Prediagnostic use of menopausal hormone therapy and long-term survival of localized epithelial ovarian cancer: The Extreme study.

Use of menopausal hormone therapy (MHT) prior to an epithelial ovarian cancer (EOC) diagnosis has been suggested to be associated with improved survival. In a recent nationwide cohort study, we found that prediagnostic long-term MHT use, especially estrogen therapy (ET), was associated with improved long-term survival in women with nonlocalized EOC. Our aim was to investigate the influence of prediagnostic MHT use on long-term survival among women with localized EOC in the same nationwide study. Our study cohort comprised all women aged 50 years or older with an EOC diagnosis in Denmark 2000-2014 (n = 2097) identified from the Extreme study. We collected information on usage of systemic ET and estrogen plus progestin therapy (EPT) from the Danish National Prescription Registry. By using pseudo-values, 5- and 10-year absolute and relative survival probabilities were estimated with 95% confidence intervals (CIs) while adjusting for histology, comorbidity, and income. Relative survival probabilities >1 indicate better survival. The 5-year absolute survival probabilities were 61% and 56%, respectively, among women who were nonusers and users of prediagnostic MHT, whereas these numbers were 46% and 41%, respectively, regarding 10-year survival. Use of MHT was not significantly associated with an improved 5- or 10-year survival in women with localized EOC (5-year relative survival probability = 0.95, 95% CI: 0.89-1.02; 10-year relative survival probability = 0.92, 95% CI: 0.84-1.02). Similar findings were seen for systemic ET or EPT use. Our findings do not suggest a positive benefit from prediagnostic MHT use on long-term survival of localized EOC.

Loss of copy numbers of retrotransposons (HERVK) on chromosome 7p11.2 impacts EGFR (Epidermal Growth Factor Receptor)-induced phenotypes for platinum sensitivity and long-term survival in ovarian cancer-A study from the OVCAD consortium.

We analyzed variations in the epidermal growth factor receptor (EGFR) gene and 5'-upstream region to identify potential molecular predictors of treatment response in primary epithelial ovarian cancer. Tumor tissues collected during debulking surgery from the prospective multicenter OVCAD study were investigated. Copy number variations in the human endogenous retrovirus sequence human endogenous retrovirus K9 (HERVK9) and EGFR Exons 7 and 9, as well as repeat length and loss of heterozygosity of polymorphic CA-SSR I and relative EGFR mRNA expression were determined quantitatively. At least one EGFR variation was observed in 94% of the patients. Among the 30 combinations of variations discovered, enhanced platinum sensitivity (n = 151) was found dominantly with HERVK9 haploidy and Exon 7 tetraploidy, overrepresented among patients with survival ≥120 months (24/29, p = .0212). EGFR overexpression (≥80 percentile) was significantly less likely in the responders (17% vs. 32%, p = .044). Multivariate Cox regression analysis, including age, FIGO stage, and grade, indicated that the patients' subgroup was prognostically significant for CA-SSR I repeat length <18 CA for both alleles (HR 0.276, 95% confidence interval 0.109-0.655, p = .001). Although EGFR variations occur in ovarian cancer, the mRNA levels remain low compared to other EGFR-mutated cancers. Notably, the inherited length of the CA-SSR I repeat, HERVK9 haploidy, and Exon 7 tetraploidy conferred three times higher odds ratio to survive for more than 10 years under therapy. This may add value in guiding therapies if determined during follow-up in circulating tumor cells or circulating tumor DNA and offers HERVK9 as a potential therapeutic target.

Indicators of cure for women living after uterine and ovarian cancers: a population-based study.

This study aims to estimate long-term survival, cancer prevalence, and several cure indicators for Italian women with gynecological cancers. Thirty-one cancer registries, representing 47% of the Italian female population, were included. Mixture cure models were used to estimate net survival, cure fraction, time to cure (when 5-year conditional net survival becomes > 95%), cure prevalence (women who will not die of cancer), and already cured (living longer than time to cure). In 2018, 0.4% (121 704) of Italian women were alive after diagnosis of corpus uteri cancer, 0.2% (52 551) after cervical cancer, and 0.2% (52 153) after ovarian cancer. More than 90% of patients with uterine cancers and 83% with ovarian cancer will not die from their neoplasm (cure prevalence). Women with gynecological cancers have a residual excess risk of death <5% at 5 years after diagnosis. The cure fraction was 69% for corpus uteri, 32% for ovarian, and 58% for cervical cancer patients. Time to cure was ≤10 years for women with gynecological cancers aged <55 years; 74% of patients with cervical cancer, 63% with corpus uteri cancer, and 55% with ovarian cancer were already cured. These results can contribute to improving follow-up programs for women with gynecological cancers and supporting efforts against discrimination of already cured ones. This article is part of a Special Collection on Gynecological Cancers.

