Late Recurrence Research Articles

The role of miR-152 in urological tumors: potential biomarkers and therapeutic targets

Urological malignant tumors pose a significant threat to human health, with a high incidence rate each year. Prostate cancer, bladder cancer, and renal cell carcinoma are among the most prevalent and extensively researched urological malignancies. Despite advancements in research, the prognosis for these tumors remains unfavorable due to late detection, postoperative recurrence, and treatment resistance. A thorough investigation into their pathogenesis is crucial for early diagnosis and treatment. Recent studies have highlighted the close association between microRNAs (miRNAs) and cancer progression. miRNAs are small non-coding RNAs composed of 19-23 nucleotides that regulate gene expression by binding to the 3’ untranslated region (3’UTR) of target mRNAs, impacting key cellular processes such as proliferation, differentiation, apoptosis, and migration. Dysregulation of miRNAs can disrupt the expression of oncogenes and tumor suppressor genes, contributing to cancer development. Among the various miRNAs studied, miR-152 has garnered attention for its role in urological malignancies. Several studies have indicated that dysregulation of miR-152 expression is significant in these cancers, warranting a comprehensive review of the evidence. This review focuses on the expression and function of miR-152 in prostate cancer, bladder cancer, and renal cell carcinoma, elucidating its mechanisms in cancer progression and exploring its potential as a therapeutic target and biomarker in urological malignancies.

Abstract A054: Oncogenic functions of alternatively spliced MDM2-ALT2 isoform in retroperitoneal liposarcoma

Abstract Retroperitoneal liposarcoma (RPLPS) is one of the most common histologic subtypes of soft tissue sarcoma (STS). Complete surgical resection remains the mainstay treatment while the high rate of locoregional recurrence constitutes the predominant cause of mortality. Well- differentiated (WDLPS) and dedifferentiated (DDLPS) liposarcoma are the most frequent subtypes of RPLPS and present amplified MDM2 gene as a hallmark. However, there are few reports evaluating the role of alternatively spliced MDM2 transcripts in RPLPS. In this study, we assessed MDM2-ALT2 expression levels in a cohort of RPLPS patients and evaluated biological functions of MDM2-ALT2 isoform in vitro in DDLPS cell lines. Using BaseScope™ and qPCR, we demonstrated that MDM2-Full Length (MDM2-FL) and MDM2-ALT2 expression levels were upregulated in RPLPS patient-derived tissue samples compared to normal adjacent to tumor tissue (NAT). DDLPS cells overexpressing MDM2-FL or MDM2-ALT2 had higher proliferation rates and increased migration and invasion capacities, as well as increased protein levels of p- AKT, mTOR, p70S6K, MMP2 and cJun. Simultaneous overexpression of MDM2-ALT2 and AKT silencing showed that AKT inhibition impaired p-p70S6K and MMP2 protein increased levels and led to significantly decreased proliferation and migration rates compared to cells overexpressing MDM2-ALT2 only. Taken together, our data suggest that MDM2-ALT2 may promote RPLPS progression. Citation Format: Fernanda Costas C. de Faria, Safiya Khurshid, Patricia Sarchet, Sayumi Tahara, Lucia Casadei, Valerie Grignol, Roma Karna, Sydney Rentsch, Nippin Sp, Joal D Beane, Luciano Mazzoccoli, Matias Montes, Giovanni Nigita, Joe T Sharick, Jennifer L Leigth, Federica Calore, Dawn Chandler, Raphael E Pollock. Oncogenic functions of alternatively spliced MDM2-ALT2 isoform in retroperitoneal liposarcoma [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A054.

Impact of Body Mass Index on the Outcomes of Cryoballoon Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation

Background: Atrial fibrillation (AF) is prevalent among obese patients, and cryoballoon ablation (CBA) is an effective strategy for the rhythm control of AF. The impact of body mass index (BMI) on the clinical outcomes of CBA for AF is not fully explored. Methods: 85 consecutive patients with paroxysmal AF were enrolled and were categorized into three groups as per their BMI: normal weight (BMI 18.5–25 kg/m2), overweight (BMI 25–30 kg/m2), and obese patients (BMI > 30 kg/m2). The primary study endpoint was a late (12 month) recurrence of AF. Early recurrence of AF, symptom improvement, and procedural outcomes were some key secondary outcomes. Results: 20 patients had normal weight, 35 were overweight, and 30 were obese. Obese patients featured a higher prevalence of diabetes mellitus, heavier exposure to smoking, and worse baseline symptoms (as assessed through EHRA class at admission and 12 months before CBA) compared to overweight and normal weight patients. Both late and early (<3 months) AF recurrence rates were comparable across the three groups. Of note, obese patients showed greater improvement in their symptoms post-CBA, defined as improvement by at least one EHRA class, compared to normal weight patients; this might be explained by improved diastolic function. Total procedure time and dose area product were significantly increased in obese patients. The multivariate logistic regression analysis indicated that early AF recurrence and the duration of hypertension are independent predictors of late AF recurrence. Conclusion: CBA is effective in overweight and obese patients with paroxysmal AF. Procedure time and radiation exposure are increased in obese patients undergoing CBA.

