Pathological Characteristics Of Patients Research Articles

Anatomical assessment of local recurrence site in breast cancer patients after breast reconstruction and post-mastectomy radiotherapy: implications for radiation volumes and techniques.

Post-mastectomy radiotherapy (PMRT) improves local control rates and survival in patients with adverse prognostic features. The dose coverage to target volumes is critical to yield maximum benefit to treated patients, increasing local control and reducing risk of toxicity. This study aims to assess patterns of breast cancer relapse in patients treated with mastectomy, breast reconstruction and PMRT. Breast cancer patients treated with PMRT between 1992 and 2017 were retrospectively reviewed. Clinical and pathological characteristics of patients were collected. Recurrences were defined as "in field," "marginal" or "out of field." Survival analyses were performed in relation to progression-free survival (PFS) and overall survival (OS). Correlation between baseline features was explored. Data of 140 patients are collected. After a median follow-up time of 72 months, median PFS and OS of 63 and 74 months were detected, respectively. Neoadjuvant chemotherapy, lympho-vascular space invasion (LVI) and size of primary tumor were all significantly associated with worst PFS and OS. Ten patients developed local recurrence: 30% "in field," 30% marginal recurrences, 20% "out of field" and 20% both "in field" and "out of field." No recurrence was detected under the expander, 80% above the device and 20% patients relapsed on IMN chain. The mean distant relapse-free survival was 39 months. Overall, 39 of 140 patients developed distant metastases. The onset of local-regional relapses occurred mainly above the expander/prosthesis, underlying the importance of inclusion of the subcutaneous tissues within the target volume. In order to refine new contouring recommendations for PMRT and breast reconstruction, future prospective studies are needed.

Construction and validation of a machine learning-based nomogram to predict the prognosis of HBV associated hepatocellular carcinoma patients with high levels of hepatitis B surface antigen in primary local treatment: a multicenter study.

Hepatitis B surface antigen (HBsAg) clearance is associated with improved long-term outcomes and reduced risk of complications. The aim of our study was to identify the effects of levels of HBsAg in HCC patients undergoing TACE and sequential ablation. In addition, we created a nomogram to predict the prognosis of HCC patients with high levels of HBsAg (≥1000U/L) after local treatment. This study retrospectively evaluated 1008 HBV-HCC patients who underwent TACE combined with ablation at Beijing Youan Hospital and Beijing Ditan Hospital from January 2014 to December 2021, including 334 patients with low HBsAg levels and 674 patients with high HBsAg levels. The high HBsAg group was divided into the training cohort (N=385), internal validation cohort (N=168), and external validation cohort (N=121). The clinical and pathological features of patients were collected, and independent risk factors were identified using Lasso-Cox regression analysis for developing a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves in the training and validation cohorts. Patients were classified into high-risk and low-risk groups based on the risk scores of the nomogram. After PSM, mRFS was 28.4 months (22.1-34.7 months) and 21.9 months (18.5-25.4 months) in the low HBsAg level and high HBsAg level groups (P<0.001). The content of the nomogram includes age, BCLC stage, tumor size, globulin, GGT, and bile acids. The C-index (0.682, 0.666, and 0.740) and 1-, 3-, and 5-year AUCs of the training, internal validation, and external validation cohorts proved good discrimination of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classification of patients with high HBsAg levels into low-risk and high-risk groups according to the risk of recurrence. There was a statistically significant difference in RFS between the two groups in the training, internal validation, and external validation cohorts (P<0.001). High levels of HBsAg were associated with tumor progression. The nomogram developed and validated in the study had good predictive ability for patients with high HBsAg levels.

Abnormally decreased functional connectivity of the right nucleus basalis of Meynert in Alzheimer’s disease patients with depression symptoms

Dysfunction of the basal forebrain is the main pathological feature in patients with Alzheimer's disease (AD). The aim of this study was to explore whether depressive symptoms cause changes in the functional network of the basal forebrain in AD patients. We collected MRI data from depressed AD patients (n = 24), nondepressed AD patients (n = 14) and healthy controls (n = 20). Resting-state functional magnetic resonance imaging data and functional connectivity analysis were used to study the characteristics of the basal forebrain functional network of the three groups of participants. The functional connectivity differences among the three groups were compared using ANCOVA and post hoc analyses. Compared to healthy controls, depressed AD patients showed reduced functional connectivity between the right nucleus basalis of Meynert and the left supramarginal gyrus and the supplementary motor area. These results increase our understanding of the neural mechanism of depressive symptoms in AD patients.

