Combination of endosonography-guided fine-needle aspiration and conventional endoscopic techniques in sarcoidosis diagnosis. Optimal strategy to achieve high diagnostic yield.

INTRODUCTION: Diagnosis of sarcoidosis is based on clinical status and radiologic specific findings. Tissue confirmation of noncaseating granulomas is crucial. Pathological confirmation of pulmonary sarcoidosis is most commonly accomplished by bronchoscopy, which has a diagnostic yield of approximately 60%-70%. OBJECTIVES: In this prospective study, we analysed potential benefit of EBUS-TBNA and EBB combination, application of cell blocks and smears with puncturing more than one station of lymph nodes in order to determine optimal strategy in diagnosis of sarcoidosis. METHODS: About 133 patients with suspicion of sarcoidosis (stage I and stage II) were included in this study. Each patient underwent conventional bronchoscopy with endobronchial biopsy (EBB) followed by the EBUS and puncturing at least two different lymph node stations. RESULTS: Positive cytopathological verification of sarcoidosis in our study was obtained in 123 patients (92.5%). EBUS-TBNA was diagnostic in 116 patients (87.2%). EBB was positive in 26 patients (19.55%). Combination of EBUS-TBNA and EBB statistically increased diagnostic yield of sarcoidosis to 92.5%. Sensitivity of EBUS-TBNA with EBB was 93.9%, specificity 100%, PPV 100% and NPV 20%. CONCLUSIONS: Combining EBUS-TBNA from at least two lymph node stations and EBB increased diagnostic yield of sarcoidosis. Such diagnostic strategy had almost 93% of diagnostic yield in stage I and stage II of sarcoidosis. Taking into account the safety of the whole procedure with endobronchial ultrasonography combined with conventional endoscopy with EBB and its cost effectiveness, TBLB can be intended to diagnose stage III or IV of pulmonary sarcoidosis.

Assessment of eating behaviours in adult residents of Greece and Poland - an original research.

BACKGROUND: The length and the quality of life are determined by, among other things, environmental factors. The place of residence is associated with certain differences in nutritional culture, with food traditions and customs being of great importance. Also, the location of a given country in a specific climate zone has an impact on the choice of food products and their preparation. OBJECTIVE: The aim of the study was to analyse eating behaviours among adult residents of Greece and Poland as well as to investigate to what extent these behaviours are impacted by the place of residence of respondents. MATERIALS AND METHODS: A total of 633 randomized respondents at the age of 50 or older (312 Greeks and 321 Poles) were included in the study. The author's questionnaire was used in the research. RESULTS: A total of 41.07% of respondents, including 31.09% of Greeks and 50.78% of Poles, declared having 4-5 meals per day. Fish was consumed 1-2 times a week by 29.27% of respondents, including 23.40% of Greeks and 15.26% of Poles. Whole wheat bread was consumed several times daily by 20.7% of respondents, including 19.55% of Greeks and 21.81% of Poles. Coarse groats and pasta were consumed a few times weekly by 23.06% of respondents, including 25.64% of Greeks and 20.56% of Poles. CONCLUSIONS: Eating behaviours in adult Poles and Greeks are varied, with healthier eating habits in the latter group. There are significant differences between the intake of food products rich in fibre and omega-3 fatty acids by residents of Greece and Poland.

Interaction of epidermal growth factor with COX-2 products and peroxisome proliferator-activated receptor-γ system in experimental rat Barrett's esophagus.