Late Local Recurrence of Carcinoma <i>in situ </i>- Only Bladder Cancer

Late recurrence (LR) of bladder cancer after radical cystectomy (RC) is rare, and few studies have been conducted. We report a case of local LR of bladder cancer 10.3 years after RC. The pathology at RC was almost carcinoma <i>in situ</i> (CIS) only. The patient underwent metastasectomy, and treatment with an immune checkpoint inhibitor (ICI) achieved a complete response (CR). A 61-year-old woman was referred to our hospital for macrohematuria and bladder irritability in June 2012. She underwent RC along with pelvic lymph node dissection and ileal conduit creation. The pathologic findings were CIS, G2>G3, pT1, pN0. She visited our hospital with complaints of lower abdominal discomfort in November 2022, and recurrence was found on the pelvic floor by abdominal computed tomography. Metastasectomy confirmed metastasis of urothelial carcinoma. As salvage therapy, systemic chemotherapy with a platinum agent and an ICI were administered, leading to CR. Long-term follow-up should be considered for patients with bladder cancer, even for early-stage CIS-only tumors. Metastasectomy could be the primary option for LR of bladder cancer after RC.

Abstract 4136182: Usefulness of Lymphocyte-to-Monocyte Ratio in Predicting Late Recurrence of Atrial Fibrillation after Catheter Ablation and its Association With the Type of Atrial Fibrillation

Introduction: Leukocyte activation is reported to be an important inflammatory pathway underlying atrial fibrillation (AF). The lymphocyte-to-monocyte ratio (LMR) is a novel, cost-effective, and widely available marker of inflammation. Research Questions: The usefulness of LMR in predicting late recurrence of AF (LRAF) after catheter ablation (CA), and the impact of AF type on its usefulness, have not yet been elucidated. Goals: We aimed to elucidate the association between LMR measured just before CA and the risk of LRAF in patients who underwent CA for AF, and to investigate whether the type of AF impacts the predictability of LMR for LRAF. Methods: We enrolled 597 consecutive patients with AF (median age, 65 years; 32% female; 334 patients with paroxysmal AF [PAF] and 263 patients with persistent AF [PeAF]) who underwent initial radiofrequency CA. LMR was measured within 3 days prior to the date of CA, and calculated by dividing the absolute lymphocyte count by the absolute monocyte count using the same blood samples. Any detectable atrial tachyarrhythmia lasting for longer than 30 s beyond a 3-month blanking period after the procedure was considered as LRAF. Patients were followed-up for a maximum of 3 years. Results: During a median follow-up of 24 months, LRAF occurred in 215 patients (96 with PAF and 119 with PeAF). Although there was no significant difference in LMR between patients with and without LRAF in PAF (5.3 [4.1–6.7] vs 5.2 [4.0–6.6], p=0.403), LMR in patients with LRAF was significantly lower than those without LRAF in PeAF (4.7 [3.9–6.4] vs 5.6 [4.5–6.8], p=0.015). Multivariate Cox analysis showed that LMR was an independent predictor of LRAF in PeAF (p=0.008), but not in PAF (p=0.662). Receiver operating characteristic curve analysis revealed that an LMR of 4.8 was a fair discriminator for LRAF in PeAF. Although there was no significant difference in the risk of LRAF between the patients with lower (LMR<4.8) and higher LMR (LMR≥4.8) in PAF, patients with lower LMR had a significantly higher risk of LRAF than those with higher LMR in PeAF (Figure). Conclusions: Pre-ablation LMR was shown to be useful for predicting LRAF in patients with PeAF who underwent CA for AF, while not in patients with PAF.

