HPV and Penile Cancer: Epidemiology, Risk Factors, and Clinical Insights.

Penile cancer (PC) is a rare malignancy predominantly of squamous cell origin. Approximately 40% of penile tumors are associated with human papillomavirus (HPV) infection. Diagnosing PC remains challenging due to its rarity and variety of clinical presentations. Furthermore, the impact of HPV on the tumor immune microenvironment complicates clinical management, although recent advancements in immune checkpoint inhibitors (ICIs) have shown some efficacy in treating HPV-associated PC. Ongoing research efforts aim to develop oncologic treatments that target HPV-induced cellular modifications. Additionally, novel therapeutic vaccines and adoptive T-cell therapies targeting HPV oncoproteins represent emerging treatment modalities. Our review highlights the complex interplay between HPV and penile carcinogenesis, emphasizing its epidemiology, etiology, clinicopathological characteristics, and potential therapeutic implications.

A comprehensive review of current knowledge on penile squamous cell carcinoma.

Neoplasm of the penis is relatively rare in most regions representing 0-2% of cancers worldwide. While the penis can be affected by sarcomas, basal cell carcinomas or even melanoma, Penile Squamous Cell Carcinoma (PSCC) represents approximately 95% of all penile neoplasms. Despite its rarity and most common presentation at later decades of life most individuals diagnosed with PSCC are faced with significant decrease in quality of life. The prevalence and incidence vary among different regions and populations, but a common trend is for diagnosis to occur late (stage 4). Underdeveloped countries are traditionally reported to have higher incidence rates; however, rates may vary significantly between urban and rural areas even in developed countries. Age adjusted rates are on the rise in some countries that used to have incidence rates of 1:100 000 or less. The list of associated risk factors is long and includes among others, lack of neonatal circumcision, poor genital hygiene, socioeconomic status, history of human papillomavirus (HPV) infection and penile intraepithelial neoplasia (PeIN). Many risk factors are widely debated among experts however HPV and PeIN are indisputable risk factors, and both also form part of the classification system for PSCC. Both conditions may have occurred in the past or be present at the time of diagnosis and identifying them plays a major role in management strategies. For such a rare condition PSCC can present in many different forms clinically making diagnosis no easy feat. Diagnosis of PSCC is done through clinical examination, including lymph node palpation, followed by a biopsy, which is essential for the classification. Lymph node involvement is a common finding at first presentation and investigation of spread to deep nodes is important and can be done with the aid of PET-CT. Treatment options for PSCC include surgery, chemotherapy, and radiation therapy. Surgical removal of the tumor is considered the most effective however can lead to severe decrease of quality of life. Chemotherapy is used in the case of fixed or bulky lymph nodes, where surgery is not indicated, and for distant metastasis. Radiation therapy is particularly effective in the case of HPV-positive PSCC.

Clinical Outcomes and Prognostic Factors in Patients With Penile Carcinoma: A Sub-Analysis From Meet-URO 23 (I-RARE) Registry Study.

INTRODUCTION: Penile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors. PATIENTS AND METHODS: Primary endpoints were overall survival and progression-free survival. Prognostic factors for OS and PFS were analyzed using univariate and multivariate analysis. From the Meet-URO 23/I-RARE database, we extracted 128 patients with diagnosis of PSCC. About 48% of patients underwent first-line of therapy. RESULTS: In the overall population, median OS from diagnosis was 34.6 months. Significant differences in median OS were observed according to ECOG PS at diagnosis (57.3 months vs. 8.3 months; P < .001), and median age (≤77y 88.8 months vs. >77y 26 months; P = .013). At multivariate analysis, ECOG PS 2-4 at diagnosis (HR 3.04) and lymph node metastases (HR 2.49) were independently associated with a higher risk of death. Among patients undergoing first-line therapy (n = 61), median OS was 12.3 months, and a statistically significant difference was found according to type of response to first-line (DCR 24.4 months vs. PD 7.1 months; P < .001). Multivariate analysis showed that only age >77 years was associated with a worse OS (HR 2.16). A statistically significant difference in PFS was found according to platinum plus 5-fluorouracil versus platinum plus taxane (4.9 vs. 3.4 months; P = .036) and regimens with 2 versus 3 drugs (3.4 vs. 8.6 months; P = .019). At the multivariate analysis only regimens with platinum plus taxane were associated with worse PFS (HR 2.83). CONCLUSION: In our registry study, PSCC is confirmed to be an aggressive disease. Poor ECOG PS, presence of lymph node metastases, and higher age at diagnosis appear to be associated with worse survival outcomes.

