Treatment of a mutant KRAS lung cancer cell line with polyisoprenylated cysteinyl amide inhibitors activates the MAPK pathway, inhibits cell migration and induces apoptosis.

KRAS mutations are the most common oncogenic mutations in lung adenocarcinoma in Black Americans. Polyisoprenylated Cysteinyl amide Inhibitors (PCAIs) constitute a group of potential cancer therapy agents that we designed to specifically disrupt and suppress hyperactive G-protein signaling, such as that caused by mutated RAS proteins. Here we determine the effects of PCAIs on the viability, G-protein levels, downstream mediators, and apoptosis-related proteins on the KRAS-mutated, Black American-derived lung adenocarcinoma cell line, NCI-H23. Of the 17 PCAIs tested, compounds NSL-YHJ-2-27 and NSL-YHJ-2-46 showed the most potency with EC50 values of 2.7 and 3.3 µM, respectively. Western blotting was used to determine the effect of the PCAIs on the phosphorylation levels of MAPK pathway enzymes. After 48 h exposure to 5 µM of the PCAIs, NSL-YHJ-2-46, the MAPK proteins BRAF, MEK1/2, ERK1/2, and p90RSK were activated through phosphorylation by 90, 190, 150 and 120%, respectively. However, CRAF/RAF1 phosphorylation decreased by 40%, suggesting significant changes in the KRAS/MAPK signaling patterns. Furthermore, 5 µM of NSL-YHJ-2-27 depleted the singly polyisoprenylated monomeric G-proteins RAC 1/2/3 and CDC42 by 77 and 76%, respectively. The depletion of these key cytoskeletal proteins may account for the observed inhibition of cell migration and invasion, and spheroid invasion observed on exposure to NSL-YHJ-2-27 and NSL-YHJ-2-46. Treatment with 5 µM of NSL-YHJ-2-27 suppressed full-length inactive caspase 3 and 7 levels by 72 and 91%, respectively. An analysis of cells treated with the fluorescently labeled active caspase 3/7 irreversible inhibitor, CaspaTagTM Caspase-3/7 in situ reagent revealed a 124% increase in active caspase at 3 µM over controls. These findings clearly show the direct effects of the PCAIs on the RAS signaling pathway. Given the profound increases observed in RPS6KA1/p90RSK phosphorylation, future work will involve a determination whether the proapoptotic isoforms of RPS6KA1/p90RSK are phosphorylated due to the PCAIs treatments. These results support the potential use of the PCAIs as targeted therapies against cancers with KRAS mutations.

Coinactivation of the Switch/Sucrose Nonfermenting Complex SMARCA4/BRG1 and SMARCB1/INI1 in a Cervical Mixed Carcinoma: A Case Report.

SMARCB1/SMARCA4-deficient malignancies of the female genital tract are rare entities, characterized by similar histologic features, such as sheet-like growth patterns and rhabdoid cells. Previous studies have shown mutually exclusive loss of SMARCA4/BRG1 and SMARCB1/INI1. Herein, we describe a unique cervical mixed carcinoma in a 77-year-old patient. The tumor consisted of 3 components, gastric-type adenocarcinoma, squamous carcinoma, and undifferentiated carcinoma. While the undifferentiated carcinoma was negtive for CK7, CK5/6 and p63, it was positive for pan-CK. DNA-based next-generation sequencing revealed a nonsense mutation in SMARCA4, copy number loss in SMARCB1, and a nonsense mutation in ARID1A. Different molecular alterations of the switch/sucrose nonfermenting complex subunits in the present case may provide further insights into the functions of the switch/sucrose nonfermenting complex in the progression of tumors.

Correlation of inflammatory indices with staging of esophageal carcinoma: A prospective study at Dr. Ruth K. M. Pfau Civil Hospital, Karachi.