The Value of Textbook Outcome in Benchmarking Pancreatoduodenectomy for Nonfunctioning Pancreatic Neuroendocrine Tumors.

BACKGROUND: Textbook outcome (TO) is a composite variable that can define the quality of pancreatic surgery. The aim of this study is to evaluate TO after pancreatoduodenectomy (PD) for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs). PATIENTS AND METHODS: All patients who underwent PD for NF-PanNETs (2007-2016) in different centers were included in this retrospective study. TO was defined as the absence of severe postoperative complications and mortality, length of hospital stay ≤ 19 days, R0 resection, and at least 12 lymph nodes harvested. RESULTS: Overall, 477 patients were included. The TO rate was 32%. Tumor size [odds ratio (OR) 1.696; p = 0.013], a minimally invasive approach (OR 12.896; p = 0.001), and surgical volume (OR 2.062; p = 0.023) were independent predictors of TO. The annual frequency of PDs increased over time as well as the overall rate of TO. At a median follow-up of 44 months, patients who achieved TO had similar disease-free (p = 0.487) and overall survival (p = 0.433) rates compared with patients who did not achieve TO. TO rate in patients with NF-PanNET > 2 cm was 35% versus 27% in patients with NF-PanNET ≤ 2 cm (p = 0.044). Considering only NF-PanNETs > 2 cm, patients with TO and those without TO had comparable 5-year overall survival rates (p = 0.766) CONCLUSIONS: TO is achieved in one-third of patients after PD for NF-PanNETs and is not associated with a benefit in terms of long-term survival.

Unique Biology of Pancreatic Ductal Adenocarcinoma Accompanied by Rapidly Impaired Diabetes: A Favorable Long-Term Survival Following Curative Resection.

BACKGROUND: Pancreatic ductal adenocarcinomas (PDACs) are sometimes diagnosed accompanied by rapidly impaired diabetes (PDAC-RID). Although this type of PDAC may have unusual biological features, these features have not been explained. METHODS: Patients with PDAC who underwent upfront pancreatectomy between 2010 and 2018 were retrospectively reviewed. PDAC-RID was defined as a glycated hemoglobin (HbA1c) value of ≥ 8.0% of newly diagnosed diabetes, and acute exacerbation of previously diagnosed diabetes. Other patients were classified as PDAC with stable glycometabolism (PDAC-SG). Clinicopathological factors, long-term survival rates, and recurrence patterns were evaluated. RESULTS: Of the 520 enrolled patients, 104 were classified as PDAC-RID and 416 as PDAC-SG. There was no significant difference regarding TNM staging, resectability, or adjuvant chemotherapy rate between the groups. However, 5-years cancer-specific survival (CSS) was significantly higher in the PDAC-RID group than in the PDAC-SG group (45.3% vs. 31.1%; p = 0.02). This survival difference was highlighted in relatively early-stage PDAC (≤ pT2N1) (CSS: 60.8% vs. 43.6%; p = 0.01), but the difference was not significant for advanced-stage PDAC. A multivariate analysis of early-stage PDAC showed that PDAC-SG was an independent risk factor of shorter CSS (hazard ratio 1.76; p = 0.02). The hematogenous metastatic rate in early-stage PDAC was lower in the PDAC-RID group than in the PDAC-SG group (18.3% vs. 35.8%; p = 0.01). CONCLUSIONS: PDAC-RID showed a favorable long-term survival rate after curative resection with low hematogenous metastases, which may be due to its unique biology.

