Excellent Survival Research Articles

The effect of chemotherapy regimens in male germ cell tumors on the development of primary hypogonadism.

Male germ cell tumors (GCT) have excellent survival. Long-term sequelae in cancer survivors are an evolving field. We evaluated the risk of patients with GCT to develop primary hypogonadism and adherence to guideline-recommended therapy in a real-world cohort. Monocentric study at a tertiary cancer centre to evaluate treated GCT-patients (2001-2019). Post therapeutic male endocrine function, International Index of Erectile Function (IIEF)-5 and The aging males' symptoms rating scale (AMS) questionnaires were assessed. The overall response rates were low, with 44 of 402 contacted patients participating in the study. From these, 32(73%) underwent blood analysis, 42(95%) answered the IIEF-5 and 43(98%) the AMS. Latent hypogonadism (serum testosterone 8-12 nmol/l) was found in n = 9 (28%) and manifest hypogonadism (testosterone < 8 nmol/l) in n = 8 (25%). 50% (n = 21) indicated erectile dysfunction on IIEF-5 (cut off ≤ 21 pts.) and 62.8% (n = 27) reported symptomatic affection on AMS (cut off ≥ 27 pts.). Majority of tested patients revealed different degrees of hypogonadism. Standard instruments were able to detect gonadal damage in > 50%, which underscored the clinical need to evaluate endocrine function in cancer survivors. We further indicated the difficulties of today's research and provided starting points to assess barriers for study participations.

OGC SO11 - Impact Evaluation of Endoscopic Mucosal Resection in the Foregut in a Tertiary Centre in the United Kingdom (UK)

Abstract Background Endoscopic mucosal resection (EMR) has emerged as a crucial technique for managing early-stage lesions in the oesophagus and stomach, encompassing precancerous and cancerous conditions.1 With fewer complications and excellent 5-year survival rates, EMR has shown potential as a less-invasive alternative to surgical resections.1 EMR achieves higher accuracy with its ability to obtain more profound and better quality tissue samples compared to conventional biopsies, which facilitates multidisciplinary team (MDT) discussions regarding treatment decisions.1 This study aims to evaluate the impact of EMR performed in an Oesophago-Gastric Cancer tertiary centre in the UK. Method This is a retrospective service evaluation of patients who underwent EMR from March 2021 to March 2024. A sample size of 73 EM (n=73) is identified. Data were collected from medical and endoscopic records, which includes patient’s demographics, American Society of Anaesthesiologists (ASA) grade, EMR indication, histology report and MDT outcome. EMRs performed were categorised into oesophageal, gastric and duodenal. Three main referral indications were identified; ‘polyp’, ‘dysplastic nodule in Barrett’s oesophagus’ and ‘possible early malignancy’. MDT outcomes were analysed thematically. Results Of the seventy-three patients identified, 78% is male and mean age at 71 years. Most patients (81%) are classified as ASA Grade 2. Polyp is identified in 37 patients (51%), making up the most common referral indication. 49% of the EMR were gastric, with remaining being oesophageal (41%) and duodenal (11%). 26% of histology results showed benign disease, 40% dysplastic disease, and 34% malignant. From histology reports, 47% of the EMRs achieved complete clearance margins. 28 patients (38%) were discharged with no further interventions and 12 patients (16%) received repeat EMR. 4 main themes were identified from MDT outcomes, with 43.8% patients needing surveillance endoscopy, 16.7% patients recommended for surgical intervention and repeated EMR each. Conclusion EMR has shown to be effective as a reference for further treatment decisions, especially for MDT discussions. It has been proven that EMR can be therapeutic in providing complete resection, particularly for benign and early dysplastic diseases.

CTNI-16. MONOGERM, A NOVEL PROOF-OF-PRINCIPLE BAYESIAN PHASE II TRIAL DESIGN OF CARBOPLATIN OR VINBLASTINE MONOTHERAPY INDUCTION PRIOR TO RADIOTHERAPY FOR INTRACRANIAL GERMINOMA