Mixed acidic-alkaline refluxate is a major pathogenic factor in chronic esophagitis progressing to Barrett's esophagus (BE). We hypothesized that epidermal growth factor (EGF) can interact with COX-2 and peroxisome proliferator-activated receptor-γ (PPARγ) in rats surgically prepared with esophagogastroduodenal anastomosis (EGDA) with healthy or removed salivary glands to deplete salivary EGF. EGDA rats were treated with 1) vehicle, 2) EGF or PPARγ agonist pioglitazone with or without EGFR kinase inhibitor tyrphostin A46, EGF or PPARγ antagonist GW9662 respectively, 3) ranitidine or pantoprazole, and 4) the selective COX-2 inhibitor celecoxib combined with pioglitazone. At 3 mo, the esophageal damage and the esophageal blood flow (EBF) were determined, the mucosal expression of EGF, EGFR, COX-2, TNFα, and PPARγ mRNA and phospho-EGFR/EGFR protein was analyzed. All EGDA rats developed chronic esophagitis, esophageal ulcerations, and intestinal metaplasia followed by a fall in the EBF, an increase in the plasma of IL-1ß, TNFα, and mucosal PGE2 content, the overexpression of COX-2-, and EGF-EGFR mRNAs, and proteins, and these effects were aggravated by EGF and attenuated by pioglitazone. The rise in EGF and COX-2 mRNA was inhibited by pioglitazone but reversed by pioglitazone cotreated with GW9662. We conclude that 1) EGF can interact with PG/COX-2 and the PPARγ system in the mechanism of chronic esophagitis; 2) the deleterious effect of EGF involves an impairment of EBF and the overexpression of COX-2 and EGFR, and 3) agonists of PPARγ and inhibitors of EGFR may be useful in the treatment of chronic esophagitis progressing to BE.NEW & NOTEWORTHY Rats with EGDA exhibited chronic esophagitis accompanied by a fall in EBF and an increase in mucosal expression of mRNAs for EGF, COX-2, and TNFα, and these effects were exacerbated by exogenous EGF and reduced by removal of a major source of endogenous EGF with salivectomy or concurrent treatment with tyrphostin A46 or pioglitazone combined with EGF. Beneficial effects of salivectomy in an experimental model of BE were counteracted by PPARγ antagonist, whereas selective COX-2 inhibitor celecoxib synergistically with pioglitazone reduced severity of esophageal damage and protected esophageal mucosa from reflux. We propose the cross talk among EGF/EGFR, PG/COX-2, and proinflammatory cytokines with PPARγ pathway in the mechanism of pathogenesis of chronic esophagitis progressing to BE and EAC.

Intraoral manifestation of systemic AL amyloidosis with unique microscopic presentation of intracellular amyloid deposition in striated muscles.

We report the history of a 59-year old patient with systemic AL amyloidosis of intraoral manifestation. The patient first presented with complaints about dysphagia and remarkable enlargement of the tongue with highly reduced mobility, as well as bilateral submucosal thickenings on the cheeks. Histopathological examination of the incisional biopsy of the buccal mucosa and underlying tissues revealed AL amyloidosis. The microscopic presentation was, however, unique, as the amyloid deposits were present intracellularly in the striated muscles. The subsequent bone marrow biopsy confirmed the diagnosis of primary amyloidosis/multiple myeloma - associated amyloidosis.

Two-stage optical system for colorectal polyp assessments.

BACKGROUND AND AIMS: Macroscopic real-time evaluations of the histopathology and degree of invasion of colorectal polyps help to select the most suitable endoscopic treatment method. Dual-focus (DF) narrow-band imaging (NBI) is a new imaging enhancement system that uses digital and optical methods to enhance the view of blood vessels on mucosal surfaces. However, the superiority of this technique over standard imaging techniques has not been previously reported. The aim of this study was to determine whether the two-stage optical systems in a new generation of endoscopes will increase the diagnostic accuracy of colorectal polyp recognition. METHODS: The study included 270 patients, and 386 colorectal polyps were diagnosed and removed. The polyps were assessed with white light and NBI using one- and two-stage optical systems, respectively. After being classified according to the Kudo pit pattern schemes, the polyps were removed and histopathologically verified. RESULTS: Regarding non-neoplastic lesions (Kudo I and II), no difference was observed in the recognition of polyps when using the NBI-DF function. We observed improved accuracy in the preliminary diagnoses of Kudo IIIL lesions (from 87.16 to 90.09%, p < 0.05) and Kudo IIIS lesions (from 87.29 to 92.79%, p < 0.01). NBI-DF also increased the accuracy of preliminary diagnoses of Kudo IV lesions (from 88.24 to 94.12%, p < 0.01). The Kudo V pit patterns were also more distinct with NBI-DF imaging, increasing the diagnostic accuracy from 91.67 to 100%. CONCLUSIONS: Using a two-stage optical system with electronic colorization of the mucosa increased diagnostic accuracy for differentiating colorectal polyps with neoplastic potential.

