J. Lee

Sertoli cells, the supportive cells in the seminiferous epithelium, orchestrate spermatogenesis by providing structural and nutritional support to germ cells. In the rat, physiological apoptosis occurs continuously to limit the size of the germ cell population to numbers that can be adequately supported. This form of germ cell death is exaggerated after testicular insults such as toxicant treatment, radiation, and heat exposure. The Fas system has been proposed as a key regulator of the activation of germ cell apoptosis. According to this model, Fas ligand (FasL) and Fas, expressed by Sertoli cells and germ cells, respectively, respond to environmental conditions and initiate germ cell death. To assess the role of the Fas system in various testicular injury models, a semiquantitative RT-PCR technique was used to evaluate the expression kinetics of both FasL and Fas after induction of massive germ cell death. Radiation exposure, which targets actively dividing germ cells, produced an up-regulation of Fas gene expression, but not FasL gene expression. However, administration of mono-(2-ethylhexyl)phthalate and 2,5-hexanedione, two widely studied Sertoli cell toxicants, resulted in up-regulated expression of both FasL and Fas. These data support the following hypotheses: 1) up-regulation of Fas is a common and critical step for initiating germ cell death in vivo; and 2) if Sertoli cells are injured, Sertoli cells up-regulate FasL to eliminate Fas-positive germ cells, which cannot be supported adequately.

Introduction: The differential for esophageal dysphagia is broad and includes anatomic obstruction from stricture or malignancy, motility disorders, and inflammatory conditions such as eosinophilic esophagitis. The approach to the diagnostic evaluation of dysphagia is largely based on patient history, but often requires endoscopic evaluation. Outcomes and treatment plans vary widely based on eventual diagnosis, so the process of determining the underlying cause of dysphagia is critical and time sensitive. Case Description/Methods: An 88-year-old woman with no significant past medical history presented to the ED with lower back pain and lower extremity weakness in the setting of a known T10 compression/burst fracture. She had been managing her pain with significant amounts of ibuprofen. She was diagnosed with spinal stenosis with thoracic myelopathy, and underwent successful orthopedic treatment with no subsequent complications. During her admission she also endorsed 3 months of progressive dysphagia, globus sensation in her upper chest with oral intake, and an accompanying 5-pound weight loss. She denied nausea, vomiting, odynophagia, abdominal pain, early satiety, or fevers. She had no family history of esophageal malignancy, denied tobacco use, and endorsed minimal alcohol intake. She had never undergone endoscopy (EGD). Oropharyngeal exam was normal. The severity of her symptoms ultimately presented a barrier to discharge. An inpatient EGD demonstrated severe esophagitis with linear white desquamating fragments of peeling esophageal epithelium, consistent with esophagitis dissecans superficialis (EDS). Biopsies were obtained. Patient was started on twice daily omeprazole, counseled on avoidance of NSAIDs, and scheduled for repeat EGD in 8 weeks. Discussion: EDS is a rare benign pathology of the esophagus characterized on EGD with long, vertical, superficial white strips of peeling esophageal epithelium with a normal underlying mucosal layer. Given its rarity, the pathogenesis of EDS is largely unknown. However, cases of EDS have been associated with trauma, motility disorders, immunosuppression, toxins, including smoking and alcohol, and medications, including NSAIDs, bisphosphonates, and anti-depressants. In the case described here, the most likely trigger was chronic NSAID use resulting in mucosal injury. Though it has dramatic esophageal findings, reassuringly this benign condition most often completely resolves with withdrawal of the causative agent (Figure 1).Figure 1.: A: Endoscopic image showing mucosal sloughing of the lower third of the esophagus. B, C: HandE stain, magnification 20x (b) and 40x (c), showing superficial strips of non-viable squamous epithelium with bacterial overgrowth consistent with toxic mucosal damage; images reveal splitting of the superficial squamous epithelium and bacterial overgrowth in between layers.