Assessment of Adherence to Cardiovascular Medicines in Saudi Population: An Observational Study in Patients Attending a Tertiary Care Hospital.

BACKGROUND: Drug adherence has been extensively evaluated in many developed countries in the West using different methods of medication adherence measurement; however, there are relatively few reports studying the adherence levels among Saudi patients. Thus, this study will evaluate the adherence to cardiovascular medicines in Saudi patients visiting (PSCC) in Al-Qassim, Saudi Arabia. METHODS: This cross-sectional observational study relied on self-administered questionnaires. This study used the Morisky, Green, and Levine (MGL) Adherence Scale, also known as the MAQ (Medication Adherence Questionnaire), in PSCC's pharmacy waiting room in Qassim, Saudi Arabia. RESULTS: This study included 993 PSCC pharmacy waiting room patients. The patients were between 11 and 50 years old, and 52.7 percent were male. Most participants (71.2%) were above 50, while 16.3% were 41-50. Non-adherent patients cited traveling or being busy (28.6%), forgetting (18.7%), daily multi-medications (7.1%), being sleepy or sleeping (6.6%), and not repeating the prescription (6.6%). The Medicine Adherence Questionnaire indicated that 62.6 percent of patients fully adhered to their medications, and 21.6 percent usually adhered. Only drug adverse effects affected adherence (p =0.0001). CONCLUSION: The current study showed that there is a good level of adherence among patients with cardiovascular diseases toward their diseases. The most common reasons for neglecting medications include traveling or being busy, forgetting multiple medications, and being tired or sleeping. Having experience with side effects was the only significant factor affecting adherence to medications.

SPP1 is associated with adverse prognosis and predicts immunotherapy efficacy in penile cancer.

BACKGROUND: The effect of SPP1 in squamous cell carcinoma of the penis (PSCC) remained unknown. We attempted to clarify the function of the SPP1 gene in PSCC. METHOD: Eight paired penile cancer specimens (including penile cancer tissue, paracancerous tissue, and positive lymph node tissue) subjected to whole transcriptome sequencing were analysed to identify differentially expressed genes. We used immunohistochemistry to detect the expression of SPP1 protein and immune cell related proteins in penile cancer tissue. Then, we performed weighted gene coexpression network analysis (WGCNA) to identify the genes related to SPP1 in penile cancer tissue and positive lymph node tissue. Based on the GSE57955 dataset, the CIBERSORT and ssGSEA algorithms were carried out to investigate the immune environment of PSCC. GSVA analysis was conducted to identify the signaling pathways related to SPP1 subgroups. Enzyme-linked immunosorbent assay (ELISA) method was adopted to detect SPP1 level in the serum of 60 patients with penile cancer. RESULTS: Differential analysis indicated that SPP1 was the most differentially upregulated gene in both penile cancer tissues and positive lymph node tissues. Survival analysis suggested that the prognosis of the low-SPP1 group was significantly poorer than that of the high-SPP1 group. Subsequently, immune-related bioinformatics showed that SPP1 was significantly associated with B cells, CD8 + T cells, CD4 + T cells, macrophages, helper T cells, neutrophils and dendritic cells. The immunohistochemical results showed that the high-SPP1 group was characterized by relatively high expression of CD16 and relatively low expression of CD4. GSVA analysis indicated that high-SPP1 group was significantly associated with immune-related pathways such as PD-L1 expression and the PD-1 checkpoint pathway in cancer and the TNF signaling pathway. ELISA demonstrated that the serum level of SPP1 in patients with positive lymph node metastasis of penile cancer was significantly higher than that in patients with negative lymph node metastasis of penile cancer. CONCLUSION: Our study shows that the SPP1 gene might be an effective biomarker for predicting the prognosis and the efficacy of immunotherapy in PSCC patients.

Sustainable thresholds, health outcomes, health expenditures and education nexus in selected African countries: quadratic and moderation modelling.