Abstract 5161: Integrating patient’s derived organoids and liquid biopsy: An exploratory study of early stage pancreatic cancer

Abstract Background: Pancreatic cancer (PC) has a 5-year survival of 12% despite recent therapeutic advancements. There is a desperate need to discover novel ways of treating PC since a large proportion of patients do not benefit from therapy and experience significant toxicity. A major cause of therapy failure is therapy resistance due to tumor heterogeneity. Nowadays, a deeper understanding of tumor heterogeneity could be assisted by the use of patients-derived organoids (PDOs). Furthermore, the use of liquid biopsy may allow for the investigation of circulating factors with predictive value and for disease monitoring over time. Methods: Patients were enrolled in the comprehensive, multiomic study of pancreatic cancer CONTAINER. Patients with early stage PC treated with preoperative chemotherapy or undergoing surgery first were selected for the present study. When possible, a surgical specimen was collected to obtain PDOs. Tissue from resected tumors was dissociated by GentleMACSTM dissociator (Miltenyi Biotec), fragments were embedded in MatrigelTMand cultured in PancreaCultTM human Organoid Media (stemcell technologies). PDO histological features were investigated by H&amp;E staining and IHC. Blood samples were collected before and one month after surgery. From blood samples circulating tumor cells (CTCs) were enriched and isolated, extracellular vesicles (EVs) were isolated from plasma with size-exclusion chromatography and their concentration and size distribution was evaluated with NanoSight NS300. Then, EV surface antigens were characterized by flow cytometry. A panel of inflammatory cytokines was finally evaluated through Ella Automated Immunoassay System. Results: In CONTAINER study 113 patients were enrolled and 30 of them underwent surgery. 21 surgical specimens were received from which 18 PDOs were successfully established. EVs with diameter ≥ 70nm were isolated from plasma, EV mean size was similar before and after surgery whereas individual variations in particle concentration and in surface antigen exposure were observed. Correlation with clinical and pathological characteristics of patients will be performed once reached an adequate sample size for statistical analyses. A panel of inflammatory cytokines (IL1β-, IFNγ, TNFα, IL6, IL8, TGFβ1, CRP and Leptin) was assessed in plasma samples obtained before and after surgery. Except for IL1β, a significant individual variation of circulating cytokines before and after surgery was observed. Conclusions: This study will contribute to unveil mechanisms of disease progression and drug resistance in PC. Possible predictive factors and mechanisms of drug resistance will be investigated taking advantage of the information derived from both in vitro models and circulating tumor-related entities. Citation Format: Michela Cortesi, Tania Rossi, Michele Zanoni, Sara Bandini, Carlo Alberto Pacilio, Alessandro Cucchetti, Martina Valgiusti, Chiara Gallio, Alessandro Passardi, Giorgia Gurioli, Sara Bravaccini, Alessandra Dubini, Giovanni Luca Frassineti, Paola Ulivi, Giovanni Martinelli, Giorgio Ercolani, Ilario Giovanni Rapposelli. Integrating patient’s derived organoids and liquid biopsy: An exploratory study of early stage pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5161.

Clinical and pathological findings of IgA nephropathy following SARS-CoV-2 infection

The features of IgA nephropathy (IgAN) after SARS-CoV-2 infection have not been well characterized. In this study, we compared the clinical and pathological characteristics of patients with IgAN who had experienced SARS-CoV-2 infection to those who had not. We conducted a retrospective study that enrolled 38 patients with biopsy-proven IgAN following SARS-CoV-2 infection with 4 months (post-SARS-CoV-2 infection group) and 1154 patients with IgAN prior to the pandemic (pre-SARS-CoV-2 infection group). Among the SARS-CoV-2 group cases, 61% were females. The average duration from SARS-CoV-2 infection to renal biopsy was 78.6 days. Prior to SARS-CoV-2 infection, the patients had different presentations of nephropathy. One patient had isolated hematuria, two had isolated proteinuria, twenty presented with both hematuria and proteinuria, and one patient had elevated serum creatinine. Additionally, there were eight cases with uncertain nephropathy history, and six cases did not have a history of nephropathy. Following SARS-CoV-2 infection, five patients experienced gross hematuria, one case exhibited creatinine elevation, and five cases showed an increase in proteinuria. The group of patients infected with SARS-CoV-2 after the COVID-19 pandemic exhibited older age, higher hypertension ratio and lower eGFR values compared to the pre-SARS-CoV-2 infection group. As for pathological parameters, a higher proportion of patients in the post-SARS-CoV-2 infection group exhibited a higher percentage of sclerotic glomeruli and glomerular ischemic sclerosis. There were no significant differences observed between the two groups in terms of therapy involving steroids, immunosuppressants, or RAS inhibitors. IgA nephropathy patients who were infected with SARS-CoV-2 were generally older and experienced more severe kidney damage compared to those without SARS-CoV-2 infection.

Laparoscopic Treatment of Perforated Peptic Ulcer: A Propensity Score-Matched Comparison of Interrupted Stitches Repair versus Knotless Barbed Suture.

