Squamous cell carcinoma of the bladder: Demographics and outcomes associated with surgery and radiotherapy.

BACKGROUND AND OBJECTIVES: Squamous cell carcinoma of the bladder (SCCB) is a rare disease composing 2%-5% of all bladder cancers with no consensus regarding treatment. The present study aims to analyze the outcomes of established treatments, namely chemotherapy, radiation, and surgery, to guide clinical decision-making for patients with non-schistosomal SCCB. METHODS: Patients with bladder SCC diagnosed between 2000 and 2018 were reviewed utilizing data from the Surveillance, Epidemiology, and End Results Registry (SEER) program. RESULTS: A total of 5653 patients with SCCB were identified; median survival was 13 months and was significantly decreased in patients treated with chemotherapy or radiation (median survival of 9 or 12 months, respectively). Patients treated with both surgery and radiotherapy saw a decreased 5 year overall survival (OS) of 14%, compared to 35% for those treated with surgery alone (p < 0.01). Furthermore, patients treated with surgery, chemotherapy, and radiotherapy saw a decreased 5 year OS of 20%, compared with 25% for those that received surgery and chemotherapy only (p < 0.01). Finally, surgical intervention provided an increased 5 year OS for patients with locoregional disease only; those with distant disease saw no increase in 5 year OS (p < 0.01). CONCLUSIONS: Based on this study's analysis, radical surgery may be the most effective treatment for this disease.

Malignant mixed mullerian tumors: a SEER database review of rurality and treatment modalities on disease outcome.

Introduction: Malignant Mixed Mullerian Tumors (MMMT) are rare and poorly understood sarcomas with limited research on risk factors, pathogenesis, and optimal treatments. This study aimed to address this knowledge gap and explore the impact of community size, patient characteristics, disease characteristics, and treatment modalities on MMMT outcomes. Methods: Using the Surveillance, Epidemiology, and End Results database (SEER), the largest SEER cohort to date of 3,352 MMMT patients was analyzed for demographic factors, treatment modalities, and histologic characteristics. Data was processed, including the removal of incomplete entries, and analyzed in Python 3.1 using packages scikit-learn, lifelines, and torch; log-rank analysis and Cox proportional hazards models were used to evaluate a number of demographic characteristics and disease characteristics for significance in regard to survival. Results: Our study found adjuvant radiotherapy and chemotherapy significantly improved survival, with modest benefits from neoadjuvant chemotherapy. Our findings also suggest age at diagnosis, disease grade, and suburban versus rural geographic locations may play key roles in patient prognosis. On multivariable analysis both disease Grade and surgical treatment were significant factors. Discussion: MMMTs remain challenging, but appropriate treatment appears to enhance survival. The present findings suggest opportunities for improved outcomes and treatment strategies for patients with MMMTs.

Radioligand therapy (RLT) used to treat cardiac metastasis of pancreatic neuroendocrine tumor.

Radioligand Therapy (RLT) in the form of [177Lu] Lu-DOTA-TATE (Lutathera®) is a promising treatment for pancreatic neuroendocrine tumors (pNETs) with cardiac metastasis. We present a patient treated with [177Lu] Lu-DOTA-TATE that showed shrinkage of metastasis after four treatments at 7.4 GBq every 8 weeks.

The Emergence of Inpatient Sleep Medicine: Screening for Sleep Disordered Breathing to Reduce the Burden of Cardiovascular Disease.

