Oncologic outcomes of the most prevalent major salivary gland cancers: retrospective cohort study from single center.

BACKGROUND: The preoperative diagnosis of salivary gland cancer (SGC) is crucial for the application of appropriate treatment, particularly involving the extension of the resection. METHODS: Retrospective search of medical database identified 116 patients treated surgically with malignant tumors of salivary gland between 2010 and 2020. Analysis included the demographical data, clinical course, type of surgical and adjuvant treatment, histology type and margin status, perivascular invasion (LVI), perineural invasion (PNI), metastatic lymph nodes (LN). Facial nerve function, recurrence-free and overall survival were evaluated. Adequate statistics were used for data analysis. RESULTS: The final cohort included 63 SGC patients, with adenoid cystic carcinoma the most common pathological type (27%, n = 17), followed by adenocarcinoma (17.4% n = 11). T1 and T2 patients accounted for majority cases (n = 46). The lymph node metastases were confirmed with the histopathology in 31.7% (n = 20). Distant metastases were observed in 4.8% of cases (n = 3). 38% (n = 24) of SGC were treated selectively with surgery, 49.2% (n = 31) had postoperative radiotherapy and 15.9% (n = 10)-radio-chemotherapy. The final facial nerve function was impaired in 38% of patients. Mean overall survival (OS) for all patients was 108.7 (± 132.1) months, and was the most favorable for acinar cell carcinoma (118.9 ± 45.4) and the poorest for squamous cell carcinoma (44 ± 32). Cox regression analysis of disease-free survival and OS identified significant association only with patients' age over 65 years, the hazard ratio of 7.955 and 6.486, respectively. CONCLUSIONS: The efficacy of treatment modalities for SGC should be verified with regard to the histopathological type, but also the patients' age should be taken into account.

Clinico-Epidemiological Analysis of Most Prevalent Parotid Gland Carcinomas in Poland over a 20-Year Period.

(1) Background: Malignant tumours of the salivary glands have different clinical and histopathological characteristics. They most commonly involve the parotid gland. Histopathologically, the most common are mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (AcCC), adenocarcinoma, carcinoma in pleomorphic adenoma (CPA), and squamous cell carcinoma (SCC). (2) Methods: We analysed 2318 patients with malignant parotid gland tumours reported to the National Cancer Registry (NCR) in Poland over 20 years (1999-2018). The demographic characteristics of patients, clinical factors, and overall survival (OS) were analysed. (3) Results: The average age was 61.33 ± 16.1 years. The majority were males (55%) and urban citizens (64%). High percentage of carcinomas was diagnosed in locoregional (33.7%) and systemic (10.4%) stadium. The most prevalent diagnoses were SCC (33.3%) and adenocarcinoma (19.6%). Surgical resection with adjuvant RT (42.1%) was the most common treatment. The OS analysis showed a median survival time of 5.6 years. The most favorable median OS was found in patients with AcCC (18.30 years), the worst for SCC (1.58 years). (4) Conclusion: AcCC has the best prognosis and SCC the worst. Tumour stadium, treatment, and demographic factors affect prognosis. Improvements in diagnosis and re-evaluation of treatment standards are necessary to enhance the outcome of patients with parotid gland cancers in Poland.

The Hygiene Hypothesis and New Perspectives-Current Challenges Meeting an Old Postulate.

During its 30 years history, the Hygiene Hypothesis has shown itself to be adaptable whenever it has been challenged by new scientific developments and this is a still a continuously ongoing process. In this regard, the mini review aims to discuss some selected new developments in relation to their impact on further fine-tuning and expansion of the Hygiene Hypothesis. This will include the role of recently discovered classes of innate and adaptive immune cells that challenges the old Th1/Th2 paradigm, the applicability of the Hygiene Hypothesis to newly identified allergy/asthma phenotypes with diverse underlying pathomechanistic endotypes, and the increasing knowledge derived from epigenetic studies that leads to better understanding of mechanisms involved in the translation of environmental impacts on biological systems. Further, we discuss in brief the expansion of the Hygiene Hypothesis to other disease areas like psychiatric disorders and cancer and conclude that the continuously developing Hygiene Hypothesis may provide a more generalized explanation for health burden in highly industrialized countries also relation to global changes.

Discovery of Stromal Regulatory Networks that Suppress Ras-Sensitized Epithelial Cell Proliferation.

