFC fell from 11.22 ± 1.60 to 7.16 ± 1.63 (right ovary) and from 11.09 ± 1.30 to 6.19 ± 0.86 (left ovary). FSH, LH, and estradiol increased; SHBG nearly doubled (36.26 → 63.77 nmol/L); total testosterone decreased markedly (27.76 → 9.34 ng/dL); FAI fell from 2.73 ± 0.85 to 0.53 ± 0.19; HOMA-IR declined from 3.94 ± 0.46 to 1.66 ± 0.56 (all p < 0.001). Spearman correlations among change scores showed inverse associations between ΔSHBG and ΔFAI (ρ = −0.420, p = 0.017), and between ΔHOMA-IR and Δtotal testosterone (ρ = −0.374, p = 0.035). Conclusions Sleeve gastrectomy was associated with marked improvements in insulin resistance and androgenic profiles, accompanied by progressive increases in SHBG and reductions in FAI, AMH, and AFC over 12 months. Rather than suggesting deterioration of ovarian function, the overall hormonal pattern appears more consistent with normalization of obesity-associated dysregulated folliculogenesis within an improved metabolic environment. While direct reproductive outcomes were not assessed, these findings support the concept that metabolic bariatric surgery may substantially remodel the endocrine milieu linked to ovarian physiology. Larger prospective studies incorporating fertility-related endpoints are required to clarify the reproductive significance of these changes.

Background: Pancreatic cancer is a leading cause of cancer-related mortality. Locally advanced pancreatic cancer (LAPC) remains associated with low resection rates and poor survival despite advances in systemic therapy. Intratumoral Phosphorus-32 (P-32) microparticle implantation is an emerging locoregional brachytherapy approach for unresectable LAPC. Methods: This prospective single-center observational cohort study included patients with unresectable LAPC treated with gemcitabine plus nab-paclitaxel and EUS-guided intratumoral P-32 microparticle implantation. Intratumoral distribution was assessed by SPECT/CT. Tumour response was evaluated according to RECIST 1.1, with local disease control rate (LDCR) assessed at approximately 16 weeks. Adverse events were graded according to CTCAE version 4.0. Results: Seventeen patients underwent P-32 implantation (median age, 70 years; ECOG PS 0–1). SPECT/CT confirmed appropriate intratumoral distribution in all patients, with no implantation-related procedural complications. At 16 weeks, 7/16 evaluable patients (43.8%) achieved partial response and 9/16 (56.2%) had stable disease, resulting in an LDCR of 100% among evaluable patients and 94.1% in the all-treated analysis. Mean target-lesion diameter decreased from 3.4 to 2.8 cm, with a median reduction of 21.4%. CA19-9 decreased by ≥50% in 13/16 evaluable patients (81.2%). Four patients (23.5%) underwent surgical resection, all achieving R0 resection. Adverse events were predominantly grade 1–2; one grade 3 event and no grade 4–5 events occurred. Conclusions: P-32 microparticle implantation combined with systemic chemotherapy was feasible and demonstrated encouraging early local activity with an acceptable safety profile. These findings support further prospective evaluation in larger cohorts.

The Breast Cancer (BRCA) genes play an important role in repairing double-strand deoxyribonucleic acid (DNA) breaks. Mutations in these genes are associated with the development of malignancies, most notably breast and ovarian cancer. Carriers of these mutations are often faced with issues that have serious implications for their reproductive choices, including the occurrence and treatment of breast or ovarian cancer, recommendations for preventive mastectomy and salpingo-oophorectomy, and the risk of transmitting the BRCA gene mutation to an offspring. These issues often lead to the search for methods of fertility preservation or assisted reproduction. This review aims to highlight and explain all the ways in which BRCA gene mutations affect fertility in women. Specifically, the effect of BRCA carriage is assessed at the molecular, histological, clinical, and laboratory levels. Next, fertility preservation methods in carriers are analyzed and evaluated in terms of their safety and effectiveness. In addition, the effect of systemic therapies for breast cancer on ovarian reserves is explained. Finally, the possibility of preimplantation diagnosis of BRCA gene carriage is also examined.