Purpose of Review: Treatment of obstructive sleep apnea (OSA) has historically been centered on outpatients given sleep testing is performed on an outpatient basis. Much of this practice originates from insurers only covering sleep testing on an outpatient basis. Over the last decade, there have been innovations made in the portability of sleep monitors which have allowed sleep testing on inpatients to be facilitated. There is also emerging data that inpatient sleep testing may reduce readmissions and healthcare costs in certain cardiovascular conditions. Accordingly, this review aims to provide comprehensive coverage of recent advances in the practice of inpatient sleep medicine and its effect on reducing the burden of cardiovascular disease. Recent Findings: Chief cardiovascular diseases that intersect with OSA in inpatients are stroke, atrial fibrillation, and heart failure. There is data from the National Inpatient Sample comparing arrhythmia burdens in patients with OSA and HFpEF showing that OSA patients have higher mortality rates, hospital durations, and medical costs. Also, OSA is associated with higher burdens of arrhythmia. It is currently unknown whether treatment of inpatients with PAP therapy lowers the occurrence of arrhythmias. Recent data suggests that costs for heart failure patients with OSA that are readmitted are higher than those for heart failure patients without OSA. A recent analysis of patients with HFpEF (heart failure with preserved ejection fraction) and OSA showed that the PAP adherent patients had fewer healthcare related costs, lower readmission rates, and fewer emergency room visits than those that were nonadherent. In broader terms, rapid initiation of PAP therapy in a large administration database query of 23 million Medicare patients appears to reduce annual healthcare costs and reduce readmissions although further study is required. Summary: OSA is globally underdiagnosed, with an estimated one billion individuals affected. OSA's pathogenesis involves a combination of risk factors, such as obesity, age, and increased neck circumference that contribute to fragmented sleep patterns and in turn, numerous cardiovascular comorbidities, such as stroke, atrial fibrillation, and coronary artery disease. Recently, inpatient sleep medicine programs have emerged as a promising avenue for improving diagnosis, patient safety, and potentially reducing readmissions. Integrating inpatient sleep medicine into healthcare systems to address the significant health and economic burden associated with undiagnosed OSA. Improved coverage of inpatient sleep testing and services will be a key driver of addressing inpatient gaps in sleep medicine care. The current research findings provide a bedrock from which further investigations may proceed in a prospective and randomized, controlled fashion to further clarify the effects of treatment of OSA on cardiovascular outcomes of inpatients.

Squamous cell carcinoma of the colon: evaluation of treatment modalities and survival.

BACKGROUND: Squamous cell carcinoma of the colon (CSCC) is a rare subtype of colon cancer. This study aimed to evaluate treatment strategies and overall survival (OS). METHODS: Using the Surveillance, Epidemiology, and End Results program database from 2008 to 2019, patients aged 18 years with CSCC were identified. Treatment strategies and OS were summarized using the Kaplan-Meier analysis and the log-rank test. Adjusted Cox proportional hazards regression model ratios were calculated to evaluate the effect of confounding variables. RESULTS: After exclusions, 153 patients met the inclusion criteria. The most common treatment modalities included surgery alone (52.1%), surgery and adjuvant chemotherapy (12.9%), and no treatment (26.4%). Kaplan-Meier analysis revealed that patients who underwent surgery and adjuvant chemotherapy had significant improvements in OS (log-rank P = .002). Cox regression analysis revealed tumor grade (hazard ratio [HR], 2.12; 95% CI, 1.17-3.86) and receipt of chemotherapy (HR, 2.66; 95% CI, 1.23-5.76) as the only factors associated with improvements in OS. CONCLUSION: Patients who underwent surgery in combination with chemotherapy had better OS than those who underwent surgery alone. Tumor grade and receipt of chemotherapy were independently associated with OS.

Demographics, Histopathology, and Treatment Outcomes of Squamous Cell Carcinoma of the Prostate.

BACKGROUND: Squamous cell carcinoma of the prostate (SCCP) is a neoplasm that comprises fewer than 1% of all primary prostate cancer diagnoses. Given its rarity, there is a paucity of data regarding the treatment of this disease. The limited literature points to the potential of local therapy in conjunction with chemotherapy to improve patient mortality. METHODS: Using the National Cancer Initiative's Surveillance, Epidemiology, and End Results (SEER) database, a retrospective review of patients diagnosed with primary SCCP between 2000 and 2018 was performed. Patient demographics, tumor characteristics, and patient outcomes based on treatment modality were analyzed. Univariate and survival analyses were conducted with p < 0.05 indicating statistical significance. RESULTS: A total of 66 patients were identified. Five-year overall survival (5y OS) was 24%; mean and median survival were 2.2 years (1.8, 2.7) and 1.2 years (0.3, 2.1), respectively. Patients with Grade I or Grade II disease had an increased 5y OS of 55% (27%, 83%). In comparison, 5y OS was 13% (-2%, 29%) for patients with Grade III and Grade IV disease (p = 0.017). Analysis of 5y OS based on disease histology revealed patients with papillary SCC had a 5y OS of 50% [9.2%, 91%], compared to 21% [9%, 34%] for patients with SCC, not otherwise specified and 0% for those with lymphoepithelial carcinoma (p = 0.048). Analysis of 5y OS stratified by treatment modality revealed no statistically significant change with any treatment (surgery, radiotherapy, and chemotherapy). No difference in 5y OS was seen between those treated with radical prostatectomy versus external beam radiation therapy. CONCLUSIONS: The literature on SCCP remains sparse; the rarity of this disease limits analysis. While the investigation undertaken in this paper does not find any change in 5y OS regardless of treatment modality, the variation in 5y OS based on histologic classification of SCCP points to a potential route for the future treatment of this disease.