Mesodermal cells signal to neighboring epithelial cells to modulate their proliferation in both normal and disease states. We adapted a Caenorhabditis elegans organogenesis model to enable a genome-wide mesodermal-specific RNAi screen and discovered 39 factors in mesodermal cells that suppress the proliferation of adjacent Ras pathway-sensitized epithelial cells. These candidates encode components of protein complexes and signaling pathways that converge on the control of chromatin dynamics, cytoplasmic polyadenylation, and translation. Stromal fibroblast-specific deletion of mouse orthologs of several candidates resulted in the hyper-proliferation of mammary gland epithelium. Furthermore, a 33-gene signature of human orthologs was selectively enriched in the tumor stroma of breast cancer patients, and depletion of these factors from normal human breast fibroblasts increased proliferation of co-cultured breast cancer cells. This cross-species approach identified unanticipated regulatory networks in mesodermal cells with growth-suppressive function, exposing the conserved and selective nature of mesodermal-epithelial communication in development and cancer.

Redeployment of Myc and E2f1-3 drives Rb-deficient cell cycles.

Robust mechanisms to control cell proliferation have evolved to maintain the integrity of organ architecture. Here, we investigated how two critical proliferative pathways, Myc and E2f, are integrated to control cell cycles in normal and Rb-deficient cells using a murine intestinal model. We show that Myc and E2f1-3 have little impact on normal G1-S transitions. Instead, they synergistically control an S-G2 transcriptional program required for normal cell divisions and maintaining crypt-villus integrity. Surprisingly, Rb deficiency results in the Myc-dependent accumulation of E2f3 protein and chromatin repositioning of both Myc and E2f3, leading to the 'super activation' of a G1-S transcriptional program, ectopic S phase entry and rampant cell proliferation. These findings reveal that Rb-deficient cells hijack and redeploy Myc and E2f3 from an S-G2 program essential for normal cell cycles to a G1-S program that re-engages ectopic cell cycles, exposing an unanticipated addiction of Rb-null cells on Myc.

Texture and color based image segmentation and pathology detection in capsule endoscopy videos.

This paper presents an in-depth study of several approaches to exploratory analysis of wireless capsule endoscopy images (WCE). It is demonstrated that versatile texture and color based descriptors of image regions corresponding to various anomalies of the gastrointestinal tract allows their accurate detection of pathologies in a sequence of WCE frames. Moreover, through classification of single pixels described by texture features of their neighborhood, the images can be segmented into homogeneous areas well matched to the image content. For both, detection and segmentation tasks the same procedure is applied which consists of features calculation, relevant feature subset selection and classification stages. This general three-stage framework is realized using various recognition strategies. In particular, the performance of the developed Vector Supported Convex Hull classification algorithm is compared against Support Vector Machines run in configuration with two different feature selection methods.

Serum adiponectin, resistin, leptin concentration and central adiposity parameters in Barrett's esophagus patients with and without intestinal metaplasia in comparison to healthy controls and patients with GERD.

BACKGROUND/AIMS: Central obesity is a risk factor for GERD, Barrett's esophagus and esophageal adeno-carcinoma. Recent studies have suggested that adipocytokines are the possible link between adiposity and Barrett's carcinogenesis. To determine the adiponectin, resistin and leptin concentration as well as the central adiposity parameters in BE patients with and without intestinal metaplasia (IM) in comparison to GERD and healthy controls. METHODOLOGY: Total of 77 patients (30 patients with GERD, 26 BE with IM and 21 BE without IM) and 30 healthy controls were investigated for the central obesity parameters. Serum levels of adipocytokines were measured with ELISA. RESULTS: The serum concentration of adiponectin was significantly lower in BE compared to those in GERD and to controls (p<0.001). Levels of leptin was slightly higher in BE than in GERD and controls (NS). Level of resistin was significantly higher in GERD compared to both control and BE patients (p<0.001). Waist circumference, WHR and WTR were significantly higher in BE patients compared to GERD (p<0.001) and to control group (p<0.001). CONCLUSIONS: Features of central obesity rather than BMI are associated with BE development. Adipokines may be important at the early step of BE development, before the IM occurrence.

Circulating levels of visfatin, resistin and pro-inflammatory cytokine interleukin-8 in acute pancreatitis.