Preoperative Prediction of Long-Term Survival After Surgery in Patients with Resectable Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Although some clinical trials have demonstrated the benefits of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC), its optimal candidate has not been clarified. This study aimed to detect predictive prognostic factors for resectable PDAC patients who underwent upfront surgery and identify patient cohorts with long-term survival without neoadjuvant therapy. PATIENTS AND METHODS: A total of 232 patients with resectable PDAC who underwent upfront surgery between January 2008 and December 2019 were evaluated. RESULTS: The median overall survival (OS) time and 5-year OS rate of resectable PDAC with upfront surgery was 31.5 months and 33.3%, respectively. Multivariate analyses identified tumor diameter in computed tomography (CT) ≤ 19 mm [hazard ratio (HR) 0.40, p < 0.001], span-1 within the normal range (HR 0.54, p = 0.023), prognostic nutritional index (PNI) ≥ 44.31 (HR 0.51, p < 0.001), and lymphocyte-to-monocyte ratio (LMR) ≥ 3.79 (HR 0.51, p < 0.001) as prognostic factors that influence favorable prognoses after upfront surgery. According to the prognostic prediction model based on these four factors, patients with four favorable prognostic factors had a better prognosis with a 5-year OS rate of 82.4% compared to others (p < 0.001). These patients had a high R0 resection rate and a low frequency of tumor recurrence after upfront surgery. CONCLUSIONS: We identified patients with long-term survival after upfront surgery by prognostic prediction model consisting of tumor diameter in CT, span-1, PNI, and LMR. Evaluation of anatomical, biological, nutritional, and inflammatory factors may be valuable to introduce an optimal treatment strategy for resectable PDAC.

Predictors for Long-Term Survival After Resection of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Improved systemic therapy has made long term (≥ 5 years) overall survival (LTS) after resection of pancreatic ductal adenocarcinoma (PDAC) increasingly common. However, a systematic review on predictors of LTS following resection of PDAC is lacking. METHODS: The PubMed, Embase, Scopus, and Cochrane CENTRAL databases were systematically searched from inception until March 2023. Studies reporting actual survival data (based on follow-up and not survival analysis estimates) on factors associated with LTS were included. Meta-analyses were conducted by using a random effects model, and study quality was gauged by using the Newcastle-Ottawa Scale (NOS). RESULTS: Twenty-five studies with 27,091 patients (LTS: 2,132, non-LTS: 24,959) who underwent surgical resection for PDAC were meta-analyzed. The median proportion of LTS patients was 18.32% (IQR 12.97-21.18%) based on 20 studies. Predictors for LTS included sex, body mass index (BMI), preoperative levels of CA19-9, CEA, and albumin, neutrophil-lymphocyte ratio, tumor grade, AJCC stage, lymphovascular and perineural invasion, pathologic T-stage, nodal disease, metastatic disease, margin status, adjuvant therapy, vascular resection, operative time, operative blood loss, and perioperative blood transfusion. Most articles received a "good" NOS assessment, indicating an acceptable risk of bias. CONCLUSIONS: Our meta-analysis pools all true follow up data in the literature to quantify associations between prognostic factors and LTS after resection of PDAC. While there appears to be evidence of a complex interplay between risk, tumor biology, patient characteristics, and management related factors, no single parameter can predict LTS after the resection of PDAC.

The Impact of Enhanced Recovery on Long-Term Survival in Rectal Cancer.

INTRODUCTION: Implementing perioperative interventions such as enhanced recovery pathways (ERPs) has improved short-term outcomes and minimized length of stay. Preliminary evidence suggests that adherence to the enhanced recovery after surgery protocol may also enhance 5-year cancer-specific survival (CSS) in colorectal cancer surgery. This retrospective study presents long-term survival outcomes and disease recurrence from a high-volume, single-center practice. METHODS: All patients over 18 years of age diagnosed with rectal adenocarcinoma and undergoing elective minimally invasive surgery (MIS) were retrospectively reviewed between February 2005 and April 2018. Relevant data were extracted from Mayo electronic records and securely stored in a database. Short-term morbidity and long-term oncological outcomes were compared between patients enrolled in ERP and those who received non-enhanced care. RESULTS: Overall, 600 rectal cancer patients underwent MIS, of whom 320 (53.3%) were treated according to the ERP and 280 (46.7%) received non-enhanced care. ERP was associated with a decrease in length of stay (3 vs. 5 days; p < 0.001) and less overall complications (34.7 vs. 54.3%; p < 0.001). The ERP group did not show an improvement in overall survival (OS) or disease-free survival (DFS) compared with non-enhanced care on multivariable (non-ERP vs. ERP OS: hazard ratio [HR] 1.268, 95% confidence interval [CI] 0.852-1.887; DFS: HR 1.050, 95% CI 0.674-1.635) analysis. CONCLUSION: ERP was found to be associated with a reduction in short-term morbidity, with no impact on long-term oncological outcomes, such as OS, CSS, and DFS.

