Search

A 56-year-old woman with cervical pain with a history of ovarian clear cell carcinoma stage IIIC was admitted to a primary care doctor. Ultrasonography revealed a microhyperechoic nodule in the thyroid gland and cervical lymph node enlargement, and fine-needle aspiration was performed. The results showed malignancy, and she was admitted to our hospital. The differential diagnoses included primary thyroid neoplasms and thyroid metastases from ovarian clear cell carcinoma. A needle biopsy of the thyroid gland was performed. Immunohistochemistry revealed that the tumor cells were positive for cytokeratin AE1/AE3, hepatocyte nuclear factor-1-beta and PAX8 and negative for thyroglobulin and thyroid transcription factor-1. Therefore, we diagnosed the patient with thyroid metastasis from ovarian clear cell carcinoma. There were no compressive symptoms at the time of the visit to our hospital, and surgery was considered unnecessary. Systemic treatment for ovarian clear cell carcinoma was continued. Three months later, she died of a stroke due to Trousseau’s syndrome.

Diabetes and obesity prevalence are rising everywhere in the world. The primary chronic diabetes consequences, which are linked to death and disability, are diabetic vascular problems. One important pathogenic trait of diabetic microvascular problems is angiogenesis. Aim of study: This study measured the level of cathepsin V and Vascular Endothelial Growth Factor-A (VEGF-A) among a group of patients with type 2 diabetes mellitus who have poor control and its correlation with each other, obesity and hyperglycemia. Methods: The research study involved 110 patients with type 2 diabetes mellitus and 70 apparently healthy subjects between the ages of 40 and 70. The Roche Cobas Integra 400 Plus was used to calculate the percentage of glycated Hemoglobin (HbA1c) and Fasting Plasma Glucose (FPG) concentration. Cathepsin V and VEGF-A levels in serum were assayed using Enzyme Linked Immunosorbent Assay (ELISA) kit. Weight/height2 was used as a formula to estimate the Body Mass Index (BMI). Results: Compared to the controls, patients with type 2 diabetes mellitus exhibited significantly higher levels of VEGF-A and cathepsin V in their blood (p<0.001). Significant positive correlation was seen between cathepsin V and VEGF-A in patient's individuals. There was a positive correlation between cathepsin V and VEGF-A levels with the duration of the disease (p=0.017). Furthermore, a significant positive correlation was observed between VEGF-A levels and serum glucose levels in patients. It was not observed significant correlation between cathepsin V and VEGF-A with Body Mass Index (BMI) in patient's individuals. Conclusions: Poor controlled diabetes mellitus patients produce more cathepsin V and VEGF-A than normal level which may contribute in excessive angiogenesis and complication of diabetes mellitus. The increased angiogenesis process in type 2 diabetes mellitus is not associated with obesity. To validate the precise mechanisms of cathepsin V action and its potential as a therapeutic target, more study is required. [ABSTRACT FROM AUTHOR]

Purpose: Brachytherapy (BT) has been used for many years for disease control in tumours of the head and neck area (H&N). It is currently performed with high dose rate (HDR) or pulsed dose rate (PDR), but its use has been reduced due to the implementation of new non-invasive external beam radiotherapy techniques such as intensity modulation (IMRT) and volumetric modulated arc therapy (VMAT) and the improvement of surgical techniques. Methods: The Spanish Brachytherapy Group (GEB) has carried out a survey to find out the number of centres in Spain that continue to use BT in H&N and its indications and expectations for the future. Results: The results were presented at the XX GEB Consensus Meeting held on October 21, 2022, in Valencia (Spain) and it was confirmed that, although there are fewer and fewer centres that use BT in H&N, there are still units with extensive experience in this technique that should be positioned as referral centres. Conclusion: It is necessary to carry out continuous work with other specialities involved, such as H&N surgeons, and other radiation oncologists, to improve the training of residents, both oncologists and medical physicists. [ABSTRACT FROM AUTHOR]

Molecular testing in breast cancer gained increasing attention and importance as specific molecular results can tailor not only oncological decisions on systemic adjuvant or neoadjuvant or in metastatic setting, but increasingly serve in diagnostic routine histopathological services to differentiate between morphologically overlapping or ambiguous histological pictures. Diagnostic tools involve in most cases a broad spectrum of immunohistochemical panels, followed by entity-specific in situ hybridization probes and in given cases NGS-based sequencing. Workflow of which methodology is applied and in which order depends on the specific entity resp. on the given differential diagnosis in question. Regarding prognostic/predictive molecular testing, the choice of assay and the workflow are based on clinical algorithms and on the evidence of targeted therapies following the molecular alterations. In this review paper, we aim to address the use of molecular technics in [1] the histological diagnostic setting (such as subtyping of invasive carcinomas/malignant spindle cell tumors and sarcomas and some B3 lesions) and [2] in the context of adjuvant or neoadjuvant or other clinical settings with special focus of targeted therapies. [ABSTRACT FROM AUTHOR]

