Prognostic Factors for Uterine Sarcoma and Carcinosarcoma: Insights from a 10-Year Follow-Up Study.

BACKGROUND Uterine sarcomas and carcinomas are rare tumors and treatment outcomes are far from expected. We investigated the prognostic significance of selected serum biomarkers and the impact of some clinical and tissue factors on overall survival (OS) at 10-year follow-up. MATERIAL AND METHODS The material for analysis was a group of 34 patients with uterine sarcomas and 18 with carcinomas. Immunohistochemistry was performed to determine Ki 67, p53 and ER and PR. Concentrations: CA 125, IL8, VEGF, SFTL1, VEGF R2, sTNFRI and MMP-9 were determined in the serum of patients before treatment and in the control group. RESULTS The most frequently elevated levels observed of sTNF RI in 94% and VEGF in 62%. On the ROC curve analysis, sTNF RI and VEGF concentrations showed the highest sensitivity. Patients with striated cell sarcoma, smooth cell sarcoma and high-grade rhabdomyosarcoma had the worst prognosis. Patient age, FIGO stage and expression of Ki67, p53, ER and PR, CA 125 (p<0.038) and IL-8 (p<0.024) were statistical prognostic factors for OS. However, in multivariate analysis, serum levels of: CA 125 concentration (p<0.045), age (p<0.010) and p53 expression (p<0.014) were found to be significant independent prognostic factors. CONCLUSIONS A 10-year follow-up of patients with uterine sarcoma indicates that age above 60 years at diagnosis and high p53 expression and elevated CA125 levels before treatment can be independent prognostic factors. The high diagnostic sensitivity of sTNF RI and VEGF suggests the possibility of using these biomarkers in the early diagnosis of uterine sarcomas.

COVID-19 Autopsies: A Case Series from Poland.

This paper presents autopsy findings of 3 COVID-19 patients randomly selected for post-mortem from two tertiary referral Polish hospitals. Analysis of macroscopic, histopathological findings with clinical features was performed. All 3 deceased patients were Caucasian males (average age 61 years, range from 56 to 68 years). Using real-time polymerase chain reaction assay, the patients were confirmed (antemortem) to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Two patients were obese, and 1 patient had type 2 diabetes mellitus. The medical history of 1 patient included hemorrhagic pancreatitis, gangrenous cholecystitis, Acinetobacter baumanii sepsis, and cholecystectomy. Pulmonary embolism was diagnosed in 2 patients. At autopsy, in 1 case, the lungs showed bilateral interstitial pneumonia with diffuse alveolar damage (DAD), while in another case, interstitial pulmonary lymphoid infiltrates and enlarged atypical pneumocytes were present but without DAD. Microthrombi in lung vessels and capillaries were observed in 2 cases. This study revealed thrombotic complications of COVID-19 and interstitial pneumonia with DAD presence as the main autopsy findings in patients with SARS-CoV-2 infection that was confirmed antemortem with molecular tests. Autopsy studies using tissue sections handled in accordance with SARS-CoV-2 biosafety guidelines are urgently needed, especially in the case of subjects who were below the age of 60.

Protein and peptide profiles in neonatal meconium.

AIM: The proteins accumulated in the meconium reflect the intrauterine environment and are naturally excreted by a neonate. The identification and classification of individual meconium proteins may be a valuable source of information about physiological and pathological processes in utero. METHODS: Proteomic analysis was used to study the protein composition in pooled 50 serial meconium portions from 10 neonates. The proteins were classified based on the gene ontology database. The amounts and relative number of proteins (%) in the identified categories and their subcategories were assessed. RESULTS: A total of 946 proteins identified in meconium, including 430 represented by two or more peptides were classified into three categories: biological process (n = 401), molecular function (n = 386) and cellular component (n = 422). The highest number of proteins (>25% of the total) was found in the subcategories: developmental processes, signaling, transport, response to stimulus, regulation, metabolic processes, ion binding, extracellular region, membrane and cytoplasm. CONCLUSION: The composition of meconium proteins identified in this study may be a rich source of new biomarkers for use in neonatology with a potential to predict later development.

Quality and practical aspects of pathological and molecular diagnostics in metastatic colorectal cancer (mCRC).