Diagnosis and treatment of ischemia-producing coronary stenoses improves 5-year survival of patients undergoing major vascular surgery.

OBJECTIVE: Patients undergoing vascular surgery procedures have poor long-term survival due to coexisting coronary artery disease (CAD), which is often asymptomatic, undiagnosed, and undertreated. We sought to determine whether preoperative diagnosis of asymptomatic (silent) coronary ischemia using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) together with postoperative ischemia-targeted coronary revascularization can reduce adverse cardiac events and improve long-term survival following major vascular surgery METHODS: In this observational cohort study of 522 patients with no known CAD undergoing elective carotid, peripheral, or aneurysm surgery we compared two groups of patients. Group I included 288 patients enrolled in a prospective Institutional Review Board-approved study of preoperative coronary CT angiography (CTA) and FFRCT testing to detect silent coronary ischemia with selective postoperative coronary revascularization in addition to best medical therapy (BMT) (FFRCT guided), and Group II included 234 matched controls with standard preoperative cardiac evaluation and postoperative BMT alone with no elective coronary revascularization (Usual Care). In the FFRCT group, lesion-specific coronary ischemia was defined as FFRCT ≤0.80 distal to a coronary stenosis, with severe ischemia defined as FFRCT ≤0.75. Results were available for patient management decisions. Endpoints included all-cause death, cardiovascular death, myocardial infarction (MI), and major adverse cardiovascular events (MACE [death, MI, or stroke]) during 5-year follow-up. RESULTS: The two groups were similar in age, gender, and comorbidities. In FFRCT, 65% of patients had asymptomatic lesion-specific coronary ischemia, with severe ischemia in 52%, multivessel ischemia in 36% and left main ischemia in 8%. The status of coronary ischemia was unknown in Usual Care. Vascular surgery was performed as planned in both cohorts with no difference in 30-day mortality. In FFRCT, elective ischemia-targeted coronary revascularization was performed in 103 patients 1 to 3 months following surgery. Usual Care had no elective postoperative coronary revascularizations. At 5 years, compared with Usual Care, FFRCT guided had fewer all-cause deaths (16% vs 36%; hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.22-0.60; P < .001), fewer cardiovascular deaths (4% vs 21%; HR, 0.11; 95% CI, 0.04-0.33; P < .001), fewer MIs (4% vs 24%; HR, 0.13; 95% CI, 0.05-0.33; P < .001), and fewer MACE (20% vs 47%; HR, 0.36; 95% CI, 0.23-0.56; P < .001). Five-year survival was 84% in FFRCT compared with 64% in Usual Care (P < .001). CONCLUSIONS: Diagnosis of silent coronary ischemia with ischemia-targeted coronary revascularization in addition to BMT following major vascular surgery was associated with fewer adverse cardiovascular events and improved 5-year survival compared with patients treated with BMT alone as per current guidelines.

Long-term survival after neoadjuvant therapy for triple-negative breast cancer under different treatment regimens: a systematic review and network meta-analysis.

BACKGROUND: Triple-negative breast cancer (TNBC) is a life-threatening subtype of breast cancer with limited treatment options. Therefore, this network meta-analysis (NMA) aimed to evaluate and compare the effect of various neoadjuvant chemotherapy (NCT) options on the long-term survival of patients with TNBC. METHODS: PubMed, Embase, Medline, Cochrane Library, Web of Science, and major international conference databases were systematically searched for randomized controlled trials (RCTs) on the efficacy of various NCT options in patients with TNBC. Searches were performed from January 2000 to June 2023. Study heterogeneity was assessed using the I2 statistic. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate disease-free survival (DFS) and overall survival (OS). Odds ratios (ORs) and 95% CIs were used to evaluate the pathologic complete response (pCR). The primary outcome was DFS. RESULTS: We conducted an NMA of 21 RCTs involving 8873 patients with TNBC. Our study defined the combination of anthracyclines and taxanes as the preferred treatment option. On this basis, the addition of any of the following new drugs is considered a new treatment option: bevacizumab (B), platinum (P), poly-ADP-ribose polymerase inhibitors (PARPi), and immune checkpoint inhibitor (ICI). Based on the surface under the cumulative ranking curve (SUCRA) values, the top three SUCRA area values of DFS were taxanes, anthracycline, and cyclophosphamide (TAC; 89.23%); CT (84.53%); and B (81.06%). The top three SUCRA area values of OS were CT (83.70%), TAC (62.02%), and B-containing regimens (60.06%). The top three SUCRA area values of pCR were B + P-containing regimens (82.7%), ICI + P-containing regimens (80.2%), and ICI-containing regimens (61.8%). CONCLUSIONS: This NMA showed that standard chemotherapy is a good choice with respect to long-term survival. Moreover, B associated with P-containing regimens is likely to be the optimal treatment option for neoadjuvant TNBC in terms of pCR.

