Tumor Size Research Articles

Expression of immune-related genes and breast cancer recurrence in women with ductal carcinoma in situ

Background and AimDuctal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer with highly variable clinical behavior, but risk stratification is still challenging. We sought to identify immune-related gene expression signatures of pure DCIS associated with different risks of breast cancer recurrence. MethodsA retrospective nested case-control study of 143 pure DCIS was performed including 70 women with subsequent ipsilateral breast event (IBE, in situ or invasive; cases) and 73 DCIS women with no IBE and matched for age, tumor size, treatment, hormone receptors/HER2 status, and follow-up time (controls). RNA was extracted from DCIS samples and subjected to next-generation sequencing gene expression analysis of 395 immune-related genes. Correlations between DCIS immune-related gene expression and IBE were analyzed using weighted Cox regression for nested case-control data. ResultsEight immune-related genes were differentially expressed between cases and controls. MAGEA10 expression (present vs. absent) and high expression levels of IFNA17 and CBLB (Q4 vs. Q1) were observed more frequently in DCIS of women with subsequent IBE, mainly invasive (p-valueFDR < 0.05). Conversely, expression of IL3RA1, TAGAP, TNFAIP8, and high expression levels of CCL2 and LRP1 were associated with a lower risk of IBE (p-valueFDR < 0.05). ConclusionThis exploratory analysis of pure DCIS showed significant differences in immune-related gene expression profiles between women with and with no subsequent IBE, particularly as invasive IBE. These results, after additional validation, could improve risk stratification and management of DCIS patients.

Initial surgical management of sporadic medullary thyroid cancer: Guidelines based optimal care - A systematic review.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor from parafollicular cells that produce calcitonin (Ct). Despite several existing guidelines for the surgical management of sporadic MTC (sMTC), optimal initial surgical management of the thyroid, the central and the lateral neck remains a matter of debate. A systematic review in PubMed and Scopus for current guidelines addressing the surgical management of sMTC and its referenced citations was conducted as per the PRISMA guidelines. Two-hundred and one articles were identified, of which 7 met the inclusion criteria. Overall, guidelines vary significantly in their recommendations for the surgical management of sMTC. Only one guideline recommended partial thyroidectomy for limited disease, but the possibility to avoid completion thyroidectomy in selected cases is acknowledged in 42% (3/7) of the remaining guidelines. The majority of guidelines (71.4%; 5/7) recommended prophylactic central neck dissection (CND) for all patients while the remaining two guidelines recommended CND based on Ct level and tumor size. The role of prophylactic lateral neck dissection based on preoperative Ct levels was recommended by 42% (3/7) of guidelines. Overall, these guidelines are based on low-quality evidence, mostly single-center retrospective series, some of which are over 20 years old. Current surgical management guidelines of sMTC should be revised, and ought to be based on updated data challenging current recommendations, which are based on historic, low-quality evidence. Partial thyroidectomy may become a viable option for small, limited tumors. Prospective, multi-center studies may be useful to conclude whether prophylactic ND is necessary in all sMTC patients.

Natural history of renal angiomyolipoma in a high-volume center: our experience during more than 15years of follow up.

To describe the natural history of AML, the clinical results and the need for treatment during long-term follow-up of renal AML. Retrospective study of patients diagnosed with AML by computed tomography or nuclear magnetic resonance between 2001 and 2019, with at least two follow-up images. Clinical and imaging variables, need for intervention, complications and follow-up time were recorded. Statistical analysis was performed using SPSS 22.0. 111 patients and 145 AML were included. The median follow-up was 6.17years (range 0.7-18.1, IQR 11.8-12.2). The median tumor size at diagnosis was 13mm (IQR 7.5-30), with 24 (16.4%) being ≥ 4cm. Most presented as an incidental finding (85.5%); in 3 (2.1%) cases, the presentation was as a spontaneous retroperitoneal hematoma. The main indication for intervention was size ≥ 4cm in 50%. Eighteen (12%) patients received a first intervention, being urgent in 3. Embolization was performed in 15 cases and partial nephrectomy in 3. The need for reintervention was recorded in five: two underwent partial nephrectomy and two total nephrectomy; one patient required a new urgent embolization. Of the non-operated patients, 43% decreased in size or did not change, while 57% increased, with the median annual growth being 0.13mm (IQR -0.11 to 0.73). There were no differences in the median growth in tumors measuring ≥ 4cm (0.16mm) at diagnosis vs. < 4cm (0.13mm) (p = 0.9). The findings of this study suggest that AML typically demonstrate a slow-progressing clinical course during long-term follow-up. Moreover, our observations, which cast doubt on tumor size as a reliable predictor of adverse clinical outcomes, advocate for a less intensive monitoring strategy in both monitoring frequency and choice of imaging modality.