Roles of MRI evaluation of pelvic recurrence in patients with rectal cancer

Abstract Developments in the multidisciplinary treatment of rectal cancer with advances in preoperative magnetic resonance imaging (MRI), surgical techniques, neoadjuvant chemoradiotherapy, and adjuvant chemotherapy have had a significant impact on patient outcomes, increasing the rates of curative surgeries and reducing pelvic recurrence. Patients with pelvic recurrence have worse prognoses, with an impact on morbidity and mortality. Although local recurrence is more frequent within 2 years of surgical resection of the primary tumor, late recurrence may occur. Clinical manifestations can vary from asymptomatic, nonspecific symptoms, to pelvic pain, bleeding, and fistulas. Synchronous metastatic disease occurs in approximately 50% of patients diagnosed with local recurrence. MRI plays a crucial role in posttreatment follow-up, whether by identifying viable neoplastic tissues or acting as a tool for therapeutic planning and assessing the resectability of these lesions. Locally recurrent tissues usually have a higher signal intensity than muscle on T2-weighted imaging. Thus, attention is required for focal heterogeneous lesions, marked contrast enhancement, early invasive behavior, and asymmetric appearance, which are suspicious for local recurrence. However, postsurgical inflammatory changes related to radiotherapy and fibrosis make it difficult to detect initial lesions. This study therefore aimed to review the main imaging patterns of pelvic recurrence and their implications for the surgical decision-making process. Critical relevance statement MRI plays a crucial role in the posttreatment follow-up of rectal cancer, whether by identifying viable neoplastic tissues or by acting as a tool for therapeutic planning. This study reviewed the main imaging patterns of pelvic recurrence. Key Points MRI aids in surgical planning and the detection of pelvic recurrence and postoperative complications. Being familiar with surgical techniques enables radiologists to identify expected MRI findings. Patterns of rectal cancer recurrence have been categorized by pelvic compartments. Neoplastic tissue may mimic postsurgical and postradiotherapy changes. Resectability of pelvic recurrence is highly related to lesion location. Graphical Abstract

Microbial profile of diabetic foot osteomyelitis from the northwest of England

BackgroundOsteomyelitis of the diabetic foot is a common and challenging complication affecting patients with diabetic foot ulcers and infections. The complexity of these infections lies in their polymicrobial nature, high rates of persistence and recurrence. This study examined the microbiological profile of diabetic foot osteomyelitis from a teaching hospital in Northwest England and their resistance patterns to understand its impact on infection persistence and to direct effective treatment.MethodsA retrospective review of 105 patients who underwent surgical management for diabetic foot osteomyelitis between 2019 and 2024. We analysed three consecutive culture samples for each patient to assess for the microbiological profile and resistance patterns of these infections and to monitor infection recurrence and persistence rates.ResultsA total of 105 patients were identified. Infection eradication was noted in 42% of the cohort, infection persistence in 18%, and late infection recurrence in 40%. Polymicrobial growth was evident in 72% of our study sample. Gram-positive bacteria made up the majority of the bacterial isolates in all 3 culture samples, 74.81% in sample 1, 69.31% in sample 2, and 55.1% in sample 3. Staphylococcus aureus was the most prevalent gram-positive bacteria, at 52.38% in sample 1, 36.19% in sample 2, and 18.09% in sample 3, followed by Haemolytic Streptococcus, Enterococcus and Corynebacterium. The frequently identified gram-negative bacteria were Pseudomonas in sample 1 (7.61%), E. coli and Proteus in sample 2 (5,71%), Pseudomonas and Proteus in sample 3 (2.85%). Gram-positive bacteria were resistant to penicillin and macrolides with resistance of staphylococcus aureus to clarithromycin identified among all 3 culture samples. Gram-negative bacteria were most resistant to amoxicillin. Staphylococcus aureus was responsible for infection persistence in most of our cohort (12/19) 63.15%. Among those patients, Staphylococcus was resistant to clarithromycin in 6 of the cases. The 5-year mortality rate for our study sample was 32.38%.ConclusionThis study highlights the prevalence of polymicrobial growth and multi-drug resistant pathogens in the scope of diabetic foot osteomyelitis. It highlights the predominance of Staphylococcus aureus and its resistant strains among patients affected by diabetic foot osteomyelitis in Greater Manchester.

Definition and Predictors of Early Recurrence in Neoadjuvantly Treated Esophageal and Gastroesophageal Adenocarcinoma: a Dual-Center Retrospective Cohort Study.