Comparison of efficacy and safety of first-line palliative chemotherapy with EOX and mDCF regimens in patients with locally advanced inoperable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma: a randomized phase 3 trial.

The aim of the study was to compare efficacy and safety of first-line palliative chemotherapy with (EOX) epirubicin/oxaliplatin/capecitabine and (mDCF) docetaxel/cisplatin/5FU/leucovorin regimens for untreated advanced HER2-negative gastric or gastroesophageal junction adenocarcinoma. Fifty-six patients were randomly assigned to mDCF (docetaxel 40 mg/m(2) day 1, leucovorin 400 mg/m(2) day 1, 5FU 400 mg/m(2) bolus day 1, 5FU 1000 mg/m(2)/d days 1 and 2, cisplatin 40 mg/m(2) day 3) or EOX (epirubicin 50 mg/m(2) day 1, oxaliplatin 130 mg/m(2) day 1, capecitabine 1250 mg/m(2)/d days 1-21). The primary endpoint was overall survival. The median overall survival was 9.5 months with EOX and 11.9 months with mDCF (p = 0.135), while median progression-free survival was 6.4 and 6.8 months, respectively (p = 0.440). Two-year survival rate was 22.2 % with mDCF compared to 5.2 % with EOX. Patients in the EOX arm had more frequent reductions in chemotherapy doses (34.5 vs. 3.7 %; p = 0.010) and delays in subsequent chemotherapy cycles (82.8 vs. 63.0 %; p = 0.171). There was no statistically significant difference in the rates of grade 3-4 adverse events (EOX 79.3 vs. mDCF 61.5 %; p = 0.234). As compared with the mDCF, the EOX regimen was associated with more frequent nausea (34.5 vs. 15.4 %), thromboembolic events (13.8 vs. 7.7 %), abdominal pain (13.8 vs. 7.7 %) and grades 3-4 neutropenia (72.4 vs. 50.0 %), but lower incidences of anemia (44.8 vs. 61.5 %), mucositis (6.9 vs. 15.4 %) and peripheral neuropathy (6.9 vs. 15.4 %). In conclusion, the mDCF regimen was associated with a statistically nonsignificant 2.4-month longer median overall survival without an increase in toxicity. This trial is registered at ClinicalTrials.gov, number NCT02445209.

Moderate exercise training attenuates the severity of experimental rodent colitis: the importance of crosstalk between adipose tissue and skeletal muscles.

Although progress has been recently made in understanding of inflammatory bowel diseases (IBD), their etiology is unknown apart from several factors from adipose tissue and skeletal muscles such as cytokines, adipokines, and myokines were implicated in the pathogenesis of ulcerative colitis. We studied the effect high-fat diet (HFD; cholesterol up to 70%), low-fat diet (LFD; cholesterol up to 10%), and the normal diet (total fat up to 5%) in rats with TNBS colitis forced to treadmill running exercise (5 days/week) for 6 weeks. In nonexercising HFD rats, the area of colonic damage, colonic tissue weight, the plasma IL-1ß, TNF-α, TWEAK, and leptin levels, and the expression of IL-1ß-, TNF-α-, and Hif1α mRNAs were significantly increased and a significant fall in plasma adiponectin and irisin levels was observed as compared to LFD rats. In HFD animals, the exercise significantly accelerated the healing of colitis, raised the plasma levels of IL-6 and irisin, downregulated the expression of IL-1ß, TNF-α, and Hif1α, and significantly decreased the plasma IL-1ß, TNF α, TWEAK, and leptin levels. We conclude that HFD delays the healing of colitis in trained rats via decrease in CBF and plasma IL-1ß, TNF-α, TWEAK, and leptin levels and the release of protective irisin.