Background: Peptic ulcers result from imbalanced acid production, and in recent decades, proton pump inhibitors have proven effective in treating them. However, perforated peptic ulcers (PPU) continue to occur with a persistent high mortality rate when not managed properly. The advantages of the laparoscopic approach have been widely acknowledged. Nevertheless, concerning certain technical aspects of this method, such as the best gastrorrhaphy technique, the consensus remains elusive. Consequently, the choice tends to rely on individual surgical experiences. Our study aimed to compare interrupted stitches versus running barbed suture for laparoscopic PPU repair. Methods: We conducted a retrospective study utilizing propensity score matching analysis on patients who underwent laparoscopic PPU repair. Patients were categorised into two groups: Interrupted Stitches Suture (IStiS) and Knotless Suture (KnotS). We then compared the clinical and pathological characteristics of patients in both groups. Results: A total of 265 patients underwent laparoscopic PPU repair: 198 patients with interrupted stitches technique and 67 with barbed knotless suture. Following propensity score matching, each group (IStiS and KnotS) comprised 56 patients. The analysis revealed that operative time did not differ between groups: 87.9 ± 39.7 vs. 92.8 ± 42.6 min (p = 0.537). Postoperative morbidity (24.0% vs. 32.7%, p = 0.331) and Clavien-Dindo III (10.7% vs. 5.4%, p = 0.489) were more frequently observed in the KnotS group, without any significant difference. In contrast, we found a slightly higher mortality rate in the IStiS group (10.7% vs. 7.1%, p = 0.742). Concerning leaks, no differences emerged between groups (3.6% vs. 5.4%, p = 1.000). Conclusions: Laparoscopic PPU repair with knotless barbed sutures is a non-inferior alternative to interrupted stitches repair. Nevertheless, further research such as randomised trials, with a standardised treatment protocol according to ulcer size, are required to identify the best gastrorraphy technique.

Skeletal muscle and visceral adipose radiodensities are pre-surgical, non-invasive markers of aggressive kidney cancer.

Most studies on body composition in kidney cancer have been conducted among patients with metastatic disease. Given that aggressive tumours can adversely impact body composition and even non-metastatic tumours can be aggressive, we evaluated associations between pre-surgical body composition features and tumour pathological features in patients with non-metastatic clear cell renal cell cancer (ccRCC). The Resolve Cohort consists of 1239 patients with non-metastatic ccRCC who underwent nephrectomy at Memorial Sloan Kettering Cancer Center between 2000 and 2020. The cross-sectional areas and radiodensities of skeletal muscle, visceral adipose, and subcutaneous adipose tissues were determined from pre-surgical computed tomography (CT) scans at the third lumbar vertebrae using Automatica software. Pearson's correlation coefficients describe inter-relationships among BMI and body composition variables, while odds ratios (OR) and 95% confidence intervals (CI) estimate associations between continuous body composition features (per 1-standard deviation) and advanced stage (Stage III vs. Stages I-II) and high Fuhrman grade (Grades 3-4 vs. 1-2) from multivariable logistic regression models that considered the potential impact of biological sex, contrast enhanced CTs, and early age at onset of ccRCC. The cohort was predominantly male (69%), white (89%), and had a median age of 58. The proportion of patients presenting with advanced stage and high-grade disease were 31% and 51%, respectively. In models that adjusted for demographics and all body composition variables simultaneously, decreasing skeletal muscle radiodensity (i.e., more fat infiltration) but increasing visceral adipose tissue radiodensity (i.e., more lipid depletion) were associated with advanced tumour features. Per 8.4 HU decrease in skeletal muscle radiodensity, the odds of presenting with advanced stage was 1.61 (95% CI: 1.34-1.93). Per 7.22 HU increase in visceral adipose tissue radiodensity, the odds of presenting with advanced stage was 1.45 (95% CI: 1.22-1.74). Skeletal muscle index (i.e., sarcopenia) was not associated with either tumour feature. Similar associations were observed for Fuhrman grade, a more direct marker of tumour aggressiveness. Associations did not differ by sex, contrast use, or age at onset of ccRCC. Lipid infiltrated skeletal muscle, but lipid depleted visceral adipose tissue were independently associated with advanced tumour features in non-metastatic ccRCC. Findings highlight the importance of evaluating the full range of body composition features simultaneously in multivariable models. Interpreting pre-surgical CTs for body composition for patients may be a novel and non-invasive way to identify patients with aggressive renal tumours, which is clinically relevant as renal biopsies are not routinely performed.

Diagnostic challenges in low-grade central osteosarcoma.