A SEER database retrospective cohort of 547 patients with penile non-squamous cell carcinoma: demographics, clinical characteristics, and outcomes.

Introduction: Little research has investigated the prevalence and distribution of the diverse pathologies of non-squamous cell carcinoma (non-SCC) of the penis. Although rare in clinical practice, these cancers have become a focus of greater importance among patients, clinicians, and researchers, particularly in developing countries. The principal objective of this study was to analyze the major types of penile non-SCC, elucidate common treatment pathways, and highlight outcomes including 5-year survival. Materials/methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried between 2000 and 2018 to identify a retrospective cohort of patients with penile non-SCC. Demographic information, cancer characteristics, diagnostic methods, treatments administered, and survival were investigated. Results: A total of 547 cases of penile non-SCC were included in the analysis. The most prevalent non-SCC cancers included epithelial neoplasms, not otherwise specified (NOS) (15.4%), unspecified neoplasms (15.2%), basal cell neoplasms (13.9%), blood vessel tumors (13.0%), nevi and melanomas (11.7%), and ductal and lobular neoplasms (9.9%). Over half (56.7%) of patients elected to undergo surgical intervention. Patients rarely received systemic therapy (3.8%) or radiation (4.0%). Five-year survival was 35.5%. Patients who underwent surgery had greater annual survival for 0-10 years compared to those who did not have surgery. Significant differences in survival were found between patients who had regional, localized, and distant metastases (p < 0.05). A significant difference in survival was found for patients married at diagnosis versus those who were unmarried at diagnosis (p < 0.05). Lower survival rates were observed for patients older than 70 years. Discussion: Although less prevalent than SCC, penile non-SCC encompasses a diverse set of neoplasms. Patients in this cohort had a high utilization of surgical management leading to superior outcomes compared to those not receiving surgery. Radiation is an uncommonly pursued treatment pathway. Patient demographics and socioeconomic variables such as marital status may be valuable when investigating cancer outcomes. This updated database analysis can help inform diagnosis, management, and clinical outcomes for this rare group of malignancies.

Primary squamous cell carcinoma of the pancreas: an update on a rare neoplasm from the SEER database.

Introduction: Pancreatic squamous cell carcinoma is a rare type of pancreatic cancer of ductal origin, composing an estimated 0.5 - 5% of pancreatic ductal malignancies. As a result, epidemiology, treatment options, and associated outcomes are poorly understood and understudied. Our aim was two-fold: to evaluate demographic trends and analyze overall survival (OS) associated with different treatment modalities for this rare malignancy. Methods: Patients with pancreatic squamous cell carcinoma diagnosed between 1992 and 2019 were eligible and reviewed utilizing the Surveillance, Epidemiology, and End Results Registry (SEER) database. Data was analyzed using SPSS and python packages lifelines and pandas. Variables of interest included stage at diagnosis as well as the receipt of surgery, radiotherapy, and/or chemotherapy. Five-year OS curves were analyzed using Kaplan-Meier probability stratified by treatment modality. Results: Of 342 cases of pancreatic squamous cell carcinoma, 170 (49.7%) were females and 172 (50.3%) were males. 72 (21.1%) of patients received radiotherapy, 123 (35.9%) patients received chemotherapy, and 47 (13.7%) received surgery. Patients who were diagnosed under the age of 50 had prolonged survival time compared to those diagnosed over the age of 50 (12 vs 8 months, respectively, p < 0.001). This trend was evident despite the lack of a significant association between age at diagnosis and presence of metastases (p = 0.524). The median OS was 3 months for the entire cohort and there was a significant difference in median survival time noted across treatment modalities: OS was prolonged in those receiving surgery compared to those receiving chemotherapy or radiotherapy alone (30 vs 2 months, respectively, (p<0.001)). Receipt of radiotherapy was not associated with a significant difference in OS compared to those who did not receive radiotherapy. Conclusion: Pancreatic squamous cell carcinoma is a rare subtype of pancreatic cancer and typically portends a poor prognosis. As demonstrated by our study, surgery offers prolonged overall survival compared to other treatment modalities. Age at diagnosis and presence of metastatic disease are also important prognostic factors likely related to patients' ability to tolerate surgery or physician willingness to offer surgery. Given the importance of surgery on outcomes, it may be reasonable to offer it in the oligometastatic setting in patients who are otherwise a good candidate. Future research on larger cohorts is warranted to investigate the role that modality selection plays in overall survival rates in this understudied malignancy.

Second-generation extracellular matrix patch for epicardial infarct repair.