BACKGROUND: Resistin and visfatin, hormones produced by adipose tissue, have pro-inflammatory potential; however, their role in acute pancreatitis (AP) has been investigated only rarely. METHODS: The study group comprised 32 patients with alcoholic AP and 30 controls. In all cases AP was classified as C according to Balthazar's CT score and as severe according to Ranson's criteria. The serum level of visfatin, resistin, and interleukin(IL)-8 immunoassays were measured by ELISA on admission and on the third and fifth day of hospitalization. RESULTS: On the admission day serum resistin and IL-8 concentrations in AP patients were significantly higher than in controls and they further increased on the third and fifth day of hospitalization. On the admission day serum visfatin levels in AP patients were significantly higher than in controls and further increased on the third day of hospitalization. On the fifth day the levels decreased; however, they were still higher than on admission. The correlation between visfatin and resistin as well as between C-reactive protein and visfatin, resistin and IL-8 levels has been found. CONCLUSION: In the course of AP, visfatin and resistin levels increase in parallel with C-reactive protein. We speculate that those parameters may provide an additional tool for the prognosis and monitoring of AP. and IAP.

Usefulness of assessing circulating levels of resistin, ghrelin, and IL-18 in alcoholic acute pancreatitis.

OBJECTIVES: Acute pancreatitis (AP) is a severe inflammatory disease with high mortality and morbidity rates. We have previously demonstrated that resistin may represent an early marker of inflammation in AP. It was also revealed that ghrelin may have anti-inflammatory potential. However, the role of adipohormones in AP-resistin and ghrelin as well as the proinflammatory cytokine interleukin (IL)-18-has not yet been fully elucidated. METHODS: The study group comprised 32 patients with alcoholic AP and 30 controls matched for age, sex, and body mass index (BMI). In all cases AP was classified as grade C according to Balthazar's computed tomography (CT) score and as severe (3 points) according to Ranson's criteria. Serum levels of resistin, ghrelin, and IL-18 were measured on first, third, and fifth day of hospitalization by enzyme-linked immunosorbent assay (ELISA). RESULTS: On first day of hospitalization the mean serum resistin concentration in AP patients was significantly higher than in controls (P < 0.05) and further increased on third and fifth day of hospitalization (17.4 ± 4.23 ng/ml and 25.8 ± 8.14 ng/ml, respectively). On first day of hospitalization the mean serum IL-18 concentration in AP patients was significantly higher than in controls (P < 0.05), on third day its level further increased, and on fifth day it decreased to a level similar to that observed on admission. The serum ghrelin concentrations on first, third, and fifth day of hospitalization were comparable, and significantly higher than in controls (P < 0.01). Significant correlation between C-reactive protein (CRP) and resistin levels (r = 0.43; P < 0.05) and between CRP and IL-18 (r = 0.58; P <0.05) on day of admission was found. CONCLUSIONS: Serum concentration of IL-18 and resistin may contribute to inflammatory response and may be useful as an early marker of inflammation in AP. We also suspect that ghrelin affects the course of AP and plays an important role in inflammatory response.

Two cases of severe de novo colitis in kidney transplant recipients after conversion to prolonged-release tacrolimus.

Diarrhea is a frequent complication in patients after solid organ transplantation. We describe two cases of severe new onset colitis in kidney transplant recipients that developed shortly after the introduction of the therapy with prolonged-release formulation of tacrolimus replacing standard twice daily formulation of tacrolimus in one case and cyclosporine A in the second case. Both patients developed severe, intermittent bloody diarrhea with abdominal pain, weight loss, dehydration and worsening graft function that required immediate hospitalization. The symptoms did not diminish after dose reduction or withdrawal of mycophenolic acid derivatives. After excluding bacterial, viral, fungal, and parasite infections, colonoscopy with colonic biopsy was performed in both patients, which revealed features typical of colitis. Both patients received mesalazine until the symptoms stopped. In one of the patients, standard formulation of tacrolimus was immediately reintroduced. The second patient was given everolimus in an acute phase of diarrhea. Although the two cases presented in this report cannot fully support a causal relationship between the prolonged-release tacrolimus and colitis, they should increase awareness among transplant physicians and prompt more close monitoring of such potential side effects as a part of the pharmacovigilance plan for a new formulation of the well-established immunosuppressive drug.

Clinical utility of serological markers in inflammatory bowel disease.

