carcinoma

Brain metastases in any gynecological cancer are a rare occurrence. Even more so, it is extremely rare for a gynecological malignancy to manifest itself with symptoms indicative of cerebral involvement. Literature regarding the association between MS and cancer is conflicting. We herein report a rare presentation of single metastasis of endometrial carcinoma in a 59-year-old woman affected by Primary Progressive Multiple Sclerosis (PPMS). A head CT scan was performed, which revealed the presence of an expansive lesion in the left parietal region. After careful assessment, a high-grade endometrial carcinoma was diagnosed and a decision was made to remove both the primary lesion and the brain metastasis in one sitting, through a conjoined surgery session involving neurosurgeons and gynecologists. The postoperative course was free from complications up until a few days after being transferred to a rehabilitation center, where she died following respiratory complications.

Introduction: Cardiac tamponade is an emergency syndrome that requires fast diagnosis and treatment; otherwise patient follows obstructive shock and cardiac arrest. Case report: A 70-year-old female was brought to the emergency department with hypoxemia. She had a history of progressive dyspnea over the past three weeks. Past medical history includes smoking. On physical examination: tachypnea, hypoxemia (SaO2 89%), jugular venous distention, arterial pressure 220/100 mmHg, heart rate rhythmic of 82 bpm. On pulmonary auscultation: diffuse and bilateral crackles. Lung ultrasound showed a bilateral B line and the echocardiogram demonstrated a pericardial effusion with signs of tamponade. A pericardiocentesis evacuated 620 ml of hemorrhagic fluid and the patient was transferred to the intensive care unit, hemodynamically stable, with SaO2 95%. At the ICU the echocardiogram, showed resolution of the cardiac tamponade and a tumor adhered to the lateral wall of the left ventricle. Chest CT demonstrated: a left lung tumor, infiltrating the pericardial sac. A pericardium biopsy demonstrated undifferentiated carcinoma. Discussion: Cardiac tamponade diagnosis requires a high level of suspicion. Respiratory failure, chest pain, and shock, observed in cardiac tamponade, are also present in different diseases. The most common finding of cardiac tamponade is dyspnea (78% of cases). Our patient had dyspnea due to pulmonary edema, secondary to left ventricle diastolic dysfunction caused by the tamponade. A bedside echocardiogram made the diagnosis of cardiac tamponade and guided the effective pericardiocentesis. Conclusion: Cardiac tamponade must be suspected in all cases of acute dyspnea. Echocardiogram is the method of choice for the diagnosis and for guiding the pericardiocentesis.

As the introduction of immune checkpoint inhibitors in the treatment of various cancers is now proven to be already acquired knowledge, so does a new challenge arise for clinicians; the understanding, diagnosis, and management of the rarest adverse effects of immunotherapy. We present a case of type-1 diabetes Mellitus (T1DM) in a patient with non-small cell lung carcinoma (NSCLC) treated with pembrolizumab. Following ten cycles of treatment, our patient was diagnosed with T1DM after being admitted for diabetic ketoacidosis and stayed hospitalized in the ICU. Later, they continued treatment with insulin, having shown disease response to pembrolizumab, and resumed immunotherapy while on insulin. Immunotherapy-induced T1DM can sometimes occur with PD1/PD-L1 blockage therapies. It has a rapid onset, is characterized by insulin deficiency due to the autoimmune destruction of beta-cells, and usually presents itself with diabetic ketoacidosis. Unlike most of the other adverse effects of immunotherapy, glucocorticoids don’t seem to be of therapeutic value, and insulin substitution is required. Regular glucose monitoring can be key to early diagnosis and prevention of hospitalization. 