Comparison of long-term outcome between clinically high risk lobular versus ductal breast cancer: a propensity score matched study

Abemaciclib is currently approved for the adjuvant treatment of high-risk, lymph node (LN)-positive, hormone receptor (HR)-positive breast cancer (BC). In a real-world setting the clinicopathologic features of patients potentially eligible for adjuvant abemaciclib remain to be defined. There are conflicting data regarding the biological behavior and long-term outcomes across invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC). In our study we retrospectively assessed the real-world data and long-term outcome of selected high-risk features ILC compared to IDC, according to the MonarchE trial inclusion criteria. We identified 15,071 patients who got surgery at the European Institute of Oncology for a first primary, non-metastatic, HR-positive, HER2-negative BC from 2000 to 2008. 11,981 (79.5%) patients had an IDC and 1524 (10.1%) an ILC. The remaining 1566 patients (10.4%) had either combined ductal and lobular breast cancer or another histological breast cancer subtype. According to the eligibility criteria of the MonarchE study, we identified two high-risk groups, based on high number of positive lymph nodes, large tumor size, or a high cellular proliferation as measured by tumor grade or biomarkers. Patients were matched by propensity score. A total of 2872 (21.3%) patients were selected as clinically high-risk, including 361/1524 ILC (23.7%) and 2511/11,981 IDC (21%). 322 high-risk ILC were matched with similar high-risk IDC. The median follow-up was 13.2 years for survival. In the matched set, invasive disease-free survival (IDFS) (log-rank P=0.09) and overall survival (OS) (log-rank P=0.48) were not statistically significantly different between the two histological groups. For IDC patients, the 5-year and 10-year IDFS rates (95% CI) were 77.7% (72.9-82.2) and 57.3% (51.7-63.1) respectively, compared to the 5-year and 10-year IDFS rates of ILC patients that were 75.5% (70.6-80.2) and 50.7% (45.0-56.6). The 5-year and 10-year distant relapse free survival (DRFS) rates were 80% (75.3-84.2) and65.3% (59.8-70.7) in IDC cohort, compared to the 5-year and the 10-year DRFS rates of 78.7% (74.0-83.1) and 61.5% (55.9-67.1) in the ILC cohort. Such data match the recent outcomes efficacy results of the MonarchE control arm. More patients in the ILC (n=17) than in the IDC group (n=10) developed axillary recurrence. At multivariable analysis, stratified for specific clinical features, age <35 years, pT2-3, axillary involvement with more than 10 positive axillary nodes were found to be predictors of unfavorable IDFS and OS in the overall matched high-risk population. Findings from this matched cohort study reported similar IDFS and DRFS rates for high risk HR positive early BC when compared to the control arm overall IDFS and DRFS rates reported from the MonarchE trial. Our study demonstrated rates of concordant long-term outcome status beyond histologic subtype. These data support an escalation strategy for these two different histological entities when diagnosed with high-risk features. In our dataset approximately 21% rate of high-risk HR positive early BC patients are potentially eligible for adjuvant abemaciclib treatment. Umberto VeronesiFoundation.

Value of long non-coding RNA HAS2-AS1 as a diagnostic and prognostic marker of glioma