Abstract BACKGROUND Current European standard-of-care for localised intracranial germinoma is multi-agent chemotherapy (carboPEI: carboplatin/etoposide/ifosfamide) followed by definitive radiotherapy, with excellent survival. MonoGerm is a de-escalation, non-inferiority trial aiming to reduce toxicity. Twelve-week carboplatin (PMID:8039122) AUC10 or vinblastine (PMIDs:32642701/34520101) induction will be evaluated to test if as effective as carboPEI from SIOP-CNS-GCT-II. A novel trial design was required to answer this question pragmatically/safely. METHODS Clinical trials in rare diseases recruit slowly, allowing continuous monitoring of efficacy outcomes. Efficacy-transition-pathways (ETP) are innovative visual tools to aid determination of trial design parameters, and an extension of the dose-transition-pathways concept introduced for dose-finding trials (PMID:28733440). RESULTS MonoGerm includes two monotherapies, with each single arm recruiting six cohorts of three patients, with interim assessment after each recruited cohort and final analysis at 18 patients (total n=36). Insufficient tumour volume response (&amp;lt;30%) at 6-week safety MRI results in 12-weeks carboPEI. Primary outcome is radiological complete response (CR) by 12-weeks of induction monotherapy. A beta-binomial conjugate analysis will generate posterior probability distributions, combining observed trial data as realisations from a binomial distribution with a minimally informative Beta (1,1) prior. Decision criteria to allow early stopping at interim analyses and go/no-go decisions at final analysis are based on probabilities from these posterior distributions. ETP visually maps out parameters used to assert decisions after each interim assessment as a pyramid decision tree. For each recruited cohort and every CR outcome, estimates of the true CR rate and probabilities with associated decisions are mapped out. ETP allows clear communication between statisticians, clinicians, and patient-public-involvement (PPI) teams, facilitating informed decisions in an efficient/realistic trial design. CONCLUSION MonoGerm, a novel Bayesian de-escalation trial, funded by Little Princess Trust (https://www.littleprincesses.org.uk/), uses ETP and continuous monitoring with built-in stopping rules to ensure patient safety in this treatment de-escalation trial.

CTNI-65. DETERMINANTS OF LONG-TERM SURVIVAL IN PATIENTS WITH IDH-MUTANT GLIOMAS

Abstract BACKGROUND Survival times of patients with IDH-mutant gliomas is variable and can extend to decades. Many studies only provide progression-free rather than overall survival times and prognostic factors remain ill-defined. Here we explored clinical disease characteristics of long-term survivors within a large cohort of patients with extended follow-up. METHODS This single-center, retrospective analysis included 114 patients with IDH-mutant glioma that either died due to tumor-related causes or survived at least 15 years after first diagnosis. Patient characteristics, outcomes, and prognostic factors were stratified by short- (&amp;lt; 15 years) versus long-term (≥ 15 years) survival. Initial diagnosis was (re-)classified according to the WHO 2016 classification. Uni- and multivariate analyses were performed. RESULTS Overall, 66 patients (58%) were diagnosed with astrocytoma and 48 patients (42%) with oligodendroglioma. Median follow-up of the survivors was 16.6 years (range 15-28.9). 62 tumor-related deaths (54%) had been reported at database closure. Patients that died before reaching 15 years survival time had been diagnosed with astrocytoma in 41 (72%) and oligodendroglioma in 16 cases (28%). The long-term survivor cohort comprised 25 patients (44%) with astrocytoma and 32 patients (56%) with oligodendroglioma. Long-term survival was associated with grade 2 histology (p &amp;lt; 0.01), smaller tumor volumes (p &amp;lt; 0.01), and lack of contrast enhancement (p = 0.02). 41 long-term survivors (72%) were initially monitored by a wait-and-scan strategy as opposed to 16 patients (28%) in the cohort of short-term survival (p&amp;lt;0.01). In patients with oligodendroglioma, a higher KPS was associated with longer survival (HR 0.25; 95% CI 0.02-0.67; p = 0.05). Tumor resection (HR 0.43; 95% CI 0.22-0.86; p = 0.02) and wait-and-scan strategies (HR 0.34; 95% CI 0.14-0.79; p = 0.01) were associated with longer survival in patients with astrocytoma. CONCLUSION Tumor resection followed by a wait-and-scan strategy may yield excellent survival times, especially in patients with IDH-mutant grade 2 astrocytoma. Age appears not be an important predictor for survival in patients with IDH-mutant gliomas.

Outcomes of patients with intermediate-risk neuroblastoma presenting with motor deficits relating to intraspinal tumor extension: A report from the Children's Oncology Group study ANBL0531.