BACKGROUND: Early recurrence after esophagectomy is often used as a surrogate for aggressive tumor biology and treatment failure. However, there is no standardized definition of early recurrence, and predictors for early recurrence are unknown. Therefore, we aimed to define an evidence-based cutoff to discriminate early and late recurrence and assess the influence of neoadjuvant treatment modalities for patients with esophageal or gastroesophageal-junction adenocarcinoma (EAC). This dual-center retrospective cohort study included patients who underwent esophagectomy for stage II-III EAC after neoadjuvant treatment with chemotherapy using 5-fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) or radiochemotherapy according to the Chemoradiotherapy for Esophageal Cancer followed by Surgery Study (CROSS)protocol from 2012 to 2022. The optimal cutoff for early versus late recurrence was calculated by using the most significant difference in survival after recurrence (SAR). Multivariable logistic regression was used to identify variables associated with early recurrence. Of 334 included patients, 160 (47.9%) were diagnosed with recurrence. Most patients had systemic (60.5%) or multiple sites of recurrence (21.1%), whereas local-only recurrence (9.2%) and carcinomatosis (9.2%) were rare. The optimal interval between surgery and recurrence for distinguishing early and late recurrence was 18 months (median SAR: 9.1 versus 17.8 months, p = 0.039) with only 24% of recurrences diagnosed after the calculated cutoff. Advanced pathologic tumor infiltration (ypT3-4, p = 0.006), nodal positivity (p = 0.013), poor treatment response (>10% residual tumor, p = 0.015), and no adjuvant treatment (p = 0.048) predicted early recurrence. Early recurrence can be defined as recurrent disease within 18 months. Hallmarks for early recurrence are poor response to neoadjuvant therapy with persisting advanced disease. In those patients, adjuvant therapy and closer follow-up should be considered.

Age and Late Recurrence in Young Patients With ER–Positive, ERBB2-Negative Breast Cancer

Young patients with breast cancer with estrogen receptor (ER)-positive, ERBB2-negative tumors have a poor prognosis. Understanding factors influencing late recurrence is crucial for improving management and outcomes. To determine whether age is an independent factor associated with late distant recurrence (DR) in young patients with ER-positive, ERBB2-negative cancers without distant metastasis within 5 years from surgery. This multicenter retrospective cohort study analyzed clinical records of patients with breast cancer who underwent surgery from January 2000 to December 2011 with at least 5 years of follow-up. The study was conducted at Samsung Medical Center, Gangnam Severance Hospital, and Seoul National University Hospital, including patients aged 45 years or younger with ER-positive, ERBB2-negative tumors, no DR within 5 years after surgery, no neoadjuvant chemotherapy, and at least 2 years of endocrine therapy. The data analysis period was from January 4, 2023, to March 21, 2024. Age, grouped as 21 to 35 years, 36 to 40 years, and 41 to 45 years. The primary outcome was the incidence of late DR at 5 to 10 years after surgery. Survival outcomes, including late distant metastasis-free survival (DMFS), were evaluated in different age groups. Among 2772 patients included, 370 (13.3%) were aged 21 to 35 years, 885 (31.9%) were aged 36 to 40 years, and 1517 (54.7%) were aged 41 to 45 years. The median (range) follow-up was 10.8 (5.0-21.4) years. The youngest group had a poorer histologic grade (eg, histologic grade 3: 107 patients aged 21-35 years [28.9%]; 149 patients aged 36-40 years [16.8%]; 273 patients aged 41-45 years [18.0%]) and more frequent chemotherapy (307 patients aged 21-35 years [83.0%]; 697 patients aged 36-40 years [78.8%]; 1111 patients aged 41-45 years [73.2%]). The youngest patients had significantly worse rates of locoregional recurrence-free survival (patients aged 21-35 years, 90.1% [95% CI, 86.8%-93.3%]; patients aged 36-40 years, 94.6% [95% CI, 93.0%-96.2%]; patients aged 41-45 years, 97.7% [95% CI, 96.9%-98.5%]), disease-free survival (patients aged 21-35 years, 79.3% [95% CI, 75.0%-83.9%]; patients aged 36-40 years, 88.7% [95% CI, 86.5%-91.0%]; patients aged 41-45 years, 94.4% [95% CI, 93.2%-95.7%]), and late DMFS (patients aged 21-35 years, 89.3% [95% CI, 86.0%-92.9%]; patients aged 36-40 years: 94.2% [95% CI, 92.5%-95.9%]; patients aged 41-45 years: 97.2% [95% CI, 96.3%-98.1%]) but not overall survival (patients aged 21-35 years, 96.9% [95% CI, 95.0%-98.9%]; patients aged 36-40 years, 98.2% [95% CI, 97.2%-99.2%]; patients aged 41-45 years, 98.9% [95% CI, 98.3%-99.5%]). Multivariable analysis showed lower hazard for late DR in the older groups compared with the youngest group (age 36-40 years: hazard ratio, 0.53; 95% CI, 0.34-0.82; P = .001; age 41-45 years: hazard ratio, 0.30; 95% CI, 0.20-0.47; P < .001). In this retrospective cohort study, age was an independent factor associated with late DR in young patients with ER-positive, ERBB2-negative breast cancer. Younger age was associated with worse locoregional recurrence-free survival, disease-free survival, and late DMFS, highlighting the importance of long-term monitoring and potential for personalized treatment approaches based on age, particularly for younger patients with ER-positive, ERBB2-negative breast cancer.

C-reactive Protein-albumin-lymphocyte Index as a Novel Biomarker for Progression in Patients Undergoing Surgery for Renal Cancer.