BackgroundGlioma presents high incidence and poor prognosis, and therefore more effective treatments are needed. Studies have confirmed that long non-coding RNAs (lncRNAs) basically regulate various human diseases including glioma. It has been theorized that HAS2-AS1 serves as an lncRNA to exert an oncogenic role in varying cancers. This study aimed to assess the value of lncRNA HAS2-AS1 as a diagnostic and prognostic marker for glioma. MethodsThe miRNA expression data and clinical data of glioma were downloaded from the TCGA database for differential analysis and survival analysis. In addition, pathological specimens and specimens of adjacent normal tissue from 80 patients with glioma were used to observe the expression of HAS2-AS1. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic ability and prognostic value of HAS2-AS1 in glioma. Meanwhile, a Kaplan–Meier survival curve was plotted to evaluate the survival of glioma patients with different HAS2-AS1 expression levels. ResultsHAS2-AS1 was significantly upregulated in glioma tissues compared with normal tissue. The survival curves showed that overexpression of HAS2-AS1 was associated with poor overall survival (OS) and progression-free survival (PFS). Several clinicopathological factors of glioma patients, including tumor size and WHO grade, were significantly correlated with HAS2-AS1 expression in tissues. The ROC curve showed an area under the curve (AUC) value of 0.863, indicating that HAS2-AS1 had good diagnostic value. The ROC curve for the predicted OS showed an AUC of 0.906, while the ROC curve for predicted PFS showed an AUC of 0.88. Both suggested that overexpression of HAS2-AS1 was associated with poor prognosis. ConclusionsNormal tissues could be clearly distinguished from glioma tissues based on HAS2-AS1 expression. Moreover, overexpression of HAS2-AS1 indicated poor prognosis in glioma patients. Therefore, HAS2-AS1 could be used as a diagnostic and prognostic marker for glioma.

Ras-Related Protein Rab24 is a Predictor for Hepatocellular Carcinoma Prognosis and Promotes Tumor Growth

Ras-related protein Rab24, a member of the small GTPase family, plays a vital role in regulating intracellular protein trafficking. Recent research has uncovered dysregulation of Rab24 in hepatocellular carcinoma (HCC), but its clinical implications and tumor-related effects require further investigation. We aimed to investigate Rab24’s expression patterns and its role in HCC progression. We analyzed Rab24 expression in HCC and adjacent tissues at the transcriptional, mRNA, and protein levels. The prognostic significance of Rab24 in HCC was assessed through univariate and multivariate analyses, along with Kaplan–Meier survival analysis. Rab24’s impact on cell proliferation was investigated through cellular and xenograft experiments. Our findings revealed elevated Rab24 expression in HCC tissues compared to adjacent liver tissues. High Rab24 expression correlated with larger tumor size and advanced tumor stage. Additionally, HCC patients with high Rab24 expression experienced poorer overall survival, with Rab24 identified as an independent prognostic factor. Manipulating Rab24 expression in HCC cell lines demonstrated its role in promoting tumor proliferation. Silencing Rab24 significantly reduced xenograft growth in vivo. This study highlights the significant association between high Rab24 expression and poorer HCC prognosis, suggesting Rab24’s potential as a novel clinical biomarker and therapeutic target.

Knockout of LINC01134 as a potential treatment for Liver Cancer in HepG2 cells

Liver cancer, a major global health issue, continues to contribute significantly to global deaths. Hepatocellular carcinoma (HCC), the most prevalent primary liver cancer, remains a leading cause of cancer-related fatalities. This study explores the potential treatment for HCC by investigating the role of LINC01134, an encoding gene for the LncRNA TLNC1, in mediating the nuclear export of p53. The hypothesis suggests that knocking out the LINC01134 gene in HepG2 cells will decrease p53 nuclear export, leading to increased p53 levels and enhanced cellular responses to DNA damage. The methods include CRISPR CAS-9 for gene knockout, RT-PCR for TLNC1 expression, Immunofluorescence for p53 within the nucleus, and xenograft mouse model for in vivo tumor size reduction. Statistical analysis will be performed using a one-sample T-test. This strategy might effectively improve the cell’s reaction to DNA damage, which could halt or slow the growth of HCC.

Ischiorectal Fossa Tumors: Thirty-Year Single Institution Experience.

Primary tumors of the ischiorectal fossa are rare and comprise a wide array of pathologies with varying malignant potential. Due to the low prevalence, there is a paucity of data in the literature. This paper presents a case-series on the management of ischiorectal fossa tumors. To present a 30-year experience managing ischiorectal fossa tumors. Retrospective single center analysis. A quaternary referral academic healthcare center. All patients treated for ischiorectal fossa tumors. All patients underwent surgical management of their disease. Disease recurrence and overall survival. A total of 34 patients (53% female) were identified with a median follow-up of 23 months. Twenty-one patients (62%) were diagnosed with benign and 13 (38%) with malignant tumors. All underwent surgical resection. Median tumor size was 8.4 cm. R0 resection was obtained in 28 patients. Twelve (35%) developed recurrence (nine following R0 resection) with a median time of 6.5 months. There were no surgical related mortalities. Limitations to the study include its retrospective nature, single center experience, and small patient sample size. Ischiorectal fossa tumors are primarily benign, however they are associated with high recurrence rates even in the setting of an R0 resection. Treatment should be approached in a multidisciplinary fashion and preferably in centers with experience treating these tumors. Close post treatment surveillance is imperative. See Video Abstract.