Tumor invasion of the spinal canal is detected radiographically in approximately 15% of patients with newly diagnosed neuroblastoma (NB). The optimal clinical approach to maintain excellent survival outcomes while minimizing long-term sequelae is yet to be defined. Patients with intermediate-risk neuroblastoma (IR-NB) and radiographically identified intraspinal tumors who were treated on the Children's Oncology Group study ANBL0531 were studied prospectively to evaluate neurologic outcomes related to cord compression. Patients were defined as being symptomatic versus asymptomatic based on reporting of neurologic motor deficits at diagnosis. Patient characteristics, tumor biology, chemotherapy treatment, surgical interventions, and neurologic and disease outcomes are reported. Of the 92 patients with intraspinal tumors, 42 (46%) were symptomatic and most (73%) had complete resolution of symptoms. Age, degree of motor deficit, and duration of symptoms at diagnosis were not associated with complete resolution. While symptomatic patients were more likely to undergo upfront laminectomy, laminectomy was not associated with improvement of motor symptoms. Administration of additional chemotherapy beyond initial treatment assigned per protocol to achieve the treatment end point was not associated with achieving symptom resolution. Patients presenting with motor deficits due to intraspinal tumor had excellent survival and favorable neurologic outcomes, with the majority reporting complete resolution of motor symptoms regardless of severity and duration of symptoms at diagnosis or neurosurgical intervention. Prompt diagnosis and initiation of first-line chemotherapy treatment remain priority, while neurosurgical intervention should be reserved for patients with rapid neurologic deterioration. Biology-based therapy and tumor response should continue to be used to maintain favorable outcomes.

Use of Hepatitis C Viremic Donors to Expand the Pediatric Donor Pool

The use of hepatitis C virus (HCV)-positive donors in organ transplantation has become increasingly viable due to advancements in direct-acting antiviral (DAA) therapies, which offer high cure rates. This review aims to evaluate the current practices, benefits, and challenges of utilizing HCV-positive donors for organ transplantation. The recent data show that transplant centers are progressively accepting HCV-positive donors for various organs, including kidneys, livers, and hearts, given the efficacy of post-transplant antiviral treatment. Using these donors has helped mitigate the organ shortage crisis, increasing the donor pool and reducing waitlist times. Despite these advantages, the approach raises concerns about viral transmission, long-term outcomes, and the cost-effectiveness of post-transplant DAA therapy. Furthermore, this review highlights the ethical implications of informed consent and the monitoring of HCV-negative recipients following transplantation. The outcomes from recent studies suggest that with proper management, transplantations from HCV-positive donors to HCV-negative recipients can be safe and effective, leading to excellent graft function and patient survival. This review synthesizes existing research and offers insights into optimizing protocols for future transplants involving HCV-positive donors.

Left atrial function and long-term survival after cardiac resynchronization therapy

Abstract Background Left atrial (LA) reservoir strain after CRT has been linked to long-term outcome, but the role of LA function in response to cardiac resynchronization therapy (CRT) is incompletely understood. LA dyssynchrony during left bundle branch block has negative effects on LA function beyond LA reservoir strain. We hypothesized that correction of LA dyssynchrony after CRT has added value to LA reservoir strain as a marker of long-term outcome. Purpose To explore the role of LA function in long-term survival after CRT. Methods In a recent prospective multicenter study of 168 patients, LA segmental and global strains were measured by speckle-tracking echocardiography before and 7 ± 1 months after CRT. LA reservoir strain was measured as the difference between peak and minimum global strain during the atrial cycle and LA dyssynchrony as the time delay between onset systolic stretch of the interatrial septum and LA lateral wall. Since LA reservoir strain &amp;lt; 18% is associated with elevated LV filling pressure, we used 18% as cutoff and for LA dyssynchrony 43 ms (mean after CRT in the present study). All-cause mortality was used as clinical endpoint during follow-up. Results After 6 years ± 21 months (mean ± SD) follow-up, 35 (21%) patients died. LA reservoir strain was significantly lower (15 ± 9% vs 20 ± 10%, p = 0.003) and LA dyssynchrony numerically higher (61 ± 68 ms vs 39 ± 69 ms, p = 0.099) in patients who died compared to survivors. LA reservoir strain ≥ 18% after CRT was associated with favorable long-term survival (HR: 0.51, 95% CI: 0.26 - 0.98) (upper panel in the Figure). LA dyssynchrony was not independently associated with mortality. However, when used in concert with LA reservoir strain ≥ 18% after CRT, it identified patients with perticularly excellent long-term survival (HR: 0.17, 95% CI: 0.05 - 0.58 vs patients with reservoir strain ≥ 18% and persistent LA dyssynchrony) (lower panel in the Figure). Patients with preserved LA reservoir strain but persistent LA dyssynchrony had similar outcome as patients with reduced LA reservoir strain (HR: 0.98, 95% CI: 0.45 - 2.12). Conclusion LA reservoir strain ≥ 18% and absence of LA dyssynchrony is associated with excellent long-term survival after CRT.LA strain after CRT and survival

Long term outcomes of patients with decompensated aortic stenosis undergoing urgent transcatheter aortic valve implantation: a TAVI-NOR subs-study