Colorectal cancer (CRC) is one of the most common malignancies worldwide. In recent years novel therapies targeted at EGFR receptor have been developed. However, this treatment can only be beneficial if no mutation in specific loci of KRAS/NRAS and BRAF genes is found in tumour specimen. Therefore, clinically useful pathological diagnosis of CRC in the era of personalised medicine is a multistep procedure, requiring good cooperation between the clinician/surgeon, pathomorphologist, and molecular biologist. Herein we propose the guidelines of colorectal cancer operating material proceedings for clinicians and pathomorphologists, which determines the correct pathomorphological diagnosis, and we discuss the colorectal cancer molecular biology issues useful in the selection of individual molecular targeted therapy. We discuss and stress the importance of each diagnostic phase: from tumour resection and sample collection at preanalytical stage, through proper pathological preparation, evaluation and selection of material for molecular testing, to molecular analysis and finally preparation of a pathological molecular report.

Viral Nucleic Acids in the Serum Are Dependent on Blood Sampling Site in Patients with Clinical Suspicion of Myocarditis.

BACKGROUND: The meaning of viral nucleic acids in the myocardium in many cases is difficult for clinical interpretation, whereas the presence of viral nucleic acids in the serum is a marker of active infection. We determined the diagnostic value of viral nucleic acids in ventricular serum and peripheral serum samples in comparison with endomyocardial biopsy (EMB) specimens in patients with clinically suspected myocarditis. METHODS: The viral nucleic acid evaluation was performed in serum samples and EMB specimens by real-time PCR in 70 patients (age: 47 ± 16 years). The biopsy specimens were examined by histo- and immunohistochemistry to detect inflammatory response. RESULTS: The viral nucleic acids were detected in ventricular and peripheral serum, and EMB samples of 10 (14%), 14 (20%), and 32 (46%) patients, respectively. Notably, viral nucleic acids of the same virus as in the EMB sample were present more often in ventricular than in peripheral serum (60 vs. 7%, p = 0.01). A significant concurrence was observed between the positive and the negative results of viral nucleic acids present in EMB and ventricular serum (p = 0.0001). CONCLUSIONS: The detection of the same viral nucleic acid type in the myocardium and in ventricular serum being significantly more frequent than in the peripheral serum may suggest that the site of the blood collection is important for more precise and reliable confirmation of the active viral replication in the heart.

Can the histological type of colorectal cancer determine the carcinogenesis pathway?

Colorectal cancer (CRC) is the most common type of gastrointestinal cancer and has three major pathways of carcinogenesis. About 80% of genomic instability concerns chromosomal instability (CIN); the rest is connected with either microsatellite instability (MSI) or CpG island methylation. Some MSI-related cancers are associated with Lynch syndrome, whereas others are caused by sporadic, acquired hypermethylation of the promoter of the MLH1 gene. These tumours have distinctive clinical and histopathological features. They may be poorly differentiated, accompanied by Crohn's-like lymphocytic infiltration and have a pushing margin. MSI-high (MSI-H) phenotype has a slightly better prognosis. We investigated 46 classic CRCs using histochemical and immunohistochemical methods (p53, MLH1, MSH2, MSH6). Based on the results, we divided patients into 4 groups. Tumours from the first and second group (27 cases) expressed the loss of MSI markers and presented a characteristic clinical and morphological image. The other 19 cases lacked significant immunohistochemical or microscopic features. These require further molecular studies to evaluate their carcinogenesis. Discovery of MSI in colorectal tumours should be taken into account in the management of patients. They do not respond to 5-fluorouracil or anti-EGFR therapy, especially the sporadic ones with BRAF mutations.

Gastric gastrointestinal stromal tumor with incomplete duplication cyst - a case with possibility of neoplasia in fetal-period malformed tissues.

The coincidence of GIST and other gastric malignancies are documented well but arising GIST from congenital anomalies is still rarity in literature. To date, only a few papers have been concerned on the possibility of arising neoplasms from duplication cyst of gastrointestinal tract. There, are dominating usual cancers, neuroendocrine cancers or lymphomas but GIST has been noted only once. Here, we report a case of 73 years old female-patient with typical gastric stromal tumor comprised centrally locked an incomplete duplication cyst.