Investigating the level of vitamin D receptor gene expression in two tumoral and healthy breast tissues in breast cancer patients and its association with prognostic factors.

Breast cancer is one of the most common cancers known among women. This study aimed to investigate the level of vitamin D receptor gene expression in two tumoral and healthy breast tissues in breast cancer patients and its association with prognostic factors. This descriptive cross-sectional study was conducted in 2022 on 50 patients with high suspicion of breast cancer who were candidates for mastectomy and lumpectomy in a learning hospital. From the patients, two tissue samples were prepared, and there was a total of 100 samples. The samples were subjected to H/E staining and evaluated by a pathologist. The presence or absence of malignancy in each sample was confirmed by two pathologists, and HER2/ER/PR indices were determined. Descriptive and analytical statistical methods and SPSS version 22 software were used. The average age of the patients was 51.60 ± 11.22 years old, and the average tumor size was 3.17 ± 1.28. Most tumors were grade 2 (48%). The expression of HER2, ER, and PR was positive in 24, 64, and 54%, respectively. The largest number of cases were in stage 2A. The expression level of vitamin D receptor (VDR) gene in healthy tissue (2.08 ± 1.01) was higher than tumoral tissue (0.25 ± 1.38) (P = 0.001). In tumoral and healthy tissue, VDR expression was not significant according to tumor grade, HER2, ER, PR, LVI, LN, disease stage, age, and tumor size. The expression level of VDR in healthy tissue was significantly higher than tumoral tissue. However, there was no significant relationship between VDR and tumor grade, HER2, ER, PR, LVI, LN, disease stage, age, and tumor size.

Risk factors, prognostic factors, and nomograms for distant metastasis in patients with diagnosed duodenal cancer: A population-based study

BACKGROUND Duodenal cancer is one of the most common subtypes of small intestinal cancer, and distant metastasis (DM) in this type of cancer still leads to poor prognosis. Although nomograms have recently been used in tumor areas, no studies have focused on the diagnostic and prognostic evaluation of DM in patients with primary duodenal cancer. AIM To develop and evaluate nomograms for predicting the risk of DM and personalized prognosis in patients with duodenal cancer. METHODS Data on duodenal cancer patients diagnosed between 2010 and 2019 were extracted from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for DM in patients with duodenal cancer, and univariate and multivariate Cox proportional hazards regression analyses were used to determine independent prognostic factors in duodenal cancer patients with DM. Two novel nomograms were established, and the results were evaluated by receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). RESULTS A total of 2603 patients with duodenal cancer were included, of whom 457 cases (17.56%) had DM at the time of diagnosis. Logistic analysis revealed independent risk factors for DM in duodenal cancer patients, including gender, grade, tumor size, T stage, and N stage (P &lt; 0.05). Univariate and multivariate COX analyses further identified independent prognostic factors for duodenal cancer patients with DM, including age, histological type, T stage, tumor grade, tumor size, bone metastasis, chemotherapy, and surgery (P &lt; 0.05). The accuracy of the nomograms was validated in the training set, validation set, and expanded testing set using ROC curves, calibration curves, and DCA curves. The results of Kaplan-Meier survival curves (P &lt; 0.001) indicated that both nomograms accurately predicted the occurrence and prognosis of DM in patients with duodenal cancer. CONCLUSION The two nomograms are expected as effective tools for predicting DM risk in duodenal cancer patients and offering personalized prognosis predictions for those with DM, potentially enhancing clinical decision-making.

Treatment selection and real-world analysis of immunotherapy with or without chemotherapy in PD-L1-high metastatic non-small cell lung cancer.