Abstract Background Aortic stenosis (AS) is a progressive disease, which untreated leads to irreversible myocardial damage and potentially death. Patients with AS may present with acute decompensation (ADAS) even during active surveillance. Purpose In this TAVI-NOR sub-study, we investigate the clinical profile, risk factors, epidemiology and long-term outcomes of patients treated with TAVI after presenting with ADAS compared to stable patients who underwent elective TAVI (no ADAS). Method A total of 600 patients with severe AS consecutively treated with TAVI between January 2012 and July 2019 were enrolled in TAVI-NOR study. Predictors and long-term clinical outcomes were explored in binary logistic and Cox regression models. Results A total of 68 patients (11.3%) received urgent TAVI due to acute hospitalization with ADAS. Age (80±8.0 years vs 81±6.0 years, p=0.662), gender (56% males vs 50% males, p=0.361) and other comorbidities at baseline such as cardiovascular disease, chronic lung disease and atrial fibrillation (AF) were comparable in patients with ADAS and no ADAS (n=532) (p&amp;gt;0.05 for all). However, patients with ADAS had greater symptom burden (NYHA III-IV 81% vs 51%, p&amp;lt;0.001), lower blood pressure, higher heart rate and lower estimated glomeruli filtration rate (52.0±10.8 vs 54.6±9.8 mL/min/1.73m2, p&amp;lt;0.045). They had also higher prevalence of ECG left ventricular (LV) hypertrophy (40% vs 27%, p=0.027), more often reduced LV ejection fraction (&amp;lt;50%) (41% vs 16%, p&amp;lt;0.001), lower stroke volume (39±11 ml/m2 vs 42±11 ml/m2 vs, p=0.030) a trend of abnormal ECG (p=0.055) and longer hospital stay (11.5 ±8.7 days 6.6± 4.9 days, p&amp;lt;0.001). Patients with ADAS were comparable with no ADAS in terms of early short-term (&amp;lt;30 days) all-cause mortality (p&amp;gt;0.05). Although 1-year mortality was comparable (1.5% in ADAS vs 2.1% in no ADAS, p&amp;gt;0.99), mid- to late-term mortality rates were significantly higher in patient with ADAS receiving urgent TAVI, with 3-, 5- and 7 years mortality of 22% vs 11%, p=0.008; 46% vs 29%, p=0.005; 53% vs 39%, p=0.033, respectively. In a Kaplan-Meier analysis, event-free survival was significantly reduced for patients with ADAS undergoing urgent TAVI compared with stable patients undergoing elective TAVI HR 1.63, 95% CI 1.15-2.31, p=0.006), confirmed by a multivariable-adjusted model (HR 1.54; 95% CI 1.05-2.25, p=0.026) independent of age, gender, AF, LV ejection fraction and time from diagnosis to TAVI (Fig). Conclusion Patients with AS presenting with acute decompensation and treated with urgent TAVI had excellent short-term survival. This was irrespective of increased symptom burden, adversely remodeled and functionally reduced LV at baseline. These findings might explain the observed higher mid- and long-term mortality compared with stable patients undergoing elective TAVI. It is essential to identify patients at risk of acute decompensation and treat them timely before irreversible myocardial damage occur.

Minimizing overtreatment and maximizing oncologic outcomes in upper tract urothelial carcinoma

Purpose of review An update on the latest advances in the management of upper tract urothelial carcinoma (UTUC), with an emphasis on strategies to optimize oncologic outcomes while minimizing overtreatment. Recent findings Recent high-quality trials have changed the landscape of UTUC treatment. Emerging tools including 3D histology and measurement of cell free tumor DNA may improve diagnostic accuracy of disease grading and staging, and be used in monitoring treatment response. Novel therapies show promise of reducing low-grade UTUC disease recurrence at the cost of significant side-effects. Platinum-based neoadjuvant chemotherapy in high-grade/muscle-invasive disease showed complete pathological response in a subset of patients, but difficult to predict responders. Adjuvant platinum-based chemotherapy exhibited a clear survival benefit, but immunotherapy did not, suggesting possible overtreatment with these agents. Molecularly-targeted therapies in metastatic UTUC have shown the greatest recent oncologic advances, but exhibit a high adverse event-rate. Summary Low-grade UTUC has the potential for overtreatment, as it exhibits low metastatic-potential and excellent survival. For high-grade and advanced-stage UTUC, these carry high mortality rates and require more aggressive treatment, but studies are limited by inaccurate grading and staging which can lead to overtreatment especially in the neoadjuvant setting. Emerging technologies will help improve diagnostic accuracy and noninvasive monitoring of treatment response.