Objective: To explore the pathologic response rate to primary progesterone treatment in patients with Endometrial Intraepithelial Neoplasia (EIN) and early-stage endometrioid-type Endometrial Adenocarcinoma (EAC).Methods: Retrospective chart data were collected for patients with either EIN or EAC receiving primary progesterone treatment between 2015 and 2022. The presence of complete or partial response, time to response, and other demographic and treatment factors were recorded to determine independent predictors of response to progestin treatment.Results: In total, 112 women who were diagnosed with EIN or EAC were treated with upfront progestin therapy, of whom 79 had sufficient follow-up to assess response. Fifty patients (63%) responded, of whom 10 (20%) ultimately relapsed. Response was more robust among patients with EIN (79%, n = 33) compared with patients who had cancer (46%, n = 17). The median time to respond was 5.8 months overall. Diagnosis of EIN, younger age at diagnosis, and any pathologic evidence of progesterone effect were all predictors of treatment response. Younger patients had a significantly shorter time to partial or complete response with a median time to response of 5.9 months in patients ≤ 45 and 13.8 months in patients > 45. Conclusion: Our study demonstrated a lower overall response rate (63%) than reported in previous studies, especially for patients with cancer (46%). Younger patients had a significantly shorter time to respond than older patients. Pathologic progesterone effect observed at any time during treatment was a significant predictor of treatment response regardless of diagnosis and could serve as an early predictor of response to therapy.

Scientific interest in low-molecular-weight pectins is not accidental. Despite the experimental material widely presented in the literature on the pharmacological effects of pectins, the clinical application of the developments has not yet been fully implemented. On the one hand, antitumor potential is registered in polymers with a mass of hundreds of kilodaltons, on the other hand, practically nothing is known about such in pectin derivatives weighing less than 20 kDa. In addition, the issues of assessing the nature of the pharmacological interaction of nanoscale pectin and conventional cytostatics are not covered. The aim of this work is an experimental study of the antitumor potential of low-molecular, low-esterified pectin in combination with a cytostatic agent on a model of Walker’s carcinosarcoma. Pectin therapy of Walker’s transplanted tumor in several series of experiments consistently caused inhibition of its growth from 60% to 80%. The combined use of pectin and cyclophosphane caused inhibition of tumor growth up to 72.4%. The increase in life expectancy in the “pectin + cyclophosphane” group versus the “cyclophosphane” group was 200%. It can be concluded that nanoscale pectin is a promising drug for in-depth study since it meets the criteria of primary screening (increase in animal life expectancy, inhibition of tumor growth, survival without tumor growth).

Background: CPTs are rare intraventricular papillary neoplasms derived from the choroid plexus epithelium. Anti-collagenase and extracellular matrix which have not been expressed in brain tumors. Objective: The purpose of this study was to investigate the expression levels of collagen type VI, anti-collagenase, laminin, MM9, claudins 1 and 5, N and E cadherins, and collagen VII, tejido, and collagen degradation enzyme complexes in choroid plexus tumors.Materials and methods: We studied the expression of adhesion molecules, extracellular matrix, and anticollagenase with an immunohistochemistry approach and electron microscopy analysis in 42 choroid plexus tumors. Results: 28(67%) were choroid plexus papillomas, 8 (19%) were atypical choroid plexus papillomas and 6 (14%) were choroid plexus carcinomas. The Ki67-li and MVD increased from CPC to ACPP, being the highest in malignant tumors as well as a strong immunoexpression of anti-collagenase and were inverse correlation with claudin 5, E, and N cadherin and collagen IV immunoexpressions which added further significant information to the prognosis and varied according to the histologic classification. By ultrastructure, the loss of basal membrane and cilia, disorganization, and proliferation of ECM were observed in CPC. Cerebral homeostasis largely results from the ability of both the Blood–Brain Barrier (BBB) at the brain microvascular endothelium and the Blood–Cerebrospinal Fluid Barrier (BCSFB) at the epithelium of the Choroid Plexuses (CPs), to control the composition of the CSF and cerebral extracellular fluid. Under expression of the tight junction proteins occludin, claudin-1 and claudin-5 are key molecular abnormalities responsible for the increased permeability of tumor endothelial tight junctions. Conclusion: The loss of basement membrane and ECM overexpression could be considered as a poor prognosis predictor in CPT. Anti-collagenase and MMP9 overexpression could be related to basal membrane and BBB plasticity in CPTs.