Uterine tumors resembling ovarian sex cord tumors, a clinicopathologic study of six cases.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) cause difficulties, both with respect to diagnosis as well as to the nomenclature. They belong to the group of low-grade malignant neoplasms, and their clinical course likely depends on the percentage of the sex cord-like component. Morphologically, they can be divided into type I and type II with less or more than 50% of sex cord-like areas, respectively. Six patients with an age range of 24 to 63 years underwent the treatment for primary UTROSCT at the Cancer Center and Institute of Oncology in Warsaw, Poland, between 2000 and 2011. In addition to the surgery, 4 patients were treated with gestagens. Biopsies or excisions from the tumors were examined microscopically and immunohistochemically. Two cases were classified as type I, and 4 cases, as type II tumors. The tumor size ranged from 3 to 24 cm. The sex cord component varied from 25% to 70%. By immunohistochemical examination, the sex cord-like component was calretinin positive, whereas the stromal component was positive for CD10 and negative for h-caldesmon in all the cases studied. In addition, progesterone receptor positivity was found in all the cases, and 4 tumors were positive for smooth muscle actin, cytokeratin AE1/3, and inhibin. No recurrences were noted in any of the 6 patients over 3 to 14.5 years of follow-up period. A correct subclassification of sarcomas of UTROSCT type is of crucial importance because most patients with this rare neoplasm respond well to gestagen therapy and have a good prognosis, compared with other uterine stromal sarcomas.

microRNAs in uterine sarcomas and mixed epithelial-mesenchymal uterine tumors: a preliminary report.

Uterine sarcomas and mixed epithelial-mesenchymal uterine tumors are a heterogeneous group of rare tumors for which there are very few diagnostic markers available. As aberrant microRNA (miRNA) expression patterns represent putative diagnostic cancer markers, we aimed to identify miRNA expression profiles of the major uterine sarcoma subtypes and mixed epithelial-mesenchymal tumors of the uterus. Eighty-eight miRNAs were assessed by quantitative RT-PCR in cancerous and non-cancerous tissue samples collected from 29 patients with endometrial sarcoma, leiomyosarcoma, and mixed epithelial-mesenchymal tumors. Tumor and control samples significantly (P < 0.05) differed in the expression of miR-23b, miR-1, let-7f, and let-7c in endometrial sarcomas, and miR-1, let-7c, miR-133b, let-7b, miR-143, let-7a, let-7d, let-7e, let-7g, miR-222, let-7i, and miR-214 in mixed epithelial-mesenchymal tumors. All the significantly changed miRNAs were down-regulated in the malignant tissues as compared to their normal counterparts. This may suggest their tumor suppressor role in these malignancies. No statistically significant changes in miRNA expression levels were found between leiomyosarcoma tumors and controls. The identified miRNAs warrant further studies as valuable candidate markers for the differential diagnosis of uterine sarcomas from benign uterine lesions and between uterine sarcoma subtypes.

Clinical, Dermoscopic, and Histological Characteristics of Melanoma Patients According to the Age Groups: A Retrospective Observational Study.

BACKGROUND: Although the role of melanoma risk factors is well documented, their correlation with patients' age is less frequently analyzed. METHOD: The analysis was performed among 189 melanoma patients in different age groups, including <30 years, 31-60 years, and >60 years, to investigate the risk factors, topography, and coexistence of morphological features of 209 melanomas (dermoscopic and histopathological). RESULTS: Among the youngest age group, no correlation with the presence of estimated risk factors was found. The most common dermoscopic pattern was spitzoid and multicomponent asymmetric. The group of middle-aged patients was the most diverse in terms of the occurrence of risk factors, solar lentiginosis, dermoscopic patterns, topography, histological subtypes, and invasiveness of melanomas. The oldest group characterized a strong correlation between solar lentiginosis, NMSC comorbidity, the prevalence of facial melanomas, the dermoscopic pattern of melanoma arising on chronic sun-damaged skin, and regression. CONCLUSION: The findings regarding the presence of age-specific features in melanoma patients, especially in the youngest and middle-aged groups, might be helpful for clinicians and to target secondary prevention efforts.

[Smooth muscle tumor of uncertain malignant potential (STUMP)--clinico-pathomorphological analysis of the cases and literature review]. / Guz gladkomiesniowy o nieokreslonym potencjale zlosliwosci (STUMP)--analiza kliniczno-patomorfologiczna przypadków oraz przeglad pismiennictwa.

