IIIA IIIB Research Articles

Intestinal monoamine oxidase activity in premature and full-term infants with surgical pathology

Advances in pediatric surgery, intensive care, and anesthesiology have significantly improved the outcomes of surgical treatment of full-term and premature infants with intestinal malformations and necrotizing enterocolitis (NEC). The main challenges in treating children of this complex group today lie in improving diagnostics, choosing treatment tactics, and ensuring the postoperative period. Monoamine oxidase (MAO) is a mitochondrial enzyme that catalyzes oxidative deamination of biogenic and xenobiotic monoamines, including those in intestinal wall cells and tissues. It can be a prognostic and diagnostic marker of the effectiveness and rate of intestinal recovery in the postoperative period, and also serve as a point of application for pharmacological correction. The aim of the study is to determine the activity of intestinal MAO in children of the first year of life with surgical pathology. Material and methods. The study included 24 patients with colon and small intestine pathologies, aged from 1 day to 3 months, who were treated at the Chelyabinsk Regional Children’s Clinical Hospital from October 2022 to May 2024. MAO-A and MAO-B activity was studied by spectrophotometry in intestinal homogenates obtained at the proximal resection margin. Results and discussion. Intestinal samples obtained from patients with diseases accompanied by pronounced inflammatory changes (NEC stage IIIA–IIIB, enterostomy closure after NEC III, intestinal neuronal dysplasia (IND), Hirschsprung’s disease) showed a significant decrease in the activity of the MAO-A isoform. A decrease in MAO-B activity was demonstrated in intestinal wall samples obtained from children with confirmed diagnoses of Hirschsprung’s disease and intestinal neuronal dysplasia, as well as in premature infants with surgical stages of NEC. The highest activity of both enzyme isoforms was found in sigmoid colon samples without pathological changes in patients with anal and rectum atresia.

Prognostic Factors in Limited-Stage Small Cell Lung Cancer

The impact of patient-specific, disease-related, and social factors on outcomes in limited-stage small cell lung cancer (LS-SCLC) is not well defined. A post hoc secondary analysis of such factors from the Cancer and Leukemia Group B (CALGB) 30610-Radiation Therapy Oncology Group (RTOG) 0538 trial may impact future trial design. To assess the comprehensive demographic, disease-related, treatment-related, and social factors for potential associations with survival outcomes and understand whether specific subpopulations may benefit from radiotherapy (RT) dose escalation in LS-SCLC. This post hoc secondary analysis of a randomized clinical trial included 638 adults with LS-SCLC treated at 186 unique treatment sites with at least 1 accrual for all patients from March 15, 2008, to December 1, 2019; 313 patients were randomized to receive RT twice daily to a dosage of 45 Gy for 3 weeks and 325 to receive RT once daily to a dosage of 70 Gy for 7 weeks. Data were locked February 28, 2022, and analyzed from November 28, 2022, to June 4, 2024. Twice-daily RT or once-daily RT. Multivariable Cox proportional hazards models evaluated the association of treatment groups and other risk factors with progression-free survival (PFS) and overall survival (OS). Patient-specific factors included age, sex, and Eastern Cooperative Oncology Group performance status. Disease-related factors included tumor, nodal, and overall cancer stages. Treatment-related factors included type of chemotherapy, timing of concurrent RT, RT technique, and prophylactic cranial irradiation. Social factors included marital status and treatment center accrual volume. Among 507 patients (260 [51.3%] female and 247 [48.7%] male; mean [SD] age, 62.6 [7.9] years) included in the multivariate survival analysis, with a median follow-up of 4.7 (IQR, 3.7-7.1) years, female sex was associated with improved OS (hazard ratio [HR], 0.73 [95% CI, 0.58-0.91]; P = .006), while being 70 years or older was associated with decreased OS (HR, 1.50 [95% CI, 1.14-1.98]; P = .004). Neither age nor sex was associated with PFS. When compared with those with N1 disease, OS and PFS were worse in patients with N2 (HRs, 1.64 [95% CI, 1.19-2.26]; P = .002 and 1.36 [95% CI, 1.02-1.81]; P = .04, respectively) and N3 (HRs, 2.03 [95% CI, 1.40-2.93]; P < .001 and 1.63 [95% CI, 1.17-2.26]; P = .004) disease. Compared with stage II cancer, OS was worse for stage IIIA (HR, 1.65 [95% CI, 1.17-2.31]; P = .004) and stage IIIB (HR, 1.94 [95% CI, 1.34-2.83]; P < .001). Compared with high-volume accrual centers, treatment at low- or middle-volume accrual centers was associated with worse PFS (HRs, 1.94 [95% CI, 1.33-2.82; P < .001] and 1.44 [95% CI, 1.15-1.82; P = .002], respectively) and worse OS (HRs, 1.55 [95% CI, 1.03-2.32; P = .03] and 1.33 [95% CI, 1.04-1.70; P = .02], respectively). This secondary analysis of the CALGB 30610-RTOG 0538 randomized clinical trial of patients with LS-SCLC found associations between female sex or being younger than 70 years and improved overall survival and between advanced nodal stage or treatment at low- or middle-volume accrual centers and worse outcomes. These findings suggest that stratification by nodal stage, clinical stage, and age should be considered in future randomized trials. ClinicalTrials.gov Identifier: NCT00632853.