Background: Tuberculosis (TB) is a significant global health problem, and extrapulmonary TB can present with no specific clinical or radiographic findings. Genito-urinary TB is often associated with elevated tumor markers and can be misdiagnosed as ovarian/fallopian tube carcinomas, especially in elderly female patients, as genitourinary TB commonly affects women of reproductive age.Objective: We present a rare case of genito-urinary TB in an elderly female patient who was initially misdiagnosed with ovarian cancer with metastasis.Case presentation: An 83-year-old woman with a medical history of diabetes and hypertension presented with complaints of abdominal distension. Diagnostic imaging revealed lesions in the ovaries and omentum and tumor markers were elevated, leading to a suspicion of ovarian cancer with metastases to the omentum. The patient underwent a diagnostic laparotomy and surgical removal of ovaries, fallopian tubes, and the lesion of the greater omentum. However, no malignancy was found during the morphological evaluation. Further histopathological examination confirmed the final diagnosis of genito-urinary tuberculosis, and the patient received anti-TB drugs. The postoperative period was uneventful, and tumor marker levels decreased.Conclusion: As the clinical presentation of genito-urinary TB can mimic ovarian cancer, a histopathological examination should be performed for differential diagnosis, thereby reducing the possibility of inaccurate treatment. This case report highlights the importance of considering genito-urinary TB as a differential diagnosis in elderly female patients presenting with elevated tumor markers, abdominal distension, and suspected genital malignancy. It is crucial to carefully evaluate these cases and explore the possibility of genital TB as an alternative diagnosis, given the overlapping clinical presentation. This highlights the importance of a comprehensive diagnostic approach that includes considering TB in addition to malignancy, even in the context of elderly female patients.

Two female patients in their fifties with a previous history of cutaneous malignant melanoma were found during follow-up to have a 'hot' lesion in the gallbladder on a Positron Emission Tomography scan. Imaging showed a gallbladder polyp. Histology revealed infiltration of the polyp mucosa by metastatic malignant melanoma. One case had a BRAF mutation. A male in his 70s was found on a staging computed tomography scan to have a suspicious intraluminal lesion in the gallbladder and thickening of the sigmoid colon. Subsequent histology confirmed metastatic malignant melanoma in the chest wall and to the gallbladder and adenocarcinoma in the colon. Molecular testing showed BRAF mutation. The metachronous adenocarcinoma in the colon was mismatch repair protein proficient and had no KRAS mutation. Histology from all cases showed that metastatic malignant melanoma to the gallbladder is superficial.Discussion: Reports from autopsy examinations revealed that metastasis from malignant melanoma to the gallbladder can be up to 15% - 20%. Most patients have mild symptoms or are asymptomatic which explains the paucity of cases reported in living patients within the published literature. Most of the previous reports showed the metastatic malignant melanoma to the gallbladder presented macroscopically as a polyploidal lesion. Conclusion: Our histological observation and previous reports showed that metastatic malignant melanoma in the gallbladder tends to be superficial. All our cases show no lymphatic or vascular invasion in the histological examination as previously published reports, however, the hematological spread is the most commonly suggested mechanism of spread.

Objective: To investigate the value of machine learning and traditional Cox regression models in predicting postoperative survivorship in patients with adenocarcinoma of the esophagogastric junction (AEG).Methods: This study analyzed clinicopathological data from 203 patients. The Cox proportional risk model and four machine learning models were constructed and internally validated. ROC curves, calibration curves, and clinical decision curves (DCA) were generated. Model performance was assessed using the area under the curve (AUC), while calibration curves determined the fit and clinical significance of the model.Results: The AUC values of the 3-year survival in the validation set for the Cox regression model, extreme gradient boosting, random forest, support vector machine, and multilayer perceptron were 0.870, 0.901, 0.791, 0.832, and 0.725, respectively. The AUC values of 5-year survival in the validation set for each model were 0.915, 0.916, 0.758, 0.905, and 0.737, respectively. The internal validation AUC values for the four machine learning models, extreme gradient boosting, random forest, support vector machine, and multilayer perceptron, were 0.818, 0.772, 0.804, and 0.745, respectively.Conclusion: Compared with Cox regression models, machine learning models do not need to satisfy the assumption of equal proportionality or linear regression models, can include more influencing variables, and have good prediction performance for 3-year and 5-year survival rates of AEG patients, among which, XGBoost models are the most stable and have significantly better prediction performance than other machine learning methods and are practical and reliable.