Background: Total gastrectomy with D2 lymph node dissection is standard for resectable esophagogastric junctional and gastric cancer, but high morbidity challenges perioperative care. ERAS guidelines advise against routine drains, yet conflicting evidence leads to inconsistent practice. Methods: The DRAG (DRains After Gastrectomy) Trial is a prospective, non-randomized study conducted from February 2020 to March 2023 at the 1st Propaedeutic Surgery Department, Hippocration General Hospital, Athens. Patients undergoing open D2 total gastrectomy had perianastomotic drains placed based on newly established criteria, offering a more tailored approach. Immediate and short-term postoperative outcomes, including recovery milestones and complications, were assessed. Results: Sixty patients were included, with 40 receiving a drain. The non-drain group had significantly lower pain scores, earlier mobilization, less postoperative nausea and vomiting, and a shorter hospital stay. Among those with complications, significant differences in surgical site infections, delayed mobilization, extra-abdominal issues, length of stay, readmissions, and reoperations suggest that drain use may increase complications and hinder recovery. Conclusion: Our study suggests that routine prophylactic drain use can be avoided in gastrectomy for esophagogastric junctional and gastric cancer when experienced surgeons in high-volume centers follow predefined criteria. Implementing these criteria may improve patient outcomes and reduce complications.

Background: Differential tumor resection efficacy between robotic and open partial nephrectomy has been extensively explored. This study comparatively evaluates the above nephron-sparing approaches focusing on the Trifecta outcome, along with its individual components, as a metric for surgical quality assessment. Methods: A literature review from August 2022 to August 2024 yielded 51 relevant studies. Trifecta attainment served as the primary outcome, while secondary end-points included the incidence of major and minor postoperative complications, positive surgical margin rates, the absolute ischemia duration, as well as the corresponding postoperative alterations in estimated glomerular filtration rate and plasma creatinine levels. Analyses were conducted using random-effects meta-analysis models, with subgroup analyses performed to manage heterogeneity. Additionally, meta-regression was implemented on a temporal and qualitative basis, and sensitivity analysis was carried out on the most statistically robust studies. Results: The robotic approach exhibited clear superiority in overall Trifecta achievement, with odds ratios ranging between 1.3-1.8 and indicating a quasi-constant comparative effect over time. Major and minor complication rates, as defined by the Clavien-Dindo classification, favored robotic surgery, demonstrating odds ratios of 0.5-0.7 and 0.5-0.6, respectively. Specifically, a consistent to increasing trend of advantage was observed for severe complications over time and across qualitative measures. Conversely, a stable and significant benefit was noted for mild complications on the chronological scale. The robotic intervention also significantly impacted the estimated glomerular filtration rate, preserving an additional 2-3 ml/min/1.73m² postoperatively compared to open surgery. However, this finding was considered of limited clinical importance due to the low magnitude of the effect. Ischemic times and positive surgical margin rates did not significantly differ between the two approaches. Finally, the findings regarding the postoperative increase in serum creatinine levels from baseline were inconclusive, with neither modality demonstrating superiority over the other. Conclusion: Robotic partial nephrectomy surpasses open surgery in Trifecta attainment and in mitigating major and minor complications. However, the clinical significance of renal function preservation is marginal and requires further prospective investigation.

Background: Total gastrectomy with D2 lymph node dissection is standard for resectable esophagogastric junctional and gastric cancer, but high morbidity challenges perioperative care. ERAS guidelines advise against routine drains, yet conflicting evidence leads to inconsistent practice. Methods: The DRAG (DRains After Gastrectomy) Trial is a prospective, non-randomized study conducted from February 2020 to March 2023 at the 1st Propaedeutic Surgery Department, Hippocration General Hospital, Athens. Patients undergoing open D2 total gastrectomy had perianastomotic drains placed based on newly established criteria, offering a more tailored approach. Immediate and short-term postoperative outcomes, including recovery milestones and complications, were assessed. Results: Sixty patients were included, with 40 receiving a drain. The non-drain group had significantly lower pain scores, earlier mobilization, less postoperative nausea and vomiting, and a shorter hospital stay. Among those with complications, significant differences in surgical site infections, delayed mobilization, extra-abdominal issues, length of stay, readmissions, and reoperations suggest that drain use may increase complications and hinder recovery. Conclusion: Our study suggests that routine prophylactic drain use can be avoided in gastrectomy for esophagogastric junctional and gastric cancer when experienced surgeons in high-volume centers follow clearly defined criteria. Implementing these criteria may improve patient outcomes and reduce complications.