Low-grade central osteosarcoma (LGCOS), a rare type of osteosarcoma, often has misleading radiological and pathological features that overlap with those of other bone tumours, thereby complicating diagnosis and treatment. We aimed to analyze the clinical, radiological, and pathological features of patients with LGCOS, with a focus on diagnosis, treatment, and outcomes. We retrospectively analyzed the medical records of 49 patients with LGCOS (Broder's grade 1 to 2) treated between January 1985 and December 2017 in a single institute. We examined the presence of malignant features on imaging (periosteal reaction, cortical destruction, soft-tissue invasion), the diagnostic accuracy of biopsy, surgical treatment, and oncological outcome. Based on imaging, 35 of 49 patients (71.4%) exhibited malignant features. Overall, 40 of 49 patients (81.6%) had undergone a biopsy before en-bloc resection: 27 of 40 patients (67.5%) were diagnosed on the first biopsy, which was more accurate when carried out by open rather than needle biopsy (91.3% vs 35.3% diagnostic accuracy, respectively; p < 0.001). Of the 40 patients treated by en-bloc resection, surgical margins were wide in 38 (95.0%) and marginal in two (5.0%). Furthermore, nine of 49 patients (18.4%) underwent curettage (intralesional margin) without previous biopsy. All patients with a positive margin developed local recurrence. Distant metastases occurred in five of 49 patients (10.2%). The mean five-year overall survival (OS) and distant relapse-free survival (D-RFS) were 89.3% (SD 5.1%) and 85.7% (SD 5.5%), respectively. Univariate analysis showed that the occurrence of distant metastasis was a poor prognostic factor for OS (hazard ratio 11.54, 95% confidence interval (CI) 1.92 to 69.17; p < 0.001). Local recurrence was a poor prognostic factor for D-RFS (HR 8.72, 95% CI 1.69 to 45.0; p = 0.002). The diagnosis of LGCOS can be challenging because it may present with non-malignant features and has a low diagnostic accuracy on biopsy. If precisely diagnosed, LGCOS can be successfully treated by surgical excision with wide margins.

Comparison of Clinicopathological Characteristics of Patients with Early and Late-onset Colorectal Adenocarcinoma: A Cross-sectional Study

Introduction: Colorectal Cancer (CRC) has been primarily considered a disease of the elderly, but recent data have shown an alarming rise among young people. It has also been suggested that young age is associated with aggressive histopathological characteristics and advanced stages of the disease at diagnosis. Aim: To assess and compare the clinical and pathological characteristics of patients with rectal cancer diagnosed at ages over and below 45 years. Materials and Method: This prospective cross-sectional study was conducted between January 2020 and August 2022 in the Departments of Surgical, Medical, Radiation Oncology, Surgical Gastroenterology, and General Surgery at All India Institute of Medical Sciences (AIIMS) Rishikesh, Uttarakand, India. All patients underwent a biopsy from the representative site for histological documentation of the disease. They then underwent treatment (surgery/chemotherapy/radiotherapy) as required. All the data were categorised into two groups: an early-onset group (age &lt;45 years) and a late-onset group (≥45 years). A comparison of the clinicopathological characteristics (age, gender, comorbidities, tumour subsite, clinical presentation, clinical stage, etc.), pathological data (grade and differentiation of tumour, as per World Health Organisation (WHO) grading system), and serum Carcinoembryonic Antigen (CEA) levels between the two groups was performed. The association between categorical variables was investigated using the Chi-square test. The mean difference was assessed using an independent t-test. A p-value of 0.05 or below was considered statistically significant. Results: A total of 51 patients with rectal cancer, 35 males and 16 females, were included in the study. The mean age was 44.73±16.47 years. Out of the total of 51 (100%) patients, lower rectum involvement was seen in 22 (43.1%) patients, followed by 7 (13.7%) patients each with ascending colon and sigmoid involvement resepectively. However, the Chi-square test showed no statistically significant association of location involved with age groups (χ2 =9.09; p=0.16). Out of 51 (100%) adenocarcinoma patients in total, three patients each under 45 years of age had signet cell adenocarcinoma and mucinous adenocarcinoma (χ2 =7.07; p=0.029). Among the total of 51 (100%) patients, moderately differentiated lesions were seen in 17 (33.3%) patients, poorly differentiated lesions were seen in 15 (29.4%) patients, and well-differentiated lesions were seen in 10 (19.6%) patients (χ2 =13.01; p=0.005). Conclusion: Younger patients tended to have larger tumours that were of a higher grade and had signet ring or mucinous histopathology. The social and clinical implications of these findings are to be explored.

Analysis of the clinical and pathological characteristics of patients with the squamous-cell lung carcinoma including group survival rates and the occurrence of symptoms depending on the extent of the tumor

Analysis of the clinical and pathological characteristics of patients with the squamous-cell lung carcinoma including group survival rates and the occurrence of symptoms depending on the extent of the tumor

The Clinical and Pathological Characteristics of Patients with Oxalate Nephropathy.