Introduction: Malignant obstructive jaundice is caused by blockage or narrowing of the bile or pancreatic ducts, often due to cholangiocarcinoma, gallbladder or pancreatic carcinoma, or metastatic lymphadenopathy. Endoscopic retrograde cholangiopancreatography (ERCP) with stent placement or percutaneous transhepatic cholangiography and biliary drainage (PTCD) are commonly performed for relieving obstruction, but stent occlusion rates are high, requiring repeated procedures for palliation. Here we describe a rare etiology of obstructive jaundice from metastatic renal cell carcinoma (RCC). Case Description/Methods: A 67-year-old male with a history of RCC status post radical nephrectomy with liver metastasis on checkpoint inhibitor therapy presented to the hospital with 2 weeks of jaundice and hyperbilirubinemia. Physical examination revealed jaundice, scleral icterus, and right upper quadrant tenderness. Laboratory analysis showed elevated Total bilirubin of 40.4mg/dL, Alkaline phosphatase 1,398 U/L, Alanine transaminase 234 U/L, Aspartate transaminase 211 U/L, and Carbohydrate antigen 19-9 of 2,026.4 U/mL. Magnetic resonance cholangiopancreatography 3 weeks prior identified an increase in soft tissue at the biliary confluence suspicious for primary Klatskin tumor or cholangiocarcinoma (Figure 1, A-B). Subsequent outpatient ERCP revealed a segmental biliary stricture in the main bile duct which was stented and biopsy samples were negative for malignancy. This was repeated again during admission with further negative biopsy samples. After developing a malignant pleural effusion, urgent endoscopic ultrasound and ERCP were performed, detecting lymphadenopathy (Figure 1, C) and multiple biliary strictures necessitating stent replacement. Tissue samples showed neoplastic cells with clear cytoplasm, irregular nuclei, and prominent nucleoli (Figure 1, D). Immunohistochemistry revealed positive results consistent with metastasis from clear cell RCC. After diagnosis, the patient was discharged with hospice services and died 1 week later. Discussion: Renal Cell Carcinoma (RCC) is an aggressive malignancy with a proclivity to spread to atypical locations, but more frequently to bone, lungs or lymph nodes. Rarely, it can metastasize to other sites and lead to obstructive jaundice. This is an extremely rare occurrence, with to the best of our knowledge less than 15 reported cases in literature. Coordinated efforts from a multidisciplinary team is required to manage patients with acute presentations.Figure 1.: Obstructive Jaundice secondary to metastatic Renal Cell Carcinoma A – Magnetic resonance imaging (MRI) Abdomen Axial Post Contrast, Ill-defined abnormal enhancing soft tissue at hepatic confluence B – MRI Abdomen Coronal T2, marked narrowing of the Common Hepatic Duct C – Endoscopic ultrasound Lymphadenopathy D – Tissue Sample at 40X Magnification – Dispersed and clustered neoplastic cells with abundant clear cytoplasm, large irregular nuclei, and prominent nucleoli infiltrating the fibrous tissue.