Oral Cancer (OC) or squamous cell carcinoma of the oral cavity accounts for approximately 3% of all cancers worldwide, with increased incidence in developing countries. The use of tobacco is directly associated with approximately 80% of oral cancers, especially in older men over 40 years of age. As nearly one-third of the Indian population over 15 years consume smokeless tobacco in one or the other forms, a recent increase has been observed in OC incidence among women and young adults. Lately, the sexual behaviors of young & homosexuals have resulted in the emergence of oropharyngeal cancers due to infection with HPV 16. About 60% of oral cancer cases in India have a five-year survival rate, and this can be improved to 70% to 90% by mere early detection in stages I and II and with various treatment modalities. Despite the well-known benefits of oral cancer screening for the whole population in developing countries remains controversial. It is imperative to address the cultural barriers and societal norms, which limit the acceptability and participation in screening programs in India and many developing countries. This unique challenge of increasing OC morbidity in India and developing countries requires horizontal integration of the health systems with new services focused on cancer control, which gives the best chance for long-term survival, improved outcomes, and affordable care!This article is based on the author’s experience of overseeing 1 case of early detection and 2 cases of delayed diagnosis, outcomes and relevant literature review, and current guidelines for the management of OC.

Background: Endometrial morular metaplasia, a clinical conundrum from a diagnostic and management angle given its rarity and low oncogenic potential, has been linked to endometrial hyperplasia and carcinoma. Case report: A 77-year-old woman with no significant past medical history, was found to have an asymptomatic thickened endometrium on pelvic imaging, after presenting with lower abdominal pain, 3yrs ago. Diagnostic hysteroscopy identified an endometrial polyp within a pyometra. Histopathology showed focal complex endometrial hyperplasia without atypia with superimposed morular metaplasia(EMM) with a negative microbiology assay.Following conservative management with multidisciplinary team(MDT) overview, as-per patient choice with 6-monthly follow-up hysteroscopy, endometrial biopsies and a short use of the Mirena® Intrauterine system (discontinued following poor tolerance), histopathology shows resolved hyperplasia with persistent EMM. Due to persistent disease, a hysterectomy is under consideration.Discussion: Current evidence suggests that a sub-type of EMM, a likely histological manifestation of beta-catenin (CTNNB1) gene mutation: could be a precursor of endometrial hyperplasia and low-grade endometrioid-endometrial carcinoma sub-type. Though low-grade in nature, the increased recurrence risk raises significant concerns.Prognostication following gene mutation identification can help with management options which include conservative, hormonal therapy with adjunct repeat endometrial sampling: or hysterectomy. The optimal frequency of endometrial sampling when uterine-sparing, is unclear, leading to a management conundrum, whilst persistent disease may require a hysterectomy.Conclusion: Management of endometrial morular metaplasia can be difficult but must reflect the woman’s choice with a MDT-overview. Immuno-histochemical tools utilizing new molecular biological advances, can simplify the diagnostic and prognostication processes, aiding clinical management.

Aim: This study examines the pathological outcomes of chronic liver injuries, with a focus on liver fibrosis. It emphasizes understanding the structural changes within the liver that may lead to cirrhosis and functional impairments, crucial for developing targeted antifibrotic therapies.Methods: Our approach reviews existing literature detailing the use of traditional diagnostic methods—biochemical and serological tests alongside liver biopsies. Additionally, we evaluate the reliability and efficacy of non-invasive techniques such as serological test panels and imaging examinations. These methods are compared to understand their viability as supplementary or alternative diagnostic tools to liver biopsy.Significance: Liver fibrosis, if unmanaged, can progress to severe conditions such as cirrhosis and hepatocellular carcinoma, making it vital to understand its progression and treatment options. This study underscores the need for precise and non-invasive diagnostic tools in the clinical management of liver fibrosis, providing insight into the progression of chronic liver diseases and potential therapeutic targets.Conclusion and future perspectives: The research confirms that while liver biopsy remains the definitive method for staging liver fibrosis, its risks and limitations necessitate the use of enhanced non-invasive diagnostic techniques. These methods have shown promising results in accuracy and are critical for broadening clinical applications and patient safety.It is recommended that the scientific community continue to develop and validate non-invasive diagnostic tools. Enhancing the accuracy and reliability of these tools can provide a cost-effective, accessible, and safer alternative for large-scale screening and management of liver fibrosis in asymptomatic populations. Additionally, integrating advancements in radiologic and serological markers can further refine these diagnostic methods, improving overall patient outcomes.

