Anemia, Iron Deficiency, and Iron Regulators in Pancreatic Ductal Adenocarcinoma Patients: A Comprehensive Analysis.

Anemia and iron deficiency (ID) are common complications in patients with pancreatic ductal adenocarcinoma (PDAC), but their underlying causes remain unclear. This study investigated the incidence and characteristics of anemia and micronutrient deficiencies in PDAC patients before initiating chemotherapy. A total of 103 PDAC patients were included, comprising 67 in the palliative and 36 in the adjuvant groups. The overall incidence of anemia was 42.7% (n = 44), with comparable rates in both groups. Normocytic and normochromic anemia were predominant, with mild and moderate cases observed in 32% and 10.7% of the cohort, respectively. ID was evident in 51.4% of patients, with absolute ID more frequent in the adjuvant than in the palliative group (19.4% vs. 13.4%). Functional ID occurred more often in the palliative than in the adjuvant group (41.8% vs. 25%). Vitamin B12 and folate deficiency occurred in <5% (n = 5) of patients. Furthermore, 8.7% (n = 9) of patients had chronic kidney disease and anemia. To elucidate mechanisms of iron deficiency, the study explored the expression of iron regulators (hepcidin (HEP), ferroportin (FPN), and ZIP14 protein) and mitochondrial mass in PDAC tissue with immunohistochemical (IHC) staining and Perl's Prussian blue to detect iron deposits on available tumor samples (n = 56). ZIP14 expression was significantly higher in less advanced tumors (p = 0.01) and correlated with mitochondrial mass (p < 0.001), potentially indicating its role in local iron homeostasis. However, no significant impact of tissue iron regulators on patient survival was observed. Perl's Prussian blue staining revealed iron deposits within macrophages, but not in pancreatic duct cells. Furthermore, the GEPIA database was used to compare mRNA expression of iron regulators (HEP, FPN, and ZIP14) and other genes encoding iron transport and storage, including Transferrin Receptor Protein 1 (TfR1) and both ferritin chain subunits (FTH and FTL), in PDAC and normal pancreatic samples. FPN, TfR1, FTH, and FTL showed higher expression in tumor tissues, indicating increased iron usage by cancer. ZIP14 expression was higher in the pancreas than in PDAC and was correlated with FPN expression. The study highlights the importance of baseline iron status assessment in managing PDAC patients due to the high incidence of anemia and iron deficiency. Furthermore, ZIP14, in addition to HEP and FPN, may play a crucial role in local iron homeostasis in PDAC patients, providing valuable insights into the underlying mechanisms of iron dysregulation.

The Clinical Tumor Lysis Syndrome in a Patient with Mixed Phenotype Acute Leukemia Undergoing Induction with Venetoclax and Azacitidine: A Case Report.

A combination of azacitidine and venetoclax (AZA-VEN) has been approved for the treatment of adult treatment-naïve acute myeloid leukemia (AML) patients, ineligible for intensive chemotherapy. The protocol may also constitute an alternative for the treatment of patients with mixed phenotype acute leukemia (MPAL), for which no established treatment guidelines exist. It may be anticipated, that alike in AML or chronic lymphocytic leukemia, the treatment of MPAL may be complicated by the tumor lysis syndrome (TLS). No case of TLS in MPAL after VEN has been however reported so far. Here, we present a case of a patient with MPAL, who received AZA-VEN. The patient had a substantial bulk of disease with generalized lymphadenopathy and increased white blood cell count. Despite preventive measures, the patient developed the clinical TLS, which was successfully treated. Based on the current case and other published cases, the incidence of TLS after AZA-VEN was established at 17%.

Leukaemia cutis for clinicians, a literature review.

Leukaemia cutis (LC) describes infiltration of the skin by leukaemia cells, resulting in clinically identifiable cutaneous lesions. LC has a wide range of clinical manifestations, which can make it difficult to distinguish LC from other skin changes. In a group of patients, LC can be the first manifestation of leukaemia, therefore skin biopsy is crucial for the diagnosis. In this mini review, we discuss various types of leukaemia most frequently represented in leukaemia cutis, in both children and adults and skin changes in multiple myeloma, focusing on the clinical presentation of LC and prognosis in patients.

