The Role of Palliative Surgery in the Management of Acute Intestinal Obstruction Secondary to Peritoneal Carcinomatosis.

Introduction: Acute intestinal obstruction secondary to extensive peritoneal carcinomatosis is an end stage event. The role of palliative surgery in these patients is debatable in view of the anticipated severe complications and its doubtful role in achieving adequate palliation. The primary objective of our study was to evaluate the feasibility and ability of patients to resume oral nutrition after palliative surgery for acute intestinal obstruction due to peritoneal carcinomatosis. Patients and Methods: It is an observational study in which we retrospectively reviewed the data from a prospectively maintained clinical database of 40 patients. The predefined pre- and intraoperative variables were obtained. The immediate outcome variables like postoperative complications, length of hospital stay, and mortality were analyzed. The short-term outcomes at 3 months in the form of survival, ability to resume enteral nutrition were analyzed. Results: Among the 40 patients 18 were males and 22 females. Ovarian cancer was the most common primary (27.5%) in the study. Twelve patients had acute intestinal obstruction as their first presentation without any past events and 25 (62.5%) patients had been operated on previously or received adjuvant systemic treatment. The palliative surgical option was technically feasible in 37 (93.5%) patients. The median length of hospitalization for the patients who were discharged was 10 days with a range of 6-18 days. Six (15%) patients died in the postoperative period. Severe post-operative complications were seen in 9 (26.4%) patients. Among the patients (n=34) discharged 26 (76.4%) were alive at 3 months. In those who were alive, 21 (80.7%) of them were on some form of oral nutrition at 3 months. Conclusion: Palliative surgery in patients with acute intestinal obstruction secondary to peritoneal carcinomatosis is feasible with acceptable morbidity and mortality. The enteral nutrition can be restored in the majority of these patients.

[Treatment strategy for low-risk papillary thyroid carcinoma with diameter smaller than 1 cm: immediate surgery vs active surveillance].

The incidence of differentiated thyroid cancer is increasing rapidly worldwide, with subcentimeter papillary thyroid carcinoma (SPTC) with a diameter of less than 1 cm accounting for more than 50%. Active surveillance (AS) as an alternative to immediate surgery for low-risk SPTC was launched in Japan in the 1990s and has been implemented in several countries, including Japan and the United States. However, the indications and safety of performing AS for low-risk SPTC remain controversial. In this article, the author summarizes the existing literature and explores its limitations of AS implementation, the effectiveness of surgical treatment, and the different attitudes of countries on AS, aiming to provide some references for the treatment options of low-risk SPTC.

Clinical features of patients with carcinoma soft tissue metastases as surgical indications: a retrospective cohort study.

BACKGROUND: Soft-tissue metastasis of carcinoma is rare. In the present study, we investigated the surgical indications and clinical features of patients with soft tissue metastases of carcinoma. METHODS: In this retrospective cohort study, we enrolled 26 patients with soft tissue carcinoma metastasis referred to our department for treatment. Sex, age, location, size, depth, pain due to the tumor, primary origin, serum C-reactive protein (CRP) level, MRI examinations, diagnosis by a previous physician, carcinoma markers from blood, history of carcinoma, other metastases, performance status (PS), and surgical procedures were documented. Associations between variables and surgery were statistically analyzed. RESULTS: The primary cancer origin was found to be the lung (n = 10), kidney (n = 7), esophagus (n = 2), stomach (n = 1), breast (n = 1), liver (n = 1), ureter (n = 1), anus (n = 1), and unknown (n = 2). The mean CRP level of all patients was 2.3 mg/dL. Seven tumors (26.9%) were originally suspected to be soft tissue metastases of carcinoma, while 19 tumors (73.1%) were considered soft tissue sarcomas or inflammatory lesions by the previous treating physician. Twenty patients (76.9%) had other metastases. The PS of the 12 patients (46.2%) was zero. Eleven patients (42.3%) underwent surgery for soft tissue metastases. Diagnosis of soft tissue metastasis by a previous physician and good PS (p < 0.05) were significantly associated with surgery. CONCLUSION: Overall, the present results show that surgical indications for soft tissue metastasis of carcinoma include diagnosis by the referring physician or good PS of the patients.