Exploration of surgical precision in robotic procedures is extensive, yet lacks a unified framework for comparability. This study examines tissue handling precision by comparing the per-minute blood loss rate between robotic and open partial nephrectomy. A literature search from August 2022 to June 2024 identified 43 relevant studies providing data on estimated blood loss and procedure duration. The expected values and standard errors of these variables were used to compute the per-minute blood loss rate (Q). Meta-analytical methods estimated pooled and subgroup-level mean differences, favoring robotic surgery (MD_Q = − 1.043 ml/min, CI_95% = [− 1.338; − 0.747]). Subgroup analyses by publication year, patient matching, referral center count, and ROBINS-I status consistently supported this advantage. Sensitivity analyses confirmed the above benefit in studies with increased accuracy in reported results (MD_Q = – 0.957 ml/min, CI_95% = [– 1.269; – 0.646]), low risk of bias involving matched comparisons (MD_Q = – 0.563 ml/min, CI_95% = [– 0.716; – 0.410]), large sample sizes and increased statistical power (MD_Q = – 0.780 ml/min, CI_95% = [– 1.134; – 0.425]), and multicenter analyses with patient matching (MD_Q = – 0.481 ml/min, CI_95% = [– 0.698; – 0.263]). The subsequent analysis of correlation between the original variables suggested a slight reduction in the robotic advantage when the latter were proportionally related. Multilevel meta-regression at both temporal and qualitative scales consistently indicated a comparative benefit of the robotic approach. Potentially, lower per-minute blood loss compared to open surgery suggests that robotic partial nephrectomy demonstrates enhanced precision in tissue handling.

Translational perspective: Ischemic heart disease remains a major medical problem with high mortality rates. Beside the great efforts devoted to research worldwide and the use of numerous experimental models, an absolute understanding of myocardial infarction and tissue loss has not yet been achieved. Furthermore, the regeneration of myocardial tissue and the improvement of myocardial activity after ischemia is one of the major areas of interest in the medical (and especially cardiovascular) community. In a novel experimental rat model, the beneficial effect of mesenchymal stem cell transplantation (MSCT) in a surgically induced ischemic myocardium was documented. From a clinical perspective, this work supports the surgical administration of MSCT in the infarcted area during coronary artery bypass surgery. Aims: The regeneration of myocardial tissue and the improvement of myocardial activity after ischemia is one of the major areas of interest in cardiovascular research. We developed a novel experimental rat model and used it to examine the effect of mesenchymal stem cell transplantation (MSCT) on myocardial ischemia evaluated by SPECT-CT and immunohistochemistry. Methods and results: An open thoracotomy took place for forty adult female Wistar rats with (n = 30) or without (n = 10) surgical ligation of the left anterior descending coronary artery (LAD) in order to cause myocardial ischemia. Myocardial viability was evaluated via SPECT/CT 7 days before surgery, as well as at 7 and 14 days post-surgery. At day 0, 15 animals received homologous stem cells injected at the ischemic myocardium area. A SPECT/CT evaluation showed decreased activity of the myocardial cells in the left ventricle one week post-infarction. Regeneration of the ischemic myocardium fifteen days post-infarction was recorded only in animals subjected to stem cell transplantation. These findings were also confirmed by histology and immunohistochemical analysis, with the significantly higher expression of GATA4 and Nkx2.5. Conclusions: The positive effect of mesenchymal stem cell transplantation in the ischemic myocardium was recorded. The application of SPECT-CT allowed a clear evaluation of both the quality and quantity of the living myocardium post-infarction, leading to a new approach in the research of cardiovascular diseases. From a clinical perspective, MSCT may be beneficial when accompanied by myocardial revascularization procedures.

: Aims: Regeneration of myocardial tissue and improvement of myocardial activity after ischemia is one of the major fields of interest in cardiovascular research. We have developed a novel experimental rat model, and used it to examine the effect of mesenchymal stem cell transplantation (MSCT) on myocardial ischemia evaluated by single photon emission computed tomography (SPECT/CT) and immunohistochemistry. Methods and results: Forty adult female Wistar rats underwent open thoracotomy with (n=30) or without (n=10) surgical ligation of the left anterior descending coronary artery (LAD), to create myocardial ischemia, which was confirmed with ECG. Myocardial viability was evaluated via SPECT/CT at 7 days before as well as at 7 and 14 days post-surgery. At day 0, 15 animals received homologous stem cells injected at the ischemic myocardium area. SPECT/CT evaluation confirmed the reduction of functional myocardial cells of the left ventricle one week post-infarction. Regeneration of the ischemic myocardium fifteen days post infarction was recorded, only in animals submitted to stem cell transplantation. Findings were also confirmed by histology and immunohistochemical analysis, with significant higher expression of GATA4 and Nkx2,5. Conclusion: The positive effect of mesenchymal stem cells transplantation in the ischemic myocardium was recorded. The application of SPECT- CT qualitative and quantitative evaluation of myocardial function may lead to a new approach in experimentation with an anticipated significant impact in the ongoing cardiovascular laboratory research. In clinical perspective, MSCT may be beneficial when accompanied with myocardial revascularization procedures.