Epithelial-to-Mesenchymal Transition-Related Markers in Prostate Cancer: From Bench to Bedside.

Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide, with 288,300 new cases and 34,700 deaths estimated in the United States in 2023. Treatment options for early-stage disease include external beam radiation therapy, brachytherapy, radical prostatectomy, active surveillance, or a combination of these. In advanced cases, androgen-deprivation therapy (ADT) is considered the first-line therapy; however, PCa in most patients eventually progresses to castration-resistant prostate cancer (CRPC) despite ADT. Nonetheless, the transition from androgen-dependent to androgen-independent tumors is not yet fully understood. The physiological processes of epithelial-to-non-epithelial ("mesenchymal") transition (EMT) and mesenchymal-to-epithelial transition (MET) are essential for normal embryonic development; however, they have also been linked to higher tumor grade, metastatic progression, and treatment resistance. Due to this association, EMT and MET have been identified as important targets for novel cancer therapies, including CRPC. Here, we discuss the transcriptional factors and signaling pathways involved in EMT, in addition to the diagnostic and prognostic biomarkers that have been identified in these processes. We also tackle the various studies that have been conducted from bench to bedside and the current landscape of EMT-targeted therapies.

Anti-Cancer Stem-Cell-Targeted Therapies in Prostate Cancer.

Prostate cancer (PCa) is the second-most commonly diagnosed cancer in men around the world. It is treated using a risk stratification approach in accordance with the National Comprehensive Cancer Network (NCCN) in the United States. The main treatment options for early PCa include external beam radiation therapy (EBRT), brachytherapy, radical prostatectomy, active surveillance, or a combination approach. In those with advanced disease, androgen deprivation therapy (ADT) is considered as a first-line therapy. However, the majority of cases eventually progress while receiving ADT, leading to castration-resistant prostate cancer (CRPC). The near inevitable progression to CRPC has spurred the recent development of many novel medical treatments using targeted therapies. In this review, we outline the current landscape of stem-cell-targeted therapies for PCa, summarize their mechanisms of action, and discuss avenues of future development.

Renal Cell Carcinoma Presenting as Syncope due to Saddle Pulmonary Tumor Embolism.

Pulmonary embolism (PE) is defined as the obstruction of the pulmonary artery or one of its branches by a blood clot, tumor, air, or fat emboli originating elsewhere in the body. A saddle PE occurs when the obstruction affects the bifurcation of the main pulmonary artery trunk. We present a case of a 46-year-old man who presented to our hospital due to an episode of syncope. Computed tomography angiography (CTA) of the chest showed extensive PE and abdominal CT scan showed a large 8 cm left renal mass with inferior vena cava (IVC) thrombus. Emergent embolectomy, left total nephrectomy, and IVC tumor removal were performed yielding the diagnosis of clear cell renal cell carcinoma (RCC). Interestingly, our patient did not experience any symptoms related to his RCC until the diagnosis of PE due to syncope, and the asymptomatic tumor was found out to be the possible cause of this PE due to the presence of tumor cells constituting the tumor embolus. It is thus recommended to improve the early screening process for RCC. Besides, clinicians should pay attention to patients presenting with uncharacteristic symptoms of RCC who might present with symptoms of saddle PE.

Clinicopathological analysis of recurrence and progression of low-grade papillary urothelial carcinoma of the urinary bladder: Predicting the outcome.