Pulmonary arteriovenous malformations in children and young adults.

Authors observed five cases of lung arteriovenous malformations in children and young adults. Clinical data and morphological pictures of these lesions were presented.

Nitric oxide-releasing aspirin but not conventional aspirin improves healing of experimental colitis.

AIM: To determine the effect of non-selective cyclooxygenase (COX) inhibitors, selective COX-2 inhibitors and nitric oxide (NO)-releasing aspirin in the healing of ulcerative colitis. METHODS: Rats with 2,4,6 trinitrobenzenesulfon-ic acid (TNBS)-induced colitis received intragastric (ig) treatment with vehicle, aspirin (ASA) (a non-selective COX inhibitor), celecoxib (a selective COX-2 inhibitor) or NO-releasing ASA for a period of ten days. The area of colonic lesions, colonic blood flow (CBF), myeloperoxidase (MPO) activity and expression of proinflammatory markers COX-2, inducible form of nitric oxide synthase (iNOS), IL-1ß and tumor necrosis factor (TNF)-α were assessed. The effects of glyceryl trinitrate (GTN), a NO donor, and 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-​tetramethyl-1H-imidazolyl-1-oxy-3-oxide, onopotassium salt (carboxy-PTIO), a NO scavenger, administered without and with ASA or NO-ASA, and the involvement of capsaicin-sensitive afferent nerves in the mechanism of healing the experimental colitis was also determined. RESULTS: Rats with colitis developed macroscopic and microscopic colonic lesions accompanied by a significant decrease in the CBF, a significant rise in colonic weight, MPO activity and plasma IL-1ß and TNF-α levels. These effects were aggravated by ASA and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (SC-560), but not celecoxib and counteracted by concurrent treatment with a synthetic prostaglandin E2 (PGE2) analog. Treatment with NO-ASA dose-dependently accelerated colonic healing followed by a rise in plasma NO(x) content and CBF, suppression of MPO and downregulation of COX-2, iNOS, IL-1ß and TNF-α mRNAs. Treatment with GTN, the NO donor, significantly inhibited the ASA-induced colonic lesions and increased CBF, while carboxy-PTIO or capsaicin-denervation counteracted the NO-ASA-induced improvement of colonic healing and the accompanying increase in the CBF. These effects were restored by co-treatment with calcitonin gene related peptide (CGRP) and NO-ASA in capsaicin-denervated animals. CONCLUSION: NO-releasing ASA, in contrast to ASA, COX-1 inhibitors, and SC-560, accelerated the healing of colitis via a mechanism involving NO mediated improvement of microcirculation and activation of sensory nerves releasing CGRP.

Exogenous lipoid pneumonia (oil granulomas of the lung).

The authors observed three cases of exogenous lipid pneumonia clinically suspected of lung carcinoma. Histological examination of material after thoracotomy gave the possibility of correct diagnosis. The lesions in lungs were characteristic granulomas around lipid material and with surrounding advanced fibrosis.

[Usefulness of non-steroid antiinflammatory drugs in patients with ulcerative colitis]. / Wplyw niesteroidowych leków przeciwzapalnych na przebieg wrzodziejacego zapalenia jelita grubego.

Non specific inflammations of the intestine are the group of chronic disorders, such as ulcerative colitis and Crohn's disease and with episodic aggravation of inflammatory lesions, called active phase and non-active phase, called remission. Non-steroid antiinflammatory drugs (NSAIDS) are one of the most frequently used medications in the World. NSAIDS therapy in ulcerative colitis patients is a very important clinical problem, because of frequent extraintestinal symptoms, such as arthritis, which make patients to take these drugs. But the mechanisms of the NSAIDS influence on the course of inflammatory diseases of inferior part of gastrointestinal tract is still not known. Our results of clinical studies indicated the influence of nonselective and selective COX2 inhibitors on ulcerative colitis activity. However clinical aggravation was detected in 8% of patients treated with conventional NSAIDS and in one person administered selective COX2 inhibitor. Administration of the conventional NSAIDS as well as coxibs, significantly influenced severity of diarrhea. Moreover conventional COX inhibitors increased severity of colon bleeding and endoscopic colon inflammatory lesions in comparison to ulcerative colitis patients, as well not administered NSAIDS as given coxibs. Total patients evaluation involving the intensity of clinical symptoms did not reveal significant differences between examined groups. The above results showed, that the balance between risk and advantages resulting from administration of NSAIDS both, non-selective and selective COX is to be accepted in ulcerative colitis patients in non-active phase.