Analysis of the experience of robot-assisted cystectomy with various types of urine derivation

BACKGROUND: Radical cystectomy is the main treatment for patients with muscle-invasive bladder cancer. Robot-assisted operations have become increasingly widespread; thus, an analysis of the results of using this technique is required. AIM: To analyze our experience with robot-assisted radical cystectomy with different types of urinary diversion and compare the results to those obtained by other centers. MATERIALS AND METHODS: The treatment results of 23 patients who underwent robot-assisted cystectomy with various types of urine derivation for bladder cancer between 2021 and 2024 were retrospectively analyzed. RESULTS: Patients who had the Studer urinary reservoir formed were slightly younger and had better functional status and a higher body mass index. Additionally, there were more patients of the very high-risk cT1 stage. In patients who underwent ureterocutaneostomy, stages sT3–4 were more common. The average duration of the operation was 418.2 minutes. The longest duration (533.5 minutes) was observed during the formation of the urinary reservoir and the shortest (294.3 minutes) during ureterocutaneostomy. The smallest (200 ml) and largest (3,500 ml) blood loss occurred in patients who underwent Bricker ileal conduit formation. Ten conversions to open surgery (5 in the group of patients who had a urinary reservoir and 5 in ileoconduit) were noted. Nine patients developed postoperative complications, with seven exhibiting Clavien–Dindo grade IIIa–IIIb complications. The median follow-up was 19.7 months. Disease progression occurred in two (9%) patients. One patient died 1.5 years after surgery due to underlying disease progression. CONCLUSIONS: Robot-assisted cystectomy is currently limited to specialized centers. The exchange of experience between them and its analysis are crucial to assess the immediate and long-term results of this technique and determine the category of patients who will benefit most from its application.

A new technique for percutaneous screw fixation for treating FFP IIIa and IIIb fragility fractures of the pelvis

To determine the presence of a consistent osseous corridor from the lateral-posterior aspect of the anterior inferior iliac spine to the sacral wing that could be used for safe trans percutaneous screw fixation for pelvic fragility fractures of the iliac wing and fracture dislocations of the sacroiliac joint (FFP types IIIa and IIIb). Computed tomography (CT) scans were obtained from 100 patients and imported to Mimics software for 3D reconstruction. Then, a cylinder was drawn to imitate the modified LC-II screw and adjusted to a maximum radius and length to obtain the feasible region. Thirteen parameters of the osseous corridor of the modified LC-II screw were measured. Differences between sex groups were compared, and significant statistical correlations were carefully studied to determine potentially important clinical relationships. The records of patients with FFP type IIIa and IIIb fragility fractures of the pelvis were extracted from our hospital. Patients who underwent modified LC-II screw fixation, LC-II screw fixation or reconstruction plate fixation were included. Patients’ operative characteristics and complications were recorded at follow-up. Fracture reduction quality was assessed using the Matta standard. Functional outcomes were evaluated using the Majeed grading system. The mean maximum diameters of the osseous corridors of the modified LC-II screw in males and females were 12.73 and 10.83 mm, respectively. The mean maximum lengths of the osseous corridors of the modified LC-II screw in males and females were 96.37 and 93.37 mm, respectively. In the treatment of patients with FFP IIIa and FFP IIIb fractures, the group of treatment by the modified LC-II screws fixation was shown significantly shorter operative time and fewer intraoperative blood loss in comparison to that by the reconstruction plates. In the present study, all the males and females had a complete osseous corridor of the modified LC-II screw. The clinical results of the patients who were treated with modified LC-II screw fixation suggest that the novel method has a good preliminary outcome.

Evaluation of miRNA 130a-3P and miRNA 301a-3P in Egyptian patients with urinary bladder carcinoma

ObjectivesTo study the role of microRNA 130a-3p and microRNA 301a-3p in urinary bladder carcinoma. BackgroundDespite the discovery of several clinical and molecular indicators for predicting outcomes in bladder cancer, it is unclear how to use these indicators in clinical practice. A recent study revealed that the miR-130 family may play a vital role in the occurrence and development of BC by regulating signal pathways through various target genes. We intend to apply them as novel, nonintrusive, and easily detectable bladder cancer indicators. Subjects and methodsThe current study involved one hundred subjects. Fifty subjects had bladder cancer diagnosed by cystoscope biopsy and histopathological examination, and the other fifty were age- and gender-matched healthy adults serving as a control group. All participants were subjected to complete history taking through medical examination and estimation of expression levels of plasma miRNA 130a-3p by reverse transcriptase – polymerase chain reaction (RT-PCR) through quantitative real-time technique. ResultsmiRNA 130a-3p and miRNA 301a-3p were expressed at higher levels in the plasma of bladder cancer patients than in the controls. The points for the diagnostic capacities of miR 130a-3p and miR 301a-3p for bladder cancer were > 0.921 and > 1.32, respectively, indicating that they are potential clinical diagnostic biomarkers for bladder cancer with good sensitivity and specificity. Moreover, stage IIIA versus stage IIIB can be discriminated as >0.96 (miR 130a-3p) and > 2.48 (miR 301a-3p), which can be utilized for estimating the clinical prognosis of bladder cancer. ConclusionmiRNA 130a-3p and miRNA 301a-3p expression levels in plasma can differentiate bladder cancer patients from healthy controls and discriminate between stage IIIA and stage IIIB. This finding may facilitate the clinical diagnosis of bladder cancer.

Clear cell adenocarcinoma of the cervix and its mimickers - A series of 19 cases from a tertiary care referral centre in India.