Neoadjuvant chemoradiotherapy in combination with deep regional hyperthermia followed by surgery for rectal cancer: asystematic review and meta-analysis.

Combining chemoradiotherapy (CRT) with deep regional hyperthermia (HT) shows promise for enhancing clinical outcomes in selected rectal cancer patients. This study aimed to integrate the evidence and evaluate the efficacy of this combined treatment approach. Asystematic search of the PubMed, Scopus, and Mendeley databases was performed. This review was conducted according to the PRISMA guidelines. The quality of studies was evaluated using the Newcastle-Ottawa scale (NOS). Random-effects meta-analyses (DerSimonian and Laird) were performed. The primary outcome was pathological complete response (pCR), and secondary endpoints were overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and toxicity. In total, 12studies were included, mostly of moderate quality. Patients with locally advanced rectal cancer (LARC; n = 760) and locally recurrent rectal cancer (LRRC; n = 22) were eligible. The pooled pCR rate was 19% (95% confidence interval [CI]: 16-22%) among all 782 patients and 19% (95%CI:16-23%) among 760 LARC patients. Due to significant study heterogeneity, survival outcomes were pooled by excluding LRRC patients. The pooled 5‑year OS rate among 433 LARC patients was 87% (95%CI: 83-90%). The pooled 5‑year DFS and LRFS in LARC patients were 75% (95%CI: 70-80%) and 95% (95%CI: 92-97%), respectively. There was alack of consistent reporting of HT treatment parameters and toxicity symptoms among the studies. The collective clinical evidence showed that neoadjuvant CRT combined with HT in rectal cancer patients is feasible, with a19% pCR rate and excellent survival outcomes in long term follow-up.

Initial Assessment of Resectability of Colorectal Cancer Liver Metastases Versus Clinical Outcome

BackgroundSurgery improves long-term survival for resectable, liver-only metastatic colorectal cancer (mCRC). With no consensus definition of “resectable” disease, decisions regarding resectability are reliant on the expertise and judgement of the treating clinician working in consultation with a multidisciplinary team (MDT). This study examines the clinical outcome versus initial assessment of resectability in an Australian population with mCRC. Patients and MethodsPatients with liver-only mCRC diagnosed January 2009 to December 2022 were identified from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry. Patients were classified based on prospectively documented treatment assessment as “resectable,” “potentially resectable,” or “unresectable.” The correlation between initial assessment of resectability and clinical outcome, and any impact of clinicopathologic factors were examined. Kaplan-Meier analysis assessed overall survival based on initial resectability assessment and resection status. Results: Of 4437 patients with mCRC identified through TRACC, 1250 (28%) had liver-only disease at presentation, with 497 (43%), 277 (24%), and 374 (33%) classified as “unresectable,” “potentially resectable,” and “resectable,” respectively. In total, 516 (41%) ultimately underwent surgical resection, including 30 (6%) of the “initially unresectable,” 148 (53%) of the “potentially resectable,” and 338 (90%) of the “resectable” at a median of 9.5, 5.9, and 2.4 months from the diagnosis of liver metastases, respectively. Resection in the “unresectable” patient population was associated with younger age (mean age 63 vs. 69, P = .0006), better performance status (ECOG 0-1 100% vs. 74%, P = .0017), and fewer comorbidities (Charlson index 0-3 in 73% vs. 53%, P = .0296) compared with no resection. Median overall survival was longer for resected versus nonresected patients across all categories: “unresectable” (59.2 vs. 17.6 months, P < .0001), “potentially resectable” (57.2 vs. 22.8 months, P < .0001), and “resectable” (108 vs. 55 months, P < .0001). ConclusionsThis real-world study demonstrates the potential for “initially unresectable” patients to become surgical candidates following systemic therapy, more likely in younger and fitter patients, with overall excellent survival outcomes in resected patients. This highlights the value of routine, repeated MDT assessments for patients with liver-only disease who are continuing to respond to systemic therapy, even for those initially considered never to be surgical candidates.

Outcome of patients with solid malignancies considered for intensive care unit admission: a single-center prospective cohort study.