Key Points Oxalate nephropathy is an underrecognized cause of CKD and ESKDWe present one of the largest native oxalate nephropathy cohorts to date from a tertiary care institution in the United StatesOxalate nephropathy has multiple etiologies and given its clinical course and poor prognosis, attention must be paid to screening for risk factors to guide prompt diagnosis and management Background Oxalate nephropathy (ON) is characterized by deposition of calcium oxalate crystals in the kidney and is commonly under-recognized. Causes of ON include primary hyperoxaluria, enteric hyperoxaluria, and ingestion of excess oxalate or its precursors. Methods We report the clinical and pathological characteristics of one of the largest series of native kidney ON to date, from January 2015 to March 2023 at the Cleveland Clinic. Results We identified 60 native biopsies with oxalate deposits and excluded patients with clinically insignificant biopsies (n=12) or lack of data (n=17). Thirty-one patients with native ON were described. The mean age at diagnosis was 66.2 years (±12.1), and 58.1% were female. 87.1% had hypertension, 58.1% had diabetes, 42% had nephrolithiasis, and 77.4% had underlying CKD, with a mean baseline creatinine of 1.8 mg/dl ±1.3. The mean creatinine at biopsy was 5.2 mg/dl ±1.7. Kidney biopsies showed abundant calcium oxalate crystal deposits, and 27 of 31 biopsies had additional diagnoses, the most common of which were acute tubular injury n=17 (54.8%) and diabetic glomerulosclerosis n=7 (22.6%). Severe and moderate interstitial fibrosis was present in 38.7% (n=12) and 51.6% (n=16) of biopsies, respectively. Ten had a single etiology of ON, ten had a multifactorial etiology (both enteric hyperoxaluria and high precursor intake), and 11 had an unclear etiology. Notably, only seven patients had a history of gastric bypass. The mean duration of follow-up was 26.8 months, and 26 patients had follow-up data &gt;1 year. Of these, 21 required dialysis, and five were dialysis-free at presentation. Five of the 26 were deceased at 1 year, with 12 patients (38.7%) deceased at last follow-up. Seventeen patients received targeted management, while nine patients did not receive targeted treatment, and all nine required hemodialysis. More patients (31.6%) had vitamin C intake after the coronavirus disease 2019 pandemic (2020–2023) versus 16.7% before 2020. Conclusions ON presents as AKI or acute on CKD. The prognosis is poor with most patients requiring dialysis at presentation with high morbidity and mortality. Clinicians need to be aware of the risk factors associated with ON to aid prompt diagnosis and management. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/K360/2024_01_26_KID0000000000000340.mp3

Development and validation of a nomogram to predict pathological complete response in patients with locally advanced gastric adenocarcinoma treated with neoadjuvant chemotherapy in combination with PD-1 antibodies.

Currently, the survival benefits of combining neoadjuvant chemotherapy with programmed death 1 (PD-1) antibody immunotherapy in advanced gastric adenocarcinoma remain controversial. Emerging evidence suggests that the survival benefits of neoadjuvant therapy in advanced gastric adenocarcinoma hinge upon the attainment of pathological complete response (pCR). Therefore, the prediction of pCR in patients undergoing neoadjuvant chemotherapy combined with PD-1 antibody immunotherapy holds significant importance and is beneficial for the individualized treatment of gastric cancer (GC) patients. Clinical and pathological characteristics of patients with GC who received neoadjuvant chemotherapy combined with PD-1 inhibitor (camrelizumab) therapy and radical gastrectomy between January 2019 and December 2020 at the Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital were retrospectively analyzed. A total of 52 patients were enrolled in the study, with all subjects assigned to the training set. The neoadjuvant regimen consisted of a combination of PD-1 inhibitor and fluorouracil analogues plus oxaliplatin, comprising two drugs. The patients were divided into a pCR group and a non-pCR group according to pCR occurrence. Multifactor logistic regression analysis was applied to determine the correlation between each factor and pCR. A prediction model was developed based on the results of the logistic regression analysis. The predictive performance of the model was evaluated using the receiver operating characteristic curves. Internal verification was completed via the bootstrapping method. The pCR was observed in 10 out of 52 patients (19.2%). The results of binary logistic regression multivariate analysis showed that cN stage [odds ratio (OR): 0.215; P=0.03], combined positive score (CPS) (OR: 6.364; P=0.026), and tumor diameter (OR: 0.112; P=0.026) were independent predictors of pCR. The nomogram prediction model for the pCR was plotted with a concordance index of 0.923 [95% confidence interval (CI): 0.8441-1]. Neoadjuvant chemotherapy combined with PD-1 antibodies may be the preferred option for patients with advanced gastric adenocarcinoma who have a small tumor diameter, no or few lymph node metastases, and high CPS. The presented nomogram model exhibits the potential to predict pCR in advanced gastric adenocarcinoma patients, showcasing satisfactory predictive performance and potentially facilitating the implementation of personalized treatment strategies.

Correlation between 18F-FDG PET-derived parameters and quantitative pathological characteristics of soft tissue sarcoma.