Objectives: To determine the correlation between inflammatory indices and the Tumour-Node-Metastasis stage of oesophageal carcinoma. METHODS: The prospective study was conducted from January 2021 to January 2023 at the Department of Upper Gastrointestinal Surgery, Dr Ruth K.M. Pfau Civil Hospital, Karachi, and comprised patients of either gender aged 18- 60 years with biopsy-proven oesophageal cancer. Blood samples were drawn and on the basis of plasma obtained, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, C-reactive protein-to-albumin ratio, lymphocyte-tomonocyte ratio and platelet-to red cell distribution width ratio were calculated. Modified Glasgow Prognostic Score was calculated on the basis of C-reactive protein and albumin levels. Values were compared with tumour length, depth of invasion, lymph node status, vascular involvement, metastasis, pathological subtype and grade of differentiation. Data was analysed using SPSS 24. RESULTS: Of the 220 patients aged 46.1±14.2 years, 120(54%) were females and 100(46%) were males. C-reactive protein-to-albumin ratio demonstrated the highest predictive power for advanced disease stage (p=0.003). Elevated neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio (p=0.010 and p=0.044) were positively correlated with node stage, while elevated platelet-to-lymphocyte ratio was associated with advanced clinical stage (p=0.046). C-reactive protein-to-albumin ratio exhibited positive association with higher tumour stage (p=0.033), node stage (p<0.001) and clinical stage IV (p<0.001). Modified Glasgow Prognostic Score was significantly associated with advanced clinical stage (p<0.001). Conclusion: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, C-reactive protein-to-albumin ratio, and Modified Glasgow Prognostic Score could be used effectively as a predictor of advanced oesophageal cancer.

Signet ring cells in the gastrointestinal tract: not always what it seems.

We describe two cases of pseudo-signet ring cells in gastric biopsies of otherwise asymptomatic adult patients. One male patient was diagnosed during follow-up of a previous intestinal type gastric adenocarcinoma and underwent surgery before recognition of this non-malignant entity. He suffered from a secondary anastomotic stenosis requiring dilatation. A second male patient was spared from surgery thanks to timely recognition by the pathologist and is still declared cancer-free until today. This extremely rare nonmalignant mimicker of cancerous signet ring cells, as seen in diffuse type gastric cancer can potentially mislead the clinician. The absence of any endoscopic abnormality should prompt a revision by an experienced pathologist, digestive oncologist and surgeon to avoid unnecessary interventions and morbidity.

Development and Validation of a Comprehensive Prognostic and Depression Risk Index for Gastric Adenocarcinoma.

Depressive disorder contributes to the initiation and prognosis of patients with cancer, but the interaction between cancer and depressive disorder remains unclear. We generated a gastric adenocarcinoma patient-derived xenograft mice model, treated with chronic unpredictable mild stimulation. Based on the RNA-sequence from the mouse model, patient data from TCGA, and MDD-related (major depressive disorder) genes from the GEO database, 56 hub genes were identified by the intersection of differential expression genes from the three datasets. Molecular subtypes and a prognostic signature were generated based on the 56 genes. A depressive mouse model was constructed to test the key changes in the signatures. The signature was constructed based on the NDUFA4L2, ANKRD45, and AQP3 genes. Patients with high risk-score had a worse overall survival than the patients with low scores, consistent with the results from the two GEO cohorts. The comprehensive results showed that a higher risk-score was correlated with higher levels of tumor immune exclusion, higher infiltration of M0 macrophages, M2 macrophages, and neutrophils, higher angiogenetic activities, and more enriched epithelial-mesenchymal transition signaling pathways. A higher risk score was correlated to a higher MDD score, elevated MDD-related cytokines, and the dysfunction of neurogenesis-related genes, and parts of these changes showed similar trends in the animal model. With the Genomics of Drug Sensitivity in Cancer database, we found that the gastric adenocarcinoma patients with high risk-score may be sensitive to Pazopanib, XMD8.85, Midostaurin, HG.6.64.1, Elesclomol, Linifanib, AP.24534, Roscovitine, Cytarabine, and Axitinib. The gene signature consisting of the NDUFA4L2, ANKRD45, and AQP3 genes is a promising biomarker to distinguish the prognosis, the molecular and immune characteristics, the depressive risk, and the therapy candidates for gastric adenocarcinoma patients.