BACKGROUND: This study aligns with Sustainable Development Goal 3 which borders on "good health and well-being for people by ensuring healthy lives and promoting well-being for all at all ages". It contributes to the health literature by evaluating the roles of health expenditures and educational quality on three health outcomes (infant mortality, maternal mortality and life expectancy at birth). METHODS: The study uses the panel spatial correlation consistent (PSCC) approach on balanced panel data on 25 selected sub-Saharan African countries from 2000 to 2020 to interrogate the nexus. RESULTS: The following findings are documented. First, health expenditures reveal significant asymmetric quadratic effects on health outcomes. Second, the interactions between health expenditures and educational quality reduce infant and maternal mortalities while enhancing life expectancy. Third, the threshold points from the interaction effects indicate that enhancing educational quality beyond some critical thresholds of 1.51 and 1.49 can induce a drop in maternal and child mortalities while a point beyond 1.84 exerts an improvement in life expectancy. CONCLUSIONS: Hence, policy makers should ensure that both health expenditures and educational quality exceed the established thresholds for sustainable health outcomes.

Development and validation of a prognostic predictive model of pulmonary spindle cell carcinoma from the surveillance, epidemiology and end results database.

Background: Pulmonary spindle cell carcinoma (PSCC) is a rare type of non-small cell lung cancer (NSCLC). The prognostic influent factors and therapeutic methods of PSCC are unclear, for there are only some case reports or small samples' analysis. This study aims to find prognosis related factors of PSCC, develop and validate a nomogram to predict their survival probability. Methods: The Surveillance, Epidemiology, and End Results (SEER) 18 Registries database (2000-2018) was searched to study PSCC. According to diagnosed time, data was divided into primary cohort (2000-2015) and validation cohort (2016-2018), both followed until December 31 2018. Chosen by Least Absolute Shrinkage and Selection Operator (LASSO) regression, age, sex, stage, surgery, chemotherapy, N, size and history of malignancy were taken out as predictive variables. The primary cohort was used to develop a nomogram to predict 1-, 3- and 5-year overall survival (OS) probability, and be validated by the validation cohort using concordance index (C-index) and calibration curves. Both cohorts were used to conduct a Cox regression to find the influential factors on OS of PSCC. Results: The nomogram shows a good concordance and discrimination on the prediction of OS, both internal (n=457 and C-index is 0.79) and external validation (n=100 and C-index is 0.76). The median survival time of PSCC is 4 months, with 20.1% OS possibility in 5 years. Multivariate analysis identified patients of older age [hazard ratio (HR), 1.02; 95% confidence interval (CI): 1.01-1.04], larger size of neoplasm (HR, 1.01; 95% CI: 1.01-1.01), M1 (HR, 2.96; 95% CI: 2.17-4.04), N2 (HR, 2.55; 95% CI: 1.81-3.59) or N3 (HR, 2.99; 95% CI: 1.58-5.66), regional stages (HR, 2.11; 95% CI: 1.29-3.44) and distant stages (HR, 6.17; 95% CI: 3.83-9.94) had a lower OS possibility, while surgery (HR, 0.39; 95% CI: 0.28-0.53) and history of malignancy (HR, 0.68; 95% CI: 0.48-0.98) was protective factors for PSCC. PSCC survived longer with surgery performed instead of chemotherapy or radiotherapy. Conclusions: Patients of PSCC have a poor prognosis, and using the nomogram developed by this study can predict their 1-, 3- and 5-year OS probability. Surgery is a better choice for PSCC and more studies are necessary to find potential treatment like targeted therapy, programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1).

Labyrinthine Fistula-Our Experience at a Tertiary Hospital.