We report a rare case of 62-year-old South Asian women who visited the Molecular Pathology and Genomics Department for hereditary germline cancer genetic testing after being diagnosed with oesophageal cancer, reported as invasive keratinizing squamous cell carcinoma metastasized to the lymph nodes. Her personal history revealed that she was diagnosed with triple-negative breast cancer five years before oesophageal cancer. Germline cancer testing showed pathogenic variants in BRCA1 gene c.68_69delAG, which proved it a hereditary breast and ovarian cancer syndrome. She was started on PARP inhibitors but developed some secondary respiratory failure and succumbed to death. Less than 10 cases have been reported in the literature of the association of germline BRCA1 and Squamous cell Carcinoma – the esophagus. The article focuses on the probable pathogenesis of BRCA1 mutation with non-classic malignancies and the response of Poly adenosine diphosphate ribose polymerase inhibitors (PARP) inhibitors in such a scenario. We report an unusual manifestation of the BRCA1 gene with second primary oesophageal squamous cell cancer occurring five years later to triple-negative breast cancer.

The spleen plays a pivotal role in our immune system by facilitating the proliferation and differentiation of lymphocytes and monocytes. Typically located in the left upper quadrant retroperitoneally, splenic tissue found outside of its usual position is termed ectopic spleen. When the tissue maintains its histological architecture and encapsulation and receives blood supply from splanchnic vessels, it is called an accessory spleen. Although it commonly presents near the splenic hilum or pancreatic tail, rare instances have been reported in the gastric, liver, gastrosplenic/lienorenal ligaments, as well as thoracic and gonadal regions. However, the case of an accessory spleen, mimicking a hepatic lesion in the right diaphragm represents a novel observation.

Cholangiocarcinoma (CCA), a rare malignancy originating from bile duct epithelial cells, often presents a challenging prognosis due to its rarity, delayed diagnosis, and early recurrence post-curative-intent treatments. Additional complexities include difficulties in achieving R0 resection during surgical intervention and the lack of effective second-line treatments following the failure of first-line regimens, particularly in unresectable advanced cases.In this case study, we demonstrate a durable response to a combination regimen of pembrolizumab and lenvatinib in a patient with distal CCA. Despite the regimen’s interim median Progression-Free Survival (PFS) of 6.1 months (95% CI, 2.1-6.4), our patient achieved a clinical and radiological PFS of approximately two years. The underlying mechanisms, potentially involving the upregulation of immune response pathways through undisclosed means or influenced by lenvatinib’s activation of T cells, might augment the sensitivity to PD-1 antibodies like pembrolizumab, contributing to the patient’s sustained response over two years.This case also highlights the significance of the patient’s initial good health condition, multidisciplinary care, and the potential impact of molecular subtyping on treatment selection in a patient with distal CCA who underwent numerous diagnostic procedures, intricate surgical interventions, and subsequent treatment regimens over seven years. Additionally, we underscore significant landmark trials and emerging combination therapies, including chemotherapies, immunotherapy, and targeted treatments in this report.

The presence of heavy metals (HMs) on Earth is essential to all forms of life. These metals are essential for plant and animal development but can have numerous negative effects on the living environment. In this review, we looked at where HMs come from, why they are harmful, and how they affect plants. Articles indexed in Google Scholar, PubMed, Research Gate, Science Direct, and a few books on heavy metals were consulted for this study. Heavy metals are essential for plant development and growth. According to this analysis, the hazardous effects of HMs are on the rise all throughout the globe, and this trend may be attributed mostly to human activity. Because of its impact on agricultural productivity and environmental changes, soil pollution caused by HMs is among the most crucial elements. Plants have evolved very sophisticated defense systems to deal with these environmental challenges. The threat that HM stress poses to plants has attracted a lot of attention worldwide because it could stunt agriculture’s long-term expansion. In spite of their importance for plants, this study found that HMs pose a significant threat to plant life. The novelty of this review lies in its detailed examination of both the beneficial and detrimental roles of HMs, providing a balanced perspective often overlooked in current literature. The significance of this work is underscored by its potential to inform sustainable agricultural practices and environmental management strategies, as it highlights the delicate balance required to harness the benefits of HMs while mitigating their risks. Despite their necessity for plant development, this review underscores the significant risks HMs pose to plant health and ecosystems.Less than 10 cases have been reported in the literature of the association of germline BRCA1 and Squamous cell Carcinoma – the esophagus. The article focuses on the probable pathogenesis of BRCA1 mutation with non-classic malignancies and the response of Poly adenosine diphosphate ribose polymerase inhibitors (PARP) inhibitors in such a scenario. We report an unusual manifestation of the BRCA1 gene with second primary oesophageal squamous cell cancer occurring five years later to triple-negative breast cancer.