Clear cell adenocarcinoma (CCAC) of cervix is a rare subtype of endocervical adenocarcinoma that accounts for 4% of all cervical adenocarcinoma with many morphological mimickers. Retrospectively study cases of cervical clear cell adenocarcinoma of the cervix. Clinical profile and pathological features of CCAC of the cervix diagnosed between 2018-2022 were retrospectively analyzed.The database of the Department of Pathology of our institute was systematically searched for patients diagnosed with clear cell adenocarcinoma of the cervix during 2018-2022.A total of 19 patients were studied with the mean age of patients being 53.72 years (range 25 -84 yrs,standard deviation-25.9) and median tumor size being 5.6cm. Lymph node metastasis was identified in 33.3% and distant metastasis were seen in 20% of the cases. Staging could not be done in 4 cases.FIGO staging of the cases included IB1(2 cases), IB2(2 cases), IIB (3 cases),IIIA (1 case)IIIB(4 cases),and IV(3 cases). On histopathological evaluation, heterogeneous architectural pattern comprising of tubulocystic, solid, and papillary patterns were seen in 13 cases (13/19,68.4%). Pure tubulocystic (3/19,15.7%), pure papillary (2/19,10.5%), and pure solid patterns (1/19,5.3%) were also identified. Tumor cells with clear cytoplasm ranged from 5% to 95%. Nuclear atypia was moderate to marked in all the cases (19/19,100%). Mitotic activity varied from 1/10hpf to 20-22/10hpf. By immunohistochemistry, tumor was positive for Napsin A in all the cases,p16INK4a was negative in majority of cases (15/19,78.9%) and ER was negative in 14 cases (14/19,73.7%) .p53 showed wild type staining except for one case . Clear cell adenocarcinoma being a rare subtype of cervical adenocarcinoma, needs to be differentiated from other Human Papilloma Virus(HPV) independent adenocarcinomas (gastric and mesonephric types) and benign entities such as endocervical glandular Arias-Stella reaction. Judicious use of a panel of immunostains is often helpful.

Effects of Trehalose Administration in Patients with Mucopolysaccharidosis Type III.

Mucopolysaccharidosis type III (MPS III) is a rare autosomal recessive lysosomal storage disease (LSD) caused by a deficiency of lysosomal enzymes required for the catabolism of glycosaminoglycans (GAGs), mainly in the central nervous system. Trehalose has been proposed as a potential therapeutic agent to attenuate neuropathology in MPS III. We conducted a single- arm, open-label study to evaluate the efficacy of trehalose treatment in patients with MPS IIIA and MPS IIIB. Five patients with MPS III were enrolled. Trehalose was administrated intravenously (15 g/week) for 12 weeks. Health-related quality of life and cognitive function, serum biomarkers, liver, spleen, and lung imaging were assessed to evaluate trehalose efficacy at baseline and trial end (week 12). TNO-AZL Preschool children Quality of Life (TAPQOL) scores increased in all patients, and the mean scores for quality of life were increased after the intervention. Serum GAG levels were reduced in all treated patients (however, the differences were not statistically significant). Alanine aminotransferase (ALT) levels were reduced in all patients post-treatment (p=0.0039). The mean levels of aspartate transaminase (AST) were also decreased after 12 weeks of treatment with Trehalose. Decreased serum pro-oxidant-antioxidant balance and increased GPX activity were observed at the end of the study. Decreases in mean splenic length were observed, whereas the liver volume did not change. Improvements in health-related quality of life and serum biomarkers (GAGs, liver aminotransferase levels, antioxidant status), as well as liver and spleen size, were found following 3 months of trehalose administration in patients with MPS IIIA and MPS IIIB.

Can a reconstruction algorithm in major acetabular bone loss be successful in revision hip arthroplasty?

The aims of this study were to determine the success of a reconstruction algorithm used in major acetabular bone loss, and to further define the indications for custom-made implants in major acetabular bone loss. We reviewed a consecutive series of Paprosky type III acetabular defects treated according to a reconstruction algorithm. IIIA defects were planned to use a superior augment and hemispherical acetabular component. IIIB defects were planned to receive either a hemispherical acetabular component plus augments, a cup-cage reconstruction, or a custom-made implant. We used national digital health records and registry reports to identify any reoperation or re-revision procedure and Oxford Hip Score (OHS) for patient-reported outcomes. Implant survival was determined via Kaplan-Meier analysis. A total of 105 procedures were carried out in 100 patients (five bilateral) with a mean age of 73 years (42 to 94). In the IIIA defects treated, 72.0% (36 of 50) required a porous metal augment; the remaining 14 patients were treated with a hemispherical acetabular component alone. In the IIIB defects, 63.6% (35 of 55) underwent reconstruction as planned with 20 patients who actually required a hemispherical acetabular component alone. At mean follow-up of 7.6 years, survival was 94.3% (95% confidence interval 97.4 to 88.1) for all-cause revision and the overall dislocation rate was 3.8% (4 of 105). There was no difference observed in survival between type IIIA and type IIIB defects and whether a hemispherical implant alone was used for the reconstruction or not. The mean gain in OHS was 16 points. Custom-made implants were only used in six cases, in patients with either a mega-defect in which the anteroposterior diameter > 80 mm, complex pelvic discontinuity, and massive bone loss in a small pelvis. Our findings suggest that a reconstruction algorithm can provide a successful approach to reconstruction in major acetabular bone loss. The use of custom implants has been defined in this series and accounts for < 5% of cases.

Improving Learning Outcomes and Learning Motivation of Students Through Teams Games Tournament Learning Model (TGT)

This research investigates the impact of the problem-based learning (PBL) model on enhancing students' critical thinking abilities within civic education in third-grade classes at SDN Srewendari, Malang City. The study aims to assess the influence of the PBL approach on students' proficiency in analyzing facts, articulating reasons and arguments, drawing conclusions, and effectively presenting their findings. Employing a quasi-experimental design with the Nonequivalent Groups Pretest-Posttest Control Group methodology, the research compares the average post-test scores of critical thinking skills between the experimental and control groups through a t-test. The study population comprises third-grade students from SDN Srewendari, Malang City, with the sample consisting of experimental class IIIa and control class IIIb. Data collection involves observation, utilizing rating scale instruments, and assessments comprising test or evaluation questions administered during class sessions. The analysis is conducted descriptively and quantitatively, employing a difference test with a confidence level exceeding 95%. Findings indicate a positive and statistically significant impact of the problem-based learning model on students' critical thinking skills within civic education.