Brd4::Nutm1 fusion gene initiates NUT carcinoma in vivo.

NUT carcinoma (NC) is an aggressive cancer with no effective treatment. About 70% of NUT carcinoma is associated with chromosome translocation events that lead to the formation of a BRD4::NUTM1 fusion gene. Because the BRD4::NUTM1 gene is unequivocally cytotoxic when ectopically expressed in cell lines, questions remain on whether the fusion gene can initiate NC. Here, we report the first genetically engineered mouse model for NUT carcinoma that recapitulates the human t(15;19) chromosome translocation in mice. We demonstrated that the mouse t(2;17) syntenic chromosome translocation, forming the Brd4::Nutm1 fusion gene, could induce aggressive carcinomas in mice. The tumors present histopathological and molecular features similar to human NC, with enrichment of undifferentiated cells. Similar to the reports of human NC incidence, Brd4::Nutm1 can induce NC from a broad range of tissues with a strong phenotypical variability. The consistent induction of poorly differentiated carcinoma demonstrated a strong reprogramming activity of BRD4::NUTM1. The new mouse model provided a critical preclinical model for NC that will lead to better understanding and therapy development for NC.

The role of germline BRCA1 & BRCA2 mutations in familial pancreatic cancer: A systematic review and meta-analysis.

BACKGROUND: Familial Pancreatic Cancer (FPC) presents a notable risk, with 3-10% of pancreatic adenocarcinoma cases having a family history. Studies link FPC to syndromes like HBOC, suggesting BRCA1/BRCA2 mutations play a role. BRCA gene functions in DNA repair impact FPC management, influencing sensitivity to therapies like PARP inhibitors. Identifying mutations not only aids FPC treatment but also reveals broader cancer risks. However, challenges persist in selectively applying genetic testing due to cost constraints. This Systematic Review focuses on BRCA1/BRCA2 significance in FPC, diagnostic criteria, prognostic value, and limitations. METHOD: Original articles published from 2013 to January 2023 were sourced from databases such as Scopus, PubMed, ProQuest, and ScienceDirect. Inclusion criteria comprised observational cohort or diagnostic studies related to the role of BRCA1/2 mutation in correlation to familial pancreatic cancer (FPC), while article reviews, narrative reviews, and non-relevant content were excluded. The assessment of bias used ROBINS-I, and the results were organized using PICOS criteria in a Google spreadsheet table. The systematic review adhered to the PRISMA 2020 checklist. RESULT: We analyzed 9 diagnostic studies encompassing 1325 families and 4267 patients from Italy, USA, and Poland. Despite the limitation of limited homogenous PICO studies, our findings effectively present evidence. BRCA1/2 demonstrates benefits in detecting first-degree relatives FPC involvement with 2.26-10 times higher risk. These mutation findings also play an important role since with the BRCA1/2 targeted therapy, Poly-ADP Ribose Polymerase inhibitors (PARP) may give better outcomes of FPC treatment. Analysis of BRCA1 and BRCA2 administration's impact on odds ratio (OR) based on six and five studies respectively. BRCA1 exhibited non-significant effects (OR = 1.26, P = 0.51), while BRCA2 showed significance (OR = 1.68, P = 0.04). No heterogeneity observed, indicating consistent results. Further research on BRCA1 is warranted. CONCLUSION: Detecting the BRCA1/2 mutation gene offers numerous advantages, particularly in its correlation with FPC. For diagnostic and prognostic purposes, testing is strongly recommended for first-degree relatives, who face a significantly higher risk (2.26-10 times) of being affected. Additionally, FPC patients with identified BRCA1/2 mutations exhibit a more favorable prognosis compared to the non-mutated population. This is attributed to the availability of targeted BRCA1/2 therapy, which maximizes treatment outcomes.

dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe.