Current myocardial infarction treatments focus on improving hemodynamics rather than addressing the problem of lost myocardium impairing left ventricular function. Epicardial infarct repair with a bioactive patch placed on the ischemic area is an emerging approach to promote endogenous myocardial repair. We report the use of a second-generation CorMatrix-extracellular matrix (ECM) patch as an adjunct to surgical revascularization in treating a young patient with diffuse, multivessel coronary artery disease unamenable to PCI and a large anterior myocardial infarction. The progressive myocardial scar shrinkage and increase in left ventricular ejection fraction from 10 to 51% are generally not observed with surgical revascularization therapy alone, suggesting this new patch has adjunctive potential to current revascularization therapy.

First reported Rhodotorula mucilaginosa brain abscess: Found as coinfection in woman with common variable immune deficiency.

Rhodotorula is a rare pathogen seen in the immunocompromised host; while cases of Rhodotorula meningitis have been reported, there are no published cases of Rhodotorula brain abscess. We describe the diagnosis and management of a woman with common variable immune deficiency presenting with concomitant Rhodotorula and Nocardia brain abscesses.

Smoky Diagnosis: Importance of Patient History in Vaping Associated Lung Injury.

E-cigarette or vaping use associated lung injury (EVALI) recently became a common cause of respiratory illness. The pathophysiology of EVALI is relatively unknown, and thus the disease remains a diagnosis of exclusion. There are no specific tests or markers that exist, although there is some belief that Vitamin E acetate is strongly linked to the increase in EVALI cases. Immediate recognition of EVALI patients is critical in order to reducing severe outcomes. For these cases, the importance of a complete patient interview is emphasized and necessary for diagnosis. We present a case of a young patient presenting with hypoxic respiratory failure due to EVALI, in which diagnosis was delayed due to incomplete patient history.

Diagnosis and Management of Rare Siliconomas in an HIV Patient.

Siliconomas are rare conditions stemming from uses of silicone injections for soft tissue augmentation, most commonly in the breast and buttocks areas. Siliconomas are known to present with suspicious morphology that mimics cases of embolism or systemic metastasis as the silicone travels through blood and lymphatics. We present the case of a 45-year-old HIV-positive male who presented with siliconomas in the breast region, chest heaviness, shortness of breath, dyspnea, and a physical exam showing gynecomastia. The patient denied any surgeries or injections around his chest. Further imaging showed abnormal fat deposition in the chest and possible metastatic lymphadenopathy to axillary, supraclavicular, and mammillary lymph nodes. Although the complications arising from silicone injections are well documented, the pathogenesis remains unknown, leaving a narrow range of therapeutic options. Despite these shortcomings, diagnostic imaging tools have shown to be vital in the diagnosis and localization of suspected siliconomas.

Primary Neurosarcoidosis Mimicking Gallbladder Pathology.

A 40-year-old African American male with long standing headaches and unintentional weight loss presented with nausea, vomiting, and blurry vision. Laboratory findings include hyponatremia and mildly raised liver enzymes. He underwent cholecystectomy six months prior for unexplained nausea and vomiting, which in hindsight was likely neurologic-induced vomiting from neurosarcoidosis. Brain imaging revealed diffuse, leptomeningeal, nodular enhancement involving the brain, brainstem, and upper cervical spinal cord. Further work up showed extensive lymphadenopathy above and below the diaphragm, solitary liver lesion, and multiple lytic lesions involving bones. Iliac spine biopsy revealed ill-defined, non-caseating granulomas with giant cell reaction infiltrating bone fragments. Acid-fast bacilli and fungal stains were negative. Patient was treated with steroids. Diagnosis of neurosarcoidosis is challenging in the absence of physical signs and symptoms. However, radiological and pathological correlation in clinical suspicion of sarcoidosis is helpful in more accurate diagnosis and timely management of the patient.

Mystery in the mediastinum: Rare case of indolent primary thoracic amyloids.

A 53-year-old African American male smoker presented with epigastric pain, tarry stools, and laboratory results indicative of acute pancreatitis. Chest X-ray showed a right perihilar mass with pleural effusion. Computed tomography scan showed multiple large right paratracheal and hilar nodes with internal calcification. The patient underwent a fiberoptic bronchoscopy with biopsies which were negative for malignancy. Mediastinoscopy was performed and revealed amyloidosis. Evaluation for multiple myeloma showed elevated kappa and lambda light chains and diffuse polyclonal gammopathy, but there was no monoclonal spike on serum protein electrophoresis. Bone marrow and abdominal fat pad were negative for amyloid, and the patient continues to lack chronic underlying systemic disease with no symptoms on cardiac or pulmonary examination.