This study has aimed to determine the anatomical site of labyrinthine fistula in patients of chronic suppurative otitis media at our centre. Labyrinthine fistulae (LF) are caused by abnormal communications between the inner ear and surrounding structures resulting in perilymph leakage and hearing loss. Labyrinthine fistula represents as erosive loss of the enchondral bone overlying the semicircular canals without loss of perilymph. The manifestations of fistula like vertigo, hearing loss vary in severity and complexity, commonly ranging from very mild to incapacitating. Cholesteatoma induced fistula most commonly involves lateral semicircular canal probably because of its close proximity to the middle ear, but can involve other semicircular canals and rarely cochlea. This is a retrospective analysis of 36 patients of chronic suppurative otitis media with history of vertigo undergoing tympanomastoid surgery in whom there was an evidence of labyrinthine fistula on HRCT scan of temporal bone. The incidence of patients with labyrinthine fistula presenting with vertigo, nystagmus, sensorineural hearing loss, history of vertigo were analysed. The anatomical location of the fistula was supported by Radiological evidence. Patients underwent either canal wall down mastoidectomy or cortical mastoidectomy. The anatomical site and length of the labyrinthine fistula were analysed. Amongst the 36 patients of chronic suppurative otitis media with labyrinthine fistula 22 (61.1%) patients had atticoantral disease, 4 (11.1%) patients had chronic otitis media with extensive granulation, 2 (5.5%) patients had Tubotympanic disease with polyps, 4 (11.1%) patients had Tuberculous otitis media, 1 (2.77%) patient had Tubotympanic disease with extensive tympanosclerosis eroding the dome of lateral semicircular canal, 1 (2.77%) patient had extensive cholesteatoma with cerebellar abscess, 1 (2.77%) patient had fistula in the promontory following trauma, 1 (2.77%) patient had extensive tympanosclerosis with erosion of promontory. It was noticed that, in 14 (38.88%) patients the fistula was at the centre, in 17 (47.22%) patients the fistula is towards the ampullary end of horizontal semicircular canal and in 5 (13.88%) patients the fistula was towards the non ampullary end of lateral semicircular canal. The maximum length of fistula noticed was 6 mm and the minimum length of the fistula noticed was 2 mm. Labyrinthine fistula are most commonly noticed in the ampullary end of the lateral semicircular canal. The average length of the fistula was found to be 4 mm. Careful elevation of the cholesteatoma matrix over the endosteal membrane and immediate placement of temporal fascia over the exposed fistula is important to avoid injury to the inner ear. Maximum number of fistula were seen in the atticoantral type of Chronic suppurative otitis media. Prior knowledge of anatomical location of the fistulous tract in HRCT temporal bone is important to address the fistula.

Approaches and Vectors for Efficient Cochlear Gene Transfer in Adult Mouse Models.

Inner ear gene therapy using adeno-associated viral vectors (AAVs) in neonatal mice can alleviate hearing loss in mouse models of deafness. However, efficient and safe transgene delivery to the adult mouse cochlea is critical for the effectiveness of AAV-mediated therapy. Here, we examined three gene delivery approaches including posterior semicircular canal (PSCC) canalostomy, round window membrane (RWM) injection, and tubing-RWM+PSCC (t-RP) in adult mice. Transduction rates and survival rates of cochlear hair cells were analyzed, hearing function was recorded, AAV distribution in the sagittal brain sections was evaluated, and cochlear histopathologic images were appraised. We found that an injection volume of 1 µL AAV through the PSCC is safe and highly efficient and does not impair hearing function in adult mice, but local injection allows AAV vectors to spread slightly into the brain. We then tested five AAV serotypes (PHP.eB, IE, Anc80L65, AAV2, and PHP.s) in parallel and observed the most robust eGFP expression in inner hair cells, outer hair cells, and spiral ganglion neurons throughout the cochlea after AAV-Anc80L65 injection. Thus, PSCC-injected Anc80L65 provides a foundation for gene therapy in the adult cochlea and will facilitate the development of inner ear gene therapy.

Multimodal Treatment Combining Salvage Surgery-Assisted Chemotherapy and Checkpoints Blockade Immunotherapy Achieves Complete Remission on a Recurrent Penile Cancer Patient: A Case Report.

Penile squamous cell carcinoma (pSCC) is a rare disease in developed countries. pSCC causes a severe health problem and social burden in developing countries. We reported a 49-year-old male recurrent pSCC patient with medium PD-L1 expression and low TMB. The patient obtained complete response after multimodal therapy (MMT). The clinical manifestation is a recurrence in the right groin with nearly ruptured pSCC. He had partial resection of penile cancer plus bilateral groin lymph node dissection and pelvic lymph node dissection during the first operation. Pathology of the recurrent tumor showed fibrous tissue with cancer infiltration and necrosis. We used MMT, including resection of palliative right inguinal metastases, four cycles of paclitaxel+bleomycin+cisplatin, and continuous sintilimab to treat the patient. The patient had a complete response (CR) after four cycles of therapy and sustained CR for 18 months with continuous sintilimab, showing a good tolerance and acceptable toxicity. This is the first case presenting a complete response in a relapsed pSCC patient. These results suggest that MMT is worth exploring.

miRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma.