The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with high mortality. We show here that depletion of the PIAS2 beta isoform with a transcribed double-stranded RNA-directed RNA interference (PIAS2b-dsRNAi) specifically inhibits growth of ATC cell lines and patient primary cultures in vitro and of orthotopic patient-derived xenografts (oPDX) in vivo. Critically, PIAS2b-dsRNAi does not affect growth of normal or non-anaplastic thyroid tumor cultures (differentiated carcinoma, benign lesions) or cell lines. PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. PIAS2b depletion promotes mitotic catastrophe at prophase. High-throughput proteomics reveals the proteasome (PSMC5) and spindle cytoskeleton (TUBB3) to be direct targets of PIAS2b SUMOylation at mitotic initiation. These results identify PIAS2b-dsRNAi as a promising therapy for ATC and other aggressive anaplastic carcinomas.

Secretory carcinoma of minor salivary glands.

Secretory carcinoma is a malignant salivary gland tumor, which typically presents as an indolent painless mass within the parotid gland. Involvement of the minor gland is reported but less common. Secretory carcinoma was often misclassified as other salivary gland mimics, particularly acinic cell carcinoma, prior to 2010. It was first recognized as a molecularly distinct salivary gland tumor harboring the same fusion gene as well as histologic and cytogenetic features seen in juvenile breast cancer. Secretory carcinoma is generally managed in the same way as other low-grade salivary gland neoplasms and has a favorable prognosis; however, high-grade transformation requiring aggressive therapeutic interventions have been documented. Recent studies of biologic agents targeting products of this fusion gene offer the promise of a novel therapeutic option for treatment of this malignancy. Due to the limited number of reported cases, the spectrum of clinical behavior, best practices for management, and long-term treatment outcomes for secretory carcinoma remain unclear. A long-standing secretory carcinoma involving minor salivary glands of the mucobuccal fold, which was detected years after it was first noted by the patient, is reported. This case brings to light the importance of a thorough clinical exam during dental visits and reviews diagnostic differentiation of this malignancy from other mimics and discusses decision making for its management.

Role of MEK1 and DIAPH3 expression in colorectal adenoma-carcinoma sequence.

BACKGROUND: It is well established that most colorectal carcinomas arise from conventional adenomas through the adenoma-carcinoma sequence (ACS) model. mitogen-activated protein kinases (MAPKs) pathway has been reported as a crucial player in tumorigenesis. The MAPK signaling pathway is activated by different extracellular signals involving the "mitogen-activated/extracellular signal-regulated kinase 1 (MEK1)", and this induces the expression of genes involved in proliferation and cellular transformation. Diaphanous-related formin-3 (DIAPH3) acts as a potential metastasis regulator through inhibiting the cellular transition to amoeboid behavior in different cancer types. OBJECTIVE: The aim of the study was to investigate the pattern of immunohistochemical expression of MEK1 and DIAPH3 in colorectal adenoma (CRA) and corresponding colorectal carcinoma (CRC) specimens. METHODS: The immunohistochemical expression of DIAPH3 and MEK1 was examined in 43 cases of CRC and their associated adenomas using tissue microarray technique. RESULTS: MEK1 was overexpressed in 23 CRC cases (53.5%) and in 20 CRA cases (46.5%). DIAPH3 was overexpressed in 11 CRA cases (about 29%) which were significantly lower than CRC (22 cases; 58%) (P = 0.011). Both MEK1 and DIAPH3 overexpression were significantly correlated in CRC (P = 0.009) and CRA cases (P = 0.002). Tumors with MEK1 overexpression had a significantly higher tumor grade (P = 0.050) and perineural invasion (P = 0.017). CONCLUSIONS: Both MEK1 and DIAPH3 are overexpressed across colorectal ACS with strong correlation between them. This co- expression suggests a possible synergistic effect of MEK1 and DIAPH-3 in colorectal ACS. Further large-scale studies are required to investigate the potential functional aspects of MEK1 and DIAPH3 in ACS and their involvement in tumor initiation and the metastatic process.