PEComa-A Rare Liver Tumor.

PEComa (perivascular epithelioid cell tumor) is a rare liver tumor. Decisions regarding patient management are currently based on a few small case series. The aim of this study was to report the clinicopathological features of PEComa in order to provide guidance for management, complemented by our own experience. This retrospective observational study included all patients with PEComa who underwent surgical treatment in two departments between 2002 and 2020. A total of 20 patients were diagnosed with PEComa following histopathological examination. The age of the patients ranged from 21 to 73 years. The majority of patients were women (85%). In most patients, the tumors were incidental. In diagnostic studies, PEComas with high arterial vascularization have been described. Liver resection was the treatment of choice. There was only one postoperative complication. During histopathological evaluation, tumors were composed mostly of epithelioid cells, rarely with spindle cell components, thick-walled vessels, and adipocytes in different proportions. Melanocytic markers (HMB45, MelanA) and at least one smooth muscle marker were expressed in all tumors. Features suggestive of malignancy were found in three cases. In conclusion, PEComa is a rare liver tumor that is usually diagnosed incidentally. In radiological studies, tumors with high arterial vascularization are observed. Liver resection is the treatment of choice.

Intraductal papillary neoplasm of the bile duct - A comprehensive review.

BACKGROUND: Intraductal papillary neoplasm of the bile ducts is a rare tumor type. Management decisions are currently based upon a small case series. The authors have large own experience with IPNB. OBJECTIVE: The review aims at reporting on clinicopathological features of IPNB in order to provide guidance for management. METHODS: We searched PubMed, Medline, Microsoft Academic and Embase databases to identify studies of relevance. The analysis of own experience was also included. RESULTS: We analyzed 59 retrospective series and 25 cases from authors' clinical experience. The main sign was jaundice and cholangitis, 33% and 48%, respectively. CT's were performed in 63-76% and MR in 40-56%. Intraductal mass was found in 31-32% and duct dilatation in 27-30%. Endoscopic Retrograde Cholangio-Pancreatography (ERCP) was performed in 48-62%. IPNB with invasive carcinoma was found in 35.7-60% and IPNB with intraepithelial neoplasia in 36-60%. Histopathological confirmation before surgery was rare. The main treatment of IPNB is resection, in our material, both, hepatectomy and hepatectomy plus bile duct resections were performed in 40% of patients. The percentage of postoperative complications was 20%. The 5-year survival rate of all IPNB's patients was 53.6%; in patients with associated invasive carcinoma - 22.2% and without invasive carcinoma - 100% (p â€‹= â€‹0.001). CONCLUSIONS: Early surgery is advisable for radiologically suspected IPNB. The results of treatment depend on histopathology. They are worse at intraductal invasive carcinoma than at neoplasm with neoplasia.

[68 Ga]Ga-Prostate-Specific Membrane Antigen PET/CT: a novel method for imaging patients with hepatocellular carcinoma.

PURPOSE: Prostate-specific membrane antigen (PSMA) is not only highly expressed on the surface prostate cancer cells but is also elevated during angiogenesis in other cancer cell types, including hepatocellular carcinoma (HCC). This study aimed to evaluate the feasibility of using PET/CT imaging with [68Ga]Ga-PSMA-11 in HCC and its impact on patient management. METHODS: Fifteen patients (13 men and two women; aged 55.6 ± 18.2 years) with HCC were enrolled in this prospective, single-institution study. All patients underwent contrast-enhanced MRI/CT, [68Ga]Ga-PSMA-11 PET/CT, and histopathological verification of lesions. RESULTS: No radiopharmaceutical-related adverse events were noted. Visual interpretation showed increased accumulation of [68Ga]Ga-PSMA-11 in all HCC patients. The tumor-to-liver ratio (TLR) was 3.6 ± 2.1, and the maximal standardized uptake value (SUVmax) was 13.5 ± 7.1. There were no significant differences in the SUVs or TLR between newly diagnosed and recurrent patients. No statistically significant relationship was found between serum concentration of tumor markers (i.e., AFP, CA 19-9, CEA) and PET parameters. Results of the [68Ga]Ga-PSMA-11 PET/CT changed the treatment strategy in five (33%) patients. PSMA staining showed visible heterogeneity in terms of intensity and distribution: the reaction was weak and only observed in a few vessels in pseudoglandular patterns of HCC, while it was homogeneously strong, with some hot spots, in trabecular patterns of HCC. CONCLUSION: [68Ga]Ga-PSMA-11 PET/CT can detect PSMA expression in vivo in patients with HCC and is useful for guiding treatment strategies. Further investigation of the clinical utility of this method in HCC is warranted.