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) has been widely used for evaluating patients with soft tissue sarcoma (STS). However, uncertainties and overlap among individuals may be observed, and the relevance of these findings remains to be further explored. The present study was aimed at investigating the correlation between PET metabolic parameters and quantitative pathological characteristics in STS. We retrospectively collected 39 patients with STS who underwent 18F-FDG PET/computed tomography (CT) examination before treatment. Metabolic parameters including the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and intratumoral FDG uptake heterogeneity (IFH) were measured. Histological grading was performed according to the French Federation of Cancer Centers grading system. Continuous staining of tissue sections and digital quantitative analysis methods were used, the characteristics of tumor nucleated cells were observed through hematoxylin-eosin staining, and the expression of CD163, CD68, CD8, and CD4 in tumor tissues was determined by immunohistochemistry (IHC), then the correlation between FDG metabolic parameters and the above quantitative pathological characteristics in patients with STS were evaluated. The SUVmax of 18F-FDG PET/CT in STS was positively correlated with the total nuclear area (r=0.355, P=0.027). SUVmax was also positively correlated with the expression levels of CD163, CD68, CD8, and CD4 (r=0.582, 0.485, 0.343, and 0.324, with P<0.001, 0.002, 0.032, and 0.044, respectively), but was not significantly correlated with cell count and mean nuclear area (all P>0.05). However, MTV, TLG, and IFH were not significantly correlated with the above quantitative pathological characteristics. Further multivariate logistic regression analysis indicated that only CD163 expression and histological grade were independently correlated with SUVmax. Moreover, SUVmax remained positively correlated with CD163 expression in the low-grade STS (r=0.820, P=0.001) and high-grade STS groups (r=0.430, P=0.028). 18F-FDG uptake was positively correlated with the quantitative pathological features of soft tissue tumors. SUVmax may be a meaningful method reflecting the level of M2 macrophage infiltration and may provide additional valuable information for preclinical evaluation of STS.

Epidemiological, Endoscopic, Clinical, and Pathological Features of Patients with Celiac Diseases in Southern Littoral of Caspian Sea.

Background: Celiac disease is an autoimmune disorder resulting from gluten consumption in genetically predisposed individuals. The present study investigated the epidemiological, endoscopic, and clinicopathological features of patients with celiac disease in the southern littoral of the Caspian Sea. Methods: 140 patients with celiac disease were interviewed and examined regarding demographic characteristics, clinical symptoms, and serologic, endoscopic, and pathological findings. Results: 44 (31.4%) of the patients were male and 68.6% were female. The mean age of the patients at diagnosis was 27.13±13.4 years (ranging from 2 to 60 years). The most common gastrointestinal (GI) symptoms were bloating (47.8%), abdominal pain (47.1%) and diarrhea (30.7%), respectively. Also, 17 (12.1%) patients did not complain of any GI symptoms.18 (12.8%) patients had aphthous stomatitis, 10.7% had dermatitis herpetiformis, 3.6% suffered from itching without a rash, two (1.4%) mentioned psoriasis and one (0.7%) had lichen planus. 19 (19.7%) of the female patients complained of menstrual bleeding disorders, 4% mentioned infertility, and 2% experienced primary amenorrhea. The most common comorbid condition was hypothyroidism in 16 (11.4%) patients. The most common endoscopic finding was duodenal scalloping (37.25%). In addition, 7.8% of the patients had a normal endoscopic appearance. 43 (30.7%) patients were classified as Marsh IIIC, 25.7% Marsh IIIB, 17.8% Marsh IIIA, 12.8% Marsh II and 12.8% were classified as Marsh I. Conclusion: Since celiac disease can present with non-GI manifestations and the majority of our patients had Marsh III classification, it seems that celiac disease must be considered as a routine screening test in GI clinics, and also, it should be kept in mind as a differential diagnosis in other specialty fields.

Atypical ductal hyperplasia on vacuum-assisted breast biopsy: a scoring system to predict the risk of upgrade to malignancy.

Our multicentric study analysed clinical, radiologic and pathologic features in patients with atypical ductal hyperplasia (ADH) diagnosed with vacuum-assisted biopsy (VAB), to identify factors associated with the risk of upgrade, to develop a scoring system to support decision making. Patients with ADH on VAB under stereotactic/tomosynthesis guidance (2012-2022) were eligible. Inclusion criteria were availability of surgical histopathological examination of the entire lesion or radiologic follow-up (FUP) ≥ 24months. VAB results were compared with surgical pathological results or with imaging FUP evolution to assess upgrade. A backward stepwise linear regression was used to identify predictors of upgrade. The discriminatory power of the model was calculated through the area under the receiver operating curve (ROC-AUC); the Hosmer-Lemeshow test was used to assess model calibration. The points system was developed based on the selected risk factors, and the probability of upgrade associated with each point total was determined. 112 ADH lesions were included: 91 (91/112, 81.3%) underwent surgical excision with 20 diagnosis of malignancy, while 21 (21/112, 18.7%) underwent imaging FUP with one interval change (mean FUP time 48months). Overall upgrade rate was 18.7% (21/112). Age, menopausal status, concurrent breast cancer, BIRADS classification and number of foci of ADH were identified as risk factors for upgrade. Our model showed an AUC = 0.85 (95% CI 0.76-0.94). The points system showed that the risk of upgrade is < 2% when the total score is ≤ 1. Our scoring system seemed a promising easy-to-use decision support tool for management of ADH, decreasing unnecessary surgeries, reducing patients' overtreatment and healthcare costs.