Some patients with renal cell carcinoma (RCC) develop early or late recurrence after surgery. However, there is no clear consensus on which patients with postoperative RCC should be treated. This study aimed to establish a biomarker for selecting patients who are at a higher risk of relapse following renal cancer surgery. A total of 378 patients who underwent nephrectomy or partial nephrectomy for a diagnosis of RCC at our hospital were included, with a focus on pT3 cases at high risk of recurrence. Factors associated with postoperative progression, including pathological and hematological parameters, were examined. Sarcomatoid features, Fuhrman grade 4, and C-reactive protein-albumin-lymphocyte (CALLY) index were statistically significant predictive factors for progression-free survival after surgery (p<0.0011, p=0.0047, and p<0.0001, respectively). In the multivariate Cox proportional regression analysis, the CALLY index was the most statistically significant predictor of the risk of postoperative recurrence (p=0.0002). In addition to the existing risk factors for RCC recurrence, such as sarcomatoid features and Fuhrman grade, we propose that the CALLY index is a predictor of postoperative recurrence and that patients with a low CALLY index are good candidates for postoperative treatment. Our study may help select patients with pT3 disease with a high risk of recurrence who require postoperative treatment.

Supervised machine learning with a novel set of 20 genes predicts the likelihood of early or late recurrence of high-grade serous ovarian cancer

Supervised machine learning with a novel set of 20 genes predicts the likelihood of early or late recurrence of high-grade serous ovarian cancer

Proteogenomic analysis dissects early-onset breast cancer patients with prognostic relevance.

Early-onset breast cancer is known for its aggressive clinical characteristics and high prevalence in East Asian countries, but a comprehensive understanding of its molecular features is still lacking. In this study, we conducted a proteogenomic analysis of 126 treatment-naïve primary tumor tissues obtained from Korean patients with young breast cancer (YBC) aged ≤40 years. By integrating genomic, transcriptomic, and proteomic data, we identified five distinct functional subgroups that accurately represented the clinical characteristics and biological behaviors of patients with YBC. Our integrated approach could be used to determine the proteogenomic status of HER2, enhancing its clinical significance and prognostic value. Furthermore, we present a proteome-based homologous recombination deficiency (HRD) analysis that has the potential to overcome the limitations of conventional genomic HRD tests, facilitating the identification of new patient groups requiring targeted HR deficiency treatments. Additionally, we demonstrated that protein-RNA correlations can be used to predict the late recurrence of hormone receptor-positive breast cancer. Within each molecular subtype of breast cancer, we identified functionally significant protein groups whose differential abundance was closely correlated with the clinical progression of breast cancer. Furthermore, we derived a recurrence predictive index capable of predicting late recurrence, specifically in luminal subtypes, which plays a crucial role in guiding decisions on treatment durations for YBC patients. These findings improve the stratification and clinical implications for patients with YBC by contributing to the optimal adjuvant treatment and duration for favorable clinical outcomes.

Combined analysis of the MF18-02/MF18-03 NEOSENTITURK studies: ypN-positive disease does not necessitate axillary lymph node dissection in patients with breast cancer with a good response to neoadjuvant chemotherapy as long as radiotherapy is provided.

The omission of axillary lymph node dissection (ALND) remains controversial for patients with residual axillary disease after neoadjuvant chemotherapy (NAC), regardless of the residual burden. This study evaluated the oncologic safety and factors associated with outcomes in patients with residual axillary disease. These patients were treated solely with sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD), without ALND, after NAC. A joint analysis of two different multicenter cohorts-the retrospective cohort registry MF18-02 and the prospective observational cohort registry MF18-03 (NCT04250129)-was conducted between January 2004 and August 2022. All patients received regional nodal irradiation. Five hundred and one patients with cT1-4, N1-3M0 disease who achieved a complete clinical response to NAC underwent either SLNB alone (n=353) or TAD alone (n=148). At a median follow-up of 42 months, axillary and locoregional recurrence rates were 0.4% (n=2) and 0.8% (n=4). No significant difference was found in disease-free survival (DFS) and disease-specific survival (DSS) rates between patients undergoing TAD alone versus SLNB alone, those with breast positive versus negative pathologic complete response, SLN methodology, total metastatic LNof one versus ≥2, or metastasis types as isolated tumor cells with micrometastases versus macrometastases. In the multivariate analysis, patients with nonluminal pathology were more likely to have a worse DFS and DSS, respectively, without an increased axillary recurrence. The omission of ALND can be safely considered for patients who achieve a complete clinical response after NAC, even if residual disease is detected by pathologic examination. Provided that adjuvant radiotherapy is administered, neither the SLNB method nor the number of excised LNs significantly affects oncologic outcomes.