Although microRNAs are described as promising biomarkers in many tumor types, little is known about their role in PSCC. Thus, we attempted to identify miRNAs involved in tumor development and metastasis in distinct histological subtypes considering the impact of HPV infection. In a first step, microarray analyses were performed on RNA from formalin-fixed, paraffin-embedded tumor (22), and normal (8) tissue samples. Microarray data were validated for selected miRNAs by qRT-PCR on an enlarged cohort, including 27 tumor and 18 normal tissues. We found 876 significantly differentially expressed miRNAs (p ≤ 0.01) between HPV-positive and HPV-negative tumor samples by microarray analysis. Although no significant differences were detected between normal and tumor tissue in the whole cohort, specific expression patterns occurred in distinct histological subtypes, such as HPV-negative usual PSCC (95 differentially expressed miRNAs, p ≤ 0.05) and HPV-positive basaloid/warty subtypes (247 differentially expressed miRNAs, p ≤ 0.05). Selected miRNAs were confirmed by qRT-PCR. Furthermore, microarray data revealed 118 miRNAs (p ≤ 0.01) that were significantly differentially expressed in metastatic versus non-metastatic usual PSCC. The lower expression levels for miR-137 and miR-328-3p in metastatic usual PSCC were validated by qRT-PCR. The results of this study confirmed that specific miRNAs could serve as potential diagnostic and prognostic markers in single PSCC subtypes and are associated with HPV-dependent pathways.

DaPeCa-9 - cohabitation and socio-economic conditions predict penile cancer-specific survival in a national clinical study from Denmark.

BACKGROUND: Cohabitation and social conditions predict prognosis in several cancers; recent data suggest this might also be the case in penile cancer. OBJECTIVE: To assess the prognostic significance of cohabitation, living arrangements and socio-economic conditions for cancer-specific survival (CSS) in patients with penile squamous cell carcinoma (pSCC). METHODS: We retrospectively evaluated CSS in 429 pSCC patients from a 10-year period. We assessed cohabitation, living arrangements and socio-economic conditions(SEC) as prognostic predictors. Kaplan-Meier estimates and Cox hazard rates (HR) with 95% confidence intervals were used for analysis. RESULTS: Out of 429 pSCC patients, 137 (32%) were living alone and 292 (68%) were cohabiting. With a Cox HR at 1.91 (95% CI 1.3-2.98) patients living alone had a significantly lower median five-year survival rate at 69% (95% CI 60-77%) compared to cohabiting patients at 83% (95% CI 78-87%), p = 0.002. Comparing 60 (14%) from higher to 202 (47%) from medium and 95 (22%) patients from lower socio-economic groups we found Cox HRs at 1, 2.4 (95% CI 1.0-5.7, p = 0.04) and 3.4 (95% CI 1.4-8.1, p < 0.01) respectively. When comparing living arrangements, the trend that patients living in apartments and institutions had poorer outcomes than patients living in a house did not reach statistical significance. CONCLUSIONS: Living alone and in poor socio-economic conditions predict poor prognosis in penile cancer in this national study. We make the case for further research in efforts to minimize cancer inequality pSCC patients.

Lessons learned from histological step-sectioning of sentinel lymph nodes in penile cancer.

AIMS: Histopathological examination of sentinel lymph nodes in penile cancer has varied during the first 10 years after introduction of the dynamic sentinel node (SLN) procedure in Denmark, and guidelines have been sparse. The aim of this study was to investigate the impact of rigorous step-sectioning of sentinel lymph nodes in penile cancer and improve guidelines. METHODS AND RESULTS: Seventy-two penile squamous cell carcinoma patients undergoing SLN procedure at a single institution in 2000-2010 were included. The archived lymph node tissues already subjected to a standard pathological examination were retrieved and the initially negative lymph nodes were subjected to an extended step-sectioning procedure. The results were compared to clinical patient outcome from a national database and subsequent pathology reports. The original histopathological examination had detected 26 SLN with metastasis, 21 macro metastases and five micro metastases. The additional step-sectioning procedure of this study generated 4606 slides; seven SLN metastases, two macro metastases and five micro metastases, were detected. One of the macro metastases originated from a patient in which a clinical relapse had occurred in the same groin. None of the other metastases detected in this study showed ipsilateral relapse during follow-up. CONCLUSION: The results underline the value of our current practice of step-sectioning sentinel lymph nodes in penile cancer and the need for histopathological routines and guidelines. The Danish national guidelines on histopathological handling of sentinel lymph nodes have been adapted to detect any potential clinically relevant metastases.