E039 Multiple myeloma and neurological complications: prevalence and risk factors

Abstract Background/Aims Multiple myeloma (MM) is a malignant haematological disorder with a highly variable clinical presentation. Few studies have explored the neurological complications (CN) associated with MM. The objectives of this study were to describe the neurological manifestations observed in MM and to determine predictive factors for neurological complications. Methods We collected data from 126 cases of symptomatic multiple myeloma patients followed in our department over a 30-year period (1993 - 2023). We gathered sociodemographic, clinical, and laboratory data. Neurological complications were diagnosed based on clinical findings and magnetic resonance imaging data. Results Our study included 126 patients with an average age of 65.23 ± 11.63 years [36-92], and a male-to-female sex ratio of 3.8. Bone pain was present in 92.1% (116 cases) with an average duration of 4 months. The mean erythrocyte sedimentation rate and C-reactive protein levels were 99.08 mm at H1 [3-190] and 27.74 [0-196], respectively. Hemoglobin levels were less than 10g/dl in 51.2% of cases, with an average of 9.902 ± 2.22 g/dl [5-13.9]. Calcium levels exceeded 2.75 mmol/l in 20% of cases, with an average of 2.49 ± 0.33 mmol/l. The mean creatinine level was 88.28 ± 77.9 μmol/l [36-587], with levels above 177 μmol/l observed in 15 cases (10.4%). The Durie and Salmon prognostic classification categorized our patients as follows: Stage IA (3.2%), Stage IIA (4%), Stage IIB (0.8%), Stage IIIA (72.2%), and Stage IIIB (18.3%). Neurological complications were present in 22.2% of patients (n = 28). Sixteen patients (12.7%) had spinal cord compression, with nine having dorsal involvement, six having conus medullaris involvement, and one having cervical involvement. Radicular pain affected 14 patients, with eight experiencing sciatalgia and four having cruralgia. Two patients (1.8%) had carpal tunnel syndrome. No cerebral involvement was observed in our series. In our study, only creatinine levels were significantly lower in patients who developed neurological complications (64.35 vs. 95.19, p = 0.004). However, the occurrence of neurological complications was independent of age (p = 0.696), duration of evolution (p = 0.669), erythrocyte sedimentation rate (p = 0.541), C-reactive protein (p = 0.963), hemoglobin (p = 0.076), or calcium levels (p = 0.274). No association was found between neurological complications and gender (p = 0.849) or prognostic stage (p = 0.119) Conclusion Neurological manifestations in MM are diverse and often underestimated. The diagnosis of MM should be considered in the presence of spinal or radicular compression, especially when the laboratory findings suggest it. Disclosure M. Dhifallah: None. I. Fenniche: None. A. Feki: None. S. Ben Djemaa: None. M. Kallel: None. H. Fourat: None. R. Akrout: None. S. Baklouti: None.

Examining the Efficacy of Arthroscopic Scaphocapitate Arthrodesis for Advanced Kienbock's Disease: Clinical and Radiological Outcomes.

Altering wrist biomechanics, Kienbock's disease leads to progressive carpal collapse that results in early arthritis and degenerative changes. By shifting the loading axis toward the radioscaphoid joint, scaphocapitate arthrodesis (SCA) has been reported as a salvage procedure effective in treating symptomatic patients with advanced Kienbock's disease. In this study, we aimed to evaluate the clinical and radiological outcomes of arthroscopic SCA in symptomatic patients with advanced stages of Kienbock's disease. Between March 2010 and February 2021, we included 15 patients with symptomatic stage IIIA (n=2) and stage IIIB (n=13) Kienbock's disease who were followed up for a minimum of 24 months after arthroscopic SCA with or without lunate excision. The lunate was excised in 6 patients and retained in 9. Visual analog scale (VAS) pain score, grip strength, range of motion (ROM), active flexion-extension arc, and modified Mayo wrist score (MMWS) were measured preoperatively and at each follow-up examination after surgery. Operation-related complications and radiographic changes were also assessed. There were 13 women and 2 men, with a mean age of 57.6 years (range, 21-74 years) at the time of undergoing arthroscopic SCA. Follow-up ranged from 24 to 116 months, with an average of 56.9 ± 32.3 months. Bony union was achieved in all patients. At preoperative examination, wrist ROM (67%) and grip strength (48%) significantly decreased, compared to the contralateral wrist. At the final follow-up, there were significant improvements in VAS, grip strength, and MMWS, whereas the active wrist ROM showed no significant change. Radioscaphoid angle recovered after surgery, while radiographic carpal collapse and ulnar translation of the carpus occurred. In subgroup analysis according to excision of the lunate, there were no significant differences in VAS, MMWS, grip strength, or total ROM. However, increased ulnar translation and decreased radial deviation were noted in the lunate excision group. Arthroscopic SCA achieved significant improvements in pain and wrist function in patients with advanced Kienbock's disease without any complications. Excision of the lunate when performing arthroscopic SCA seemed to induce progressive carpal ulnar translation, with no apparent clinical benefits over retaining it.