To identify the predictors and outcomes of ICU triage decisions in patients with solid malignancies (SM) and to investigate the usefulness of the National Early Warning Score (NEWS) and quick Sequential Organ Failure Assessment (qSOFA) score at triage. All patients with SM for whom ICU admission was requested between July 2019 and December 2021 in a French university-affiliated hospital were included prospectively. Of the 6262 patients considered for ICU admission, 410 (6.5%) had SM (age, 66 [58-73] years; metastases, 60.1%; and performance status 0-2, 81%). Of these 410 patients, 176 (42.9%) were admitted to the ICU, including 141 (80.1%) subsequently discharged alive. Breast cancer, hemoptysis, and pneumothorax were associated with ICU admission; whereas older age, performance status 3-4, metastatic disease, and request at night were associated with denial of ICU admission. The NEWS, and the qSOFA score in patients with suspected infection, determined at triage performed poorly for predicting hospital mortality (area under the receiver operating characteristics curve, 0.52 and 0.62, respectively). Performance status 3-4 was independently associated with higher 6-month mortality and first-line anticancer treatment with lower 6-month mortality. Hospital mortality was 33.3% in patients admitted to the ICU after refusal of the first request. Patients with SM were frequently denied ICU admission despite excellent in-ICU survival. Poor performance status was associated with ICU admission denial and higher 6-month mortality, but none of the other reasons for denying ICU admission predicted 6-month mortality. Physiological scores had limited usefulness in this setting.

Case Report: Headaches and Hormonal Disruptions

Craniopharyngiomas are rare, relatively benign, and slow-growing tumors that arise near the pituitary gland and hypothalamus and in the vicinity of the center of the brain. Therefore, the tumor is usually discovered to be big enough to cause presenting symptoms, including headaches, vomiting, and visual problems. Variable hormone deficiencies that lead to poor growth or absent puberty might also be found in children and adolescents, while in adults, such as thyroid underactivity, adrenal crises, gonadotropin deficiency, and diabetes insipidus. Although patients with craniopharyngioma have an excellent survival rate, this tumor’s tendency to adhere to important parts of the brain renders complete resection unattainable and, therefore, leads invariably to tumor recurrence. Thus, patients with this type of tumor must undergo regular, appropriate imaging, by MRI or CT scan.

Design of randomized controlled trials to estimate cancer-mortality reductions from multicancer detection screening.

Determining whether screening with multicancer detection (MCD) tests saves lives requires randomized controlled trials (RCTs). To inform RCT design, we estimated cancer-mortality outcomes from hypothetical MCD RCTs. We used the Hu-Zelen model, previously used to plan the NLST, to estimate mortality reductions, sample-size, and power for 9 cancers for different RCT design parameters and MCD test parameters. Our base-case RCT with 5 yearly screens and 100,000 people ages 60-74 in each arm, who also undergo standard-of-care screens, has 87-89% power to detect an 9-10% mortality reduction (NNS = 578-724) over 7-9 years. The majority of prevented deaths were from lung-cancers (base-case (64-66%) and all sensitivity analyses), 8-10% from colorectal-cancer, and 26% from the other 7-cancers, mostly from stomach/ovary/esophagus (due to excellent stage-1 survival) and less from liver/pancreas (poor stage-1 survival) or head/neck-cancer/lymphoma (excellent stage-4 survival). There was limited power for mortality reductions at most individual cancer sites. Base-case findings were sensitive to test sensitivity, stage-shifts, and mean sojourn times in the preclinical state (especially for lung-cancer), but 90% power could be recovered by recruiting a substantially higher risk population. Large-scale MCD RCTs would have 89% power to detect a ∼10% cancer-mortality reduction over a relatively short 7-9 year timeframe from trial entry. The estimated NNS for MCD RCTs compares favorably to mammographic screening. Most prevented cancer-deaths in a well-powered MCD RCT would likely be from lung-cancer. Non-lung/CRC cancer sites could be a meaningful proportion of prevented cancer-deaths but power is insufficient to isolate non-lung-cancer mortality reductions.

Total knee replacement in severe genu recurvatum. High prosthetic survival rate without deformity recurrence, using rotating hinge prosthesis