Lung cancer is the leading cause of cancer death in Australia. Immunotherapy has improved outcomes in patients with metastatic non-small cell lung cancer (NSCLC). Pembrolizumab is approved in first-line treatment as single-agent immunotherapy (SAI) or combination chemoimmunotherapy (CIT). In metastatic NSCLC programmed death-ligand 1 (PD-L1) ≥50% either regimen may be used. We aim to identify patient and tumour characteristics that influence treatment selection. This is a retrospective observational study. Pharmacy records identified patients with metastatic/recurrent NSCLC receiving pembrolizumab at two metropolitan centres in Victoria, Australia, since 2018. Demographics, tumour characteristics, Charlson Comorbidity Index (CCI) and treatment data were collected. Descriptive and multivariate analyses were performed. Sixty-one patients had metastatic NSCLC PD-L1 ≥50% and received pembrolizumab with median age of 65.6 years, Eastern Cooperative Oncology Group 0-1 in 82%. CIT was administered to 23% (14) with no difference in rate of delivery between centres (P = 0.808). CCI mean score differed (3.38 SAI vs 2.36 CIT, P = 0.042). Patients with high CCI score (≥2) were less likely to receive CIT (OR = 0.15, P = 0.003, 95% confidence interval (CI) 0.04-0.57). Primary tumours over 5 cm were more likely to receive CIT (OR = 3.74, P = 0.043, 95% CI = 1.04-13.42). Site-specific metastases of liver, brain and pericardial effusion were not associated with CIT. Patients with higher comorbidity score were less likely to receive CIT, suggesting chemotherapy avoidance in comorbid patients. Larger tumours are associated with CIT use, indicating that oncologists may use tumour size as a surrogate of disease burden. Limitations include small sample size and data cut-off. Future prospective studies could incorporate comorbid status and a validated disease burden score to stratify patients.

Pre-operative enhanced magnetic resonance imaging combined with clinical features predict early recurrence of hepatocellular carcinoma after radical resection

BACKGROUND Indentifying predictive factors for postoperative recurrence of hepatocellular carcinoma (HCC) has great significance for patient prognosis. AIM To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) combined with clinical features in predicting early recurrence of HCC after resection. METHODS A total of 161 patients with pathologically confirmed HCC were enrolled. The patients were divided into early recurrence and non-early recurrence group based on the follow-up results. The clinical, laboratory, pathological results and Gd-EOB-DTPA enhanced MRI imaging features were analyzed. RESULTS Of 161 patients, 73 had early recurrence and 88 were had non-early recurrence. Univariate analysis showed that patient age, gender, serum alpha-fetoprotein level, the Barcelona Clinic Liver Cancer stage, China liver cancer (CNLC) stage, microvascular invasion (MVI), pathological satellite focus, tumor size, tumor number, tumor boundary, tumor capsule, intratumoral necrosis, portal vein tumor thrombus, large vessel invasion, nonperipheral washout, peritumoral enhancement, hepatobiliary phase (HBP)/tumor signal intensity (SI)/peritumoral SI, HBP peritumoral low signal and peritumoral delay enhancement were significantly associated with early recurrence of HCC after operation. Multivariate logistic regression analysis showed that patient age, MVI, CNLC stage, tumor boundary and large vessel invasion were independent predictive factors. External data validation indicated that the area under the curve of the combined predictors was 0.861, suggesting that multivariate logistic regression was a reasonable predictive model for early recurrence of HCC. CONCLUSION Gd-EOB-DTPA enhanced MRI combined with clinical features would help predicting the early recurrence of HCC after operation.

The clinical value of iodine-125 seed implantation in the treatment of iodine-refractory differentiated thyroid carcinoma