Metastatic Upper Thoracic Intramedullary Spinal Cord Tumor of Ovarian Adenocarcinoma: A Rare Case Report and Literature Review.

BACKGROUND: Intramedullary spinal cord metastasis (ISCM) is uncommon and usually occurs in advanced malignancies. Effective management methods are not clearly defined, and the outcomes of current treatments vary. Currently, there is no universal strategy for managing patients with intramedullary spinal metastases. CASE: To the best of our knowledge, we present a case of ovarian adenocarcinoma that was managed surgically in a 70-year-old woman with metastasis to the upper thoracic spinal cord, and we assess pertinent literature and deliberate management approaches. CONCLUSIONS: Progression in early diagnosis and advanced therapeutic methods for ISCMs have contributed to the increased incidence and prevalence of this condition. There is no established consensus regarding the definitive patient management methods. Consequently, we offer multidisciplinary management with individualization based on the patient's functional status, requirement for a definitive diagnosis for potential additional adjuvant therapies, and assessment of the extent of systemic disease, which can influence the desired quality of life and survival duration.

Characterization of mitochondrial metabolism related molecular subtypes and immune infiltration in colorectal adenocarcinoma.

Colorectal adenocarcinoma (COAD) is the most common subtype of colorectal cancer. Due to the imperfect prognosis of COAD, related prognostic factors and possible mechanisms need to be further investigated. During tumor development, mitochondria help tumor cells survive in a variety of ways, so that further screening of mitochondrial metabolism related targets has positive implications for COAD. We screened the mitochondrial metabolism-related genes (MMRG) associated with the COAD prognosis and explored the MMRG-related molecular subtype characteristics of by unsupervised consensus clustering analysis. Using ESTIMATE and ssGSEA algorithms, we evaluated the immunoinfiltration characteristic landscape of different molecular subtypes defined by MMRG. Combining the expression profiles of differentially expressed genes associated with the MMRG subgroup and the survival characteristics of COAD, we constructed an MMRG prognostic model using LASSO-univariate Cox analysis and successfully validated its impact on independently predicting risk stratification of COAD. The potential clinical value of the MMRG score was subsequently evaluated by subgroup immunoinfiltration characteristics and drug susceptibility prediction analysis. We also offer SEC11A as a new potential target for COAD by single-cell sequencing analysis. The effect of SEC11A on the proliferation, invasion abilities and mitochondrial dysfunction of COAD cells was confirmed through in vitro experiments. Our study provides new insights into the role of MMRG and new target for COAD potential intervention.

Pancancer analysis of NDUFA4L2 with focused role in tumor progression and metastasis of colon adenocarcinoma.