Eosinophilic gastroenteritis and graft-versus-host disease induced by transmission of Norovirus with fecal microbiota transplant.

Fecal microbiota transplantation (FMT) was performed to decolonize gastrointestinal tract from antibiotic-resistant bacteria before allogeneic hematopoietic cells transplantation (alloHCT). AlloHCT was complicated by norovirus gastroenteritis, acute graft-versus-host disease, and eosinophilic pancolitis. Norovirus was identified in samples from FMT material. Symptoms resolved after steroids course and second norovirus-free FMT from another donor.

Tandem Allogeneic Hematopoietic Stem Cell Transplantation for Salvage Treatment of Acute Myeloid Leukemia Refractory to Induction Chemotherapy: A Case Report.

BACKGROUND: Primary refractory acute myeloid leukemia (AML) is associated with dismal prognosis. No standard treatment options are available, and it remains an unmet clinical need. Here, we report a case of a tandem allogeneic hematopoietic stem cell transplantation (allo-HSCT) performed in a patient who did not achieve remission after 2 courses of induction chemotherapy. METHODS CASE REPORT: The treatment was approved by the Bioethical Commission of the Medical University of Warsaw and was performed in accordance with the Declaration of Helsinki. The patient gave informed consent. RESULTS: A 41-year-old woman was diagnosed with AML, high cytogenetic risk, with concomitant skin and central nervous system involvement, bone marrow necrosis, and hemophagocytic lymphohistiocytosis. She received "3+7" induction and HAM (cytarabine, mitoxantrone) reinduction, after which she did not achieve remission and hematopoietic recovery. Tandem allo-HSCT was performed from the same HLA-identical brother---the first after reduced intensity conditioning (cladribine, cytarabine, mitoxantrone, melphalan) and the second after myeloablative conditioning (BuCy--busulphan, cyclophosphamide). The patient obtained complete remission after the first allo-HSCT and remains disease-free after the second for 5 years CONCLUSION: Tandem allo-HSCT may be a treatment option for primary refractory AML.

Expression of resistin in the liver of patients with non-alcoholic fatty liver disease.

Adipokines are cytokines that presumably connect the pathologies of metabolic syndrome. One of the adipokines is resistin, the role of which in insulin resistance, obesity, and non-alcoholic fatty liver disease (NAFLD) needs to be determined. Liver biopsy specimens were obtained intraoperatively from 214 obese patients. Histological assessment was based on NAFLD activity score according to Kleiner. Statistical analysis involved semi-quantitive immunohistochemistry assessment of resistin staining and: NAFLD status in obese patients compared with a non-obese control group, selected clinical data (age, sex, body mass index - BMI), selected biochemical data, comorbidities (hypertension, type 2 diabetes mellitus, dyslipidaemia), and metformin treatment in patients with type 2 diabetes mellitus. Resistin expression was observed in the histiocytes of inflammatory infiltrate, Kupffer cells, and histiocytes surrounding the hepatocytes with steatosis. There was a positive correlation between the total expression of resistin and: (1) NAFLD advancement (NAFLD Activity Score- NAS), (2) AST, ALT, BMI, glucose, insulin, Homeostasis Model Assessment (HOMA), LDH, GGT, triglycerides (TG), and glycated haemoglobin (HbA1c). Resistin expression was more intense in patients with type 2 diabetes mellitus and dyslipidaemia and less intense in the control group. Resistin probably plays a role in the pathogenesis of hepatic insulin resistance and aggravates pathologic changes in the liver of patients with NAFLD.