Granulosa cell tumor – Different faces of one neoplasm. A case series

IntroductionGranulosa cell tumor (GCT) accounts for 3–5 % of all ovarian malignancies, being the most common among those originating from the sex cords and ovarian stroma. GCTs can be divided into juvenile and adult types, with the latter occurring mostly in perimenopausal women. These hormonally active tumors present diverse clinical manifestations, primarily related to elevated estrogen levels. The treatment is primarily surgical; other methods, mainly chemotherapy, are also used. Presentation of casesThree cases highlight the heterogeneity of GCTs. Case 1 involved a 34-year-old woman diagnosed with ovarian tumor during routine gynecological follow-up. Stage IA GCT was diagnosed. Fertility-sparing surgery followed by chemotherapy led to a favorable outcome, including two pregnancies. Case 2 involved a postmenopausal woman with a large pelvic mass. Surgery revealed a Stage IA GCT. Chemotherapy was stopped early due to complications. Case 3 featured a 47-year-old with acute abdominal symptoms caused by a ruptured GCT, leading to emergency surgery and subsequent radical treatment. DiscussionGCTs are hormonally active, causing symptoms such as abnormal bleeding or abdominal discomfort. Prognosis is generally favorable, especially in early-stage cases. Long-term surveillance is essential due to the potential for late recurrences. Fertility-sparing surgery is feasible in young patients, while chemotherapy is mainly used for advanced disease or recurrence. ConclusionGCTs, in addition to being rare, present with a wide range of clinical manifestations. Individualized treatment based on patient age, tumor stage, and fertility plans is crucial for favorable outcomes. Long-term monitoring is recommended due to the risk of late recurrence.

Prognostic significance of early and multiple recurrences after curative resection for hepatocellular carcinoma

BackgroundIn hepatocellular carcinoma (HCC), postoperative recurrence remains high. This study aimed to evaluate the recurrence patterns and prognosis of HCC after curative hepatectomy.MethodsAmong 352 patients with primary HCC who underwent initial hepatectomy between January 2002 and December 2022, 151 with recurrence were assessed for the relationship between recurrence pattern and prognosis.ResultsThe early recurrence group (within 6 months postoperatively; n = 38) had significantly higher serum alpha-fetoprotein (p = 0.002), des-γ-carboxyprothrombin (DCP; p = 0.004) levels and Barcelona Clinic Liver Cancer (BCLC) stage (p < 0.001), larger tumor size (p < 0.001), higher incidence of multiple tumors (p = 0.002) and lower overall survival (OS) (p < 0.001) than the late recurrence group (> 6 months postoperatively; n = 113). The tumor size (p = 0.013) and BCLC stage (p = 0.001) were independent risk factors for early recurrence within 6 months in multivariate analysis.The multiple recurrence group (intrahepatic multinodular recurrence or distant metastasis; n = 89) had significantly lower prognostic nutritional index (p = 0.026), larger tumor size (p = 0.017), lower incidence of liver cirrhosis (p = 0.03) than the single recurrence group (single nodule recurrence; n = 62). The multiple recurrence group, especially patients with ≥ three intrahepatic nodules and distant metastases, had lower postoperative OS (p < 0.001) and shorter time to recurrence (p < 0.001) than the single recurrence group.When the patients were classified into three groups: late recurrence with one or two tumors (Group A; n = 74), early recurrence or three or more tumors or distant metastasis (Group B; n = 54), and early recurrence with three or more tumors or distant metastasis (Group C; n = 23), OS was significantly lower in Groups B and C than Group A (p < 0.001).ConclusionsPatients with early recurrence within 6 months after surgery and three or more recurrence nodule or distant metastasis exhibited poor prognosis after initial recurrence, and they should be carefully followed up.

Long-term recurrence risk, metastatic potential and length of cystoscopic surveillance of low-grade non-muscle invasive bladder cancer.