Colon adenocarcinoma (COAD) is a prevalent gastrointestinal malignant disease with a high mortality rate, and identification of novel prognostic biomarkers and therapeutic targets is urgently needed. Although NDUFA4L2 has high expressions in various tumors and affects tumor progression, its role in COAD remains unclear. The role of NDUFA4L2 in COAD was analyzed utilizing datasets available from public databases including The Cancer Genome Atlas, The Genotype-Tissue Expression (GTEx), Gene Expression Omnibus, Alabama Cancer Database (UALCAN), and The Human Protein Atlas databases. The prognostic value of NDUFA4L2 was determined using Kaplan-Meier analysis and Cox regression analysis. To investigate the possible mechanism underlying the role of NDUFA4L2 in COAD, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were employed. The correlation between NDUFA4L2 expression and immune cell infiltration levels was examined through single-sample gene set enrichment analysis (ssGSEA). The NDUFA4L2 expression levels in COAD patients and cell lines were validated through immunohistochemistry, immunofluorescence, qRT-PCR, and Western blot. Wound healing assay was also performed to evaluate the effect of NDUFA4L2 on COAD metastasis. Furthermore, the NDUFA4L2 mediated competing endogenous RNA (ceRNA) regulatory network was predicted and constructed through a variety of databases. The comprehensive pan-cancer analysis showed that NDUFA4L2 possesses diagnostic and prognostic value in many cancers, especially in COAD. GO-KEGG and GSEA analyses indicated that NDUFA4L2 was associated with multiple biological functions including epithelial-mesenchymal transition and adaptation to hypoxia. The ssGSEA analysis showed that NDUFA4L2 expression was associated with immune infiltration. In vitro experiments confirmed upregulation of NDUFA4L2 in COAD tissues and cell lines, and NDUFA4L2 overexpression significantly promoted migration of COAD cells. In addition, the C9orf139 /miR-194-3p axis was speculated as the possible upstream regulators of NDUFA4L2 in COAD. This study demonstrated that NDUFA4L2 upregulation was correlated with tumor progression, relapsed prognosis and aggressive migration of COAD, suggesting that NDUFA4L2 can act as an effective prognostic biomarker and a promising therapeutic target for COAD treatment.

Elevated fibrinogen-albumin ratio is an adverse prognostic factor for patients with primarily resected gastroesophageal adenocarcinoma.

PURPOSE: Serum fibrinogen and albumin play important roles in systemic inflammation and are implicated in tumor progression. The fibrinogen-to-albumin ratio (FAR) has shown a prognostic impact in several malignancies. This study aims to assess the prognostic value of the pretherapeutic FAR in patients with adenocarcinoma of the gastroesophageal junction (AEG) who underwent upfront resection. METHODS: Consecutive patients who underwent surgical resection at the Department of Surgery at the Medical University of Vienna between 1992 and 2014 were included into this study. Optimal cut-off values were determined with the receiver-operating characteristic (ROC) curve, uni- and multivariate analyzes were calculated by the Cox proportional hazard regression model for overall survival (OS). RESULTS: Among 135 included patients, the majority were male (79.26%), with a mean age of 66.53 years. Elevated FAR correlated significantly (p = 0.002) with shorter OS in univariate analysis, also confirmed as independent prognostic factor (p = 0.005) in multivariable analysis. The ROC curve of FAR (AUC = 0.744) outperformed fibrinogen (AUC = 0.738) and albumin (AUC = 0.378) in predicting OS for AEG patients. CONCLUSION: The FAR serves as an independent prognostic factor for OS in patients undergoing primarily resection for AEG. Given its routine availability and ease of calculation, FAR could help in diagnosis and treatment selection for AEG patients. Further validation studies are warranted to confirm these findings conclusively.

Appendiceal adenocarcinoma associated with Amyand's hernia: a case report.

We encountered a rare case of appendiceal carcinoma associated with Amyand's hernia, which was difficult to diagnose preoperatively. A 74-year-old man presented to our hospital with right lower abdominal pain. A hard mass was palpable in the right lower abdomen, and blood tests showed a slightly elevated inflammatory response. Computed tomography revealed a 7 × 5 cm mass with indistinct borders and heterogeneous internal density extending from the cecum to the right lower abdominal wall. We diagnosed appendiceal abscess, however, percutaneous biopsy which was performed for differential diagnosis with appendiceal carcinoma showed no malignancy. Thereafter, the patient was followed up. Two months later, a blood test showed insignificant changes in the inflammatory response and a high serum carcinoembryonic antigen level (48.6 ng/mL). An ultrasound showed a mass contiguous to the appendix, extending to the abdominal wall, with abundant blood flow signals. Fluorodeoxyglucose-positron emission tomography showed a high accumulation of fluorodeoxyglucose in the mass. Four months after the initial visit, the patient had an open ileocecal resection combined with an abdominal wall resection based on the preoperative diagnosis of appendiceal carcinoma invading the abdominal wall. During laparotomy, an enlarged appendix tip extended from the internal inguinal ring outside the inferior epigastric artery to the abdominal wall. Histopathological examination of the appendiceal tumor revealed well-differentiated adenocarcinoma, T4b (abdominal wall), N0, Ly0, and V0. When a right lower abdominal mass extends from the cecum to the abdominal wall, appendiceal tumors associated with Amyand's hernia should be considered.