IntroductionGenu recurvatum can originate from neurological and non-neurological causes. Its presence associated with knee osteoarthritis represents 1 % of the causes of total knee replacement (TKR). The aim of this retrospective study was to show the functional outcomes, recurrence rate and prosthetic survival in patients with genu recurvatum treated with articulated rotating hinge prostheses. Methodsbetween January of 2008 and December of 2021, we performed 3224 primary TKR, of which 34 (1 %) had recurvatum. This was defined as hyperextension ≥10°. Inclusion crirteria were patients with primary TKR and recurvatum that were treated with a rotating hinge prosthesis (Endo Model, Walderman Link, Ham, Germany), and completed a minimum follow-up of 24 months. Final series consisted in 23 patients with 25 TKR with 15 (65.22 %) females and a mean age of 66.8 ± 14.2 years old. The median follow-up was 5.0 (range 2.11–11.5). Clinical analysis was performed with the use of Knee Society Score (KSS) and Western Ontario & McMaster Universities Osteoarthritis Index (WOMAC). Prosthetic survival rate was calculated with a Kaplan-Meier curve considering as the endpoint of the analysis revision due to any reason. Recurrence was defined as the presence of hyperextension ≥ 5° after surgery. Resultsof the 23 patients, 9 (39.13 %) had history of neurological disorders. Median recurvatum observed was 20.12° (range 13.0° - 30.2°). A median of 19.6° (range 10.1° - 55.4°) valgus misalignment was observed in 19 patients and 10.7° (range 2.0–23.5°) of varus was observed in 6 (24 %) patients. Clinical and functional KSS improved significantly after 12 months (from 34.2 ± 9.8 and 40.1 ± 12.6 to 82.1 ± 7.5 and 89.2 ± 6.8 respectively; p < 0.01) and at the end of the study (84.3 ± 7.5 and 90.0 ± 11.3; p < 0.01). Final mean WOMAC value was 24.1 ± 9.6. One (4.0 %) complication was registered after surgery (superficial infection). Four (16.0 %) patients had demarcation. Prosthetic survival rate was 100 % at the end of the study. ConclusionThe rotating hinge prosthesis restores joint function in patients with severe knee osteoarthritis with and without neurological disorders, without recurrence of misalignment and with excellent survival rates.

The impact of the physicochemical properties of calcium phosphate ceramics on biocompatibility and osteogenic differentiation of mesenchymal stem cells

ObjectiveIn this study we have focused on biocompatibility and osteoinductive capacity analysis of self-manufactured single-phase (HAP) and two-phase (HAP and β-ТСР) bioactive ceramics with various chemical modifications (Fig. 1).ResultsWe demonstrate a reduction in solubility for all analyzed composite after the treatment with H2O and H2O2, accompanied by an enhancement in adsorption activity. This modification also resulted in an increase in micro- and macroporosity, along with a rise in the open porosity. Adipose-derived mesenchymal stromal cells demonstrated excellent cell adhesion and survival when cultured with these ceramics. Calcium phosphate ceramics (H-500, HT-500, and HT-1 series) stimulated alkaline phosphatase expression, promoted calcium deposition, and enhanced osteopontin expression in ADSCs, independently inducing osteogenesis without additional osteogenic stimuli. These findings underscore the promising potential of HAP-based bioceramics for bone regeneration/reconstruction.Graphical

Interstitial brachytherapy for periocular nonmelanoma skin cancers: Impact on organ and function preservation

PurposeTo study the local control, toxicity, organ and functional preservation and cosmetic outcomes after interstitial brachytherapy for periocular nonmelanoma skin cancers. Methods and MaterialsPatients with skin cancers of upper and lower eyelid, medial and lateral canthus and the infra-orbital region treated with high dose rate (HDR) interstitial brachytherapy (ISBT) using 192-Iridium (192Ir) between December 2010 and July 2022 were included and data collected from a prospectively maintained database. Local control, survival outcomes, acute and late RTOG toxicity, functional and cosmetic outcomes were analysed. ResultsSixteen patients were included. Nine patients had lower eyelid tumors, 5 patients had tumors in canthi and two patients had skin tumor in the infra-orbital region. The median dose for definitive ISBT was 49 Gy in 14 fractions. After a median follow up of 73 months, all patients treated with definitive and adjuvant ISBT were locally controlled. Three of the four patients who received salvage ISBT for post-surgical failure had local recurrences and all were effectively managed with salvage re-surgery. Of the two deaths, none were disease related. Organ and function preservation was achieved in 15 (93.7 %) and 13 (81.2 %), respectively, with one patient being lost to follow up. Excellent, good, fair and poor cosmesis was seen in 6 (40 %) patients, 6 (40 %) patients, 2 (14 %) patients and 1(6 %) patient, respectively. ConclusionHDR-ISBT was safe and effective for skin tumors around the eye and resulted in excellent local control and survival outcomes preserving organ and function in majority of patients with good-excellent cosmesis.

Survival in Thyroid Cancer in Sweden From 1999 To 2018.