Patients with Ta low-grade (LG) non-muscle invasive bladder cancer (NMIBC) rarely develop metastases or die from it. Long-term data are scant and length of follow-up poorly defined. This retrospective study included 521 patients diagnosed with primary TaLG (n=491) or papillary urothelial neoplasm of low malignant potential (PUNLMP, n=30) from 1989-2019 at an Academic center. Patient data was acquired using patient records chart review and a bladder cancer informatics registry at the center. Risk of recurrence, progression in stage, to muscle invasion, metastases and death due to BC were analyzed. RNAseq assessed the transcriptomic profiles of four TaLG that metastasized. Interobserver variability in pathological grading (WHO 2004/2022 and 1973, n=80) was blindly assessed by three expert pathologists. Median follow-up was 9.6 (95%CI: 8.6-10.2) years. Among 521 patients (73% men, median age 67.0 years), 350 recurred, 57 progressed in stage, 20 developed metastases, and 15 died from BC (median of 9.6 years after diagnosis). Cancer-specific survival probabilities were 0.99, 0.98 and 0.96 at 5-, 10- and 15- years, respectively. Fifty patients who were recurrence-free for the first 5 years developed late recurrences and 2 of them died of BC. Metastatic TaLG had more adverse transcriptomic findings in keeping with higher grade tumors despite phenotypically similar to indolent tumors. Grading concordance for the 2004/2022 system and WHO 1973 was 0.78 (95%CI: 0.65-0.90) and 0.41 (95%CI: 0.32-0.50), respectively. This study with long-term data challenges the assumption that primary TaLG NMIBC nearly never progresses to lethal disease if followed long enough. However, the risk of BC-related mortality is extremely low in patients who are recurrence-free for the first 5 years. Minimizing variability in pathological grading remains an unmet need.

Prediction of atrial fibrillation recurrence after ablation: the impact of machine learning and recurrence during the blanking period

Abstract Introduction Pulmonary vein isolation is superior to antiarrhythmic drugs for rhythm control in patients with atrial fibrillation (AF). Nevertheless, recurrences within the first year are still significant. Several clinical risk scores were developed to predict AF recurrence; however, despite good results in development cohorts, the results in external validation are usually poor, limiting the general applicability of these scores. Purpose We aimed to develop machine learning (ML) models to predict AF recurrences within the first year after catheter ablation and compare their performance with conventional risk scores. Methods We used a retrospective dataset of a tertiary hospital center, including all consecutive patients submitted to the first AF ablation between 2017 and 2021. The dataset included 76 features: patient characteristics, medical history, baseline echocardiography, calcium score, procedure variables, and early recurrence (ER) during the 90-day blanking period. The outcome was defined as the occurrence of an electrocardiographically documented late recurrence (LR) of atrial tachycardia/AF &amp;gt; 30s between 3-12 months. Three different supervised ML models (penalized logistic regression, random forests, and XGBoost) were developed on the training cohort, and hyperparameters were tuned using 10-fold cross-validation. A testing dataset was held out to estimate the final performance (25%). The following risk scores were calculated: APPLE, CAAP-AF, and BASE-AF2 (the last includes ER). Areas under the curve (AUC) of receiver operating characteristic curves were compared using DeLong’s test. Results 679 patients were included: 62.7% males, median age of 59±16 years, and 78.2% with paroxysmal AF. The median time from diagnosis to ablation was 2±4 years. 74.2% underwent radiofrequency ablation and the remaining cryoablation. ER occurred in 12.5%, and most of these patients also experienced LR (68.7 vs 19.6% in those without ER, p&amp;lt;0.001). LR was observed in 25.6%. The XGBoost model showed the best performance with an AUC 0.774, 95% confidence interval (CI) 0.688–0.844) outperforming existing scores (picture 1): APPLE score AUC 0.607, 95% CI 0.562–0.653, p-value&amp;lt;0.001; CAAP-AF score AUC 0.622, 95% CI 0.576–0.668, p-value=0.002; BASE-AF2 AUC 0.628, 95% CI 0.581–0.675, p-value= 0.003. Variable importance analysis showed a significant drop in the performance of the models when ER was not considered, indicating its high importance in predicting LR (picture 2). Conclusions Recurrence during the blanking period was the most important predictor of LR in our population. The ML model was superior to conventional risk scores. ML models might be an essential tool to improve the prediction of outcomes and clinical decision-making for optimal follow-up.ROC curvesFeature Importance

Impact of obesity and early recurrence of atrial fibrillation on very late recurrence following cryoballoon pulmonary vein isolation

Abstract Background Obesity and early recurrence of atrial fibrillation (ERAF) post cryoballoon (CB) pulmonary vein isolation (PVI) both portend a lower 1-year success rate of ablation. Even after an initial successful ablation, about 1/3 of patients develop a very late recurrence (VLR) of AF, defined as the first AF recurrence more than a year after ablation (excluding an initial 90 day blanking period [BP]). The impact of obesity and ERAF on VLR is still unknown. Purpose To evaluate the impact of obesity and ERAF on VLR following CB PVI. Methods We enrolled consecutive patients with symptomatic AF who underwent CB PVI and had an implantable loop recorder for long-term ECG monitoring. We identified patients who had no AF recurrence (outside the BP) in the first-year post ablation. ERAF was defined as any episode of AF recorded in the first 90 days post ablation. Patients were grouped as either obese (BMI ≥ 30 kg/m2) or non-obese (BMI &amp;lt;30 kg/ m2). AF recurrences after 1-year post-ablation were ascertained using the loop recorder. Results From the initial cohort of 210 patients, 109 (52%) patients (64 ± 10 years; 75 [68%] male; 64 [59%] PAF; CHA2DS2-VASc 2.3 ± 1.4, 38 [35%] with obesity and 41 [38%] had ERAF) were AF-free during the first year. During a follow-up of 961 ± 196 days, 51 (47%) patients had VLR. Non-obese patients without ERAF had the best outcome (Figure). In multivariate analysis, obesity and ERAF were the only significant predictors of VLR (Table). As compared to non-obese patients without ERAF, obese patients with ERAF had a 4-fold greater likelihood of VLR. Conclusions About 50% of patients have no AF recurrence in the first year after CB PVI. Non-obese patients have the best outcome regardless of ERAF occurrence. On the other hand, obese patients with ERAF almost always have VLR.