History of autoimmune disease and long-term survival of epithelial ovarian cancer: The extreme study.

OBJECTIVE: Patients with autoimmune disease may have impaired cancer survival. The aim was to investigate the association between autoimmune disease and ovarian cancer survival. METHODS: From the Extreme study, we included women diagnosed with epithelial ovarian cancer (EOC) in Denmark during 1990-2014 (n = 11,870). Information on exposure and covariates was retrieved from nationwide registries. Using pseudo-values, we estimated absolute and relative 5- and 10-year survival probabilities with 95% confidence intervals (CIs) for autoimmune diseases combined and for the four most common individual disorders in our study population, namely type 1 diabetes, rheumatoid arthritis, Graves' disease, and inflammatory bowel disease. RESULTS: The overall 5- and 10-year absolute survival probabilities were 35% and 24%, respectively, in women with EOC without autoimmune disease. Autoimmune diseases combined was not significantly associated with survival among women with EOC (5-year adjusted relative survival probability = 1.01, 95% CI: 0.94-1.09; 10-year adjusted relative survival probability = 0.90, 95% CI: 0.81-1.00). However, stratification by disease stage showed an impaired 10-year survival in women with autoimmune disease and a localized EOC (relative survival probability = 0.86, 95% CI: 0.76-0.97). None of the individual autoimmune diseases were statistically significantly associated with EOC survival. CONCLUSIONS: Only among women with localized EOC, there seemed to be a long-term survival loss associated with a history of autoimmune disease. In contrast, no significant association between a history of autoimmune disease and survival was observed in women with nonlocalized EOC where the survival is already low.

A novel methylation signature predicts extreme long-term survival in glioblastoma.

PURPOSE: Glioblastoma (GBM) is the most common malignant primary brain tumor with a dismal prognosis of less than 2 years under maximal therapy. Despite the poor prognosis, small fractions of GBM patients seem to have a markedly longer survival than the vast majority of patients. Recently discovered intertumoral heterogeneity is thought to be responsible for this peculiarity, although the exact underlying mechanisms remain largely unknown. Here, we investigated the epigenetic contribution to survival. METHODS: GBM treatment-naïve samples from 53 patients, consisting of 12 extremely long-term survivors (eLTS) patients and 41 median-term survivors (MTS) patients, were collected for DNA methylation analysis. 865 859 CpG sites were examined and processed for detection of differentially methylated CpG positions (DMP) and regions (DMR) between both survival groups. Gene Ontology (GO) and pathway functional annotations were used to identify associated biological processes. Verification of these findings was done using The Cancer Genome Atlas (TCGA) database. RESULTS: We identified 67 DMPs and 5 DMRs that were associated with genes and pathways - namely reduced interferon beta signaling, in MAPK signaling and in NTRK signaling - which play a role in survival in GBM. CONCLUSION: In conclusion, baseline DNA methylation differences already present in treatment-naïve GBM samples are part of genes and pathways that play a role in the survival of these tumor types and therefore may explain part of the intrinsic heterogeneity that determines prognosis in GBM patients.

Enteric pathogen survival, food safety incidents, and potential mitigation strategies to address microbial contamination in wheat-based foods: a review.

Wheat-based foods has emerged as another potential vehicle for foodborne illness in humans. The recent occurrence of recalls involving wheat-based foods requires a full understanding of how these pathogens thrive in these food products and developing potential intervention strategies to address pathogen contamination. This manuscript is the second of a two-part review covering the status of the food safety of wheat-based products. In this manuscript, available information on the survival of enteric foodborne pathogens, food safety issues, and potential pathogen reduction steps on wheat-based foods were reviewed. Shiga toxin-producing E. coli and Salmonella are capable of surviving in wheat flours and grains for extended periods (≤ 2 years). Based on the food safety issues linked to wheat flour, the main enteric pathogens of concern are STEC (O157, O121, O26, and O103) and Salmonella. Diverse interventions such as tempering treatments, thermal treatments, and non-thermal technologies all effectively reduced the pathogenic loads of wheat grains and wheat flours (2 to 6 log CFU/g reduction). Addressing pathogen contamination of wheat-based foods is a major concern for the milling industry. Future studies could be focused on improving pathogen reduction performance and validating their effects against diverse product and process conditions.