DICE: A Drug Indication Classification and Encyclopedia for AI-Based Indication Extraction.

Drug labeling contains an 'INDICATIONS AND USAGE' that provides vital information to support clinical decision making and regulatory management. Effective extraction of drug indication information from free-text based resources could facilitate drug repositioning projects and help collect real-world evidence in support of secondary use of approved medicines. To enable AI-powered language models for the extraction of drug indication information, we used manual reading and curation to develop a Drug Indication Classification and Encyclopedia (DICE) based on FDA approved human prescription drug labeling. A DICE scheme with 7,231 sentences categorized into five classes (indications, contradictions, side effects, usage instructions, and clinical observations) was developed. To further elucidate the utility of the DICE, we developed nine different AI-based classifiers for the prediction of indications based on the developed DICE to comprehensively assess their performance. We found that the transformer-based language models yielded an average MCC of 0.887, outperforming the word embedding-based Bidirectional long short-term memory (BiLSTM) models (0.862) with a 2.82% improvement on the test set. The best classifiers were also used to extract drug indication information in DrugBank and achieved a high enrichment rate (>0.930) for this task. We found that domain-specific training could provide more explainable models without performance sacrifices and better generalization for external validation datasets. Altogether, the proposed DICE could be a standard resource for the development and evaluation of task-specific AI-powered, natural language processing (NLP) models.

Disclosure of familial implications of pathogenic variants in breast-cancer genes to patients: Opportunity for prompting family communication.

Familial communication of pathogenic genetic variants is necessary to maximize the clinical utility of genetic testing and its public health benefits. Insights to family communication considerations may be obtained from existing clinical documentation available in medical records. The goal of this study was to describe and characterize information about family communication of pathogenic variants and cascade genetic testing from genetic counseling summary notes. We completed structured content analysis of 656 summary notes describing pathogenic variants in breast cancer genes, for patients seen at a tertiary cancer center. Patients were 89.5% female, median age of 49 years, 32.6% non-White, and were counseled by 23 unique genetic counselors (GCs) with mean post-certification experience of 3.7 years. Cascade genetic testing was documented in 92.2% of all notes. Specific relatives (i.e., relationship to patient) who would benefit from genetic counseling and cascade testing were referenced in 33.1% of notes. Specific risk messaging was 2.5 times more likely to be present in notes of high- compared to moderate-risk genes (OR=2.53, 95% CI: 1.71-3.80), and when summary notes indicated the presence of a friend or relative (OR=2.29, 95% CI: 1.50-3.48). Summary notes frequently attempted to contextualize the patients' familial relationships by referencing positive family communication patterns (41.6%) or negative communication issues (2.4%) and included various strategies to address barriers to communication and assist relatives with cascade testing. Overall, GCs consistently documented family communication recommendations when pathogenic variants are identified on patients' genetic testing, albeit with heterogeneous use of specific communication prompts.

Impact of aging on diaphragm muscle function in male and female Fischer 344 rats.

The diaphragm muscle (DIAm) is the primary inspiratory muscle in mammals and is active during ventilatory behaviors, but it is also involved in higher-force behaviors such as those necessary for clearing the airway. Our laboratory has previously reported DIAm sarcopenia in rats and mice characterized by DIAm atrophy and a reduction in maximum specific force at 24 months of age. In Fischer 344 rats, these studies were limited to male animals, although in other studies, we noted a more rapid increase in body mass from 6 to 24 months of age in females (~140%) compared to males (~110%). This difference in body weight gain suggests a possible sex difference in the manifestation of sarcopenia. In mice, we previously measured transdiaphragmatic pressure (Pdi) to evaluate in vivo DIAm force generation across a range of motor behaviors, but found no evidence of sex-related differences. The purpose of this study in Fischer 344 rats was to evaluate if there are sex-related differences in DIAm sarcopenia, and if such differences translate to a functional impact on Pdi generation across motor behaviors and maximal Pdi (Pdimax ) elicited by bilateral phrenic nerve stimulation. In both males and females, DIAm sarcopenia was apparent in 24-month-old rats with a ~30% reduction in both maximum specific force and the cross-sectional area of type IIx and/or IIb fibers. Importantly, in both males and females, Pdi generated during ventilatory behaviors was unimpaired by sarcopenia, even during more forceful ventilatory efforts induced via airway occlusion. Although ventilatory behaviors were preserved with aging, there was a ~20% reduction in Pdimax , which likely impairs the ability of the DIAm to generate higher-force expulsive airway clearance behaviors necessary to maintain airway patency.