PENGARUH MODEL PROBLEM BASED LEARNING TERHADAP HASIL BELAJAR PADA MATERI ENERGI DAN PERUBAHANNYA

Based on the results of observations carried out in class III of SD Negeri Cimayang 01, Pamijahan District, Bogor Regency, for the 2023/2024 academic year, information was obtained that the learning process carried out was still teacher-oriented (Teacher Centered) and had not obtained optimal results. Students tend to be passive, tend to chat with their friends, are not able to express opinions and have no desire to ask questions. Meanwhile, the teacher in the learning process only uses the Direct Instruction (Lecture) learning model. The aim of this research is to determine the effect of the Problem Based Learning (PBL) model on learning outcomes in the material Energy and its Changes. This research method uses quasi-experimental research. Experimental research is defined as a research method used to find the effect of certain treatments on others under controlled conditions. This research was conducted three times in each class group. Sampling was carried out using a cluster random sampling technique, namely class IIIA (as Experiment Class) and class IIIB (as Control Class) with a total of 40 students. Data collection techniques used test, documentation and observation techniques. Research data was collected using an initial ability test (pretest) and final ability test (posttest). Based on the results of the N-Gain calculation in the experimental class, an average value of 58.03 (medium category) was obtained, which means that the implementation of learning was quite effective. Meanwhile, in the control class, an average score of 49.93 (medium category) was obtained, which means learning was quite effective. Based on the results of this research, it can be concluded that the problem based learning model has an influence on learning outcomes regarding Energy and its Changes. This is shown by the value of tcount = 0.0339 while ttable = 0.05 with db 40. Thus it is known that tcount &lt;ttable, namely 0.0339 &lt;0.05, which means Ha is accepted and Ho is rejected. This shows that there is a significant influence of the use of the problem based learning model on the learning outcomes of the Energy and Changes material for class III of SD Negeri Cimayang 01 Pamijahan, Bogor Regency, Academic Year 2023/2024.

Orthotopic Heart Transplantation Followed By Autologous Stem Cell Transplantation in Patients with Cardiac AL Amyloidosis: Results from a Single Centre Prospective Study

Background: Patients with advanced cardiac AL amyloidosis have a dismal prognosis, with an overall survival (OS) of only 5 months for Stage IIIb patients (Palladini et al, 2023). Induction chemotherapy followed by high dose chemotherapy and autologous stem cell transplantation (HDT and ASCT) has been widely used as treatment for AL amyloidosis. However, patients with advanced cardiac AL amyloidosis are often not suitable for HDT and ASCT due to high transplant related mortality (TRM). Orthotopic cardiac transplantation (OHT) following induction treatment may improve patient fitness and thus allow HDT and ASCT to deepen and prolong responses. We present our single centre, prospective study of patients with Stage IIIa and Stage IIIb cardiac AL amyloidosis who received OHT followed by sequential HDT and ASCT. Aims: The primary outcomes were 3 year OS and progression-free survival (PFS). Efficacy and safety were assessed as secondary outcomes. Efficacy was evaluated by light chain and cardiac response after ASCT. Safety was assessed by rate of TRM, cardiac rejection, opportunistic infections, and cytopenia related complications. Methods: During 2015 to 2021, patients with Stage IIIa or Stage IIIb AL amyloidosis aged under 65 years underwent OHT followed by HDT and ASCT. Patients with multiple myeloma were excluded. At approximately 6 months following OHT, patients underwent stem cell mobilization with granulocyte colony-stimulating factor alone followed by peripheral blood apheresis stem cell collection. Mycophenolate immunosuppression was temporarily withheld during stem cell mobilization and collection. Patients then received a high dose melphalan ASCT followed by 3-6 monthly assessments. Results: Nine patients (median age of 53 years, range 47-60 years) completed both OHT and ASCT. Seven other patients were screened but did not proceed with OHT. The cohort included both stage IIIa (55%) and stage IIIb (44%) patients. Most patients received cyclophosphamide-bortezomib-dexamethasone induction therapy (89%) and one patient received lenalidomide-bortezomib-dexamethasone. The median time from diagnosis of AL amyloidosis to OHT was 11 months (range 5-57 months) and median time from OHT to ASCT was 7 months (range 5-8 months). 3 year OS was 83% and PFS was 56% (Figure 1). At a median follow up of 37 months (range 17-69 months), 89% of patients remain alive. One patient with Stage IIIa disease who underwent HDT and ASCT with progressive disease (PD) died 28 months following ASCT due to PD. Subgroup analysis demonstrated 3 year OS in Stage IIIa patients of 75% compared to 100% in Stage IIIb (p=0.48). 3 year PFS was 53% in Stage IIIa patients and 66% in Stage IIIb (p=0.8). Patients in complete remission (CR) prior to ASCT had an improved 3 year OS of 100% compared to 66% for those in partial remission (PR) or with PD (p=0.32). 3 year PFS was significantly improved at 100% when ASCT occurred in CR compared to 0% in those in PR or with PD (p=0.01) (Figure 2). All patients either maintained a CR or achieved an improved haematological response following HDT and ASCT, with 89% of patients in CR at 6 months post ASCT. At the median follow up of 37 months, 78% were in CR and 22% had PD. At last follow up, there has been no documented amyloid recurrence in a cardiac allograft. There was no TRM noted in this study. All patients had cardiac rejection with 66% developing Grade 3A/2R rejection requiring methylprednisone. The most common infective complication was CMV reactivation (44%). Other infective complications included cryptococcal infection (11%), aspergillus and MAC infection (11%) and HSV reactivation requiring hospitalization (11%). During admission for HDT and ASCT, 89% had febrile neutropenia and there were no bleeding complications. Conclusions: We have demonstrated, in a prospective design, that sequential OHT/ASCT following induction therapy is safe in patients with Stage IIIa/b cardiac AL amyloidosis without an increase in TRM. This approach was associated with excellent survival outcomes compared with historical cohorts. Given the deep and prolonged responses seen with daratumumab based induction, a risk adapted strategy may be more appropriate moving forward, with only those not achieving a haematological CR undergoing consolidation ASCT following OHT.

