Systematic Review of Calcineurin Inhibitors and Incidence of Skin Malignancies after Kidney Transplantation in Adult Patients: A Study of 309,551 Cases.

The purpose of this systematic review and meta-analysis was to compare the risk of non-melanoma skin cancer (NMSC) and melanoma development in renal transplant recipients who receive calcineurin inhibitors to that of patients treated with other immunosuppressive agents, and investigate the possible association between the type of maintenance immunosuppression and the incidence of NSMC and melanoma in this group of patients. The authors searched databases such as PubMed, Scopus, and Web of Science for articles that would help establish the influence of calcineurin inhibitors on skin cancer development. The inclusion criteria for the study consisted of randomized clinical trials, cohort studies, and case-control studies that compared patients who received kidney transplants and were treated with a calcineurin inhibitor (CNI), such as cyclosporine A (CsA) or tacrolimus (Tac), to those who received alternative immunosuppressants and did not receive a CNI. Seven articles were analyzed overall. The results revealed a correlation between CNI treatment in renal transplant recipients and increased total skin cancer risk (OR 1.28; 95% CI: 0.10-16.28; p < 0.01), melanoma risk (OR 1.09; 95% CI: 0.25-4.74; p < 0.01), and NMSC risk (OR 1.16; 95% CI: 0.41-3.26; p < 0.01). In conclusion, the calcineurin inhibitors used after kidney transplantation are associated with a higher risk of skin cancer-both non-melanoma and melanoma-when compared with other immunosuppressive therapies. This finding suggests that careful monitoring for skin lesions in post-transplant patients must be conducted. However, the decision on the kind of immunotherapy used should always be considered on an individual basis for each renal transplant recipient.

Conventional versus Reduced-Frequency Follow-Up in Early-Stage Melanoma Survivors: A Systematic Review with Meta-Analysis.

To date, there have been multiple studies and clinical guidelines or recommendations for complex management of melanoma patients. The most controversial subjects included the frequency of follow-up. This study provides a coherent and comprehensive comparison of conventional vs. reduced-frequency follow-up strategies for early-stage melanoma patients. The value of our study consists in the precise analysis of a large collection of articles and the selection of the most valuable works in relation to the topic according to rigorous criteria, which allowed for a thorough study of the topic. The search strategy was implemented using multiple databases. The inclusion criteria were randomized clinical trial or cohort studies that compared the outcomes of a conventional follow-up schedule versus a reduced-frequency follow-up schedule for patients diagnosed with melanoma. In this study, authors analyzed recurrence and 3-year survival. Meta-analysis of outcomes presented by Deckers et al. and Moncrieff et. al. did not reveal a significant difference favoring one of the groups (OR 1.14; 95%CI: 0.65-2.00; p = 0.64). The meta-analysis of 3-year overall survival included two studies. The statistical analysis showed no significant difference in favor of the conventional follow-up group. (OR 1.10; 95%CI: 0.57-2.11; p = 0.79). Our meta-analysis shows that there is no advantage in a conventional follow-up regimen over a reduced-frequency regimen in early-stage melanoma patients.

Nanog expression in patients with squamous cell carcinoma of oropharynx in relation to immunohistochemical score.

This study aimed to compare prognostic potential of Nanog expression analysed by three immunohistochemical scores in the group of 63 squamous cell carcinomas of oropharynx. Immunoreactivity of Nanog expression was analyzed by semiquantitative score, immunoreactive score and H-score. For all three scores, the cut-off points for Nanog overexpression and its lack, allowing for optimal separation of overall and disease free survival curves, were search by minimal p-value method. In semiquantitative score, the best separation of overall and disease free survival curves was obtain by cut-off point lack of staining vs. week/moderate/strong staining, although statistical significance was not reach (OS: HR = 1.016, p = 0.081, DFS: HR = 6.876, p = 0.061). The cut-off points for immunoreactive score and H-score were, respectively: 1 (OS: HR = 6.977, p = 0.014, DFS: HR = 6.002, p = 0.019) and 50 (OS: HR = 6.977, p = 0.014, DFS: HR = 6.002, p = 0.019). The cut-off points found for these two scores allow to identify the same subgroups of patients with lack of Nanog expression (11.1%) and its overexpression (88.9%). All patients with tumors characterized by lack of Nanog overexpression identifying by immunoreactive score and H-score survived 5 years without evidence of cancer progression. In multivariate analysis Nanog immunoreactivity analysed by QRS and IRS was independent prognostic factor for OS (HR = 10.195, p = 0.024). Immunohistochemical score using to distinguish Nanog overexpression or its lack has influence on prognostic potential of this biomarker.

Does It Really Pay-Off? Comparison of Lymphadenectomy versus Observational Approach in Skin Melanoma with Positive Sentinel Node Biopsy: Systematic Review and Meta-Analysis.