Enhancing long-term survival prediction with two short-term events: Landmarking with a flexible varying coefficient model.

Patients with cardiovascular diseases who experience disease-related short-term events, such as hospitalizations, often exhibit diverse long-term survival outcomes compared to others. In this study, we aim to improve the prediction of long-term survival probability by incorporating two short-term events using a flexible varying coefficient landmark model. Our objective is to predict the long-term survival among patients who survived up to a pre-specified landmark time since the initial admission. Inverse probability weighting estimation equations are formed based on the information of the short-term outcomes before the landmark time. The kernel smoothing method with the use of cross-validation for bandwidth selection is employed to estimate the time-varying coefficients. The predictive performance of the proposed model is evaluated and compared using predictive measures: area under the receiver operating characteristic curve and Brier score. Simulation studies confirm that parameters under the landmark models can be estimated accurately and the predictive performance of the proposed method consistently outperforms existing methods that either do not incorporate or only partially incorporate information from two short-term events. We demonstrate the practical application of our model using a community-based cohort from the Atherosclerosis Risk in Communities (ARIC) study.

Ischemia-Guided Coronary Revascularization Following Lower-Extremity Revascularization Improves 5-Year Survival of Patients With Chronic Limb-Threatening Ischemia.

PURPOSE: To determine whether diagnosis of asymptomatic (silent) coronary ischemia using coronary computed tomography (CT)-derived fractional flow reserve (FFRCT) together with targeted coronary revascularization of ischemia-producing coronary lesions following lower-extremity revascularization can reduce adverse cardiac events and improve long-term survival of patients with chronic limb-threatening ischemia (CLTI). MATERIALS AND METHODS: Prospective cohort study of CLTI patients with no cardiac history or symptoms undergoing elective lower-extremity revascularization. Patients with pre-operative coronary computed tomography angiography (CTA) and FFRCT evaluation with selective post-operative coronary revascularization (FFRCT group) were compared with patients with standard pre-operative evaluation and no post-operative coronary revascularization (control group). Lesion-specific coronary ischemia was defined as FFRCT≤0.80 distal to a coronary stenosis with FFRCT≤0.75 indicating severe ischemia. Endpoints included all-cause death, cardiac death, myocardial infarction (MI) and major adverse cardiovascular (CV) events (MACE=CV death, MI, stroke, or unplanned coronary revascularization) during 5 year follow-up. RESULTS: In the FFRCT group (n=111), FFRCT analysis revealed asymptomatic (silent) coronary ischemia (FFRCT≤0.80) in 69% of patients, with severe ischemia (FFRCT≤0.75) in 58%, left main ischemia in 8%, and multivessel ischemia in 40% of patients. The status of coronary ischemia in the control group (n=120) was unknown. Following lower-extremity revascularization, 42% of patients in FFRCT had elective coronary revascularization with no elective revascularization in controls. Both groups received guideline-directed medical therapy. During 5 year follow-up, compared with control, the FFRCT group had fewer all-cause deaths (24% vs 47%, hazard ratio [HR]=0.43 [95% confidence interval [CI]=0.27-0.69], p<0.001), fewer cardiac deaths (5% vs 26%, HR=0.18 [95% CI=0.07-0.45], p<0.001), fewer MIs (7% vs 28%, HR=0.21 [95% CI=0.10-0.47], p<0.001), and fewer MACE events (14% vs 39%, HR=0.28 [95% CI=0.15-0.51], p<0.001). CONCLUSIONS: Ischemia-guided coronary revascularization of CLTI patients with asymptomatic (silent) coronary ischemia following lower-extremity revascularization resulted in more than 2-fold reduction in all-cause death, cardiac death, MI, and MACE with improved 5 year survival compared with patients with standard cardiac evaluation and care (76% vs 53%, p<0.001). CLINICAL IMPACT: Silent coronary ischemia in patients with chronic limb-threatening ischemia (CLTI) is common even in the absence of cardiac history or symptoms. FFRCT is a convenient tool to diagnose silent coronary ischemia perioperatively. Our data suggest that post-surgery elective FFRCT-guided coronary revascularization reduces adverse cardiac events and improves long-term survival in this very-high risk patient group. Randomized study is warranted to finally test this concept.