The World Drug Report highlights that the prevalence of hepatitis C virus (HCV) is one of the leading causes of cirrhosis and hepatocellular carcinoma globally. This report estimates that HCV is responsible for the annual death of around 700,000 people due to liver disease and is associated with high levels of morbidity and mortality with high health and socio-economic costs. This exploratory study aims to evaluate the socio-economic return provided by HCV treatment of individuals integrated into the MOP developed by the NGO Ares do Pinhal in Portugal. Using the SROI (Social Return on Investment) methodology is estimated that for every euro invested in this program, the return for society is 3,75€. This is a significantly positive SROI value, highlighting the importance of this investment in the creation of monetized value for society, as well as to provide greater well-being to those who need it and to society as a whole.

Verrucous carcinoma is a rare, slow-growing squamous cell carcinoma that can occur in acral regions, including the plantar surface, being named carcinoma cuniculatum. The tumor presents as a well-demarcated, exudative lesion, resembling benign conditions like warts or infections. In this case, a verrucous lesion on the left plantar surface initially appeared to be non-malignant, with multiple incisional biopsies showing only inflammation. A final excisional biopsy of a large part of it confirmed the initial suspicion of malignancy, prompting complete excision and appropriate management. This case underscores the importance of performing wide and deep biopsies for early diagnosis and timely treatment of a suspected verrucous carcinoma.

Epithelioid angiomyolipomas (AML) are uncommon mesenchymal neoplasms, belonging to the group of perivascular epithelioid cell neoplasms (PECOMA). Hepatic PECOMA is even rarer. It’s difficult to diagnose in preoperative by imaging, especially when the fatty component is scant or absent. The gold standard for the diagnosis is histologic examination coupled with an immunohistochemical study. Positive HMB45 immunostaining of the myoid cells is a major diagnostic feature. Herein, we report a particular case of hepatic angiomyolipoma in a middle-aged woman with no significant medical past history. The preoperative diagnosis was difficult given the absence of specific clinical manifestations, even the radiologists considered high suspicion of hepatocellular carcinoma. The final diagnosis has been made by post-operative histology coupled with an immunohistochemistry study.

Bartholinitis, or Bartholin's gland abscess, is a relatively common gynecological condition among women of reproductive age. Its annual incidence is estimated at approximately 0.5 per 1,000 women, which corresponds to a lifetime cumulative risk of about 2%. The condition primarily affects patients between 20 and 50 years old, with a peak frequency observed between 35 and 50 years.After menopause, due to the natural involution of the gland, Bartholin's cysts and abscesses become less frequent, although they can still occur. Moreover, in women over 50, the appearance of a new mass in the gland region should prompt caution, as it may, in rare cases, indicate a carcinoma of the Bartholin's gland or an adjacent vulvar cancer. Therefore, for patients over 40 presenting with a newly emerged cyst or abscess, clinical guidelines recommend performing a biopsy or excision to rule out malignancy. We present the case of a 50-year-old woman with no significant medical history, who was urgently referred to the gynecological emergency department due to confusion, unexplained fever of 40 °C, and resistant leucorrhoea following a week of corticosteroid antibiotic therapy. Clinical examination revealed a large, tender right vulvar mass, indicative of an acute Bartholin's abscess. The patient exhibited signs of septic shock and was admitted to the ICU. Following a diagnosis of sepsis, broad-spectrum antibiotic therapy was initiated, alongside fluid resuscitation and norepinephrine support. Surgical drainage of the abscess confirmed the presence of E. coli. The patient's condition improved rapidly, and she was discharged on postoperative day 8 with no complications. This case underscores that while Bartholin's abscess is typically benign, severe complications, including septic shock, can occur—especially in patients over 50. The appearance of a new Bartholin's region mass in older women should prompt consideration of malignancy, necessitating biopsy or excision. Recent studies compare various therapeutic approaches including simple incision and drainage, Word catheter placement, marsupialization, silver nitrate application, and complete gland excision. Each method has its advantages and drawbacks, with marsupialization offering lower recurrence rates and higher patient satisfaction in many instances.