Study on carotid artery stenosis after radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: This study investigated carotid artery stenosis (CAS) and associated risk factors in patients with nasopharyngeal carcinoma (NPC) post-radiotherapy. MATERIALS AND METHODS: The observation group comprised 86 reexamined patients with NPC, divided into Group 1 and Group 2 based on post-radiotherapy duration, alongside 34 newly diagnosed patients with NPC (Group 0). Carotid artery ultrasonography and chi-square analysis were performed. RESULTS: Moderate-to-severe vascular abnormalities were exclusively in Group 2. Considering mild vascular abnormalities as the standard, the overall vascular abnormality rates in Group 2 and Group 0 were 65.9% and 41.2%, respectively. In Group 2 and Group 0, the abnormality rates for unilateral carotid artery (UCA), common carotid artery (CCA), internal carotid artery (ICA), and external carotid artery (ECA) were 47.4% and 30.9%, 44.3% and 22.1%, 44.3% and 16.2%, and 39.8% and 5.9%, respectively. Comparing group 1 to group 0, only UCA abnormalities were statistically significant (45.4% vs. 30.9%). Considering moderate-to-severe vascular abnormalities as the standard, Group 2 had higher overall vascular, UCA, CCA, ICA, and ECA abnormality rates compared to Group 0. The age at revisit over 45 years, T stage, and N stage may influence CAS. CONCLUSION: Radiation increasing CAS incidence after 3 years. So, regular examinations are recommended to dynamically monitor CAS after 3 years of radiotherapy.

Developing a nomogram based on SEER database for predicting prognosis in choroid plexus tumors.

Choroid plexus tumors (CPT) are rare and highly vascularized neoplasms that have three histologically confirmed diagnoses, including choroid plexus papilloma, atypical choroid plexus papilloma, and choroid plexus carcinoma (CPC). This study aimed to determine the epidemiology and survival of patients with CPTs and develop a nomogram to quantify the prognosis of the patients with CPT. Data of 808 patients who were diagnosed as CPT between 2000 and 2020 was obtained from the surveillance, epidemiology, and end results database. Descriptive analysis was used to assess the distribution and tumor-related characteristics of the patients with CPT. Independent prognostic factors for patients with CPT were identified by univariate and multivariate Cox regression analysis. The nomogram was established and evaluated by receiver operating characteristic curve, and decision curve analysis (DCA), calibration curves. The independent prognostic factors for patients with CPT are age, tumor size, surgery, chemotherapy, tumor number, pathologies, and race. For the prognostic nomogram, the area under the curve (AUC) of 60-, 120-, and 180-months were 0.855, 0.869 and 0.857 in the training set and 0.836, 0.864 and 0.922 in the test set. The DCA and calibration curve indicated the good performance of the nomogram. Patients with CPTs can be diagnosed at any age. Among the three histopathological tumors, patients with CPC had the worst prognosis. The nomogram was established to predict the prognosis of patients with CPT, which had satisfactory accuracy, and clinical utility may benefit for clinical decision-making.

Multimodal Therapy Approaches for NUT Carcinoma by Dual Combination of Oncolytic Virus Talimogene Laherparepvec with Small Molecule Inhibitors.

NUT (nuclear-protein-in-testis) carcinoma (NC) is a highly aggressive tumor disease. Given that current treatment regimens offer a median survival of six months only, it is likely that this type of tumor requires an extended multimodal treatment approach to improve prognosis. In an earlier case report, we could show that an oncolytic herpes simplex virus (T-VEC) is functional in NC patients. To identify further combination partners for T-VEC, we have investigated the anti-tumoral effects of T-VEC and five different small molecule inhibitors (SMIs) alone and in combination in human NC cell lines. Dual combinations were found to result in higher rates of tumor cell reductions when compared to the respective monotherapy as demonstrated by viability assays and real-time tumor cell growth monitoring. Interestingly, we found that the combination of T-VEC with SMIs resulted in both stronger and earlier reductions in the expression of c-Myc, a main driver of NC cell proliferation, when compared to T-VEC monotherapy. These results indicate the great potential of combinatorial therapies using oncolytic viruses and SMIs to control the highly aggressive behavior of NC cancers and probably will pave the way for innovative multimodal clinical studies in the near future.