OBJECTIVES: This retrospective study was designed to evaluate the clinical and pathological features and outcomes of patients diagnosed with uterine smooth muscle tumor of uncertain malignant potential (STUMP). MATERIAL AND METHODS: Ten patients diagnosed with uterine STUMP and seen between 2008 and 2011 at the Memorial Cancer Center--Institute of Oncology in Warsaw were identified using the institution databases. Variables of interest included histopathological details, age at diagnosis, types of treatment and recurrence rate. RESULTS: The mean age at diagnosis was 41 years (range 25-56 years). The mean follow-up time was 16 months (range 4-29 months). Diameter of the tumors ranged from 3 to 29 cm. Uterine bleeding was the second most frequent symptom observed in this cohort In three cases conservative procedure was performed, whereas in other patients hysterectomy was performed. No recurrence was observed during the follow-up period. In all tumors mitoses were less than 10 per 10/hpf, atypia of middle or severe type, and in 3 cases necrosis was observed. In half of the tumors expression of TP53 was found, and value of MIB 1 was estimated at 2-35%. CONCLUSIONS: STUMP should be diagnosed by experienced pathologists due to the fact that they are often misdiagnosed as leiomyosarcomas. Clinical behavior of these tumors allows to consider a conservative management in patients wishing to preserve fertility

Diabetes Mellitus and Pancreatic Ductal Adenocarcinoma-Prevalence, Clinicopathological Variables, and Clinical Outcomes.

BACKGROUND: pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related deaths with increasing incidence and link to the onset of diabetes mellitus (DM). The aim of this study is to describe the prevalence of DM among patients with the diagnosis of PDAC, analyse the association between the occurrence of DM and clinicopathological factors, and detect variables influencing overall survival. METHODS: a retrospective analysis of medical records was performed. The patients were divided into non-DM (n = 101) and DM (n = 74) groups. Statistical analysis with the usage of appropriate tests was conducted. RESULTS: Patients in the groups of DM and NODM had significantly longer median OS than the non-DM group. Nodal involvement, tumour location, level of CEA, CRP and CRP/lymphocytes ratio were significantly associated with OS among patients with any type of DM. Neutropenia was less frequently observed in the DM group. CONCLUSIONS: DM is prevalent among patients with pancreatic cancer. In our study, patients with DM receiving palliative chemotherapy had significantly higher median OS than those without DM. The increased comprehension of the mechanisms of the relationship between DM and pancreatic cancer needs further research, which might provide avenues for the development of novel preventive and therapeutic strategies.

Polish Consensus on Gastric Cancer Diagnosis and Treatment - Update 2022.

This document - "Polish Consensus on Gastric Cancer Diagnosis and Treatment - Update 2022" - represents an expert consensus following a year's worth of dedicated effort by a team of specialists throughout 2021, put forward in a conference in December 2021 in Krakow, and finalized below for publication in 2022. The effective date of this document is June 14th 2022. The work that went into updating this consensus was made under auspices of the Polish Society of Surgical Oncology and the Association of Polish Surgeons.

Update of the diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours) [Aktualizacja zalecen ogólnych dotyczacych postepowania diagnostyczno-terapeutycznego w nowotworach neuroendokrynnych ukladu pokarmowego (rekomendowane przez Polska Siec Guzów Neuroendokrynnych)].

Continuous progress in the diagnostics and treatment of neuroendocrine neoplasms (NENs), the emerging results of new clinical trials, and the new guidelines issued by medical societies have prompted experts from the Polish Network of Neuroendocrine Tumours to update the 2017 recommendations regarding the management of neuroendocrine neoplasms. This article presents the general recommendations for the management of NENs, resulting from the findings of the experts participating in the Fourth Round Table Conference, entitled "Polish Guidelines for the Diagnostics and Treatment of Neuroendocrine Neoplasms of the gastrointestinal tract, Zelechów, June 2021". Drawing from the extensive experience of centres treating these cancers, we hope that we have managed to formulate the optimal method of treating patients with NENs, applying the latest reports and achievements in the field of medicine, which can be effectively implemented in our country. The respective parts of this work present the approach to the management of: NENs of the stomach and duodenum (including gastrinoma), pancreas, small intestine, and appendix, as well as large intestine.