Angiogenesis in CD5-positive Diffuse Large B Cell Lymphoma: A Morphometric Analysis.

BACKGROUND: CD5-positive diffuse large B cell lymphoma (DLBCL) is the least frequent immunohistochemical subgroup of DLBCL. The relatively little available data suggests a worse outcome in this population, resulting from a resistance to chemotherapy. OBJECTIVES: The aim was the comparative assessment of angiogenesis in both CD5-positive and CD5-negative DLBCL, as well as in lymphatic tissues without lymphoproliferative diseases. MATERIAL AND METHODS: The analysis included 36 cases of CD5-positive DLBCL (19 females and 17 males) aged 29-87 years (mean age 69), diagnosed and treated in the Maria Sklodowska-Curie Institute and Oncology Center and Medical University of Warsaw in 2002-2013. The control group comprised 28 cases of CD5-negative DLBCL (14 females and 14 males) aged 24-82 years (mean age 58.5). The secondary control group (13 cases) consisted of normal lymphatic tissue obtained from patients without lymphoproliferative diseases. The level of angiogenesis was assessed on the basis of immunohistochemical CD34, vWF and HIF1α expression measured using morphometric methods. RESULTS: CD5-positive DLBCL, in comparison to CD5-negative DLBCL, was characterized by: (1) higher mean of total blood vessel area, (2) higher mean total ratio of blood vessel area and staining intensity, (3) higher mean of total blood vessel area in regions defined as hot spots, (4) higher mean of total ratio of blood vessel area and staining intensity in hot spots. The measurements in lymph nodes without lymphoproliferative diseases lay between the values obtained in both DLBCL subgroups. CONCLUSIONS: We observed a significant exacerbation of angiogenesis in CD5-positive DLBCL in comparison to the CD5-negative subgroup, possibly explaining its more aggressive clinical course. Our data does not substantiate the hypothesis that angiogenesis is more pronounced in frequent CD5-negative DLBCL subgroup in comparison to benign lymphatic tissue.

Epstein-Barr Virus-Positive Diffuse Large B cell Lymphoma in the Experience of a Tertiary Medical Center in Poland.

The role of Epstein-Barr virus (EBV) in the biology and clinical characteristics of diffuse large B cell lymphoma (DLBCL) is still poorly defined. A new provisional entity EBV-positive DLBCL of the elderly has been described in Asian population. Its incidence and prognosis remains unknown in middle European patients. Clinical data and tissue samples were collected from 74 Caucasian patients with DLBCL, aged between 23 and 86 years, treated at a single institution. Lymphoma morphology was reassessed, laboratory procedures included in situ hybridization specific for EBV-encoded small RNAs (EBER), immunohistochemical staining for latent membrane protein and serological testing for EBV-specific antibodies. EBER staining revealed 12.2 % of EBV-positive cases, whereas 9.5 % were diagnosed as EBV-positive DLBCL of the elderly. Serologic EBV markers did not correlate with the presence of EBV in tissue samples (P > 0.10). Elderly EBV-positive cases had lower BCL-6 (P = 0.038) and higher CD30 (P = 0.049) expression and were characterized by higher progression risk (median time-to-progression 12.5 months vs not reached; P = 0.029) and a trend towards worse overall survival (median overall survival 24.5 months vs not reached; P = 0.059). EBV-positive DLBCL of the elderly occurs relatively frequently in Polish population and may be associated with inferior prognosis in comparison with DLBCL, not otherwise specified.

[A rare CD5-positive subgroup of diffuse large B-cell lymphoma - clinical, morphological and immunophenotypic features in Polish patients].