Long Term Outcomes of the Gore Excluder Low Permeability Endoprosthesis for the Treatment of Infrarenal Aortic Aneurysms.

OBJECTIVE: This study evaluated the long term outcomes of endovascular aneurysm repair using the Gore Excluder Low Permeability (LP) endoprosthesis across high volume Dutch hospitals. METHODS: A retrospective analysis was conducted of patients treated with the Excluder LP for infrarenal abdominal aortic aneurysm (AAA) in four hospitals between 2004 and 2017. Primary outcomes were overall survival, freedom from re-interventions (overall, inside and outside instructions for use, IFU), and AAA sac dynamics: growth (> 5 mm), stabilisation, and regression (< 5 mm). Secondary outcomes were technical success (device deployment), procedural parameters, and re-interventions. Follow up visits were extracted from patient files, with imaging assessed for complications and AAA diameter. RESULTS: Five hundred and fourteen patients were enrolled, with a median (IQR) follow up of 5.0 (2.9, 6.9) years. Survival rates were 94.0% at one year, 73.0% at five years, and 37.0% at 10 years, with freedom from re-interventions of 89.0%, 79.0%, and 71.0%, respectively. 37.9% were treated outside IFU, leading to significantly more re-interventions over 10 years compared with those treated inside IFU (36.0% vs. 25.0%, respectively; p = .044). The aneurysm sac regressed by 53.5% at one year, 65.8% at five years, and 77.8% at 10 years, and grew by 9.8%, 14.3%, and 22.2%, respectively. Patients with one year sac growth had significantly worse survival (p = .047). Seven patients (1.4%) had a ruptured aneurysm during follow up. Over 15 years, type 1a endoleak occurred in 5.3%, type 1b in 3.1%, type 3 in 1.9%, type 4 in 0.2%, and type 2 in 35.6% of patients. CONCLUSION: This multicentre study of real world endovascular aneurysm repair data using the Gore Excluder LP endoprosthesis demonstrated robust long term survival and re-intervention rates, despite 37.9% of patients being treated outside IFU, with type 4 endoleak being rare. Treatment outside IFU significantly increased re-intervention rates and one year sac growth was associated with statistically significantly worse survival.

Longitudinal assessment of Leydig cell function in male survivors of childhood cancer.

BACKGROUND: As the number and longevity of childhood cancer survivors increases, assessing treatment-associated late effects remains crucial. We longitudinally examined the incidence of and associated risk factors for Leydig cell dysfunction (LCD) and Leydig cell failure (LCF) in men treated for pediatric cancers at our institution. PROCEDURE: We performed a retrospective longitudinal cohort study of adult male survivors treated for various childhood cancers who are at risk for LCD. The outcomes of interest were serum testosterone and luteinizing hormone (LH) levels during childhood and adulthood. Risk factors assessed included treatment with stem cell transplant, total body irradiation (TBI), and exposure to alkylating agents. RESULTS: Out of 118 eligible subjects, 7.6% had LCF and 14.4% had LCD. Median age at last testosterone level was 20 years. Subjects with sufficient testosterone levels in adulthood (N = 105) remained sufficient for a mean of 11.1 years following completion of cancer treatment. We found significant associations between LCF and treatment with TBI (p < .003) and between LCF in adulthood and testosterone insufficiency in childhood (p < .001). No statistically significant association was found between LCF and cyclophosphamide equivalent dose greater than 20 g/m2 (p = .2). LCF/LCD occurred in a small number of nonirradiated patients treated with the highest doses of alkylators. CONCLUSIONS: Incidence of LCF and LCD are low in male survivors of childhood cancer. Longitudinally, there is an association between childhood testosterone insufficiency and LCF in adulthood. Alkylating agents and stem cell transplant without TBI were not associated with LCF in our study.

A nonrandomized controlled trial: long-term outcomes of LATG/LAPG for cStage I gastric cancer: Japan Clinical Oncology Group Study JCOG1401.