Factores de mal pronóstico en 113 pacientes sometidos a duodenopancreatectomía cefálica por colangiocarcinoma distal / Prognostic risk factors in 113 patients undergoing cephalic duodenopancreatectomy for distal cholangiocarcinoma

Introducción El colangiocarcinoma distal es una neoplasia epitelial maligna que afecta a los conductos biliares extrahepáticos, per debajo del conducto cístico. Existe poca evidencia sobre la relación entre factores perioperatorios y peor evolución a largo plazo tras la resección quirúrgica. Objetivo Analizar los factores de riesgo de mortalidad y recidiva a largo plazo del colangiocarcinoma distal de los pacientes resecados. Material y métodos Se ha analizado una base de datos prospectiva unicéntrica de pacientes intervenidos por colangiocarcinoma distal entre los años 1990 y 2021 con la finalidad de investigar los factores de mortalidad y recidiva. Resultados Se han intervenido 113 pacientes, con una supervivencia actuarial media de 100,2 (76-124) meses tras la resección. El estudio bivariante no evidenció diferencias entre los pacientes dependiendo de la edad o variables preoperatorias estudiadas. La presencia de adenopatías afectadas fue un factor de riesgo de mortalidad a largo plazo en el estudio multivariante. La presencia de adenopatías afectadas, la recidiva tumoral y la fístula biliar durante el postoperatorio implicaron peor supervivencia actuarial al comparar las curvas de Kaplan-Meier. Conclusiones La presencia de adenopatías afectadas influyen en el pronóstico de la enfermedad. La aparición de fístula biliar durante el postoperatorio del colangiocarcinoma distal podría agravar los resultados a largo plazo, hallazgo que debe ser reafirmado en futuros estudios. (AU)

Introduction Distal cholangiocarcinoma is a malignant epithelial neoplasia that affects the extrahepatic bile ducts, below the cystic duct. No relevant relationship between perioperative factors and worse long-term outcome has been proved. Objective To analyze the risk factors for mortality and long-term recurrence of distal cholangiocarcinoma in resected patients. Materials and methods A single-center prospective database of patients operated on for distal cholangiocarcinoma between 1990 and 2021 was analyzed in order to investigate mortality and recurrence factors. Results One hundred and thirteen patients have undergone surgery, with mean actuarial survival of 100.2 (76–124) months after resection. The bivariate study did not show differences between patients depending on age or preoperative variables studied. When multivariate analysis was performed, the presence of affected adenopathy was a risk factor for long-term mortality. The presence of affected lymph nodes, tumor recurrence, and biliary fistula during the postoperative period implied worse actuarial survival when comparing the Kaplan–Meier curves. Conclusions The presence of affected lymph nodes influence the prognosis of the disease. The occurrence of biliary fistula during postoperative cholangiocarcinoma distal could aggravate long-term outcomes, a finding that should be reaffirmed in future studies. (AU)

[Application of acellular dermal matrix in prevention of laryngeal stenosis in glottic carcinoma].

Objective:To investigate the effect of acellular dermal matrix in preventing laryngeal stenosis in glottic carcinoma patients. Methods:Fifty-five patients with glottic carcinoma（T2, T3） from February 2018 to December 2022 were divided into experimental group（28 cases） and control group（27 cases） according to their wishes. Acellular dermal matrix was placed in the operation cavity in the experimental group after laryngofission, while control group 12 cases were sutured by pulling the upper and lower edges, 15 cases were repaired with sternohyoid muscle fascia flap. Results:In the experimental group, 1 case had laryngeal stenosis caused by laryngeal mucosa swelling after operation, and extubated successfully after symptomatic treatment. In the control group, 7 cases had laryngeal stenosis after operation, of which 3 cases were caused by granulation tissue hyperplasia in laryngeal cavity, and extubated after symptomatic treatment. 2 cases extubated after operation suffered from progressive dyspnea during radiotherapy, and underwent tracheotomy again, extubation successful after treatment. 2 cases caused by laryngeal mucosa swelling, after symptomatic treatment, one case was successfully extubated, and one case had long-term intubation. The laryngeal stenosis rate of the experimental group was 3.6%（1/28） , which was lower than control group 25.9%（7/27）, and the therapeutic effect of the experimental group was significantly better than control group （χ²=5.526, P=0.019）. Conclusion:Implanting acellular dermal matrix in the operation cavity of glottic carcinoma can reduce the occurrence of laryngeal stenosis and have satisfactory preventive effect on laryngeal stenosis.

Early and late outcomes of congenital biliary dilatation in pediatric patients.