Discordance between left atrial volume and scar burden in patients with atrial fibrillation and its impact on atrial fibrillation recurrence after catheter ablation

Abstract Background Large left atrial (LA) volume and a high burden of LA low voltage zone (LVZ) are associated with atrial fibrillation (AF) recurrence after AF catheter ablation. There is a scarcity of information on the association between LA volume and LVZ and its impact on the risk of AF recurrence. Purpose To investigate the relationship between the LA volume and LVZ, as well as how these factors contribute to the recurrence of atrial fibrillation (AF). Methods From Nov 2021 to Oct 2023, drug-refractory AF patients who underwent AF catheter ablation were included. LA volume was assessed using the LA volume index (LAVI) using echocardiography. The LVZ was evaluated by conducting high-density electroanatomical mapping using a multipolar catheter. The cut-off value associated with AF recurrence was 48ml/m2 in LAVI and 4.5% in scar burden. Patients were categorised into four groups according to the LAVI and scar burden: Group 1 (Low LVZ and small LA), group 2 (Low LVZ and large LA), group 3 (High LVZ and small LA), and group 4 (High LVZ and large LA). Results A total of 170 patients were included (mean age 62± 9 years, 82% of men, 68.2% of non-paroxysmal AF and 81 [48%] in group 1; 32 [19%] in group 2, 27 [16%] in group 3, 30 [17%] in group 4, respectively). Among total, mean follow-up duration was 266.5 ± 174.4 days, and 8.8% of patients received additional LA ablation beyond pulmonary vein isolation. Among the four groups, group 2 and 4 were significantly associated with higher risks of AF recurrence compared to group 1 (HR 2.36 [1.04-5.34], p=0.039; 3.56 [1.59-7.95], p=0.002, respectively). The risk of AF recurrence was highest in group 4, followed by group 2 (log-rank P=0.002). Comparing group 2 and 3, AF recurrence occurred predominantly within 6-month after catheter ablation in group 2, while after 1-year in group 3 (log-rank P=0.83). Conclusion About one-third of patients showed discordance between the LAVI and LVZ, which are both independent predictors for AF recurrence. A substantial LA volume seems to contribute to early AF recurrence, whereas a high scar burden appears to affect late AF recurrence.

HBcrAg is associated with prognosis of hepatitis B virus-related hepatocellular carcinoma in patients after hepatectomy undergoing antiviral therapy.

Serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aimed to explore the prognostic value of HBcrAg on patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative hepatectomy undergoing antiviral therapy (AVT). Data of 949 consecutive patients with HBV-related HCC undergoing curative resection between 2010 and 2013 were reviewed. Serum HBcrAg levels were measured at surgery (baseline) for all patients and at the time of 2 years postoperatively (on-treatment) for those without recurrence. Primary endpoint was tumor recurrence. High HBcrAg levels are associated with malignant phenotypes. HBcrAg independently affected both recurrence and overall survival (OS) in patients with negative hepatitis B e antigen (HBeAg-, p = .007 and p = .042, respectively) but not in their positive HBeAg (HBeAg+) counterparts (p = .100 and p = .075, respectively). Patients with high baseline HBcrAg had higher late, but not early recurrence rates than those with low baseline HBcrAg levels, regardless of HBeAg status (HBeAg+: p = .307 for early, p = .001 for late; HBeAg-: p = .937 for early, p < .001 for late). On-treatment HBcrAg independently affected late recurrence in patients stratified by both cirrhosis and HBeAg (p < .001 for all). The predictive power of HBcrAg kinetics for late recurrence was better than that of the baseline and on-treatment HBcrAg. High HBcrAg levels during long-term AVT are associated with late recurrence of HCC after hepatectomy. Combining baseline and on-treatment HBcrAg might be valuable in identifying patients at a high risk of relapse and stratifying surveillance strategies postoperatively.