Expression of Types I and III Collagens and Ultrastructure of the Extracellular Matrix in Rectal Adenocarcinoma of Different Differentiation Degree after Neoadjuvant Radiation Therapy.

The structural organization of the extracellular matrix of rectal adenocarcinoma of different differentiation degrees without and after neoadjuvant radiation therapy was studied on postoperative material using immunohistochemistry and electron microscopy. The differences in the expression of types I and III collagens, as well as in the ultrastructural organization of the extracellular matrix of rectal adenocarcinoma of different differentiation degrees without and after neoadjuvant radiation therapy were revealed. We observed high expression of collagen I and wide channels in the collagen matrix in the central areas of the well differentiated adenocarcinomas without neoadjuvant radiation therapy and in poorly differentiated adenocarcinomas after neoadjuvant radiation therapy, which can be associated with metastasis and poor prognosis for the patients.

LungHist700: A dataset of histological images for deep learning in pulmonary pathology.

Accurate detection and classification of lung malignancies are crucial for early diagnosis, treatment planning, and patient prognosis. Conventional histopathological analysis is time-consuming, limiting its clinical applicability. To address this, we present a dataset of 691 high-resolution (1200 × 1600 pixels) histopathological lung images, covering adenocarcinomas, squamous cell carcinomas, and normal tissues from 45 patients. These images are subdivided into three differentiation levels for both pathological types: well, moderately, and poorly differentiated, resulting in seven classes for classification. The dataset includes images at 20x and 40x magnification, reflecting real clinical diversity. We evaluated image classification using deep neural network and multiple instance learning approaches. Each method was used to classify images at 20x and 40x magnification into three superclasses. We achieved accuracies between 81% and 92%, depending on the method and resolution, demonstrating the dataset's utility.

[Surgical Resection of High-grade Fetal Adenocarcinoma of the Lung:Report of a Case].

A 79-year-old woman was revealed to have an abnormal shadow in the right upper lung field by a chest radiography at the time of medical examination. Contrast-enhanced chest computed tomography( CT) revealed a solid, irregularly-shaped nodule with pleural indentation and total/solid diameter of 26 mm in the S3 segment of the right upper lobe. A diagnosis could not be made with bronchoscopy, although positron emission tomography( PET)-CT showed accumulation of 18F-fluoro-2-deoxy-D-glucose( FDG) in the same area. The lung cancer in the right upper lobe was considered to be cT1cN0M0 stage ⅠA3, and surgery (thoracoscopic right upper lobectomy ND2a-1) was performed for diagnostic and therapeutic purposes. The histopathological diagnosis was high-grade fetal adenocarcinoma of the lung with metastasis to the #12 lymph node, pT1cN1M0 stage ⅡB. Currently, 3.5 years postoperatively, the patient has shown no apparent metastasis or recurrence. In future, the epidemiology and treatment methods of high-grade fetal adenocarcinoma of the lung should be established by accumulating more cases.

Machine learning to predict distant metastasis and prognostic analysis of moderately differentiated gastric adenocarcinoma patients: a novel focus on lymph node indicators.