Histiocytic necrotizing lymphadenitis without granulocytic infiltration (the so called Kikuchi-Fujimoto disease).

The report describes five cases of a rare disorder--necrotizing lymphadenitis--diagnosed in Polish patients in the Department of Pathomorphology, Collegium Medicum, Jagiellonian University, Krakow, in the years 1993-2006. The disease was firstly described by Kikuchi and Fujimoto in the Oriental population of Japan in 1972 and for this reason it is called Kikuchi-Fujimoto disease (or Kikuchi lymphadenitis). Its characteristic histological picture includes necrosis without granulocytic infiltrate surrounded by plasmocytoid monocytes, histiocytes (CD68+, lysozyme+, myeloperoxidase+) and immunoblasts, sometimes with atypia, with concomitant lymphocytes, predominantly cytotoxic T CD8+. The histology together with the rare occurrence of the disease in Poland may be a considerable diagnostic challenge for a pathologist, leading to misdiagnosing the lesion as a neoplastic process (malignant lymphoma).

Gastric solid glomus tumor and multiple glomangiomyomas of the large bowel with intravascular spread, multifocal perivascular proliferations and liver involvement.

The authors present a case of multiple glomus tumors (GTs) of the gastrointestinal tract, representing the type of a gastric glomus tumor proper and large bowel glomangiomyomas with myopericytoma-like features, observed in a 46-year old female, with multifocal perivascular proliferations of primitive cells and hepatic involvement. Histologically, the multilobular gastric tumor and hepatic lesions corresponded to a typical glomus tumor, while the tumor situated in the transverse colon, up to 7 cm in diameter, presented as a glomangiomyoma infiltrative (with myopericytoma-like foci), and satellite tumors in the large bowel mucosa, 0.5-0.7 cm in diameter, represented small glomangiomyomas. In addition, the patient demonstrated two types of concomitant vascular lesions: 1/ intravascular spread in the form of neoplastic plugs that obliterated the lumen of medium-size veins, and 2/ microscopic perivascular proliferation of primitive, small cells seen in the vicinity of the main tumor and in the adjacent adipose tissue. The patient has been ill for 2.5 years; she has been subjected to a partial colectomy with a resection of the small intestinal loop, greater omentum and the right ovary, followed by chemotherapy. At present, she is stable, and the infiltration--especially in the epigastric region--has decreased. The picture may confirm the theory that multiple GTs develop in association with multifocal proliferation of perivascular stem cells, as well as that their ability to penetrate into the lumen of large vessels gives origin to satellite tumors, which are not necessarily metastatic. It seems that at present, the group of perivascular SMA+ tumors may include infantile-type myofibromatosis in adults, myopericytoma, glomangio(myo)pericytoma, glomangiomyoma, glomus tumor proper, and glomangioma. Most likely, also some tumors previously classified as hemangiopericytomas belong to this group. The distinctive feature present in at least some of the above listed perivascular tumors is their synchronous or metachronous growth in a particular region and their ability to occupy intravascular space as nodules or solid bands, which in turn may give origin to satellite tumors. Multifocal lesions associated with a short survival in a given patient will obviously support the presence of metastatic disease. In the remaining cases, determination whether the patient has metastatic disease requires deep consideration and caution, also while deciding on treatment to be employed.

High grade intermediate cell neuroendocrine cancer of the larynx--case report.

Primary poorly differentiated neuroendocrine carcinomas are rare pathological findings in the upper respiratory tract, approximately 650 cases have been reported in the literature. We report a case of 51-year old male with a high grade intermediate cell neuroendocrine epiglottic cancer. The current classification according to the WHO Classification of Tumors published in 2005 is discussed.