BACKGROUND: Urothelial carcinoma of the urinary bladder is the most common malignancy of the urinary system. Patients with low grade papillary urothelial carcinoma (LGPUC) usually have a low risk for tumor recurrence and progression; yet a subset of patients develop recurrence or grade/stage progression to high-grade papillary urothelial carcinoma (HGPUC). The clinicopathological and molecular factors that contribute to this progression are yet to be determined. OBJECTIVES: In our study, we aimed to assess the incidence and clinicopathological factors associated with tumor recurrence/progression of LGPUC. METHODS: Using a pathological database of surgical specimens from patients who underwent bladder biopsies and/or transurethral resection of bladder tumors (TURBTs) between August 01, 2011, and July 31, 2021, at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed. RESULTS: Of the total 258 patients included, 157 (60.9 %) had "no recurrence", 85 (32.9 %) had ≥1 "recurrence of LGPUC", and 16 (6.2 %) had "grade progression to HGPUC". The mean follow-up time was 31.5 ± 32 months. Patients with "grade progression" and "recurrence of LGPUC" had larger mean tumor size on initial biopsy and multiple lesions on initial cystoscopy compared to those with "no recurrence." Interestingly, former smokers had 2.5- and 8.5-times higher risk of recurrence of LGPUC and grade progression, respectively. CONCLUSION: Since the majority of our patients did not develop recurrence, we question whether there is tendency to overclassify the papillomas as LGPUC based on the 2004 WHO/ISUP consensus grading classification.

Hemophagocytic Lymphohistiocytosis in the Setting of Therapy-Induced Acute Myeloid Leukemia: An Autopsy Report.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory disorder that occurs due to immunologic dysregulation. HLH can be primary (hereditary) or secondary to infections, autoimmune diseases, immune deficiencies, metabolic diseases, drugs, or malignancies. Lymphoid neoplasms mostly accompany malignancy-associated HLH. We present a case of a 12-year-old boy with a history of precursor B lymphoblastic leukemia (B-ALL), who subsequently developed chemotherapy-induced acute myeloid leukemia (t-AML). The patient was admitted for febrile neutropenia and initial laboratory tests revealed hemophagocytic lymphohistiocytosis (HLH). The hospital course was complicated by multiple infections and septic shock. The patient received several broad-spectrum antimicrobials, dexamethasone, as well as a pericardial drain to drain the hemorrhagic pericardial effusion. Despite intervention, the patient expired, and an autopsy was performed. We provide a synopsis of the main autopsy findings.

Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An alternative way to treat PCa is by repurposing of existing drugs that were initially intended for other conditions. By extrapolating the effects of previously approved drugs to the intracellular processes of PCa, treatment options will expand. In addition, drug repurposing is cost-effective and efficient because it utilizes drugs that have already demonstrated safety and efficacy. This review catalogues the drugs that can be repurposed for PCa in preclinical studies as well as clinical trials.

Magnetic resonance imaging-ultrasound fusion-targeted biopsy combined with systematic 12-core ultrasound-guided biopsy improves the detection of clinically significant prostate cancer: Are we ready to abandon the systematic approach?

BACKGROUND: Multiparametric (mp) magnetic resonance imaging (MRI)-ultrasound fusion-targeted biopsy (TB) has improved the detection of clinically significant prostate cancer (csCaP) using the Prostate Imaging Reporting and Data System (PI-RADS) reporting system, leading some authors to conclude that TB can replace the 12-core systematic biopsy (SB). We compared the diagnostic performance of TB with SB at our institution. METHODS: Eighty-three men with elevated prostate-specific antigen levels (6.6 ng/mL, interquartile range [IQR] 4.5-9.2) and abnormal mp-MRI (127 lesions, PI-RADS ≥3, median size: 1.1 cm, IQR 0.8-1.6) underwent simultaneous TB and SB. Diagnosis of any CaP (Gleason score, [GS] ≥6) and csCaP (GS ≥7) was compared using the McNemar's exact test. RESULTS: SB showed higher, but not statistically significant, detection rates of any CaP and csCaP (51.8% and 34.9%) versus TB (44.6% and 28.9%) (P = 0.286 and P = 0.359, respectively). TB outperformed SB in the quantification of 56.6% CaP and detecting cancer in anterior sectors (7.2%). Compared to SB, TB missed twice the amount of any CaP and csCaP. SB alone detected 22.2% of all csCaPs and upgraded 20.6% of TB-detected CaP. SB identified cancer invisible on mp-MRI (13.7% of all CaP) or missed by TB due to a small size (<1 cm) and sampling error (7% of lesions). CONCLUSION: A combination of SB with TB remained necessary for achieving the highest cancer detection rates. Limiting prostate biopsy to TB alone can miss csCaP due to the presence of synchronous high-grade cancer invisible on MRI or failure to hit the target. TB is the best approach for anterior lesions and tumor quantification.