The aim of this meta-analysis was to answer the question as to whether performing CLND (complete lymph node dissection) is necessary in every case of the melanoma patient after the positive SNB (sentinel node biopsy). To resolve doubts the authors reanalyzed previous articles and systematized the knowledge about the concerning medical problem. The databases such as PubMed, Scopus and Web of Science were screened to find articles that will be helpful to answer the controversial question if performing lymphadenectomy is crucial. The inclusion criteria consisted of randomized clinical trials, comparison of lymphadenectomy versus observation and positive sentinel node biopsy. After which, seven articles were examined. Authors analyzed parameters such as: recurrence, 3-year survival and 5-year survival. There was no relationship between the performance of CLND and melanoma recurrence (OR 1.04; 95% CI: 0.82-1.31; p = 0.75). However, no CLND group had higher 3-year survival (OR 1.22; 95% CI: 1.03-1.44; p = 0.02) and 5-year survival (OR 1.30; 95% CI: 1.19-1.85; p = 0.008). In conclusion, the observational approach to the melanoma patients with positive sentinel node biopsy is associated with comparable or slightly improved 3- and 5-year survival, then in case of routine lymphadenectomy. Although, in each melanoma patient a decision to perform or withhold lymphadenectomy should always be considered individually. Patients with low perioperative risk could be considered for surgical approach. The study was registered in PROSPERO and was assigned with the unique identifying number "CRD42021241272".

Lack of CD44 and Sox-2 Overexpression as Two Independent Favourable Prognostic Factors in HPV Positive Patients with Oropharyngeal Cancers.

INTRODUCTION: In our earlier publications, in the group of 63 patients with oropharyngeal cancer, we have found HPV16 infection (assessed by qPCR) in 25 tumours (39.7%), immunohistochemical overexpression of CD44, CD98, ALDH1/2 and Nanog in, respectively: 43 (68.2%), 30 (47.6%), 33 (52.4%), and 53 (84.1%) cancers. Analysing CD44, CD98, ALDH1/2, we have also shown that lack of CD44 overexpression indicates excellent prognosis in patients with HPV16 positivity. The aim of the present study was to compare prognostic potential of Nanog, Oct3/4, Sox-2 expression in relation to CD44, CD98, ALDH1/2 immunoreactivity (assessed by us earlier) and clinicopathological features in the subgroups of patients: with HPV16 positivity and HPV16 negativity. METHODS: Status of Oct3/4 and Sox-2 expression was assessed for 63 patients with oropharyngeal cancers based on immunohistochemistry. In survival analysis, two endpoints were applied: overall survival (OS) and disease-free survival (DFS). RESULTS: Overexpression of Oct3/4 and Sox-2 was found in 0 (0.0%) and 27 (42.9%) of patients. In the subgroup with HPV16 positivity, the DFS for patients with lack of Sox-2 overexpression was significantly (p = 0.003) higher than for patients with Sox-2 overexpression. In the subgroup with HPV16 negativity, Nanog and Sox-2 immunoexpression did not significantly influence OS and DFS. In multivariate analysis performed for the subgroup with HPV16 positivity, lack of CD44 overexpression (p = 0.012) and lack of Sox-2 overexpression (p = 0.027) were positive independent prognostic factors. CONCLUSION: Based on CD44 and Sox-2 immunoreactivity, it is possible to differentiate the prognosis of HPV16-positive patients with oropharyngeal cancers.

Low frequency of HPV positivity in breast tumors among patients from south-central Poland.

BACKGROUND: Some studies suggest that Human Papilloma Virus (HPV) infection is important factor in carcinogenesis of breast tumors. This study' objective was to analyze HPV prevalence in breast cancers of patients from south-central Poland. MATERIALS AND METHODS: The study was performed based on archival paraffin embebbed and formalin fixed blocks in the group of 383 patients with breast cancer. HPV prevalence and its genotype were assessed, respectively by: nested PCR (with two groups of primers: PGMY09/PGMY11 and GP5+/GP6+), quantitative PCR (qPCR). Tumors were classified as HPV positive in case of at least one positive result in nested PCR and positive results in genotyping procedure. For all HPV positive tissues P16 immunostaining was applied in order to confirm active viral infection. RESULTS: In the group of 383 breast cancers, HPV positivity was found in 17 samples (4.4%) in nested PCR. All these samples were subjected to HPV genotyping. This analysis revealed presence of HPV type 16 into two tumors (0.5%). In these two cancers, P16 overexpression was reported. CONCLUSION: In breast tumors of patients from south-central Poland in Poland, HPV positivity is demonstrated in very low percentage of cases.

The prevalence of HPV infection in rectal cancer - Report from South - Central Poland (Cracow region).

Some studies suggest that HPV infection may be important carcinogenic factor in development of some part of colorectal cancers. However, in the worldwide literature concerning this type of tumours, the great variability in HPV frequency is noticed. In Poland, the incidence of HPV infection in colorectal cancers was examined in five studies so far and their results are also conflicting. Therefore, the aim of the present study was to assess the HPV presence in the group of 120 patients with adenocarcinomas of rectum. HPV infection was assessed on the basis of DNA extracted from collected formalin fixed paraffin embedded tumour specimens. Viral presence was evaluated using two PCR based methods: nested PCR and quantitative PCR (qPCR) with primers specific for HPV16. All HPV positive samples were subjected to virus genotyping using AmoyDx® Human papillomavirus (HPV) Genotyping Detection Kit and P16 immunostaining. Among 120 evaluated colorectal tumours, HPV DNA was detected in 2 cancers (1.67%) by nested PCR and in 2 (1.67%) tumours by qPCR, including 1 sample diagnosed as HPV positive on the basis of both PCR variants. Two HPV positive cancers had HPV16 infection and other one HPV18. All three tumours with positivity of HPV DNA were P16 negative. In south - central Poland, HPV infection in rectal cancers probably has not influence on rectal carcinogenesis.