High Responses Rates with Single Agent Belantamab Mafodotin in Relapsed Systemic AL Amyloidosis

Introduction: Systemic AL amyloidosis, a rare incurable plasma cell disorder, has no approved treatments at relapse. Belantamab mafodotin is an antibody-drug conjugate which targets BCMA antigen approved for relapsed refractory myeloma. We report our results using belantamab mafodotin monotherapy for the treatment of patients with relapsed refractory AL amyloidosis including those traditionally excluded from clinical trials (eGFR&amp;lt;30 ml/min/1.73m 2 and cardiac Mayo stage IIIb disease). Methods: All patients treated with belantamab mafodotin monotherapy at standard dose (2.5 mg/kg) or dose reduction between April 2021 - July 2023. Standardised assessments including measurement of cardiac biomarkers, clonal parameters and imaging were performed and disease assessment was reported as per International Society of Amyloidosis consensus criteria. Results: Twenty-seven patients were included. The median age at was 65 years (range 41-76) and eight (30%) patients were aged &amp;gt;70 years. Eighteen (67%) had λ AL-type and nine (33%) κ AL-type. A median of two organs were involved at baseline (range 1-4) with renal and cardiac involvement in 20 (74%) and 15 (56%) respectively (3 each for Mayo stage IIIa and stage IIIb). The median time from AL amyloidosis diagnosis to first administration of belantamab mafodotin was 69 (range 5-174) months (~6 years) with a median of 3 prior lines of treatment (range 2-6). Prior drug class exposure included proteasome inhibitors (100%), immunomodulatory drugs (81%) and anti-CD38 antibody (81%) therapy. Ten patients (37%) had undergone prior melphalan-conditioned autologous stem cell transplantation. At the time of first belantamab mafodotin dose, the median involved free light chain concentration was 118mg/l (range 31-1778), eGFR was 40 ml/min (range 7 - 120) and a third (9/27) with an eGFR &amp;lt;30 ml/min/1.73m 2. NT-proBNP was 845 ng/l (range 99-70,000). At data cut-off, a median of 5 (range 1-11) doses of belantamab mafodotin were delivered. Of those with evaluable disease, best haematological overall response rate (partial response or better) was 80% (20/25) at a median time to best haematological response of 2 months (95% CI 1-4, range 1-17). Complete response (CR) or very good partial response (VGPR) was achieved in 64% (16/25). Two patients have only had 1 cycle and too early to perform response assessment. Reasons for treatment discontinuation (n=12) were: inadequate response/progression (n=7), keratopathy (n=1), grade 3 thrombocytopenia (n=1), physician choice (n=3: discontinued due to treatment for unrelated metastatic squamous cell carcinoma but remains in CR; facilitation of renal transplant; prior to BCMA-directed CAR-T in VGPR). At a median follow-up of 13 months follow-up (95% CI 4-18, range 1-27) from belantamab mafodotin initiation, 15 patients (56%) remain on therapy. Two patients died (1 due to progressive disease, 1 unrelated) and seven patients progressed and had subsequent line of therapy at a median time of 6 months (95% CI 2-4) in those that had a next line of therapy. Median treatment-free survival or death was 27 months (10-NR), and 1-year treatment-free survival/death was 69% (95% CI 41-86). Median overall survival (OS) is not reached. 1-year OS is 88% (95% CI 59-97). Bilateral microcystic corneal keratopathy, the most frequent adverse event, was seen in 19 (70%) patients (5%; 1/19 grade 4).Ocular adverse events improved in all patients after treatment delay. Only one patient required treatment cessation due to ocular toxicity (despite achieving PR after one dose). Thrombocytopenia was reported in 3 (11%) (grade 3: 1; grade 2: 1). Only two patients remained on the standard dose of 2.5mg/kg for &amp;gt;3 cycles. Nine patients had eGFR &amp;lt;30ml/min and 6/9 started at a dose of 1.25mg/kg with no unexpected side effects (1 patient had grade 3 keratopathy). One patient post-renal transplantation (on tacrolimus and mycophenolate) had no significant toxicity and achieved a CR after cycle 3. No treatment-related deaths, cardiac or renal toxicities observed in our cohort. Conclusion: Belantamab mafadotin has high efficacy and good tolerability in multiply relapsed AL amyloidosis including efficacy in patients otherwise excluded from clinical trials. Treatment-emergent adverse events (especially keratopathy) do not preclude delivery of drug with appropriate dose reductions.

Survival outcomes of 2018 FIGO stage IIIC versus stages IIIAand IIIB in cervical cancer: A systematic review with meta-analysis.

To assess the difference in survival outcomes between stage IIIC and stages IIIA and IIIB in the 2018 FIGO cervical cancer staging system. The PubMed, EMBASE, MEDLINE and Web of Science were searched for articles published from November 1, 2018 to January 31, 2023. Articles published in English were considered. The included studies compared the survival outcomes of patients with cervical cancer in FIGO 2018 stage IIIC with those in stages IIIA and IIIB. Studies focused on rare histopathological types were excluded. The statistical analyses were performed using Stata 17 software. The endpoints were overall survival (OS) and progression-free survival (PFS). Ten retrospective cohort studies were eligible, involving 2113 (6.2%), 9812 (28.6%), 44 (0.1%), 10 171 (29.7%), 11 677 (34.1%) and 445 (1.3%) patients in stage IIIA, IIIB, IIIA&B, IIIC, IIIC1, and IIIC2, respectively. In the OS group, stage IIIC/C1 was significantly associated with superior survival compared with stage IIIA (hazard risk [HR] 0.62, 95% confidence interval [CI] 0.41-0.93, P = 0.022; I2 = 92.9%) and stage IIIB(A&B) (HR 0.56, 95% CI 0.44-0.71, P < 0.001; I2 = 94.0%). The FIGO 2018 stage IIIC2 was not associated with an increased mortality risk compared with stage IIIA and stage IIIB(A&B). In the PFS group, the outcome of FIGO 2018 stage IIIC/C1 was similar to stage IIIA (HR 0.66, 95% CI 0.27-1.64, P = 0.371; I2 = 65.6%), but better than stage IIIB(A&B) (HR 0.75, 95% CI 0.68-0.83, P < 0.001; I2 = 0.0%). The FIGO 2018 stage IIIC2 has similar PFS outcomes to stage IIIA and stage IIIB(A&B). Our findings demonstrate that survival outcomes of stage IIIC are no worse than those of stage IIIA and stage IIIB in the 2018 FIGO cervical cancer staging system. In cervical cancer, FIGO 2018 stage IIIC1 has significantly better OS outcomes than stage IIIA and stage IIIB.