The lethal twist - a story of unspoken pain: small intestinal volvulus in cerebral palsy.

Small intestinal volvulus (SBV) is the abnormal twisting of bowel around the axis of its mesentery, leading to obstruction and vascular compromise, resulting in bowel ischemia and necrosis which are life-threatening. Risk factors include malformation, malrotation, and adhesions. Its rare incidence and vague clinical presentation make it a difficult diagnosis, more so in a nonverbal patient who cannot express his pain, which is the first and most prominent symptom. Studies suggest an increased frequency of intestinal obstruction in cerebral palsy patients. There are no reported cases of small intestinal volvulus in association with cerebral palsy. We present a case of a 21-year-old man with severe cerebral palsy and kyphoscoliosis. The patient presented to the emergency room with respiratory distress and abdominal distension. An acute abdomen was noted. Abdominal X-rays revealed gas patterns suggestive of small intestinal obstruction. The patient rapidly deteriorated, and resuscitation attempts were unsuccessful. Autopsy revealed peritoneal cavity filled with extensively dilated and thin-walled loops of small intestine. Twisting of the small intestine, showing 360° rotation around the mesenteric root in a clockwise manner at two separate sites, was noted. On bowel dissection, mucosal folds were absent, and mucosa was green with patchy areas of hemorrhage consistent with ischemic necrosis. There was no evidence of any malformation, malrotation or adhesions. Small intestinal volvulus is a rare entity with a nonspecific clinical presentation that poses a diagnostic challenge. This autopsy highlights the need to maintain a high index of suspicion for small intestinal volvulus in cases of bowel obstruction in cerebral palsy patients to expedite surgery and prevent mortality. The primary caregivers of non-verbal cerebral palsy patients living outside of healthcare facilities need to be trained in recognition of life-threatening medical emergencies such as gastrointestinal obstruction and seek emergent attention at the earliest to prevent treatment delays.

Histologic Findings and Cytological Alterations in Thyroid Nodules After Radioactive Iodine Treatment for Graves' Disease: A Diagnostic Dilemma.

Unlike the well-documented relation between radiation to the neck and development of papillary thyroid carcinoma, a causal association between radioactive iodine treatment for Graves' disease and development of thyroid malignancy is less defined. However, patients with a background of thyroid dysfunction presenting with clinically palpable thyroid nodules are followed more closely than the average population, and fine needle aspiration is recommended in such circumstances. Cytological examination of aspirates, and histologic examination of tissue provided from patients with a known history of Graves' disease, managed by radioactive iodine therapy can create a diagnostic dilemma, as the distinction between radiation effect and a malignant primary thyroid neoplasm can be very challenging. Thus, pathologists should be aware of the existence of these changes in the setting of radiation therapy for Graves' disease. Providing pathologists with appropriate clinical history of Graves' disease treated with radioactive iodine is of paramount importance in order to prevent an overdiagnosis of malignancy.

Multifocal Polymorphous Hemangioendothelioma of the Liver: Case Report and Review of Literature.