Thyroid cancer (TC) is diagnosed in several histological types which differ in their clinical characteristics and survival. We aim to describe how they influence TC survival in Sweden. Cancer data were obtained from the Swedish cancer registry between years 1999 and 2018, and these were used to analyze relative survival. Relative survival for all TC improved when analyzed in 10-year periods, and female survival improved more than male survival. Female survival advantage appeared to be present also for specific histological types, although case numbers were low for rare types. Female 5-year relative survival for TC was 100% for follicular, 95.1% for oncocytic, 93.4% for papillary, 89.7% for medullary, and 6.1% for anaplastic cancer. Among the clinical TNM classes, only T4 and M1 stages were associated with decreased survival compared to T1-3 and M0. Anaplastic cancer presented most often at high T and M1 stages, in contrast to other TC. Curiously, the diagnostic age for anaplastic M1 patients was lower than that for M0 patients. Both anaplastic and medullary cancers did not show age-dependent increases in the probability of metastases, in contrast to the main histological types. This could indicate the presence of several types of anaplastic and medullary cancers. The poor survival for anaplastic TC is an extreme contrast to the excellent survival of differentiated TC. As less than 20% of anaplastic cancer patients survived one year, urgent diagnosis and initiation of treatment are important. Facilitated treatment pathways have been instituted in Denmark resulting in improved survival. Anaplastic cancer should be a target of a major research focus.

Thoracoscopic removal of cranial mediastinal masses in dogs is associated with a low conversion rate, excellent survival to discharge, and good long-term outcome.

To report the complications and outcomes associated with thoracoscopic cranial mediastinal mass resection in dogs. 49 client-owned dogs that underwent thoracoscopic cranial mediastinal mass removal. This was a retrospective cohort study (January 1, 2014, to July 31, 2023), and the medical records of 49 client-owned dogs that underwent thoracoscopic cranial mediastinal mass removal were reviewed. The signalment, history, clinicopathologic features, perioperative complications, and long-term outcome were recorded. Preoperative myasthenia gravis (MG) and megaesophagus (ME) were identified in 17 of 49 (35%) dogs and 11 of 49 (22%) dogs, respectively. The median maximal tumor diameter on CT images was 4.7 cm (range, 2.7 to 8.5 cm). Nonemergent conversion to an open procedure was necessary in 4 of 49 (8%) dogs, and dogs with conversion to an open procedure had a significantly larger median maximal CT tumor diameter than dogs without conversion (P = .03). The most common tumor type was thymoma (37/49 [76%]). The overall median survival time for dogs with thymoma was 1,102 days (95% CI, 482 to upper bound not reached). The median survival time for dogs with thymoma and concurrent presurgical MG was 182 days (95% CI, 14 to upper bound not reached). Presurgical diagnosis of MG (P = .44) or ME (P = .69) was not associated with survival time. Thoracoscopic removal of cranial mediastinal masses was associated with low conversion and complication rates. Long-term survival is possible, and thoracoscopic removal should be considered for select cases.

Nine Years of Continuous Flow LVAD (HeartMate 3): Survival and LVAD-Related Complications before and after Hospital Discharge.

End-stage heart failure is associated with high mortality. Recent developments such as the left ventricular assist device (LVAD) have improved patient outcomes. The HeartMate 3 LVAD is a novel centrifugal pump that was developed to provide hemodynamic support in heart failure patients, either as a bridge-to-transplant (BTT), myocardial recovery, or destination therapy (DT). Our objective was to evaluate the survival rates and LVAD-related complications of the HeartMate 3 LVAD before and after hospital discharge in our center. We retrospectively reviewed all patients implanted with the HeartMate 3 LVAD in our institute between September 2015 and June 2024. Patients who received a Heart Ware Ventricular Assist Device (HVAD) and HeartMate 2 LVAD devices were excluded. The primary endpoint was survival before and after hospital discharge. The secondary endpoints included an incidence of serious LVAD adverse events (bleeding, major infection, hemolysis, device thrombosis and malfunction, and neurological dysfunction) and the causes of re-admission along the follow-up period. A total of 48 consecutive HeartMate 3 LVAD patients were enrolled in this study. The mean age was 56.1 ± 10.6 years. A total of 72.9% of patients received LVAD therapy as a BTT, 14.6% as DT, 10.4% as a bridge-to-decision, and 2.1% as a bridge-to-recovery. A total of 85.4% of patients were discharged after implantation. The main cause for in-hospital mortality was right ventricular failure (8.3%), followed by stroke, abdominal bleeding, and multi-organ failure (2.1% each). One patient (2.1%) had successful heart transplantation, 26 patients (63.4%) are still on LVAD support, and 11 (26.8%) patients have died during follow-up. The main cause of mortality after hospital discharge was sepsis, which occurred in 9.8% of patients, followed by right ventricular failure, non-LVAD-related causes, unknown causes with two (4.9%) cases each, and one case of fatal stroke (2.4%). During the follow-up, there was no need for LVAD replacement. HeartMate 3 LVAD is associated with excellent in-hospital survival rates in patients with end-stage heart failure. Right ventricular failure was the main cause of death before hospital discharge, whereas sepsis was the main cause of death after hospital discharge.