Evaluation of combined pathological responses in primary tumor and lymph nodes following neoadjuvant chemoimmunotherapy in non-small cell lung cancer

BackgroundInconsistent pathological responses of tumor and lymph nodes (LNs) were frequently observed in non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy. However, there is a lack of studies to report the prognostic significance and the relevant clinicopathological factors of tumor-nodal inconsistent responses after neoadjuvant immunotherapy or chemoimmunotherapy. Therefore, this study aimed to depict the inconsistent pathological combined tumor-nodal responses in NSCLC patients after neoadjuvant chemoimmunotherapy as well as the underlying clinical significance. MethodsA total of 81 node-positive NSCLC patients who underwent neoadjuvant chemoimmunotherapy were eligible for inclusion. Demographic, radiologic, and pathological features of patients were recorded. Patients with pathological complete response of both tumor (ypT(pCR)) and LNs (ypN0) were classified into the combined good responder group and the relevant clinicopathological features were evaluated. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis. ResultsThe ypN0 and ypT(pCR) rates were 74.1 % and 42.0 %, respectively. A significant correlation was observed between ypT(pCR) and ypN0 (P = 0.003), but inconsistent responses remained. The combined responses of the primary tumor and LNs demonstrated a significant association with the prognosis outcome (P = 0.005). Notably,patients who received at least twice of their infusions of immune checkpoint inhibitors after 15:30 had a worse prognosis (P = 0.015). ConclusionA significant but not absolute correlation was observed between good tumor response and good nodal response in NSCLC patients after neoadjuvant chemoimmunotherapy, but inconsistent responses were also found. The combination of tumor and nodal responses is significantly associated with prognosis and combined good responder can be used as a reliable prognosis predictor.

Racial Difference in Outcomes in Breast Cancer Patients with Residual Nodal Disease after Neoadjuvant Chemotherapy

African Americans (AA) requiring neoadjuvant chemotherapy (NAC) have been associated with worse outcomes. Residual nodal disease (ypN+) after NAC represents a highly unfavorable risk factor. We hypothesized that even within this unfavorable subgroup, that racial differences in outcome would persist. An IRB-approved retrospective review of breast cancer (BC) patients in a multi-institutional study was performed between 2005-2018 to identify ypN+ patients (excluding metastatic or inflammatory BC). Clinico-pathologic parameters stratified by race were collected and analyzed. For molecular subtype analyses, patients were stratified into triple negative (TN), hormone receptor (HR)+/HER2-, and HR+/HER2+, and HR-/HER2+ subtypes. Overall survival (OS), disease free survival (DFS) and recurrence outcomes were obtained, and univariate and multivariate (MVA) logistic regression models were constructed and analyzed. Among 404 ypN+ patients, 107 (26%) were AA, and 297 (74%) were non-AA. Median follow-up for the non-AA group was 3.8 years (y) (IQR 2.4-6.3) and 3.5y (IQR 2.0-6.2) for the AA group. Clinical and pathologic patient characteristics (age, molecular subtypes, BRCA status, histology, grade, smoking status, primary surgery type, axillary/reconstruction surgery rates, margin status, stage) were without significant statistical differences between the non-AA and AA group, except the non-AA group had proportionally more cN3 disease (10.5% vs. 5.1%; p = .01). Despite this, AA demonstrated worse OS and DFS outcomes (Table). AA also had significantly worse local (15% vs. 6.7%, p = .02), regional (11.2% vs. 5.1%, p = .05) and distant recurrences (32.7% vs. 22.6%, p = .05) compared to non-AA. On MVA for OS and DFS, HR+ status, clinical stage, and AA race (HR 2.1 (CI 1.3-3.4), p = .004 and HR 1.7 (CI 1.1-2.6), p = .01 respectively) remained significant. Molecular subtype analysis demonstrated that AA with HR+/HER2- but not the TN subtypes demonstrated significantly worse outcomes (Table). Utilization of endocrine therapy was not different between AA and non-AA patients (94% vs. 97%, p = 0.3) to explain this discrepancy. Worse outcomes in HER2 subtype for AA group was suggested but could not be statistically verified due to insufficient sample size. There was no discernible difference in chemotherapy and radiation therapy regimen or compliance between the AA and non-AA groups. AA patients who fail to achieve nodal clearance with NAC had higher local, regional and distant recurrence, and worse survival compared to non-AA, particularly those with non-TN status. These differences could not be readily explained by therapeutic disparity, or compliance. These hypothesis generating findings suggest need to explore biological implications, and alternative therapeutic strategies for this unfavorable subgroup.