BACKGROUND: This study aimed to reveal the early and late postoperative complications and outcomes after surgery for congenital biliary dilatation (CBD) by reviewing cases over the past 40 years. METHODS: We retrospectively evaluated 59 patients with CBD who underwent radical surgery for complications and outcomes, based on medical records. Early complications were defined as those requiring treatment within 5 years of the initial operation. Late complications were defined as those treated more than 5 years later. RESULTS: The median age at the first surgery was 37 months. Regarding biliary reconstruction, 54 of the 59 patients (91.5%) underwent hepaticojejunostomy. Although three patients underwent cholecystoduodenostomy and one patient underwent hepaticoduodenostomy, all were converted to hepaticojejunostomy after a median of 12.5 years. One patient developed synchronous biliary carcinoma and underwent pancreaticoduodenectomy. Early complications occurred in seven patients with 10 events (surgical site infection, n = 3 bile leakage, n = 3; ileus, n = 3; bile duct obstruction, n = 1 and intussusception, n = 1). Late complications occurred in nine patients with 12 events (ileus, n = 3; anastomotic stricture, n = 3; hepatolithiasis, n = 3; asynchronous biliary carcinoma, n = 2; pancreatolithiasis, n = 1). Two of the three patients with hepatolithiasis underwent hepatectomy refractory to the endoscopic approach. Two patients developed asynchronous biliary carcinoma at 34 and 13 years after last operation; both ultimately died of the carcinoma. Only 35 patients (61.4%) underwent a follow-up examination. A total of 11 female patients (45.8%) eventually married, and all successfully gave birth. CONCLUSION: Although the long-term prognosis is excellent with complete cyst excision and hepaticojejunostomy, we emphasize the importance of long-term follow-up.

[Non-primary solid malignancies of breast in needle core biopsy: a clinicopathological analysis of 23 cases].

Objective: To investigate the accurate diagnosis and differential diagnosis of non-primary solid malignant tumors in breast needle core biopsy. Methods: Twenty-three cases of breast, axilla or neck lymph nodes pathologically diagnosed as non-primary solid malignant tumors were collected at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from January 2013 to March 2023. The differential diagnoses and diagnostic features were analyzed, based on combining clinical data, histology, and expression characteristics of biomarkers. Results: All patients were female, with age ranging from 29 to 75 years (average 56 years). The average time from the diagnosis of primary tumor to the current diagnosis was 21 months (0 to 204 months).The primary sites included the ovary (9 cases), the lung (5 cases), the gastrointestinal tract (4 cases), the pancreas, intrahepatic bile duct, thyroid gland, nasal cavity and forearm skin (1 case each). No carcinoma in situ was found in any of the cases. The morphological differences were significant among the tumors, but similar to the primary tumors. The tumors of neuroendocrine and female reproductive tract had great morphological and immunophenotypic overlaps with breast cancer. Metastatic lung cancer cells showed obvious atypia and tumor giant cells. The morphology and immunophenotype of metastatic serous carcinoma of female reproductive system might resemble invasive micropapillary carcinoma of the breast. Metastatic adenocarcinoma of the gastrointestinal tract often had features of mucous secretion. Metastatic neuroendocrine tumors were bland in appearance and morphologically similar to solid papillary carcinoma of breast, but negative for ER. TRPS1 was mostly negative (18/23) and variably positive in ovarian (4/9) and intrahepatic bile duct (1/1) tumors. Conclusions: The diagnosis of breast needle core biopsy specimen should be combined with clinical history, imaging study, and careful examination of histological features, such as presence of in situ component, morphological similarity between the primary and metastatic tumors, and using appropriate markers to differentiate the primary from metastatic tumors.

Multiple carcinomas in a woman with HIV infection: a case report and literature review.

Non-acquired immunodeficiency syndrome-defining cancers (NADCs) are malignancies in persons living with human immunodeficiency virus (PLWHIV) and are not primarily due to the host's immunodeficiency. There is renewed clinical interest in long-term morbidities in PLWHIV as well as malignancies that occur in this population. We herein describe a 36-year-old woman with a 2-year history of an anal wound and right breast mass. She had been diagnosed with HIV infection prior to the development of these lesions. Clinical and laboratory evaluations led to diagnoses of breast and anal cancers. Chemotherapy and antiretroviral therapy were begun, but the patient discontinued these treatments early and was lost to follow-up. NADCs will continue to be a major clinical issue as the global population ages. This presentation of two NADCs (breast and anal cancers) in a PLWHIV further highlights the burden of multiple malignancies on the depleted health of HIV-infected patients. Early identification and treatment of HIV upon patients' presentation to cancer care sites and screening for NADCs at HIV/AIDS care sites are recommended for improved outcomes.