ObjectiveTo explore the clinical benefits of 125I seed implantation for iodine-refractory differentiated thyroid cancer (RAIR-DTC).MethodsA retrospective analysis was conducted on 36 patients with RAIR-DTC who underwent radioactive 125I seed implantation from January 2015 to February 2022, involving 73 lesions. Prescription dose: 80~120 Gy. All cases were followed up at 1, 3, and 5 months postoperatively to monitor changes in tumor size, serum thyroglobulin (Tg), and serum anti-thyroglobulin antibody levels in thyrotropin-inhibited states, pain scores, and postoperative adverse reactions. The data were processed and analyzed using IBM SPSS 26.0. LER (Local Effective Rate) and LCR (Local Control Rate) were expressed as n (%), tumor diameter, Tg, and pain scores were represented as Median (Q1, Q3). Pairwise comparisons were conducted using the Wilcoxon signed-rank test, and a p-value of less than 0.05 indicated statistical significance.ResultsTumor size was significantly reduced after treatment (all P &amp;lt; 0.001): tumor length diameters were 32.67 (17.70, 45.72) mm, 27.45 (12.30, 39.98) mm, 20.70 (11.98, 37.58) mm, and 20.39 (10.56, 33.20) mm in the preoperative, 1-, 3-, and 5-months postoperative periods, respectively. Additionally, two consecutive post-treatment results were more minor and statistically significant than the previous results (P &amp;lt; 0.001). The LER at 1-, 3-, and 5-months post-surgery was 23.73%, 38.98%, and 52.54%, respectively, while the LCR at the same time points was 98.31%, 96.61%, and 94.92%, respectively. Patients’ serum Tg levels decreased significantly after surgery. (P &amp;lt; 0.001). Serum Tg levels were measured before surgery and 1-, 3-, and 5-months post-surgery. The results showed that serum Tg levels were 249.45 (79.39, 4718.75) ng/ml, 193.40 (44.53, 2829.00) ng/ml, 192.10 (25.58, 1758.00) ng/ml, and 136.25 (16.57, 1553.25) ng/ml, respectively. Two consecutive post-treatment results were more minor and statistically significant than the previous results (P &amp;lt; 0.001). The patients’ pain symptoms were significantly relieved after 125I brachytherapy (P &amp;lt; 0.001). The pain scores before 125I seed implantation and at 1, 3, and 5 months after the operation were 5.00 (4.00, 6.00), 3.00 (2.25, 4.00), 2.00 (2.00, 3.00), and 2.00 (1.00, 3.00), respectively.ConclusionMost lesions treated with 125I seed implantation in RAIR-DTC patients showed shrinkage and improved pain symptoms.Clinical trial registrationhttps://www.clinicaltrials.gov, identifier NCT06362772.

Laparoscopic liver resection or enucleation for giant hepatic hemangioma: how to choose?

Laparoscopic treatment has been increasingly adopted for giant hepatic hemangioma (HH), but the role of liver resection or enucleation remains uncertain. The aim of this study is to compare the laparoscopic resection (LR) with laparoscopic enucleation (LE) for HH, and to provide evidence on how to choose the most suitable approach for HH. A retrospective analysis of HH patients underwent laparoscopic treatment between March 2015 and August 2022 was performed. Perioperative outcomes were compared based on the surgical approaches, and risk factors for increased blood loss was calculated by logistic regression analysis. A total of 127 patients in LR group and 287 patients in LE group were enrolled in this study. The median blood loss (300 vs. 200mL, P < 0.001) was higher in LE group than that in LR group. Independent risk factors for blood loss higher than 400mL were tumor size ≥ 10cm, tumor adjacent to major vessels, tumor occupying right liver or caudate lobe, and the portal phase enhancement ratio (PER) ≥ 38.9%, respectively. Subgroup analysis showed that LR was associated with less blood loss (155 vs. 400mL, P < 0.001) than LE procedure in patients with high PER value. Both LR and LE approaches exhibited similar perioperative outcomes in patients with low PER value. Laparoscopic treatment for HH could be feasibly and safely performed by both LE and LR. For patients with PER higher than 38.9%, the LR approach is recommended.

Personalized surgical recommendations and quantitative therapeutic insights for patients with metastatic breast cancer: Insights from deep learning

AbstractBackgroundThe role of surgery in metastatic breast cancer (MBC) is currently controversial. Several novel statistical and deep learning (DL) methods promise to infer the suitability of surgery at the individual level.ObjectiveThe objective of this study was to identify the most applicable DL model for determining patients with MBC who could benefit from surgery and the type of surgery required.MethodsWe introduced the deep survival regression with mixture effects (DSME), a semi‐parametric DL model integrating three causal inference methods. Six models were trained to make individualized treatment recommendations. Patients who received treatments in line with the DL models' recommendations were compared with those who underwent treatments divergent from the recommendations. Inverse probability weighting (IPW) was used to minimize bias. The effects of various features on surgery selection were visualized and quantified using multivariate linear regression and causal inference.ResultsIn total, 5269 female patients with MBC were included. DSME was an independent protective factor, outperforming other models in recommending surgery (IPW‐adjusted hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.19–0.78) and type of surgery (IPW‐adjusted HR = 0.66, 95% CI: 0.48–0.93). DSME was superior to other models and traditional guidelines, suggesting a higher proportion of patients benefiting from surgery, especially breast‐conserving surgery. The debiased effect of patient characteristics, including age, tumor size, metastatic sites, lymph node status, and breast cancer subtypes, on surgery decision was also quantified.ConclusionsOur findings suggested that DSME could effectively identify patients with MBC likely to benefit from surgery and the specific type of surgery needed. This method can facilitate the development of efficient, reliable treatment recommendation systems and provide quantifiable evidence for decision‐making.