Introduction: Strongyloidiasis, caused by the parasitic nematode Strongyloides stercoralis, can present with nonspecific gastrointestinal (GI) symptoms such as abdominal pain or weight loss. Immunosuppressed patients are at risk of disseminated strongyloidiasis which is often fatal thus early recognition is important. Here we present a case of a patient on chronic steroids experiencing odynophagia and weight loss, whose esophagogastroduodenoscopy (EGD) unexpectedly revealed Strongyloides. Case Description/Methods: A 56-year-old man who immigrated from Cambodia 30 years ago with history significant for IgG4-related membranous glomerulonephritis on chronic prednisone 40 mg once daily presented to the hospital for several weeks for odynophagia. Labs showed signs of poor PO intake with weight loss, and elevated CRP of 34 with no leukocytosis or eosinophilia. Gastroenterology was consulted given odynophagia in an immunocompromised patient. EGD was performed and revealed white nummular lesions on the esophageal mucosa, consistent with candida esophagitis, along with diffuse moderate inflammation with edema, erosions and friability of the duodenum, which was biopsied (Figure 1-1). Duodenal biopsy showed mildly active duodenitis and surprisingly, parasites within the crypts, consistent with strongyloidiasis (Figure 1-2, 1-3). Infectious disease was consulted and patient was started on ivermectin 200mcg/kg daily for 2 days, and prednisone dosage was lowered to 20mg once daily. After treatment, the patient was able to tolerate PO intake without odynophagia. Further chart review revealed elevated Strongyloides IgG antibody levels of 3.9. Patient was also found to have copper deficiency and it was presumed to be secondary to malabsorption from duodenal Strongyloides. Evaluations for Wilson’s disease with liver biopsy did not show copper toxicity. Discussion: This case highlights the importance of considering Strongyloidiasis in immunosuppressed patients presenting with nonspecific GI symptoms. While Strongyloidiasis is typically associated with eosinophilia, patients on chronic steroids usually exhibit no eosinophilia, especially in the setting of fatal disseminated strongyloidiasis, thus timely recognition and treatment in this population is necessary. Endoscopic findings of strongyloidiasis such as erythema, mucosal edema, ulcers, or friability can be nonspecific, making biopsy a valuable diagnostic tool that enables direct visualization of the Strongyloides within the affected mucosa.Figure 1.: 1- 1: EGD view of the duodenum. 1- 2: 10X view of the duodenum mucosa with mild active inflammation and worms consistent with Strongyloides stercoralis (black arrow). 1-3: 20X view.

The major histocompatibility complex (MHC) genes are known to be capable of influencing the susceptibility of many cancers. All mammalian cells, including cancer cells, express MHC class I molecules consisting of human leukocyte antigens (HLA) A, B, and C. The tumor susceptibility of HLA-A, B, and C alleles has not been studied extensively in solid tumors.HLA-A, B, and C genotypes of 179 solid tumors were collected from Caris Comprehensive Tumor Profiling reports, including 45 GU, 44 GI, 28 pancreaticobiliary, 21 thoracic, 15 breast, 13 Gyn, among others. The tumors were mainly from Caucasians (82%). The HLA allele frequencies in the tumors were compared to those of respective ethnic populations in the US National Marrow Donor Program (NMDP) database. Fisher's exact tests were performed, adjusted P values were calculated using Benjamini-Hochberg's method for false discovery rate (FDR), and Prevalence ratios (PRs) were calculated to quantify associations.Twenty-one alleles were not listed in the NMDP. Among them, A*11:303 alone was present in 11 carcinomas, and B*08:222 was seen in 4 tumors. Among the alleles listed in the NMDP, C*08:02, B*14:02, A*03:02, and B*44:06 were significantly associated with tumors in Caucasian Americans (PR: 2.50-170), while B*44:02 appeared protective (PR: 0.36). Alleles with less significant associations were listed.From the HLA-A, B, and C data of the 179 tumors, we identified several susceptible alleles and one protective allele. Of interest, 21 alleles were not listed in the NMDP. The limited cases prevented our analysis from identifying cancer-susceptible alleles in other races.

No AccessJournal of UrologyUrological Survey: Abstracts: Male Infertility1 Aug 1998The Fas System is a Key Regulator of Germ Cell Apoptosis in the Testis J. Lee, J.H. Richburg, S.C. Younkin, and K. Boekelheide J. LeeJ. Lee More articles by this author , J.H. RichburgJ.H. Richburg More articles by this author , S.C. YounkinS.C. Younkin More articles by this author , and K. BoekelheideK. Boekelheide More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(01)62980-XAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "The Fas System is a Key Regulator of Germ Cell Apoptosis in the Testis." The Journal of Urology, 160(2), p. 623 Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island© 1998 by American Urological Association, Inc.FiguresReferencesRelatedDetails Volume 160Issue 2August 1998Page: 623 Advertisement Copyright & Permissions© 1998 by American Urological Association, Inc.MetricsAuthor Information J. Lee More articles by this author J.H. Richburg More articles by this author S.C. Younkin More articles by this author K. Boekelheide More articles by this author Expand All Advertisement Loading ...