Background: Moderately differentiated gastric adenocarcinoma (MDGA) has a high risk of metastasis and individual variation, which strongly affects patient prognosis. Using large-scale datasets and machine learning algorithms for prediction can improve individualized treatment. The specific efficacy of several lymph node indicators in predicting distant metastasis (DM) and patient prognosis in MDGA remains obscure. Methods: We collected data from MDGA patients from the SEER database from 2010 to 2019. Additionally, we collected data from MDGA patients in China. We used nine machine learning algorithms to predict DM. Subsequently, we used Cox regression analysis to determine the risk factors affecting overall survival (OS) and cancer-specific survival (CSS) in DM patients and constructed nomograms. Furthermore, we used logistic regression and Cox regression analyses to assess the specific impact of six lymph node indicators on DM incidence and patient prognosis. Results: We collected data from 5,377 MDGA patients from the SEER database and 109 MDGC patients from hospitals. T stage, N stage, tumor size, primary site, number of positive lymph nodes, and chemotherapy were identified as independent risk factors for DM. The random forest prediction model had the best overall predictive performance (AUC = 0.919). T stage, primary site, chemotherapy, and the number of regional lymph nodes were identified as prognostic factors for OS. Moreover, T stage, number of regional lymph nodes, primary site, and chemotherapy were also influential factors for CSS. The nomograms showed good predictive value and stability in predicting the 1-, 3-, and 5-year OS and CSS in DM patients. Additionally, the log odds of a metastatic lymph node and the number of negative lymph nodes may be risk factors for DM, while the regional lymph node ratio and the number of regional lymph nodes are prognostic factors for OS. Conclusion: The random forest prediction model accurately identified high-risk populations, and we established OS and CSS survival prediction models for MDGA patients with DM. Our hospital samples demonstrated different characteristics of lymph node indicators in terms of distant metastasis and prognosis.

Long-term outcomes for Advanced Colorectal Polyps in the BowelScreen Programme.

Aims: Colonoscopies performed as part of a colorectal cancer screening programmes regularly identify large non-pedunculated colorectal polyps (LNPCPs). Endoscopic Mucosal Resection (EMR) is a minimally invasive endoscopic resection strategy, for effective management of LNPCPs. There is limited published data on clinical outcomes for EMR carried out within screening programmes. Methods: A retrospective analysis of a prospectively-maintained EMR database of BowelScreen patients in a single centre over a 5 year period. Results: Fifty-two polyps in 50 patients underwent EMR in the study period. Median polyp size was 25mm (range 20-70mm). Adenocarcinoma was identified in 7.8% of resection specimens (n 4/51). Complications were recorded in 5.7% of EMRs (n 3/52). Surveillance was completed for 87.8% (n=36/41) of eligible patients with a site-check recurrence rate of 8.3% (n 3/36). Recurrence was successfully managed endoscopically through the surveillance programme with an 18 month recurrence rate of 2.7% (n 1/36). Surgery was avoided in 92% (n 46/50) of patients undergoing EMR. Discussion: Complex polyps identified in the colorectal cancer screening programme are effectively and definitively managed by minimally invasive endoscopic resection.. Low recurrence and complication rates underscore the value of EMR as part of a screening programme. Post-EMR surveillance identifies a small number of endoscopically manageable recurrences, with encouragingly high levels of compliance.

Effectiveness of peritoneal lavage fluid circulating tumour cells and circulating tumour DNA in the prediction of metachronous peritoneal metastasis of gastric cancer (pT4NxM0/pT1-3N+M0) after radical resection: protocol of a prospective single-centre clinical study.