Development and validation of a nomogram to predict the recurrence of hepatocellular carcinoma patients with dynamic changes in AFP undergoing locoregional treatments.

Serum alpha-fetoprotein (AFP) is an important clinical indicator for screening, diagnosis, and prognosis of primary hepatocellular carcinoma (HCC). Our team's previous study showed that patients with negative AFP at baseline and positive AFP at relapse had a worse prognosis (N-P). Therefore, the aim of our study was to develop and validate a nomogram for this group of patients. A total of 513 patients with HCC who received locoregional treatments at Beijing You'an Hospital, Capital Medical University, from January 2012 to December 2019 were prospectively enrolled. Patients admitted from 2012 to 2015 were assigned to the training cohort (n = 335), while 2016 to 2019 were in the validation cohort (n =183). The clinical and pathological features of patients were collected, and independent risk factors were identified using univariate and multivariate Cox regression analysis as a basis for developing a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves in the training and validation cohorts. The content of the nomogram includes gender, tumor number, tumor size, lymphocyte, direct bilirubin (DBIL), gamma-glutamyl transferase (GGT), and prealbumin. The C-index (0.717 and 0.752) and 1-, 3-, and 5-year AUCs (0.721, 0.825, 0.845, and 0.740, 0.868, 0.837) of the training and validation cohorts proved the good predictive performance of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classify of patients with dynamic changes in AFP into three groups according to the risk of recurrence: low risk, intermediate risk, and high risk. There was a statistically significant difference in RFS between the three groups in the training and validation cohorts (P<0.001). The nomogram developed and validated in this study had good predictive power for patients with dynamic changes in AFP.

Correlation of ChREBP Gene Methylation with Pathological Characteristics of Type 2 Diabetes Mellitus.

The objective of this study is to investigate the expression of the carbohydrate response element binding protein (ChREBP) gene in type 2 diabetes mellitus (T2DM) and its correlation with pathological features.For obtaining and exploring the pathological features in patients, sixty T2DM patients (the research group) and thirty healthy controls (the control group) presented to our hospital between January 2019 and June 2019 were selected as the research participants. After DNA extraction from peripheral blood mononuclear cells (PBMCs) and modification of target gene methylation with bisulfite, differences in methylation were verified, and the correlation of ChREBP methylation level with T2DM pathological features and single nucleotide polymorphism (SNP) typing was discussed.According to the prediction results of UCSC Genome Browser Home, there were two CpG islands in the promoter region of the ChREBP gene, and the first exon was selected for research. The ChREBP methylation rate was statistically higher in the research group versus the control group (P < 0.05). Age, FPG, TC, and TG were confirmed by the multiple linear regression analysis to be correlated with the ChREBP methylation rate (P < 0.05). Finally, there was no difference in ChREBP methylation level between CT- and CC-type patients at rs17145750 and rs1051921 loci (P > 0.05).Peripheral blood ChREBP methylation is elevated in T2DM patients and is closely related to age, blood glucose, and blood-lipid level, which is expected to be a new direction for future T2DM diagnosis and treatment.

Assessing the impact of lymphovascular invasion on overall survival in surgically treated renal cell carcinoma patients: A nationwide cohort analysis

Lymph-vascular invasion (LVI) is recognized as an adverse pathological feature in patients with renal cell carcinoma (RCC). However, its impact on overall survival (OS) is not clear and scarcely addressed in the literature. We aimed to assess the prognostic ability of LVI as a predictor of OS in RCC patients using a large, North American cohort. We included 95,783 cM0 RCC patients, diagnosed between 2010 and 2015, who underwent partial or radical nephrectomy within the National Cancer Database. Kaplan-Meier curves and log-rank tests were used to depict and compare survival curves. Cox regression analysis tested the impact of LVI on OS, after adjusting for all available confounders. Mean age (SD) was 59 (12), and most patients had pT1 stage (72.2%). Nodal status was pN0, pN1, and pNx, in 14.5%, 2.3%, and 83.3%, respectively. Overall, 9.0% of patients had LVI. The mean (SD) follow-up of the cohort was 39 months (24). At 5 years, OS was 65% in patients with LVI vs. 86% in patients without LVI (p<.0001). When patients were stratified based on nodal stage, these rates were 64% vs. 78% in pN0 patients, 31% vs. 41% in pN1 patients, and 69% vs. 87% in pNx patients (all P < 0.001). On multivariable analysis, and in comparison to patients without LVI, those with LVI had 1.37- (P < 0.001), 1.18- (P = 0.068), and 1.53-fold (P < 0.001) greater risk of death, when also harboring pN0, pN1, and pNx disease, respectively. Our findings are the first, to our best knowledge, to illustrate the clear detrimental impact of LVI on OS in surgically treated RCC patients. These findings might be useful in postoperative patient counseling and need to be accounted for when designing future clinical trials.