BACKGROUND/AIMS: The role of perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) assessment in inflammatory bowel disease (IBD) diagnosis and differentiating is still imprecise and controversial. The aim of the study was to determine the accuracy of pANCA and ASCA in patients with IBD subgroups. METHODOLOGY: The study was performed in 125 patients: 71 patients with ulcerative colitis (UC), 31 with Crohn's disease (CD) and 23 with indeterminate Colitis (IC). Control group consists of 45 patients with functional intestinal disorders. pANCA and ASCA (IgA and IgG) were measured with ELISA, using commercial antibody panel. RESULTS: In UC patients the prevalence of pANCA was 68%, which was significantly higher than in CD-29%. ASCA were found significantly more often in CD-80.6% than in UC patients-26.8%. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of pANCA for UC diagnosis was 68%, 84%, 75% and 78%; and ASCA for CD: 81%, 78%, 45,5% and 95%, respectively. The combined use of these two markers gave changes in diagnostic accuracy: pANCA+/ASCA- in UC: 42%, 100%, 100% and 43%, and for pANCA-/ASCA+ in CD: 52%, 98.6% 94% and 82%, respectively. CONCLUSIONS: The specificity of these combined markers tends to be higher than sensitivity, what made them more useful in the differentiation of the IBD subtypes rather than population screening. The characteristic IC serotype pANCA(-)ASCA(-) leads to further controversies about origin of this IBD subtype.

Serum leptin, adiponectin, and resistin concentration in colorectal adenoma and carcinoma (CC) patients.

INTRODUCTION: Leptin, adiponectin, and resistin are the proteins secreted by adipocytes, which affects the metabolism. While the role of leptin in colon carcinogenesis is documented, the effect of adiponectin and resistin remains unclear. It has been indicated that while leptin may potentiate the cancer cells growth, adiponectin and resistin may act oppositely. AIM: The aim of this study is to determine the concentration of leptin, adiponectin, and resistin in patients with adenomatous polyps and colorectal cancer. METHODS: The serum concentration investigated adipohormones had been measured with ELISA in 37 patients with colorectal adenomas, 36 with colorectal cancer (CC) and in 25 controls with no colorectal pathology. Endoscopically removed polyps and CC biopsies had been evaluated with histopathology. Mean BMI value was calculated for all patients. RESULTS: Among 37 adenomas, 25 revealed high-grade dysplasia (HGD) and 12 low-grade dysplasia (LGD). All cases of CC were adenocarcinomas. No difference in the level of investigated adipohormones in serum between patients with HGD and LGD polyps was observed. The serum concentration of leptin and adiponectin in CC patients was lower than in patients with adenomas (p < 0.05; p < 0.05, respectively) as well as in controls (p < 0.01; p < 0.05, respectively). The concentration of resistin in CC was not significantly different in the adenoma group (p > 0.05) but higher than in controls (p < 0.05). There was a correlation between adiponectin and leptin serum concentration (r = 0.61). CONCLUSION: We conclude that serum concentration of adiponectin and resistin may play an important role in colon carcinogenesis. We also assume that leptin may possibly have the prognostic value useful in clinical practice and its concentration is independent of BMI value.

[Resistin-- a new laboratory marker useful in diagnosis of acute pancreatitis?]. / Rezystyna--nowy marker laboratoryjny przydatny w rozpoznaniu ostrego zapalenia trzustki?

UNLABELLED: Acute pancreatitis (AP) is the severe disease with high mortality and morbidity which pathomechanism is still not clearly elucidated yet. Serum pro-inflammatory cytokines like Interleukin-18, TNF alpha, and C-reactive protein (CRP) are elevated in patients with AP, particularly of severe clinical course. Adipocytes hyperplasia is a trigger factor that initiates chronic inflammatory state which release adipocytokines, like TNF alpha or leptin or resistin. The aim of the present study was to assesses the serum resistin concentrations in AP patients and evaluate the correlation between resistin and the well known inflammation marker--CRP. MATERIAL AND METHODS: The study group comprised 30 patients with acute pancreatitis class B according to Balthazar scale, aged 35-82, in which during first 24h of hospitalization serum resistin and CRP has been assessed. Control group consisted of 30 healthy volunteers, aged 33-76. RESULTS: The mean serum resistin concentration was significantly higher in AP patients than in controls (8,38 +/- 4.87 ng/ml vs. 3.58 +/- 1.51 ng/ml) (fig. 1). The positive correlation between serum resistin and CRP concentrations has been observed (r = 0.57, p < 0.05) (fig. 2). CONCLUSIONS: The results of our study suggest, that the serum concentration of resistin may represent the useful additionary marker of inflammatory response in AP

Transforming growth factor beta 1 and metalloproteinase-9 overexpression in colorectal cancer (CC) and adenoma.