BACKGROUND: Gastric cancer (GC) is the fourth leading cause of cancer mortality worldwide. Peritoneal metastasis (PM) is a significant cause of death in patients with GC, and presents a major challenge in clinical diagnosis and treatment. Predicting the occurrence of PM in high-risk patients, and diagnosing and treating PM in advance to improve patient survival, remains an unsolved problem in clinical practice. Given the low positive rate of cytology and difficulty in diagnosing occult PM, new molecular markers and detection technologies for early diagnosis require urgent validation. The primary objective of this study is to observe and evaluate the predictive effect of intraoperative peritoneal lavage fluid (PLF) circulating tumour cells (CTC) and circulating tumour DNA (ctDNA) levels in patients with pT4NxM0/pT1-3N+M0 GC on metachronous PM after R0 resection. METHODS AND ANALYSIS: This prospective single-centre clinical study is conducted at Renji Hospital, Shanghai Jiao Tong University School of Medicine. In this study, 200 cases of patients with pT4NxM0/pT1-3N+M0 gastric adenocarcinoma older than 18 years will be screened. Participants will undergo intraoperative PLF CTC and ctDNA testing and will be followed up for 2 years, with imaging assessments performed every 3-6 months until PM occurrs. The primary outcome is the incidence of PM 1 year after surgery, which will be estimated using Clopper-Pearson method, with 95% CIs calculated and compared between groups. Secondary outcome include the incidence of PM 2 years after surgery, overall survival and disease progression. Data will be analysed using the Kaplan-Meier method and the log-rank test. ETHICS AND COMMUNICATION: Informed consent has been obtained from all subjects. This protocol has been approved by the Ethics Committee of Renji Hospital, Shanghai Jiao Tong University School of Medicine (LY2023-142-B). The findings will be disseminated through peer-reviewed manuscripts, reports and presentations. TRIAL REGISTRATION NUMBER: ChiCTR2300074910.

Adenocarcinoma of the esophagogastric junction: characteristics of female patients and young adult patients based on a 12-year retrospective and prospective multicenter clinicoepidemiological cohort study in Japan.

BACKGROUND: Adenocarcinoma of the esophagogastric junction (AEGJ) is most common in men and the elderly, but the disease is becoming more common in female and young adult persons. We have investigated the clinicoepidemiological characteristics of female and young adult patients with AEGJ and the 12-year trends in the Kurashiki area for young adult patients with AEGJ. METHODS: Patients diagnosed with AEGJ in 12 hospitals between January 2008 and December 2019 were included in this study. Patients were divided into three groups by age (young adult [≤50 years], middle-aged [51 to 70 years], and elderly [>70 years]). Factors associated with AEGJ such as obesity, smoking, hiatal hernia and male, which were reported in our previous study, were identified. RESULTS: One hundred and eighty-eight AEGJ patients, including 36 females and 20 young adults, were characterized. There was no significant change in the annual incidence of AEGJ among female (p=0.078) and young adult patients (p=0.89). Female patients without any associated factors, accounting for 53% (19/36) of the female patients and young adult patients, had significantly more histologically undifferentiated cancers than patients with at least one associated factor (58% [11/19] vs. 30% [50/169], p=0.025) and middle-aged and elderly patients (60% [12/20] vs. 30% [25/83] vs. 28% [24/85], p =0.026). Smoking was significantly less common in women than in men (8% [3/36] vs. 57% [87/152], p < 0.01). There were no significant differences between ages in the proportions of these associated factors. CONCLUSIONS: Histologically undifferentiated AEGJ cancers were more frequent in female patients without any associated factors and in young adult patients. Factors associated with AEGJ may differ between women and men, but they are similar in young adults and older adults. No increase in young adult patients with AEGJ was observed in the 12-year study.

The association of preoperative radiotherapy and surgery for AJCC stage I-III rectal adenocarcinoma: a population-based study.