Bilateral synchronous breast cancer developed as metachronous malignancy after therapy of other primaries.

OBJECTIVES: Cancer morbidity rates have been increasing steadily. A longer lifespan and easier access to modern diagnostic and therapeutic methods are the main reasons for the growing number of cancer survivors. Additionally, some types of oncological treatment, such as radiotherapy or immunosuppression, may also increase the risk of secondary tumors. These factors have resulted in an increased incidence of primary multiple cancers. Multiple primary cancers are generally under-stood as either synchronous, in which the cancers occur at the same time, or metachronous, in which the cancers follow in sequence (for instance, more than 2 months apart).The results published in other studies show that between 2% and 15.8% of all cancer patients have more primary multiple cancers. Within this group with multiple primary cancers, some have bilateral breast cancer, and our study focuses on patients from this group. MATERIAL AND METHODS: Our study describes 10 patients who were treated for bilateral synchronous breast cancer at the Cracow Branch of the Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology during the years 1992-2014 and who developed another primary tumor after their treatment bilateral synchronous breast cancer. RESULTS: In our discussion we present detailed data on the incidence of metachronous cancers in the 10 patients, including breast cancer, following the treatment of their other primary tumors. CONCLUSION: The 10 cases of our study, and clinical experiences and publications in general show how important it is for patients to continue medical follow-up after treatment of primary tumors, not only to detect recurrences as early as pos-sible, but also to diagnose any other malignancies occurring in other sites, including secondary, treatment-related tumors.

Differences in the prognosis of HPV16-positive patients with squamous cell carcinoma of head and neck according to viral load and expression of P16.

PURPOSE: To evaluate the impact of HPV16 load (VL-the number of virus genome copies per cell) and P16 expression on prognosis of patients with squamous cell carcinomas (SCCs) of head and neck (HN). MATERIALS AND METHODS: HPV16 presence was assessed in the group of 109 patients with HNSCCs by quantitative polymerase chain reaction (qPCR). VL (assessed by qPCR) and P16 expression (evaluated by immunohistochemistry) were analysed only in the subgroup of HPV16-positive tumours. These features were correlated with 5-year overall survival (OS) and disease-free survival (DFS). RESULTS: HPV16 infection was found in 36 tumours (33.0%). Virus-positive patients had better OS and DFS than those without infection (P = 0.041 and 0.005). Among HPV16-positive HNSCCs, 18 (50.0%) had higher VL (median value > 6764.3 copies/cell) and 25 (73.5%) P16 over expression. The significant differences in OS and DFS (P = 0.008 and 0.004) were noticed according to VL, wherein 100% DFS was found for patients with higher VL. According to P16 expression, significant difference was found only for OS (P = 0.020). In multivariate analysis, VL (P = 0.045; HR = 2.795; CI 0.121-1.060) and the level of smoking (P = 0.023, HR = 2.253; CI 1.124-4.514) were independent factors affecting DFS of HPV16-positive patients. CONCLUSION: On the basis of viral load, it is possible to differentiate prognosis of patients with HPV16-positive HNSCCs. In this subgroup, viral load has stronger prognostic potential than P16 expression.

Impact of different type of cancer treatment on the effectiveness of breast reconstruction.

For women undergoing mastectomy as part of their breast cancer treatment, breast reconstruction is an important part of therapy. However, neoadjuvant, adjuvant treatments as well as other patient-related factors can compromise the results of breast reconstruction techniques. In this article we have reviewed current approaches to the management of complications and risks that neoadjuvant and adjuvant therapies pose on breast reconstruction after mastectomy for breast cancer. Non-treatment related factors influencing reconstruction techniques were reviewed as well.

Clinical and Molecular Features of Laron Syndrome, A Genetic Disorder Protecting from Cancer.

Laron syndrome (LS) is a rare, genetic disorder inherited in an autosomal recessive manner. The disease is caused by mutations of the growth hormone (GH) gene, leading to GH/insulin-like growth factor type 1 (IGF1) signalling pathway defect. Patients with LS have characteristic biochemical features, such as a high serum level of GH and low IGF1 concentration. Laron syndrome was first described by the Israeli physician Zvi Laron in 1966. Globally, around 350 people are affected by this syndrome and there are two large groups living in separate geographic regions: Israel (69 individuals) and Ecuador (90 individuals). They are all characterized by typical appearance such as dwarfism, facial phenotype, obesity and hypogenitalism. Additionally, they suffer from hypoglycemia, hypercholesterolemia and sleep disorders, but surprisingly have a very low cancer risk. Therefore, studies on LS offer a unique opportunity to better understand carcinogenesis and develop new strategies of cancer treatment.