Real-world treatment patterns and survival outcomes for patients with stage III non-small cell lung cancer in Spain: a nationwide cohort study.

The burden of non-small cell lung cancer (NSCLC) remains high in Spain, with lung cancer accounting for 20% of cancer-related deaths annually. Programs such as the Spanish Thoracic Tumour Registry (TTR) and the global I-O Optimise initiative have been developed to observe patients in clinical practice with the aim of improving outcomes. This analysis examined treatment patterns and survival in patients with stage III NSCLC from the TTR. These patients represent a heterogenous group with complex treatment pathways. The TTR is an ongoing, observational, prospective, and retrospective cohort multicentre study (NCT02941458) that follows patients with thoracic cancer in Spain. Adults aged ≥18 years with stage IIIA/IIIB NSCLC enrolled in the TTR between 01 Jan 2010 and 31 Oct 2019 were included in this analysis. Initial treatment received was described by cancer stage and histology (squamous and non-squamous NSCLC). Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were calculated over a 5-year period. A total of 1,838 patients were included in the cohort, including 1,082 with stage IIIA (58.9%) and 756 with stage IIIB (41.1%). Median follow-up was 18.3 months. The median age of patients was 66 years, and most had non-squamous NSCLC (54.0%), were male (81.2%), and were active or former smokers (93.4%). Overall, 26.3% of patients received surgical resection (37.0% for stage IIIA and 11.1% for stage IIIB). The most frequent initial treatment received was concurrent chemoradiotherapy for stage IIIA (30.2%) and stage IIIB (37.0%) patients. Median OS was lower in patients with stage IIIB than stage IIIA (28 vs. 37 months) disease and was lower for patients with squamous than non-squamous histology (19 vs. 26 months). Median PFS and OS varied when patients were stratified by initial treatment. This TTR analysis describes the clinical reality surrounding the initial management and survival outcomes for stage III NSCLC in Spain and presents survival outcomes comparable with other real-world evidence. It provides insights into the diverse approaches used before the availability of immunotherapies and targeted treatments in the non-metastatic NSCLC setting.

Prospective Phase II Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy (SBRT) Followed By Concurrent Mediastinal Chemoradiation and Adjuvant Immunotherapy for Locally-Advanced Non-Small Cell Lung Cancer (LA NSCLC)

To report the efficacy and toxicity outcomes of a prospective phase II trial of primary tumor SBRT followed by conventional chemoradiation to the lymph nodes and adjuvant immunotherapy in patients (pts) with unresectable LA NSCLC. Eligible pts included stage II-III LA NSCLC with peripheral primary tumors ≤ 7cm or centrally based tumors that had at least 2 cm separation from involved nodal disease. Pts received SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by standard radiation to 60 Gy in 30 fractions to the involved lymph nodes with concurrent platinum doublet chemotherapy. The trial was amended to allow pts without disease progression after chemoradiation to receive adjuvant durvalumab per the PACIFIC trial. The primary endpoint was 1 year progression free survival (PFS), evaluated as a binary variable. Frequencies and proportions were used for reporting this primary endpoint, in addition to adverse events and patterns of failure. Median PFS and OS were estimated using Kaplan Meier methods. Safety and efficacy is reported on the first 50 pts enrolled in the trial with a median follow-up of 24 months (mos) (range, 1-54 mos). Pts were primarily stage IIIA (60%) or stage IIIB (34%), with 6% of pts stage IIB. Overall grade 3 or higher toxicity related to SBRT and/or mediastinal radiation was 8% with two pts (4%) developing grade 3 pneumonitis and one pt having a grade 5 lung infection possibly related to radiation. Overall grade 2 pneumonitis related to SBRT or mediastinal radiation was 20%. Only one pt (2%) developed grade 3 esophagitis. No late cardiac events have been observed. The one-year PFS for all pts was 62% with a median PFS of 26.3 mos and median overall survival of 40.8 mos. Of the 50 pts enrolled, 37 received at least one dose of adjuvant durvalumab. The one-year PFS for pts who received at least one dose of durvalumab was 70.3% with a median PFS not yet reached in this group (median follow-up 24 mos). Patterns of failure were mostly distant with 26% of pts experiencing distant failure, 6% regional, and 2% distant and regional. There was only one local failure (2%) after SBRT in all 50 pts. SBRT to the primary tumor followed by conventional chemoradiation to the involved lymph nodes and adjuvant immunotherapy was well tolerated and showed improved 1-year PFS compared to prior conventional chemoradiation trials for locally advanced NSCLC. The results of this trial will be further evaluated in a randomized phase III study, NRG LU-008. Pts will receive either conventional chemoradiation vs. SBRT to the primary tumor followed by chemoradiation to the involved lymph nodes followed by consolidative immunotherapy to evaluate the possibility of utilization of SBRT as a new standard of care for LA NSCLC.

Effect of sevoflurane on CD4+CD25+FOXP3+ regulatory T cells in patients with gastric cancer undergoing radical surgery.