Peritumor Mucosa in Advanced Laryngeal Carcinoma Exhibits an Aberrant Proangiogenic Signature Distinctive from the Expression Pattern in Adjacent Tumor Tissue.

The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the "classical" borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer-the process of tumor neoangiogenesis.

Inhibition of Proliferation and Induction of Apoptosis in Prostatic Carcinoma DU145 Cells by Polysaccharides from Yunnan Rosa roxburghii Tratt.

OBJECTIVE: This study aimed to investigate methodologies for the extraction and purification of polysaccharides from Rosa roxburghii Tratt fruits and their impact on various cellular processes in prostate cancer DU145 cells, including survival rate, migration, invasion, cell cycle, and apoptosis. RESULTS: Compared to the control group, the polysaccharide exhibited a significant reduction in the viability, migration, and invasion rates of DU145 cells in a time- and dose-dependent manner within the polysaccharide-treated groups. Additionally, it effectively arrested the cell cycle of DU145 cells at the G0/G1 phase by downregulating the expressions of CDK-4, CDK-6, and Cyclin D1. Furthermore, it induced apoptosis by upregulating the expressions of Caspase 3, Caspase 8, Caspase 9, and BAX. METHODS: Polysaccharides were extracted from Rosa roxburghii Tratt sourced from Yunnan, China. Extraction and decolorization methods were optimized using response surface methodology, based on a single-factor experiment. Polysaccharide purification was carried out using DEAE-52 cellulose and Sephadex G-100 column chromatography. The optimal dosage of R. roxburghii Tratt polysaccharide affecting DU145 cells was determined using the CCK-8 assay. Cell migration and invasion were assessed using transwell and scratch assays. Flow cytometry was employed to analyze the effects on the cell cycle and apoptosis. Western blotting and Quantitative real-time PCR were utilized to examine protein and mRNA expressions in DU145 cells, respectively. CONCLUSIONS: Rosa roxburghii Tratt polysaccharides, consisting of D-mannose, L-rhamnose, N-acetyl-D-glucosamine, D-galacturonic acid, D-glucose, D-galactcose, D-xylose, L-arabinose, and L-fucose, possess the ability to hinder DU145 cell proliferation, migration, and invasion while inducing apoptosis through the modulation of relevant protein and gene expressions.

Metformin Loaded Zein Polymeric Nanoparticles to Augment Antitumor Activity against Ehrlich Carcinoma via Activation of AMPK Pathway: D-Optimal Design Optimization, In Vitro Characterization, and In Vivo Study.

Metformin (MET), an antidiabetic drug, is emerging as a promising anticancer agent. This study was initiated to investigate the antitumor effects and potential molecular targets of MET in mice bearing solid Ehrlich carcinoma (SEC) as a model of breast cancer (BC) and to explore the potential of zein nanoparticles (ZNs) as a carrier for improving the anticancer effect of MET. ZNs were fabricated through ethanol injection followed by probe sonication method. The optimum ZN formulation (ZN8) was spherical and contained 5 mg zein and 30 mg sodium deoxycholate with a small particle size and high entrapment efficiency percentage and zeta potential. A stability study showed that ZN8 was stable for up to three months. In vitro release profiles proved the sustained effect of ZN8 compared to the MET solution. Treatment of SEC-bearing mice with ZN8 produced a more pronounced anticancer effect which was mediated by upregulation of P53 and miRNA-543 as well as downregulation of NF-κB and miRNA-191-5p gene expression. Furthermore, ZN8 produced a marked elevation in pAMPK and caspase-3 levels as well as a significant decrease in cyclin D1, COX-2, and PGE2 levels. The acquired findings verified the potency of MET-loaded ZNs as a treatment approach for BC.