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INTRODUCTION & OBJECTIVES: In few other cancers lymph node involvement has as clear a prognostic significance as in penile cancer. The latest revision of the Union for International Cancer Control Tumour Node Metastasis (TNM) - criteria for penile cancer in 2009 amended the pathological nodal (pN) stage so extranodal metastatic extension entails stage pN3. We report population based national survival data from 454 Danish penile cancer patients staged according to the TNM 2009 criteria and evaluate the survival impact of lymph node staging at diagnosis. MATERIAL & METHODS: Penile squamous cell carcinoma patient data from five university hospitals from the period 2000 - 2010 was retrospectively collected by one medical doctor. Vital status was defined in October 2014. Survival was assessed by the means of the Kaplan-Meier method and hazard ratios estimated by Cox regression with 95% confidence intervals. Survival impact of lymph node staging was evaluated in a multivariate cox regression model with adjustment for tumour stage, age and Charlson comorbidity score. RESULTS: Of a total of 454 men 39 did not undergo lymph node staging of any kind. Median follow-up of patients who survived was 7.5 years (interquartile range: 5.6-10.5 years). Figure 1 shows the Kaplan-Meier curves for all-cause and penile cancer specific survival related to lymph node stage. All cause 5-year survival for pN0, pN1, pN2, pN3 and pNx patients was 84 (79-87) %, 60 (42-75) %, 54 (33-71) %, 12 (5-22) and 31 (17-45) %. Penile cancer-specific 5-year survival for pN0, pN1, pN2, pN3 and pNx patients was 97 (94-98)%, 82 (62- 92)%, 57 (36-74)%, 12 (5-22)% and 53 (35-69)%. Lymph node staging had a significant impact on penile cancer specific survival after adjustment for age, T-stage and comorbidity (Nx vs all N0, N1, N2, N3 patients) with a hazard ratio of 3.5 (95% CI 2.0 to 6.0). CONCLUSIONS: In this national study, we found both cancer specific and all-cause survival significantly correlated to TNM-2009 lymph node stage at penile cancer diagnosis. Delayed lymph node staging (Nx) was significantly correlated to poorer prognosis underlining the importance of performing lymph node staging at diagnosis.

INTRODUCTION & OBJECTIVES: Nodal involvement is a strong prognosticator in penile cancer and lymph node staging is crucial. Sentinel node biopsy (SNB) has proven a useful staging tool with few complications, but evidence rely mostly on single institution publications with a short follow-up. In this study we estimated the diagnostic accuracy of SNB in patients with squamous cell carcinoma of the penis and assessed procedure-related complications in a multicentre setting with long-term follow-up. MATERIAL & METHODS: Data was retrospectively collected from medical records by one medical doctor at the four university centres where the procedure was performed. Thus, the study covers all SNB procedures performed in Denmark in the 11-year period 2000-2010. Included patients were newly diagnosed and had either non-palpable lymph nodes (cN0) in one or both groins or had a palpable mass in the groin, from which aspiration cytology was unable to detect malignancy. Routine ultrasound of cN0 groins was not used. Patients were injected with nanocolloid technetium and a scintigram was recorded before the surgical SNB. A gamma probe and intraoperative palpation of the exposed inguinal wound was used for the detection of lymph nodes. In addition 1 ml of Patent blue was used intradermally in the circumference of the proximal penile shaft just prior to surgery in 3 centres. Diagnostic accuracy was calculated on the basis of histopathology and complete follow-up until October 2014. RESULTS: 409 groins in 222 patients were examined by SNB. Median follow-up of patients who survived was 6.6 years (interquartile range: 5-10). No patient was lost to follow-up. A total of 1004 lymph nodes were removed of which 93 nodes (9.3 %) harboured metastatic tissue at histopathological examination. All groins with positive SNB underwent complementary ipsilateral ILND. Sixteen groins (24 %) contained further positive lymph nodes, while 50 groins (76 %) had no further metastases on histopathological examination of ILND specimen. In total 66 groins (52 patients) had positive SNB and 343 groins had negative SNB. During a median follow-up of 73 (IQR 53- 102) months 8 false negative groins were encountered. Sensitivity was 89.2% (95% CI, 79.8-95.2%) per groin and false negative rate was 10.8% (95% CI, 4.8-20.2%). Remarkably, four of 67 T1G1 patients had a positive SNB. This is interesting considering the current EAU recommendation with no surgical staging of T1G1 tumours. Twenty-eight of 222 (13%) patients experienced 39 postoperative complications of Clavien-Dindo grade I-IIIa to SNB during follow-up. Complications were encountered after 30 of 409 (7%) procedures and were primarily grade I. One patient was readmitted because of severe wound infection, the remaining complications were handled as a part of primary hospitalization, or in the outpatient clinic. 8 patients experienced more than one SNB-related complication. No patient needed to return to the operating room because of SNB related complications. No patient died from complications. CONCLUSIONS: To our knowledge, this is the first complete national study on sentinel node biopsy. Penile cancer sentinel node biopsy with a close follow-up is a reliable lymph node staging and has few complications in a national multicentre setting. Inguinal lymph node dissection which has complication rates of 30 - 70 % was avoided in 76 % of patients. The EAU guideline recommendation with no surgical staging of T1G1 tumours should be reconsidered.

Background: Proteins play a central role in psoriasis as they are involved in the structural phenotypic changes and inflammation that characterize the disease. This systematic review aimed to assess which proteins have been consistently reported as upregulated or downregulated in the skin and blood from patients with psoriasis., Methods: We included proteomic studies reporting differentially expressed proteins (DEPs) in at least one of four predefined comparisons using a standardized procedure to extract and align data. Network analysis of functional protein associations was made with StringApp in Cytoscape. A protocol for this review was registered in the PROSPERO database (ref:CRD42022363226)., Results: We identified and assessed 772 studies published between December 2, 1996, and April 28, 2023, among which 30 studies met the inclusion and data availability criteria for analysis that together reported a sum of 5,314 DEPs. The majority of consistently reported upregulated and downregulated proteins were found in lesional versus non-lesional skin (n = 313), followed by lesional versus healthy skin (n = 185), blood from patients with psoriasis versus blood from healthy individuals (n = 140), and non-lesional versus healthy skin (n = 1). Network analysis of upregulated proteins revealed different functional clusters with interleukin (IL)-6, IL-8, IL-17A, C-C motif chemokine (CCL) 20, signal transducer and activator of transcription (STAT) 3, and interferon (IFN)-γ along with less well-studied proteins playing central roles. Some of the reported changes are associated with anti-inflammatory effects. Additionally, the proteomic dysregulation also included antimicrobial peptides, alarmins, angiogenic factors, and proteins related to protein synthesis., Conclusion: Our findings generally support current understandings of the pathological mechanisms in psoriasis. Importantly, some consistent findings have not been discussed before and deserve attention in future research., (© 2023 The Author(s). Published by S. Karger AG, Basel.)