BACKGROUND: A previous report confirmed the safety of laparoscopy-assisted total and proximal gastrectomies (LATG and LAPG) (JCOG1401). This report demonstrates the 5-year relapse-free survival (RFS) and overall survival (OS) after long-term follow-up to confirm the efficacy of these surgical methods as key secondary endpoints for cStage I gastric cancer. METHODS: This study enrolled patients who had histologically proven gastric adenocarcinoma and were diagnosed with clinical T1N0, T1N(+), or T2N0 tumors according to the 14th edition of the Japanese Classification of Gastric Carcinoma (3rd English edition). RESULTS: Between April 2015 and February 2017, 246 patients were enrolled, although one patient was excluded because of misregistration. Meticulous follow-up was continued for > 5 years for each patient, and the data were analyzed in March 2022. The 5-year RFS was 90.0% (95% confidence interval [CI] 85.5-93.2%), and the 5-year OS was 91.2% (95% CI 86.9-94.2%) in all enrolled patients. Grade 3 or 4 late postoperative complications were detected in 12.7% of patients. CONCLUSIONS: This single-arm study showed that the long-term outcomes of LATG/LAPG for cStage I gastric cancer were acceptable, which is considered one of the standard treatments when performed by experienced surgeons. Trail registration UMIN000017155 ( http://www.umin.ac.jp/ctr/ ).

FRailty in Australian patients admitted to Intensive care unit after eLective CANCER-related SURGery: a retrospective multicentre cohort study (FRAIL-CANCER-SURG study).

BACKGROUND: The association between frailty and short-term and long-term outcomes in patients receiving elective surgery for cancer remains unclear, particularly in those admitted to the ICU. METHODS: In this multicentre retrospective cohort study, we included adults ≥16 yr old admitted to 158 ICUs in Australia from January 1, 2018 to March 31, 2022 after elective surgery for cancer. We investigated the association between frailty and survival time up to 4 yr (primary outcome), adjusting for a prespecified set of covariates. We analysed how this association changed in specific subgroups (age categories [<65, 65-80, ≥80 yr], and those who survived hospitalisation), and over time by splitting the survival information at monthly intervals. RESULTS: We included 35,848 patients (median follow-up: 18.1 months [inter-quartile range: 8.3-31.1 months], 19,979 [56.1%] male, median age 69.0 yr [inter-quartile range: 58.8-76.0 yr]). Some 3502 (9.8%) patients were frail (defined as clinical frailty scale ≥5). Frailty was associated with lower survival (hazard ratio: 1.72, 95% confidence interval [CI]: 1.59-1.86 compared with clinical frailty scale ≤4); this was concordant across several sensitivity analyses. Frailty was most strongly associated with mortality early on in follow-up, up to 10 months (hazard ratio: 1.39, 95% CI: 1.03-1.86), but this association plateaued, and its predictive capacity subsequently diminished with time up until 4 yr (1.96, 95% CI: 0.73-5.28). Frailty was associated with similar effects when stratified based on age, and in those who survived hospitalisation. CONCLUSIONS: Frailty was associated with poorer outcomes after an ICU admission after elective surgery for cancer, particularly in the short term. However, its predictive capacity with time diminished, suggesting a potential need for longitudinal reassessment to ensure appropriate prognostication in this population.

Sarcopenic obesity predicts short- and long-term outcomes after neoadjuvant chemotherapy and surgery for gastric cancer.

BACKGROUND: Sarcopenic obesity (SO) affects outcomes in various malignancies. However, its clinical significance in patients undergoing neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer (LAGC) remains unclear. This study investigated the impact of pre- and post-NAC SO on postoperative morbidity and survival. METHODS: Data from 207 patients with LAGC, who underwent NAC followed by radical gastrectomy between January 2010 and October 2019, were reviewed. Skeletal muscle mass and visceral fat area were measured pre- and post-NAC using computed tomography to define sarcopenia and obesity, the coexistence of which was defined as SO. RESULTS: Among the patients, 52 (25.1%) and 38 (18.4%) developed SO before and after NAC, respectively. Both pre- (34.6%) and post- (47.4%) NAC SO were associated with the highest postoperative morbidity rates; however, only post-NAC SO was an independent risk factor for postoperative morbidity [hazard ratio (HR) = 9.550, 95% confidence interval (CI) = 2.818-32.369; P < .001]. Pre-NAC SO was independently associated with poorer 3-year overall [46.2% vs. 61.3%; HR = 1.258 (95% CI = 1.023-1.547); P = .049] and recurrence-free [39.3% vs. 55.4%; HR 1.285 (95% CI 1.045-1.579); P = .017] survival. CONCLUSIONS: Pre-NAC SO was an independent prognostic factor in patients with LAGC undergoing NAC; post-NAC SO independently predicted postoperative morbidity.