BACKGROUND: With the increasing application of neoadjuvant therapy in rectal adenocarcinoma, there remain many controversies in clinical practical applications. Preoperative radiotherapy (PR) can limit the surgical plane and potentially affect the quality of surgical treatment. This study aimed to investigate the potential impact of PR on the surgical quality of rectal adenocarcinoma. METHODS: This retrospective study analyzed the clinicopathological data from 6,585 AJCC stage I-III rectal adenocarcinoma in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. Kaplan-Meier survival analysis and multivariate Cox proportional were used to assess the impact of PR on survival. Propensity score matching (PSM) was employed to balance the baseline covariates between the PR and non-PR groups and to compare postoperative pathological differences. RESULTS: After PSM, PR did not improve overall survival (OS) in stages I (p = 0.33), II (p = 0.37), and III (p = 0.14) patients. Multivariate Cox analysis indicated that PR was not an independent prognostic factor for patients. Restricted cubic spline (RCS) analysis demonstrated a nonlinear negative correlation between OS hazard ratios and both circumferential resection margin (CRM) and lymph node evaluation (LNE). Compared to the non-PR group, patients in the PR group had lower tumor deposits (TD) (p < 0.001), positive CRM (p = 0.191), and perineural invasion (PNI) (p = 0.001). CONCLUSION: PR is not an independent prognostic factor for rectal adenocarcinoma patients. However, PR can reduce the likelihood of TD, CRM, and PNI, thereby potentially influencing the quality of surgery.

Overdiagnosing giant bullous emphysema as metastatic adenocarcinoma: a case report.

BACKGROUND: Giant bullous emphysema is characterized by large bullae occupying at least one-third of the hemithorax and leading to compression of the surrounding lung parenchyma. Overdiagnosis can occur because of the atypical appearance of hyperplastic type II pneumocytes, which may be mistaken for malignant cells. CASE PRESENTATION: A 48-year-old male with a history of smoking and occupational exposure presented with dyspnea and drowsiness. Initial chest X-ray revealed a tension pneumothorax, and subsequent chest CT revealed extensive bullous emphysema and lung cancer in the right middle lobe (RML). Pathologic examination initially indicated resected bullae to metastatic adenocarcinoma, but upon review, it was determined that the reactive alveolar cells were misdiagnosed as malignant. CONCLUSIONS: This case emphasizes the need for thorough histopathological assessment and prudent interpretation of atypical cellular morphology.

Metastatic prostate adenocarcinoma to the brain - a clinicopathologic analysis of 21 cases.

BACKGROUND: Brain metastasis from prostate adenocarcinoma (PCa) is rare, often leading to death within a year. Its infrequent occurrence and atypical histopathologic features contribute to lower consideration in the differential diagnosis of tumor brain metastasis. This study aims to assess the clinical characteristics and distinctive histopathologic features of metastatic PCa in the brain for timely and enhanced diagnostic accuracy. DESIGN: A retrospective search spanning 20 years (2003-2022) was conducted on our archives and identified 21 cases diagnosed as "metastatic prostate adenocarcinoma (mPCa)" in brain biopsies and resections. All existing slides were thoroughly reviewed to evaluate the histopathology of the mPCa. RESULT: The mean age at presentation for brain metastasis was 70 years. Of 21 cases, 5 were dural-based lesions, 16 were true intraparenchymal metastases, including 2 sellar/suprasellar masses, 3 frontal, 3 temporal, 3 occipital, 1 cerebellum, and 4 involving multiple brain lobes. The average interval between initial diagnosis and brain metastasis was 90.75 months. Notably, brain metastasis was the initial presentation for one patient, while another patient, initially diagnosed with prognostic grade group (GG) 2 PCa in 1/12 cores, presented with isolated brain metastasis two years later. Architecturally, tumor cells were arranged in sheets or nests in most cases; however, four cases showed histologic cribriform patterns, and five displayed papillary architecture. Cytohistology varied from uniform monomorphic to highly pleomorphic cells with prominent nucleoli (8/19) and high mitotic activity. Interestingly, 1 case showed small round blue cell morphology, another had focal areas of rhabdoid and spindle cell differentiation, and 6 had cytoplasmic clearing. Almost half of the cases (47%) showed necrosis. CONCLUSION: mPCa to the brain can present with variable histomorphology. Therefore, consideration of mPCa in the differential diagnosis of metastatic brain lesions, even with non-suggestive imaging, is imperative in male patients with or without a history of primary disease. Accurate and prompt diagnosis is crucial, given the recent advancements in treatment that have improved survival rates.