Pancreatic neuroendocrine neoplasms - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne trzustki - uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polska Siec Guzów Neuroendokrynych)].

In this paper, we present the current guidelines for the diagnostics and management of pancreatic neuroendocrine neoplasms (PanNENs) developed by Polish experts providing care for these patients in everyday clinical practice. In oncological diagnostics, in addition to biochemical tests, molecular identification with the use of NETest liquid biopsy and circulating microRNAs is gaining importance. Both anatomical and functional examinations (including new radiopharmaceuticals) are used in imaging diagnostics. Histopathological diagnosis along with immunohistochemical examination still constitute the basis for therapeutic decisions. Whenever possible, surgical procedure is the treatment of choice. Pharmacological management including biotherapy, radioisotope therapy, targeted molecular therapy and chemotherapy are important methods of systemic therapy. Treatment of PanNENs requires a multidisciplinary team of specialists in the field of neuroendocrine neoplasms.

Gastroduodenal neuroendocrine neoplasms including gastrinoma - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne zoladka i dwunastnicy z uwzglednieniem gastrinoma - uaktualnione zasady postepowania (rekomendowane przez Polska Siec Guzów Neuroendokrynnych)].

After another meeting of experts of the Polish Network of Neuroendocrine Tumours, updated recommendations for the management of patients with gastric and duodenal neuroendocrine neoplasms, including gastrinoma, have been issued. As before, the epidemiology, pathogenesis and clinical symptoms of these neoplasms have been discussed, as well as the principles of diagnostic procedures, including biochemical and histopathological diagnostics and tumour localisation, highlighting the changes introduced in the recommendations. Updated principles of therapeutic management have also been presented, including endoscopic and surgical treatment, and the options of pharmacological and radioisotope treatment. The importance of monitoring patients with gastric and duodenal NENs, including gastrinoma, has also been emphasised.

Colorectal neuroendocrine neoplasms - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne jelita grubego - uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polska Siec Guzów Neuroendokrynych)].

Colorectal neuroendocrine neoplasm (CRNEN), especially rectal tumours, are diagnosed with increased frequency due to the widespread use of colonoscopy, including screening examinations. It is important to constantly update and promote the principles of optimal diagnostics and treatment of these neoplasms. Based on the latest literature and arrangements made at the working meeting of the Polish Network of Neuroendocrine Tumours (June 2021), this paper includes updated and supplemented data and guidelines for the management of CRNEN originally published in Endokrynologia Polska 2017; 68: 250-260.

Neuroendocrine neoplasms of the small intestine and the appendix - update of the diagnostic and therapeutic guidelines (recommended by the Polish Network of Neuroendocrine Tumours) [Nowotwory neuroendokrynne jelita cienkiego i wyrostka robaczkowego - uaktualnione zasady diagnostyki i leczenia (rekomendowane przez Polska Siec Guzów Neuroendokrynnych)].

Updated Polish recommendations for the management of patients with neuroendocrine neoplasms (NENs) of the small intestine (SINENs) and of the appendix (ANENs) are presented here. The small intestine, and especially the ileum, is one of the most common locations for these neoplasms. Most of them are well-differentiated and slow-growing tumours; uncommonly - neuroendocrine carcinomas. Their symptoms may be untypical and their diagnosis may be delayed or accidental. Najczesciej pierwsza manifestacja ANEN jest jego ostre zapalenie. Typical symptoms of carcinoid syndrome occur in approximately 20-30% of SINENs patients with distant metastases. In laboratory diagnostics the assessment of 5-hydroxyindoleacetic acid concentration is helpful in the diagnosis of carcinoid syndrome. The most commonly used imaging methods are ultrasound examination, computed tomography, magnetic resonance imaging, colonoscopy and somatostatin receptor imaging. Histopathological examination is crucial for the proper diagnosis and treatment of patients with SINENs and ANENs. The treatment of choice is a surgical procedure, either radical or palliative. Long-acting somatostatin analogues (SSAs) are essential in the medical treatment of functional and non-functional SINENs. In patients with SINENs, at the stage dissemination with progression during SSAs treatment, with high expression of somatostatin receptors, radioisotope therapy should be considered first followed by targeted therapies - everolimus. After the exhaustion of the above available therapies, chemotherapy may be considered in selected cases. Recommendations for patient monitoring are also presented.