Neurological outcomes after surgery for spinal metastases in symptomatic patients: Does the type of decompression play a role? A comparison between different strategies in a 10-year experience.

INTRODUCTION: The impact of neurological deficits plays a role of inestimable importance in patients with a neoplastic disease. The role of surgery for the management of symptomatic spinal cord compression (SSCC) cannot be overemphasized, as surgery represents often the first and paramount step in patients presenting with motor deficits. The traditional paradigm of simple bilateral laminectomy for the treatment of spinal cord compression has been reviewed. The need to achieve a proper circumferential decompression of the spinal sac has been progressively highlighted in combination with the development of the more comprehensive and multidisciplinary concept of separation surgery. OBJECTIVE: The aim of this paper is to analyze different strategies of decompression, while evaluating whether circumferential/anterior decompression is able to guarantee a better control and restoration of neurological functions in patients with motor impairment, if compared to traditional posterior decompression. MATERIALS AND METHODS: This is a retrospective observational study investigating symptomatic patients that underwent surgical treatment for spinal metastases at author's Institutions from January 2010 to June 2019. Data recorded concerned patient demographics, tumor histology, peri-operative and follow-up neurological status (ASIA), ambulation ability, stability (SINS), grade (ESCC) and source of epidural compression and type of decompression (anterior/anterior-lateral (AD); posterior/posterior-lateral (PD/PDL); circumferential (CD)). RESULTS: A total number of 84 patients was included. AD/CD patients showed higher chance of neurological improvement and reduced rates of worsening compared to PD/PLD group (94.1%/100% vs 60.4%; 11.8% vs 45.8% respectively). Univariate logistic regression identified immediate post-operative improvement to be a significative protective factor for worsening at last follow-up. Stratifying patients for site of compression and considering anterior and circumferential groups, immediate post-operative neurological improvement, was mostly associated with AD and CD (p 0.011 and 0.025 respectively). Walking at last follow up was influenced by post-operative maintenance of ambulation (p 0.001). CONCLUSION: The necessity to remove the epidural metastatic compression from its source should be considered of paramount importance. Since the majority of spinal cord compression involves firstly the ventral part of the sac, CD/AD are associated with better neurological outcomes and should be achieved in case of circumferential or anterior/anterolateral compression.

Incidence trends and survival outcomes of penile squamous cell carcinoma: evidence from the Surveillance, Epidemiology and End Results population-based data.

BACKGROUND: To provide the latest incidence trends and explore survival outcomes of penile squamous cell carcinoma (PSCC) patients with or without a previous primary malignancy. METHODS: Patients diagnosed with PSCC between 1975 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database were retrospectively included. Then, we calculated the age-adjusted incidence rates (IRs) and annual percentage changes (APCs). Multivariate Cox analysis and Kaplan-Meier (KM) survival curves were conducted to investigate prognostic variables for cancer-specific survival (CSS). RESULTS: A total of 6,122 PSCC patients were enrolled, 1,137 of whom had a prior malignancy. The age-adjusted IR for the general population in men declined before 1987, fluctuated slightly between 1987 and 1997, and showed an upward trend after 1997, which was basically consistent with that in patients without a previous primary malignancy. The incidence trend of PSCC in the general population was similar with that in those without a previous malignancy. However, the IRs of PSCC in men with a previous malignancy have been increasing since 1975 regardless of race. Furthermore, age at diagnosis, pathological grade, extent of disease, marital status, the administration of surgery and presence of previous primary malignancy were identified to be significantly related to CSS. CONCLUSIONS: The IRs of PSCC have been increasing in recent years. Several independent prognostic factors for CSS were identified, allowing surgeons to assess the individualized risk in advance.

Recurrent Metastatic Penile Cancer Patient with Positive PD-L1 Expression Obtained Significant Benefit from Immunotherapy: A Case Report and Literature Review.