Mesothelial inclusion cysts (so-called benign cystic mesothelioma)--a clinicopathological analysis of six cases.

The report presents six cases of mesothelial inclusion cysts (MIC), detected in five females (22-53 years of age) and one male (47 years old). The lesions were unifocal (four cases) and multifocal (two cases), and were located on the surface of the peritoneum in the cul de sac, on the intestines, urinary bladder, uterine adnexa, also involved round ligament within the pelvis and in the inguinal canal (one patient). Additionally, in one female, small cysts, free-floating in the peritoneal cavity were present. In three patients, clinical signs resulted directly from the presence of MIC. One female had been 7 years previously operated on due to endometrioid ovarian cysts. Apart from MIC, three patients presented with concomitant diseases: appendicitis (two cases), peritoneal pseudomyxoma or primary ovarian carcinoma. Gross appearance: the lesions were polycystic, the surgical materials ranging from three fragments measuring 0.5 cm each to seven fragments, with the maximum size of 14x6 cm. The cysts were from microscopic size to 2 cm in diameter, the majority were thin-walled, semitranslucent, filled with clear or yellowish fluid or gelatinous contents. In one case, the cyst walls were thicker and showed intense inflammatory lesions and fibrinous exudate. Microscopically, the majority of cysts were lined with a single layer of flattened or cuboid mesothelial cells (CK+, calretinin+). In two patients, the mesothelium demonstrated diffuse squamous cell metaplasia; in one individual, the cells focally formed small papillae and were vacuolated. No mucus was observed either in the cytoplasm or outside the cells. Immunohistochemical reactions to CEA, ER, PR and MIB-1 were negative. Intramural proliferations and intracystic detached clumps of cells showed both mesothelial cells (without any mitotic activity and signs of atypia) and macrophages (CD68+). To date, the follow-up has been 7 years and 3 years in two individuals, and from 1 to 7 months in the remaining three patients--all of them are free from recurrent disease. One female failed to report for follow-up examinations. The report also presents the review of literature.

Gastrointestinal stromal tumors. A multicenter experience.

The report presents 200 cases of gastrointestinal stromal tumors (GIST). The material originated from six diagnostic centers in Poland and was reclassified according to the current criteria. Among lesions other than GISTs, 14 were identified as smooth muscle tumors and seven as neural tumors. GISTs were located in the stomach (51-63.3% of the investigated series), small intestine (27.4-33.8%), colon (approximately 4.5%), abdominal cavity, i.e. in the peritoneum and omentum (6%), and in the retroperitoneal space (2.5%). A slight predominance of women was noted (53-56%). The age of the patients ranged between 14 and 93 years of life, with the mean age of 62.4 years. Individuals younger than 45 years of age accounted for 10% of the group. In ten patients (five of them less than 45 years of life), multiple tumors were detected, their number ranging from two to less than 20; these individuals constituted 5% of the entire series. Moderately and highly aggressive tumors predominated. In the series, when multiple tumors were excluded, a total of 24 epithelioid GISTs (12%) were observed; of this number, 13 were situated in the stomach, six--in the small intestine, two--in the abdominal cavity and another two in the retroperitoneal space. Synchronic tumors observed in patients with GISTs were seen in seven patients, including an adenocarcinoma of the colon, two adenocarcinomas of the stomach, a carcinoid tumor of the small intestine, a pheochromocytoma of the retroperitoneal space, an anaplastic lymphoma and a disseminated squamous cell carcinoma. In immunohistochemical reactions (CD117, CD34, SMA, S-100, DES), attention was focused on the immunoreactivity of small GISTs, below 2 cm in size, and of multiple tumors. Immunohistochemical reactions were equally differentiated as to their presence and intensity in small tumors and in highly aggressive lesions above 5-10 cm in size. In multiple GISTs, immunohistochemical tests strongly indicated the heterogeneity of neoplastic cells, which, nevertheless, showed no consistent association with the location of the tumor, its aggressiveness, cellular structure or a tendency to form multiple foci.