This review highlights the effect of carcinomas on the results of the examination of autosomal genetic traits for identification and paternity tests when carcinoid tissue is the only source and no other samples are available. In DNA typing or genetic fingerprinting, variable elements are isolated and identified within the base pair sequences that form the DNA. The person’s probable identity can be determined by analysing nucleotide sequences in particular regions of DNA unique to everyone. Genetics plays an increasingly important role in the risk stratification and management of carcinoma patients. The available information from previous studies has indicated that in some incidents, including mass disasters and crimes such as terrorist incidents, biological evidence may not be available at the scene of the accident, except for some unknown human remains found in the form of undefined human tissues. If these tissues have cancerous tumours, it may affect the examination of the genetic traits derived from these samples, thereby resulting in a failure to identify the person. Pathology units, more often, verify the identity of the patients who were diagnosed with cancer in reference to their deceased tumorous relatives. Genetic fingerprinting (GF) is also used in paternity testing when the alleged parent disappeared or died and earlier was diagnosed and treated for cancer.

Objective: To assess the proportion of adequate surgery in head and neck cancers. Study Design: Prospective longitudinal study. Place and Duration of Study: Medical Oncology Department, Jinnah Postgraduate Medical Center, Karachi Pakistan, from Jan to Dec 2020. Methodology: One fifty-nine patients aged over 20-65 years, of either gender with a confirmed diagnosis of squamous cell carcinoma of the Head and neck were included. Surgery was performed upfront in all patients without any preoperative/ induction chemotherapy. Data regarding socio-demographic and histopathology findings were noted. Surgery was labelled as inadequate when the number of resected lymph nodes recovered was less than 36, and the margins of the tumour were

Background & Aims: Although incidence rates of hepatocellular carcinoma (HCC) began to decline in the United States in the past decade, disparities in rates among racial/ethnic groups have persisted. Whether disparities in stage at diagnosis have remained over time, however, is unclear. Methods: National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) program has created a new staging-over-time variable that facilitates the examination of trends in HCC stage. Thus, the proportions of HCCs diagnosed by stage between 1992 and 2019 were examined among non-Hispanic White, non-Hispanic Black (NHB), Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native (AI/AN) individuals. HCC incidence between 1992 and 2019 was also analysed using Joinpoint regression. Results: Between 1992 and 2019, the proportion of stage 1 HCCs increased and the proportion of stage 4 HCCs decreased among non-Hispanic White, NHB, Hispanic, and Asian/Pacific Islander individuals. Among AI/AN persons, the proportion of stage 1 tumours remained stable, and the proportion of stage 4 tumours declined. In the most recent time period, NHB individuals had the lowest proportions of stage 1 HCCs (32%) and the highest proportion of stage 4 HCCs (20%) of any group. Joinpoint analysis found that HCC incidence began to decline by 2013 among all groups except AI/AN individuals, the only group that had an increase in incidence. Conclusions: Despite generally favourable trends in HCC stage and incidence rates, disparities remain. NHB persons continue to have less favourable stages at diagnosis, and incidence rates continue to increase among AI/AN persons. Impact and implications: HCC incidence rates among most United States racial/ethnic groups began to decline in recent years, but whether stage at diagnosis also improved was unclear. As a result, a new SEER stage variable was used to examine stage trends by race/ethnicity. Although the finding of generally favourable trends in stage as well as incidence is encouraging, continuity disparities in both stage and incidence require serious attention.

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGCs) is an extremely rare morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC), exhibiting a characteristic component of reactive osteoclast-like giant cells admixed with neoplastic mononuclear cells. Sommers and Meissner first described it in 1954 as an "unusual carcinoma of the pancreas". Later it acquired many different names. In 2010, the WHO classified these tumors as a variant of PDAC under the heading of "undifferentiated carcinoma with osteoclast-like giant cells". Here we describe the first case of pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) composed of UCOGC and pancreatic neuroendocrine tumor (NET), which occurred in a 78-year-old man with biliary colic and pancreatitis. The mass did not respond to the chemotherapy, and he soon developed liver metastasis from the NET component, and unfortunately, the patient passed away 10 months later. Since UCOGC is extremely rare, and its association with NET has not been reported yet, our case expands the knowledge regarding its unusual presentation and poor prognosis.