BACKGROUND: Penile squamous cell carcinoma (PSCC) bears poor prognosis due to its rarity and limited treatment options, especially after failure of standard treatments. Effective therapeutic options were desperately needed. CASE PRESENTATION: We report a recurrent metastatic PSCC patient with positive programmed death ligand 1 (PD-L1) expression (≥10%) and tumor mutation burden (TMB) of 8.87 (Muts/Mb) who obtained significant response to immunotherapy, with progression-free survival (PFS) exceeding 10 months. CONCLUSION: This is the first case presenting remarkable response to immunotherapy in a Chinese PSCC patient. The remarkable response might be associated with PD-L1 expression, indicating that PD-L1 expression could be a promising biomarker for immunotherapy in PSCC. TMB ranking may also contribute to patient selection. However, large clinical trials are needed to validate these notions.

Primary squamous cell carcinoma (PSCC) of the thyroid: a case report and review of the literature.

Primary squamous cell carcinoma (PSCC) is a rare neoplasm of the thyroid with a very poor prognosis. We report a case of a 42-year-old woman with occasionally found mass in the right anterior area of the neck. After a total thyroidectomy, histopathology and immunohistochemistry tests confirmed primary squamous cell carcinoma of the thyroid with the exclusion of all other possible primary tumor locations. 5 months later, PET scan discovered abnormality in right cervical lymph nodes with a fine needle aspiration confirming to be tumor recurrence. After a modified radical neck dissection was performed with pathological results of the neoplasms being PSCC of the thyroid origin, a full course consecutive radiotherapy was then followed. Due to a prompt diagnosis and the complete dissection of primary tumor and metastatic lymph nodes, no recurrence was observed at the follow-up visits. Comparing to the published cases of PSCC of the thyroid, our paper stated a whole process of diagnosis and standardized treatment, together with classical matched figures of pre-op examinations and dissected specimen. Furthermore, a review of the present literatures summarized the diagnosis, treatment and prognosis of thyroid PSCC. The management of PSCC requires a multi-disciplinary approach.

Pulmonary papillary squamous cell carcinoma: a population-based analysis of incidence, treatment, and prognosis.

BACKGROUND: Pulmonary papillary squamous cell carcinoma (PSCC) is a rare variant of pulmonary squamous cell carcinoma (SCC). This study aims to improve relevant understanding and demonstrate the incidence, treatment, and prognosis of pulmonary PSCC using a population-based database. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to extract data of cases diagnosed with PSCC from 1973 to 2015 and analyze the incidence, treatment, and prognosis. RESULTS: A total of 151 pulmonary PSCC cases were identified. The incidence of pulmonary PSCC cases in 2015 was 0.009 per 100,000 persons. The tumor grade of pulmonary PSCC cases was significantly lower than that of SCC cases (P<0.001). Both cancer-specific (CSS) and overall survival (OS) of pulmonary PSCC were significantly higher than those of other pulmonary SCCs (P<0.001). The outcomes of pulmonary PSCC cases receiving surgery were significantly better than cases without surgery (P<0.001). On the contrary, patients with radiotherapy had a worsened prognosis compared with those without radiotherapy (P<0.05). As expected, the prognosis of pulmonary PSCC cases receiving surgery was significantly better than that of pulmonary PSCC cases receiving chemotherapy and radiotherapy (both P<0.05). CONCLUSIONS: Our population-based evidence shows that pulmonary PSCC, as a rare cancer, has a better prognosis compared with other pulmonary SCCs. Surgery was the only effective treatment to improve CSS and OS, while chemotherapy was ineffective and radiotherapy worsened prognosis.

Amplatzer septal occluder and atrioventricular block: A case report and literature review.

Transcatheter closure of secondum atrial septal defect (ASD) is an alternative option to open heart surgery with good short and long-term outcomes. For this purpose, the Amplatzer septal occluder (ASO) device is widely used. Arrhythmias are known complications of ASD device closure including atrial ectopy and heart block. We report a seven-year-old female patient who developed second degree atrioventricular block (AVB) within few hours after ASD device closure using ASO device. At the seventh post-procedure day; while under close observation; patient regained sinus rhythm which was maintained thereafter. A 3-day course of prednisolone was given.