We report a case of polymorphous hemangioendothelioma, a rare vascular neoplasm, arising in the liver of a 51-year-old woman. Microscopically, this neoplasm is characterized by a polymorphous blend of solid, primitive vascular and angiomatous areas in variable proportions. Polymorphous hemangioendothelioma is considered to be an intermediate-grade vascular neoplasm. In most of the reported cases, its occurrence has been in lymph nodes, but a few cases have been found in extranodal sites such as the mediastinum, spinal cord, and liver. Its classification among other soft tissue neoplasms is still controversial due to an insufficient number of cases to allow prediction of its biologic behavior. The aim of this article is to report a rare case of extranodal hepatic polymorphous hemangioendothelioma primary to the liver and to offer a summary of the reported cases in the literature, with emphasis on the differential diagnosis and diagnostic pitfalls in daily practice.

Giant Fungating Basal Cell Carcinoma of the Scrotum.

We present an unusual case of basal cell carcinoma (BCC) arising from a non-sun-exposed area. The patient was 69-year-old male with an enlarging giant fungating mass protruding from his scrotum for which he did not seek medical treatment until recently. The mass did not involve the scrotum or epididymis and was confirmed on ultrasound. The patient underwent wide surgical excision and was diagnosed with BCC of the scrotum. Scrotal BCC appears to be more aggressive and more likely to metastasize compared with lesions arising from other areas of the body.

Non-grafted Vaginal Depth Augmentation for Transgender Atresia, Our Experience and Survey of Related Procedures.

INTRODUCTION: Neovaginal atresia especially following male-to-female transgender vaginoplasty is a distressing concern. A pelvic space must be re-created. Traditionally, an epithelial or mucosal lining is employed to cover the space. However, in our series of 18 patients, a non-grafted approach has been equally efficacious, as previously described by others. AIM: To follow the outcome of male-to-female transsexuals undergoing secondary depth enhancement without use of graft or flap. METHODS: Patient selection included two operated on elsewhere, one of whom had a lower abdominal skin graft, and the remainder done here using an inverted penile skin flap supplemented by a scrotal graft extension as needed. The time lag from primary to revision surgery varied from 5 months to 23 years, average 3.7 years. The fascial plane of Denonvilliers was reopened and packed for 7 days to facilitate maintenance of a pelvic space. Patients are requested to perform serial self-dilations with a stent set indefinitely to maintain patency and procure additional depth. Immuno-histochemistry staining was performed to demonstrate estrogen receptor (ER) presence in male genital skin. Estrogen cream may be utilized to facilitate wound healing. Main outcome measures were post-operative depth results and Female Sexual Function Index (FSFI) scores. Several attempts were made to contact all patients for completion of a FSFI. Ten out of 18 responded. RESULTS: Following revision of the pelvic space, static depths increased two-fold on average, from 2.4 in. (6.2 cm) to 5.0 in. (12.7 cm). The FSFI domain scores (of desire, arousal, lubrication, orgasm, satisfaction, and pain) were all mid-range or above. Full scale FSFI scores (compilation score) averaged 23.4 (range limits 2-36). Histologic staining showed the presence of ER in genital skin of all genetic males tested regardless of estrogen usage and perceived gender. CONCLUSIONS: Given adequate development of the rectal-vesical space and preservation of that space with self-dilation, epithelialization will ensue providing sexual gratification for patient and partner (as per patient). LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Metastatic melanoma presenting as intussusception in an 80-year-old man: a case report.

Malignant melanoma of the gastrointestinal tract is an uncommon neoplasm that could be primary or metastatic. Small intestine represents the most common site for the metastatic melanoma; however, it could be found anywhere in the gastrointestinal tract. Intussusception is a rare cause of intestinal obstruction in adults compared to children. In 90% of the cases, the underlying cause can be found, and in 65% of the cases, intussusception is caused by the neoplastic process. The majority of the neoplasms are benign, and about 15% are malignant. Metastatic melanoma is one of the most common metastatic malignancies to the gastrointestinal tract; however, the premortem diagnosis is rarely made. Here, we report an uncommon clinical presentation of metastatic melanoma causing intussusception in an 80-year-old man. This diagnosis should be considered in a differential diagnosis in any patient who presents with gastrointestinal symptoms and a history of melanoma.