Abstract Aims To investigate the efficacy and safety of lenvatinib and idarubicin‐loaded drug‐eluting beads transarterial chemoembolization (IDADEB‐TACE) in primary advanced hepatocellular carcinoma (HCC). Methods This retrospective study included patients with primary advanced HCC who received either lenvatinib monotherapy or lenvatinib plus IDADEB‐TACE as first‐line treatment from September 2019 to September 2020 at three institutes. Overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events were compared. Propensity score‐matching was used to reduce the influence of confounding factors on the outcomes. Results The study reviewed 118 patients who received lenvatinib plus IDADEB‐TACE (LIDA group) and 182 who received lenvatinib alone (LEN group). After propensity score‐matching, 78 pairs of patients remained. Compared to patients in the LEN group, those in the LIDA group had better post‐treatment ORR (57.7% vs. 25.6%, p

Adherens junctions (AJs) are a defining feature of all epithelial cells. They regulate epithelial tissue architecture and integrity, and their dysregulation is a key step in tumor metastasis. AJ remodeling is crucial for cancer progression, and it plays a key role in tumor cell survival, growth, and dissemination. Few studies have examined AJ remodeling in cancer cells consequently, it remains poorly understood and unleveraged in the treatment of metastatic carcinomas. Fascin1 is an actin‐bundling protein that is absent from the normal epithelium but its expression in colon cancer is linked to metastasis and increased mortality. Here, we provide the molecular mechanism of AJ remodeling in colon cancer cells and identify for the first time, fascin1's function in AJ remodeling. We show that in colon cancer cells fascin1 remodels junctional actin and actomyosin contractility which makes AJs less stable but more dynamic. By remodeling AJs fascin1 drives mechanoactivation of WNT/β‐catenin signaling and generates "collective plasticity" which influences the behavior of cells during cell migration. The impact of mechanical inputs on WNT/β‐catenin activation in cancer cells remains poorly understood. Our findings highlight the role of AJ remodeling and mechanosensitive WNT/β‐catenin signaling in the growth and dissemination of colorectal carcinomas. [ABSTRACT FROM AUTHOR]

All-trans retinoic acid is a morphogen during embryogenesis and a teratogen. Cancer is an error of development, and the retinoic acid receptors (RAR) for all-trans retinoic acid play a role in cancer. Expression of the cytosolic aldehyde dehydrogenases, which mediate the last step to the synthesis of all-trans retinoic acid, is deregulated in various human cancers. Inhibiting these enzymes using a variety of agents reduced the proliferation of lung cancer cells, reduced the proliferation and induced apoptosis of ovarian, prostate, squamous, and uterine cancer cells, and sensitised breast, colorectal and ovarian cancer cells to chemotherapeutic agents. RARγ is an oncogene within some cases of AML, cholangiocarcinoma, colorectal cancer, clear cell renal cell carcinoma, hepatocellular carcinoma, pancreatic ductal adenocarcinoma, prostate cancer, and ovarian cancer. Pan-RAR and RARγ antagonist inhibition of the action of RARγ led to necroptosis of human prostate and pediatric brain tumour cancer stem cells. Treatment of hepatocellular carcinoma cells with the flavenoid acacetin, which interferes with the action of RARγ, decreased cell growth and induced apoptosis. Targeting the retinoic acid pathway is promising regarding the development of new drugs to eradicate cancer stem cells. [ABSTRACT FROM AUTHOR]

Fibromatosis-like metaplastic carcinoma (FLMC) is a rare subtype of metaplastic carcinoma of the breast. Diagnosing this entity poses significant challenges, particularly in core biopsies due to limited sampling and overlap with benign spindle cell lesions such as nodular fasciitis and fibromatosis. We present an example of FLMC in an asymptomatic middle-aged woman. As her breast imaging revealed an irregular lobulated mass, a core biopsy was performed which showed benign breast tissue with fibrosis. However, this was discordant with her imaging findings, hence a subsequent vacuum-assisted biopsy was done which revealed low-grade spindle cell proliferation, consistent with FLMC. This report emphasizes the necessity of a triple assessment and highlights the potential pitfalls in diagnosing FLMC, particularly the risk of misinterpretation due to its histological similarities with benign entities. Understanding these challenges will be crucial to avoid diagnostic delays of this rare breast cancer subtype. [ABSTRACT FROM AUTHOR]