MiRNA Signatures Related to Invasiveness and Recurrence in Patients With Non-Functioning Pituitary Neuroendocrine Tumors.

This preliminary study aimed to analyze and identify differentially expressed miRNAs in Bulgarian patients with non-functioning pituitary neuroendocrine tumors (NFPitNET). The relationship between deregulated miRNAs and tumor invasiveness, recurrence, and size was determined. Twenty patients with NFPitNET were selected and fresh pituitary tumor tissues were collected. RNA containing miRNAs were isolated using miRNAeasy mini kit and analyzed by quantitative real-time polymerase chain reaction (PCR) using LNA miRNA Cancer-Focus PCR Panel (Qiagen). Three miRNAs (miR-210-3p, miR-149-3p, and miR-29b-3p) were deregulated in invasive compared to non-invasive NFPitNETs. Differential expression of four-miRNA signatures - miRNA-17, miR-19, miR-106a, and miR-20, correlated with patient recurrence. This prospective pilot study selected a unique miRNA expression profile, that correlates with invasiveness and recurrence in non-functioning pituitary neuroendocrine tumors. Moreover, some of the selected miRNAs are reported for the first time in patients with this disease, shedding light on the molecular mechanisms involved in pituitary pathogenesis. The identified miRNAs demonstrate potential as biomarkers, deserving further investigation in a larger cohort to validate their clinical applicability.

Impact of the diagnosis of metabolic dysfunction-associated fatty liver disease and non-alcoholic fatty liver disease in patients undergoing liver transplantation for hepatocellular carcinoma

PurposeWhether the diagnosis of non-alcoholic fatty liver disease or metabolic dysfunction-associated fatty disease has a different impact on liver transplant recipients with hepatocellular carcinoma is not yet clear.MethodsData from a two-center retrospective cohort study were collected to compare and investigate the differences between non-alcoholic fatty liver disease and metabolic dysfunction-associated fatty liver disease in clinicopathologic parameters and prognosis among liver transplant recipients with hepatocellular carcinoma.ResultsA total of 268 liver transplant recipients with hepatocellular carcinoma were included. The prevalence among pre- and post-transplant metabolic dysfunction-associated fatty liver disease was 10.82% and 30.22%, while for non-alcoholic fatty liver disease, it was 7.09% and 26.87%, respectively. The clinicopathological parameters were similar between the two pre-transplant groups. In contrast, the post-transplant group with metabolic dysfunction-associated fatty liver disease exhibited a higher prevalence of diabetes mellitus and a greater body mass index. However, the other parameters were similar between the two post-transplant groups (p &amp;gt; 0.05). Factors such as the largest tumor size &amp;gt; 4 cm, microvascular invasion, lack of tumor capsule, post-transplant metabolic dysfunction-associated fatty liver disease, and decreased post-transplant lymphocyte percentage were related to an increased risk of recurrence.ConclusionIn patients undergone liver transplantation for hepatocellular carcinoma, the diagnosis of metabolic dysfunction-associated fatty disease is more strongly associated with metabolic abnormalities than the diagnosis of non-alcoholic fatty liver disease and is an independent predictor of hepatocellular carcinoma recurrence.

Utility of clinical and MR imaging parameters for prediction and monitoring of response to capecitabine and temozolomide (CAPTEM) therapy in patients with liver metastases of neuroendocrine tumors.