BACKGROUND AND AIMS: Although the role of transforming growth factor beta (TGFbeta) 1 and metalloproteinase-9 (MMP-9) is well documented in colorectal cancer (CC), there is a little evidence supporting its role in early carcinogenesis. The aim of the study was to determine the pattern of immunohistochemical expression of TGFbeta1, MMP-9, and Ki-67 in CC and adenomatous polyps. PATIENT/METHODS: The study group comprised 50 patients with colorectal polyps and 33 patients with CC. Endoscopically removed polyps and CC biopsies had been evaluated with histopatologic examination and immunohistochemistry. The biopsies from 30 healthy objects served as a control group. For all antibodies labeling indices (LI) had been calculated. RESULTS: Among 62 adenomas, 33 high-grade dysplasia (HGD) and 29 low-grade dysplasia (LGD) had been detected. Mean TGFbeta1, MMP-9, and Ki-67 LI in CC were significantly higher (p < 0.01, 0.01, and 0.01, respectively) than in HGD polyps. Mean TGFbeta1, MMP-9, and Ki-67 LI in HGD polyps were significantly higher than in LGD polyps (p < 0.01, 0.01, and 0.01, respectively). There had been no statistical difference in TGFbeta1, MMP-9, and Ki-67 LI between LGD and the control group (p > 0.05, 0.05, and 0.05, respectively). There was a positive correlation between TGFbeta1 and MMP-9 (r = 0.898), Ki-67 and MMP-9 (r = 0.938), and TGFbeta1 and Ki-67 (r = 0.913). We did not observe any correlation between TGFbeta1, MMP-9, Ki-67 LI and the clinical parameters evaluated. CONCLUSION: The increased expression of TGFbeta1, MMP-9 observed in colorectal adenomas seems to be related to the grade of dysplasia. We assume that overexpression of TGFbeta1, MMP-9 represent an early event in colorectal carcinogenesis and may possibly have the prognostic value.

[Theoretical background of cancer treatment targeting EGF-R signal transduction pathways]. / Podstawy teoretyczne leczenia nowotworów ukierunkowane na drogi sygnalowe receptora czynników wzrostowych rodziny naskórkowego czynnika wzrostu.

Epidermal growth factor receptor (EGFR) belongs to the most extensively studied binding sites with considerable biological significance. Activation of tyrosine kinase, localised in the intracellular domain of this receptor, initiates the next steps in the intracellular signal transduction pathway. Recently, many compounds that block the particular stages of signal transducting pathways of this receptor have been appeared. Some of them are currently applied to clinical research. The other went through the research phase and were registered for medical treatment. The aim of this paper was to show the mechanism of blocking of the EGFR by these compounds as a potential way of curative cancer therapy.

[Tumor necrosis factor alpha (TNF-alpha) and its receptors: sTNF-alphaRI i sTNF-alphaRII in chronic pancreatitis]. / Czynnik martwicy nowotworu alfa (TNF-alpha) i jego receptory: sTNF-alphaRI i sTNF-alphaRII w przewleklym zapaleniu trzustki.

The exact immunologic mechanisms underlying chronic pancreatitis (CP) are not clearly identified yet. The role of TNF-alpha in CP has been evaluated only rarely. The possible pathogenetic role of the cytotoxic TNF-alpha signal transduction pathway in the clinical course of CP has been recently suggested. The aim of the study was to assess the plasma concentration of TNF-alpha as well as its receptors: sTNF-alpha RI and sTNF-alphaRII in patients with CP of different clinical stage. TNF-alpha, sTNF-alpha RI and sTNF-alpha RII plasma concentrations have been measured with enzyme-linked immunosorbent assay (ELISA) in 39 patients with CP as well as in age- matched healthy volunteers. The percentage of smokers was not different in CP and the control group. The CP stage has been classified according to Cambridge scoring system. The correlation between above mentioned parameters and clinical data, as disease duration and concomitant diabetes has been assessed. The mean TNF-alpha concentration in patients with CP was 24,6 +/- 15,07 pg/ml which was significantly higher (p<0,01) than in control group--11,3 +/- 2,01 pg/ml. The mean values of TNF-alpha receptors concentrations: sTNF-alphaRI and sTNF-alphaRII have also been significantly higher (p<0,01) in patients with CP, compared to controls. No significant differences in TNF-alpha, sTNF-alphaRI, sTNF-alphaRII values dependently on patient alcohol consumption, diabetes and the disease duration have been found. However, the significantly higher TNF-alpha and sTNF-alphaRII concentration (p<0,05) has been observed in patients with Cambridge IV stage compared to patients of all other stages. We conclude that TNF-alpha signal transduction pathway may play a significant role in chronic pancreatitis, particularly of advanced clinical stage.