Aims: To investigate the efficacy and safety of lenvatinib and idarubicin‐loaded drug‐eluting beads transarterial chemoembolization (IDADEB‐TACE) in primary advanced hepatocellular carcinoma (HCC). Methods: This retrospective study included patients with primary advanced HCC who received either lenvatinib monotherapy or lenvatinib plus IDADEB‐TACE as first‐line treatment from September 2019 to September 2020 at three institutes. Overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events were compared. Propensity score‐matching was used to reduce the influence of confounding factors on the outcomes. Results: The study reviewed 118 patients who received lenvatinib plus IDADEB‐TACE (LIDA group) and 182 who received lenvatinib alone (LEN group). After propensity score‐matching, 78 pairs of patients remained. Compared to patients in the LEN group, those in the LIDA group had better post‐treatment ORR (57.7% vs. 25.6%, p < 0.001, respectively), median OS and TTP (15.7 vs. 11.3 months, hazard ratio [HR] = 0.50, p < 0.001; 8.0 vs. 5.0 months, HR = 0.60, p = 0.003, respectively), 6‐ and 12‐month OS rates (88.5% vs. 71.4%; 67.6% vs. 43.4%, respectively), and progression‐free rates at 6 and 12 months (60.3% vs. 42.3%; 21.1% vs. 10.3%, respectively). Vascular invasion, α‐fetoprotein level, and treatment type were independent OS predictors, and vascular invasion and treatment type were independent TTP predictors. Incidences of nausea/vomiting, fever, abdominal pain, and increased ALT/AST were higher in the LIDA group than in the LEN group. Conclusions: Lenvatinib plus IDADEB‐TACE is well‐tolerated and more effective than lenvatinib monotherapy in patients with advanced HCC. [ABSTRACT FROM AUTHOR]

Objective: To observe hepatic changes induced by Gold Kushta. In our study the histopathological effects of Gold Kushta was seen in livers of Wistar rats. Study Design: Experimental study. Setting: Department of Pathology, Sahiwal Medical College, Sahiwal. Period: 1st July 2019 to 31st Dec 2019. Material & Method: Total of 28 wistar rats of 6 - 8 weeks of age and weighing 200 - 250 grams which were then randomly divided into 4 groups each containing 7 rats. The groups were labelled as G I, II, III and IV. These groups were given preparations of gold in the form of kushta for a period of 8 weeks. The gold kushta was given in the form of pellets. Group I was taken as Control, G II was given single dose kushta 0.15 mg and G III was given double dose kushta 0.3mg on alternate days. Group IV was given a single dose of BSA (bovine serum albumin) 75mg (250mg/kg body wt) at the start of experiment and Gold kushta 0.3 mg on alternate days. Histopathological changes were then seen in lobules, sinusoids, kupffer cells and central veins of livers of wistar rats. Results: The histological examination of liver showed sinusoidal congestion and central vein congestion, apoptosis, necrosis and hydropic degeneration as common features. In addition fatty degeneration, inflammation and kupffer cell hyperplasia were also seen in few cases. These changes were observed in all the above groups except group G I serving as control. More changes were seen in high dose groups and the groups given BSA inj. (Group II, III and IV). Conclusion: Thus, indigenous preparations of gold kushta have detrimental effects over livers of wistar rats and are thus hepatotoxic. [ABSTRACT FROM AUTHOR]

Background: Gastric carcinoma is a major cause of cancer-related morbidity and mortality worldwide. Gastric neoplasms arise from genetic and epigenetic changes in various genes. Present study evaluates the immunoexpression of PTEN, HER2/neu, and Ki-67 in endoscopic gastric carcinoma biopsies and correlates the expression of these proteins with clinicopathological features. Material and Methods: Adequate endoscopic biopsies of 27 cases of gastric carcinoma were evaluated for World Health Organization (WHO) and Lauren's classification subtypes along with HER2/neu, PTEN, and Ki-67 immunoexpression. HER2/neu immunostaining was scored as proposed in the Trastuzumab for gastric cancer (ToGA) trial while PTEN staining and downregulation were assessed using an immunoreactive score. The cut-off for Ki-67 expression was taken as 90th percentile of the values in adjacent non-neoplastic tissue. All statistical analysis was done at 5% level of significance with SPSS v22 statistical software. Results: Tubular adenocarcinoma was the commonest WHO histological subtype and 56% of cases were of intestinal type as per Lauren's classification. 55.6% of cases showed a complete loss of PTEN expression in neoplastic tissue. 17 of the 19 cases with adjacent non-neoplastic tissue showed PTEN downregulation in neoplastic tissue. 81.5% of cases had a high Ki-67 index and HER2/neu overexpression was noted in 36% of cases. All the four cases who died had high Ki-67 proliferation indices; 3 patients had loss of PTEN expression and HER2/neu overexpression. Conclusion: We conclude that these immunomarkers can play important role in the behavior of gastric carcinomas and can be targeted for new therapies.