The aim of the study was to assess the incidence of CD5-positive diffuse large B-cell lymphoma (DLBCL) in the Polish population and to describe its morphologic and clinical characteristics. The study included 36 patients with CD5-positive DLBCL, diagnosed and treated in the Maria Sklodowska-Curie Institute and Oncology Centre, Warsaw, Poland and the Medical University of Warsaw, Poland in the years 2002-2013. The control group consisted of 28 patients with CD5-negative DLBCL. CD5-positive DLBCL accounted for 6.26% of all DLBCL cases diagnosed in the Maria Sklodowska-Curie Institute and Oncology Centre in the years 2008-2012. The incidence is comparable to other European countries, lower than noted in Japan and higher than in the US. Patients with CD5-positive DLBCL, in comparison to the CD5-negative group, were characterized by: (1) older age (≥ 60 vs. younger) and worse general status (ECOG ≥ 2 vs. < 2), (2) lower frequency of complete remission (CR), (3) higher expression of unfavorable prognostic factors (BCL2, FOXP1, CD44) and MMP-9, and (4) lower expression of favorable prognostic factors (CD30, cyclin D1, cyclin D3) and TIMP-2.

C4d in acute rejection after liver transplantation and its usefulness in differential diagnosis between acute liver rejection and hepatitis C recurrence.

BACKGROUND: Acute liver graft rejection is still a common complication after liver transplantations. The diagnostics of this process is based on histological findings, resembling the presentation of HCV infection. Correct differentiation between acute rejection and recurrent HCV hepatitis is very important because of differences in treatment. From the practical point of view, C4d could be used in liver transplantology for differential diagnostics of acute graft rejection and recurrence of HCV infection. MATERIAL AND METHODS: The study was performed in liver graft biopsies obtained from 57 patients with acute rejection and from 26 patients with hepatitis C recurrence. The sections were probed immunohistochemically using antibody specific to C4d. The following parameters were analyzed statistically: the percentage of immunoreactive biopsies, the localization of C4d deposits, and the relationships between C4d-positive biopsies with acute rejection and hepatitis C recurrence. RESULTS: Within liver graft biopsies with acute rejection and hepatitis C recurrence, the immunoreactivities of C4d were present almost exclusively along venous, arterial, and arteriolar endothelium in the portal spaces. C4d deposits were found in 33 patients with acute rejection (57.9%) and in 17 patients with hepatitis C recurrence (65.38%). The study demonstrated no statistically significant difference in C4d expression in liver biopsies from acute graft rejection patients as compared with HCV infection recurrence (chi-squared =1.5566774 df=1 p=0.45560). Both groups demonstrated positive reactions within biopsies. CONCLUSIONS: Our results suggest that C4d deposits are insufficient in differentiation between both examined liver pathologies, but could be a useful marker in the diagnostics of acute liver rejection with humoral component.

Epithelioid hemangioendothelioma of the liver as a rare indication for liver transplantation.

AIM: To investigate the indications and outcomes of liver transplantation for hepatic epithelioid hemangioendothelioma (HEHE). METHODS: Between 1989 and August 2013, in the Department of General, Transplant, and Liver Surgery, Medical University of Warsaw, 1306 orthotopic liver transplantations (OLTx) were performed, including 72 retransplantations. Unresectable HEHE was an indication for OLTx in 10 patients (0.8% of primary OLTx), the mean age of the patients was 40.5 ± 13.3 years (range 23-65 years), and the male-to-female ratio was 2:8. Kaplan-Meier survival analysis in HEHE, hepatocellular carcinoma (HCC), and other OLTx recipients groups was performed. The differences in mortality were compared using the χ(2) test. A P-value < 0.05 indicated statistical significance. RESULTS: No concomitant liver disease was found in any patient. There was no neoadjuvant chemotherapy or radiotherapy. Liver function test results were normal in most of the patients. The levels of alpha-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen 19-9 were normal. In immunohistochemical staining, the neoplastic cells were positive for factor VIII-related antigen, CD31, and CD34, which are endothelial cell markers, and negative for cytokeratin 19, cytokeratin 7, and HepPar-1. Nine patients were alive without tumor recurrence. One patient died 2 mo after OLTx due to septic complications. No morbidity was observed. Maximum follow-up was 11.4 years, with a minimum of 1 mo. The cumulative survival rate at the end of follow-up in HEHE patients was 87.5% compared with 54.3% in the HCC group and 76.3% in the other OLTx recipients group (χ(2) test = 1.784, df = 2, P = 0.409). CONCLUSION: Unresectable HEHE, without extrahepatic metastases is an excellent indication for liver transplantation. Long-term survival is very good and much better than in HCC patients and the entire group of OLTx patients.