This study explores the predictive and monitoring capabilities of clinical and multiparametric MR parameters in assessing capecitabine and temozolomide (CAPTEM) therapy response in patients with neuroendocrine tumors (NET). This retrospective study (n = 44) assessed CAPTEM therapy response in neuroendocrine liver metastases (NELM) patients. Among 33 monitored patients, as a subgroup of the overall study cohort, pretherapeutic and follow-up MRI data (size, apparent diffusion coefficient [ADC] values, and signal intensities), along with clinical parameters (chromogranin A [CgA] and Ki-67%), were analyzed. Progression-free survival (PFS) served as the reference. Responders were defined as those with PFS ≥ 6 months. Most patients were male (75%) and had G2 tumors (76%) with a pancreatic origin (84%). Median PFS was 5.7 months; Overall Survival (OS) was 25 months. Non-responders (NR) had higher Ki-67 in primary tumors (16.5 vs. 10%, p = 0.01) and increased hepatic burden (20% vs. 5%, p = 0.007). NR showed elevated CgA post-treatment, while responders (R) exhibited a mild decrease. ADC changes differed significantly between groups, with NR having decreased ADCmin (-23%) and liver-adjusted ADCmean/ADCmean liver (-16%), compared to R's increases of ADCmin (50%) and ADCmean/ADCmean liver (30%). Receiver operating characteristic (ROC) analysis identified the highest area under the curve (AUC) (0.76) for a single parameter for ∆ ADC mean/liver ADCmean, with a cut-off of < 6.9 (76% sensitivity, 75% specificity). Combining ∆ Size NELM and ∆ ADCmin achieved the best balance (88% sensitivity, 60% specificity) outperforming ∆ Size NELM alone (69% sensitivity, 65% specificity). Kaplan-Meier analysis indicated significantly longer PFS for ∆ ADCmean/ADCmean liver < 6.9 (p = 0.024) and ∆ Size NELM > 0% + ∆ ADCmin < -2.9% (p = 0.021). Survival analysis emphasizes the need for adapted response criteria, involving combined evaluation of CgA, ADC values, and tumor size for monitoring CAPTEM response in hepatic metastasized NETs.

Low-Level Expression of p-S6 Is Associated with Nodal Metastasis in Patients with Head and Neck Cutaneous Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer. The incidence of metastasis for cSCC is estimated to be around 1.2–5%. Ribosomal protein S6 (p-S6) and the p21 protein (p21) are two proteins that play central roles in other cancers. These proteins may be equally important in cSCC, and together, these could constitute a good candidate for metastasis risk assessment of these patients. We investigate the relationship of p-S6 and p21 expression with the impact on the prognosis of head and neck cSCC (cSCCHN). p-S6 and p21 expression was analyzed by immunohistochemistry on paraffin-embedded tissue samples from 116 patients with cSCCHN and associations sought with clinical characteristics. Kaplan–Meier estimators and Cox proportional hazard regression models were also used. The expression of p-S6 was significantly inversely associated with tumor thickness, tumor size, desmoplastic growth, pathological stage, perineural invasion and tumor buds. p21 expression was significantly inversely correlated with &gt;6 mm tumor thickness, desmoplastic growth, and perineural invasion. p-S6-negative expression significantly predicted an increased risk of nodal metastasis (HR = 2.63, 95% CI 1.51–4.54; p &lt; 0.001). p21 expression was not found to be a significant risk factor for nodal metastasis. These findings demonstrate that p-S6-negative expression is an independent predictor of nodal metastasis. The immunohistochemical expression of p-S6 might aid in better risk stratification and management of patients with cSCCHN.

Prediction of hematologic toxicity in luminal type breast cancer patients receiving neoadjuvant chemotherapy using CT L1 level skeletal muscle index

This study aims to explore the correlation between the CT-L1 and L3 body composition parameters and analyze the relationship between L1 body composition and hematologic toxicity in luminal-type breast cancer patients undergoing neoadjuvant chemotherapy. Data from 140 luminal-type breast cancer patients who underwent surgical treatment after neoadjuvant chemotherapy were analyzed retrospectively. Spearman analysis was used to assess the correlation between CT-L1 and CT-L3 body composition parameters pre-neoadjuvant chemotherapy. Additionally, univariate and multivariate logistic regression analyses were performed to identify factors influencing hematologic toxicity. CT-L1 body composition parameters were positively correlated with CT-L3 body composition parameters in 34 patients. Severe hematological toxicity occurred in 46 cases among the patient cohort. A skeletal muscle index (SMI) of < 32.91 cm2/m2, initial tumor size ≥ 3.335 cm, and a glucose-to-neutrophil ratio (GLR) ≥ 2.88 were identified as independent risk factors for severe hematologic toxicity during neoadjuvant chemotherapy in luminal-type breast cancer patients. The sample size in this study is small, and the predictive capacity of GLR in hematologic toxicity requires further research for comprehensive validation. CT-L1 analysis represents a viable alternative to CT-L3 analysis for body composition assessment. Patients with a low skeletal muscle index were more prone to experiencing severe hematologic toxicity during neoadjuvant chemotherapy.