Abstract Circular RNAs (circRNAs) are classified as noncoding RNAs because they are devoid of a 5’ end cap and a 3’ end poly (A) tail necessary for cap-dependent translation. However, increasing numbers of translated circRNAs identified through high-throughput RNA sequencing overlapping with polysome profiling indicate that this rule is being broken. CircRNAs can be translated in cap-independent mechanism, including IRES (internal ribosome entry site)-initiated pattern, MIRES (m6A internal ribosome entry site) -initiated patterns, and rolling translation mechanism (RCA). CircRNA-encoded proteins harbour diverse functions similar to or different from host proteins. In addition, they are linked to the modulation of human disease including carcinomas and noncarcinomas. CircRNA-related translatomics and proteomics have attracted increasing attention. This review discusses the progress and exclusive characteristics of circRNA translation and highlights the latest mechanisms and regulation of circRNA translatomics. Furthermore, we summarize the extensive functions and mechanisms of circRNA-derived proteins in human diseases, which contribute to a better understanding of intricate noncanonical circRNA translatomics and proteomics and their therapeutic potential in human diseases.

Breast cancer is the second most frequent neoplasm in the Cuban woman. Image techniques play a fundamental role for the diagnosis, staging and monitoring of the disease. This work had the objective of: Implement the Clinical Protocol for the scintimammography with 99mTc-MIBI for the detection of palpable tumor lesions in dense breasts, difficult mammographic assessment and suspected axillary metastatic lymph nodes employing a craft device of prone decubitus positioning. 35 patients were included with an average age of 51 years, who attended the central consultation of breast pathology at Dr. Salvador Allende Hospital. It was designed and constructed an artisanal device that made it possible to carry out the studies from an anatomical position pendant or pendulum of the breast, demonstrating its usefulness in the medical assessment of the scintimammography images. Of the studies carried out 17.1 % was positive for malignant mammary neoplastic tissue, with a specificity of 100 %. The number of unnecessary biopsies by false positive mammograms or inconclusive in lesions greater than 10 mm in diameter was decreased by 82.9 %. The clinical protocol was implemented for the scintimammography with 99mTc-MIBI for the detection of palpable tumor lesions in dense breasts, difficult mammographic assessment and suspected axillary metastatic lymph nodes employing a craft device of prone decubitus positioning. It proved to be a simple, reproducible and non-invasive test, which can facilitate and improve the diagnosis of breast cancer. [ABSTRACT FROM AUTHOR]

Carcinomas are characterized by a widespread upregulation of intercellular junctions that create a barrier to immune response and drug therapy. Desmoglein 2 (DSG2) represents such a junction protein and serves as one adenovirus receptor. Importantly, the interaction between human adenovirus type 3 (Ad3) and DSG2 leads to the shedding of the binding domain followed by a decrease in the junction protein expression and transient tight junction opening. Junction opener 4 (JO-4), a small recombinant protein derived from the Ad3 fiber knob, was previously developed with a higher affinity to DSG2. JO-4 protein has been proven to enhance the effects of antibody therapy and chemotherapy and is now considered for clinical trials. However, the effect of the JO4 mutation in the context of a virus remains insufficiently studied. Therefore, we introduced the JO4 mutation to various adenoviral vectors to explore their infection properties. In the current experimental settings and investigated cell lines, the JO4-containing vectors showed no enhanced transduction compared with their parental vectors in DSG2-high cell lines. Moreover, in DSG2-low cell lines, the JO4 vectors presented a rather weakened effect. Interestingly, DSG2-negative cell line MIA PaCa-2 even showed resistance to JO4 vector infection, possibly due to the negative effect of JO4 mutation on the usage of another Ad3 receptor: CD46. Together, our observations suggest that the JO4 vectors may have an advantage to prevent CD46-mediated sequestration, thereby achieving DSG2-specific transduction. [ABSTRACT FROM AUTHOR]

The heterogeneous population of macrophages in the spleen perform a variety of important functions. Studies of spleen macrophages have mostly been carried out in experimental models. Much remains unexplored. This review summarizes data on the characteristics of macrophages in different functional areas of the spleen in human beings and animals. The role of spleen macrophages in the utilization of senescent erythrocytes, iron metabolism, immunogenesis, immunosuppression, elimination of cells in the state of apoptosis, phagocytosis of hematogenous spread pathogens and the participation of tuftsin in this process, as well as the spleen role as a reservoir of monocytes involved in inflammation and regeneration are discussed. It was attempted to find data on the possible role of spleen macrophages in the rare occurrence of metastatic lesions in this organ. Some important but poorly studied functional aspects of human and animal spleen macrophages are discussed. [ABSTRACT FROM AUTHOR]