[Portal vein thrombosis as the main symptom of unclassified JAK2-positive myeloproliferative neoplasm--case report]. / Zakrzepica ukladu wrotnego jako glówny objaw niesklasyfikowanego JAK2-dodatniego nowotworu mieloproliferacyjnego--opis przypadku.

We report a case of a patient with a diagnosis of myeloproliferative neoplasm, unclassifiable, manifested only portal vein thrombosis and followed by cirrhosis of the liver. 37-year-old patient, previously healthy, without congenital thrombophilia, without prior thrombosis, with normal peripheral blood morphology were signs of extensive portal vein system, with massive collateral circulation. Patient did not meet the criteria for diagnosis of any of the classic myeloproliferative neoplasms. Bone marrow examination revealed hyperplasia and presence of single polymorphic megakaryocytes. Positive JAK2V617F mutation status was typical for myeloproliferative neoplasm. Therefore, that the portal system thrombosis is, sometimes accompanying symptom of other myeloproliferative neoplasm, caused by mutations, including polycythemia vera, essential thrombocythaemia and primary myelofibrisis, one can assume that between this mutation and observed in this patient thrombosis is relationship, despite the absence of changes in peripheral blood. This may suggest that we are dealing with myeloproliferative neoplasm, in which platelets are indeed produced in normal numbers, but they are functionally activated, causing disturbances apparently unusual for cancer. This requires confirmation in further studies.

Role of C3d and C4d complement fragments in the diagnostics of acute allograft rejection after transplantations.

Transplantation is a widely recognized method of treatment at the terminal stages of many renal, cardiac, hepatic and pulmonary diseases. Despite considerable advances in that field, graft rejection is still an important clinical problem. The reaction of the graft recipient to an organ presenting foreign antigens is dependent on complex immune mechanisms, involving both acquired and congenital immune responses. In most general terms, cellular and humoral immunity can be distinguished. The kidneys and the heart are the organs whose acute humoral rejection has been thoroughly investigated and defined, and the role of C4d and C3d fragments of the complement system has been confirmed by numerous studies. The studies concerning C4d and C3d expression in patients with acute humoral lung and liver rejection conducted to date have given contradictory results. Some of them confirm, while others fail to confirm, the correlation between their increased expression and AHR. From the practical point of view, C4d and C3d could be used in liver transplantology for differential diagnostics of acute graft rejection and recurrence of HCV infection. A few preliminary studies suggest the usefulness of these markers in the diagnostics of AMR and differentiation between both liver pathologies. There are only single reports concerning the role of C4d complement fragment in the diagnostics of acute rejection with a humoral component in case of small intestine grafts, as well as complex ones such as the hands and face, and their results suggests that these complement fragments are not important markers of acute rejection of these organs.

[Acute hypercalcaemic crisis in the course of PTH-rP producing squamous cell carcinoma of the skin--a case report]. / Przelom hiperkalcemiczny w przebiegu raka plaskonablonkowego kolczystokomórkowego skóry wydzielajacego PTH-rP--opis przypadku.

Hypercalcemia is one of the most common paraneoplastic syndromes, where it may result from the presence of osteolytic metastases or from humoral effect of factors produced by tumor cells. One of such factors is the parathyroid hormone-related protein (PTH-rP). This protein is usually produced by solid tumors, especially by squamous cell carcinomas. In the case of squamous cell carcinoma of the skin hypercalcemia is very rare and symptomatic hypercalcemia is unusual. We present a case of acute hypercalcemic crisis as a consequence of overproduction of PTH-rP in a patient with spinocellular squamous cell carcinoma of the skin, which was proved by immunohistochemical staining of the tissue samples from the neoplastic lesion, metastases in bone and in lung, and also from kidney and liver.