In this study, the proportion of CD4+CD25+FOXP3+ regulatory T (Treg) cells in CD4+ T cells in the peripheral blood of gastric cancer patients before anesthesia induction (T1), after surgery (T2) and the first day after surgery (T3) was studied to explore the effect of sevoflurane and propofol anesthesia on the prognosis of gastric cancer patients. Forty patients with advanced gastric cancer were recruited and randomly divided into the sevoflurane group (S group) and the propofol group (T group). Flow cytometry was used to detect the proportion of CD4+CD25+FOXP3+ Treg cells in CD4+ T cells in the peripheral blood of patients with T1, T2 and T3, respectively. Compared with stage ⅡB, the proportion of CD4+CD25+FOXP3+ Treg cells in T1, T2 and T3 of stage ⅢA and stage ⅢB patients was increased. Compared with the T group, the expression of CD4+CD25+FOXP3+ Treg cells in the peripheral blood of T2 and T3 in the S group was decreased. The results showed that the expression of CD4+CD25+FOXP3+ Treg cells might be related to the TNM stage of gastric cancer and sevoflurane could alleviate the inhibition of postoperative immune function more than propofol. Sevoflurane effectively reduced the expression level of CD4+CD25+FOXP3+ Treg cells in peripheral blood of T2 and T3 of patients with gastric cancer, providing the theoretical basis for the selection of surgical anesthetics for patients with gastric cancer.

Outcomes of Stage IIIa and Well-Selected Stage IIIb or Oligometastatic Stage IV Non-Small Cell Lung Cancers Managed by Multimodal Therapy Including Immunotherapy and Surgery

Abstract Background Resectable locally advanced non-small cell lung cancers (NSCLCs) are managed by multimodal approaches including systemic therapies followed by surgery. The recent inclusion of immunotherapy in neoadjuvant protocols has significantly improved tumor responses. In selected situations, bulky N2, N3 or oligometastatic NSCLCs with treated metastasis have shown excellent regression following chemo-immunotherapy and could be considered for surgery. Aims We here compare the oncological outcomes of stage IIIA (single N2) with stage IIIB (bulky N2, N3) or oligometastatic stage IV NSCLCs managed by chemo-immunotherapy followed by surgery. Methods We reviewed all patients treated in our institution between April 2017 and June 2022 for a locally advanced or oligometastatic NSCLC with chemo-immunotherapy followed by surgery in our prospectively collected database. We recorded, for each patient, the clinico-pathological characteristics, perioperative complications and oncological outcomes. Results Forty-eight patients (27 single station N2 stage IIIA (group 1) and 21 bulky N2, N3 or oligometastatic NSCLC (group 2)) were identified. Patient characteristics were comparable between groups. Surgery consisted in lobectomy (81%), bilobectomy (17%) or pneumonectomy (2%). Complete resection was achieved in 46 (95%) patients with R1 resection in two patients due to lymph node effraction. Complete tumor pathological response was achieved in 26% in group 1 and 33% in group 2. Postoperative morbidity was 48% in group 1 and 81% in group 2 (p=0.05). There was no mortality. Median follow-up was 16 months (IQR: 9-32). Progression-free survival was 6 months (IQR: 3-18) in group 1 and 5 months (IQR: 2-7) in group 2 (p=0.04). Overall recurrence rate was 40% (comparable between groups (p=0.08)) and consisted, in majority, of distant metastasis. Overall survival was comparable between groups (p=0.05). Conclusions The inclusion of immunotherapy in induction protocols has improved tumor response and allowed to consider advanced NSCLCs for surgical resection with good postoperative and oncological outcomes.

Enrolling patients in Cardiac Amyloid Reaching for Extended Survival (CARES) trials: Two placebo-controlled, double-blind, randomized, international phase 3 trials assessing CAEL-101 in patients with Mayo stage IIIa or stage IIIb AL amyloidosis.

TPS8071 Background: Light-chain (AL) amyloidosis is a rare, progressive, systemic disorder caused by plasma cell dyscrasia (PCD). Amyloid fibrils deposit in organs leading to progressive organ damage and death. Prognosis is poor for patients with cardiac involvement. Median survival is 24 and 4 months for patients in Mayo Stages IIIa and IIIb (based on the 2013 European Modification of the Mayo 2004 staging criteria), respectively. The standard of care (SoC) is anti-PCD therapy to suppress amyloid fibril generation. As yet, there are no therapies that remove deposited fibrils. CAEL-101 is a monoclonal antibody that binds to amyloid fibrils and may facilitate their systemic removal, improve organ function, and patient survival. These ongoing trials will evaluate the efficacy and safety of CAEL-101 as first-in-class treatment to reduce amyloid burden in patients with cardiac AL amyloidosis. Notably, 301 (Mayo Stage IIIb) is the first randomized, placebo-controlled efficacy clinical trial to formally assess the effects of a pharmacological in this severely ill population. Because the median expected survival for Mayo Stage IIIb patients is far shorter than for Mayo Stage IIIa patients, the resulting sample size required for the Mayo Stage IIIb study is less than for the Mayo Stage IIIa study. The objective of these trials is to evaluate the efficacy and safety of CAEL-101 when administered concurrently with SoC anti-PCD therapy in treatment-naïve patients with cardiac AL amyloidosis in Mayo Stages IIIb (NCT04504825; 301) or IIIa (NCT04512235; 302). Methods: These international, multicenter, double-blind, randomized, phase 3 trials, initiated in 2020, are enrolling patients at &gt; 100 sites in &gt; 20 countries. Newly diagnosed adults with AL amyloidosis stage IIIb or IIIa measurable hematologic disease, and histopathological diagnosis of amyloidosis with cardiac involvement are eligible. Patients with other forms of amyloidosis, symptomatic orthostatic hypotension, or supine systolic blood pressure &lt; 90 mm Hg are ineligible. Patients in Mayo Stages IIIb (N = 124) and IIIa (N = 267) are being randomized 2:1 to receive once-weekly IV infusions of CAEL-101 (1000 mg/m2) or placebo for 4 weeks, followed by maintenance dosing every 2 weeks. In these event-driven studies, treatment will continue to a minimum of 101 and 79 events for 301 and 302, respectively. Patients will receive concurrent institutional SoC anti-PCD therapy at the discretion of the investigator. Overall survival (primary endpoint) will be analyzed via time-to-event log-rank statistics. Secondary endpoints include functional outcomes, quality of life, and echocardiography. Clinical trial information: NCT04504825 , NCT04512235 .