The Stable Gastric Pentadecapeptide BPC 157 Pleiotropic Beneficial Activity and Its Possible Relations with Neurotransmitter Activity.

We highlight the particular aspects of the stable gastric pentadecapeptide BPC 157 pleiotropic beneficial activity (not destroyed in human gastric juice, native and stable in human gastric juice, as a cytoprotection mediator holds a response specifically related to preventing or recovering damage as such) and its possible relations with neurotransmitter activity. We attempt to resolve the shortage of the pleiotropic beneficial effects of BPC 157, given the general standard neurotransmitter criteria, in classic terms. We substitute the lack of direct conclusive evidence (i.e., production within the neuron or present in it as a precursor molecule, released eliciting a response on the receptor on the target cells on neurons and being removed from the site of action once its signaling role is complete). This can be a network of interconnected evidence, previously envisaged in the implementation of the cytoprotection effects, consistent beneficial particular evidence that BPC 157 therapy counteracts dopamine, serotonin, glutamate, GABA, adrenalin/noradrenalin, acetylcholine, and NO-system disturbances. This specifically includes counteraction of those disturbances related to their receptors, both blockade and over-activity, destruction, depletion, tolerance, sensitization, and channel disturbances counteraction. Likewise, BPC 157 activates particular receptors (i.e., VGEF and growth hormone). Furthermore, close BPC 157/NO-system relations with the gasotransmitters crossing the cell membrane and acting directly on molecules inside the cell may envisage particular interactions with receptors on the plasma membrane of their target cells. Finally, there is nerve-muscle relation in various muscle disturbance counteractions, and nerve-nerve relation in various encephalopathies counteraction, which is also exemplified specifically by the BPC 157 therapy application.

From Selye's and Szabo's Cysteamine-Duodenal Ulcer in Rats to Dopamine in the Stomach: Therapy Significance and Possibilities.

We reviewed gastric ulcer healing by dopamine considering several distinctive duodenal key points. Selye and Szabo describe the cysteamine-induced duodenal ulcer in rats as a duodenal stress ulcer in patients. Szabo's cysteamine duodenal ulcer as the dopamine duodenal healing and cysteamine as a dopamine antagonist signifies the dopamine agonists anti-ulcer effect and dopamine antagonists ulcerogenic effect. From these viewpoints, we focused on dopamine and gastric ulcer healing. We mentioned antecedent studies on the dopamine presence in the stomach and gastric juice. Then we reviewed, in the timeline, therapy significance arising from the anti-ulcer potency of the various dopamine agonists, which is highly prevailing over the quite persistent beneficial evidence arising from the various dopamine antagonists. Meanwhile, the beneficial effects of several peptides (i.e., amylin, cholecystokinin, leptin, and stable gastric pentadecapeptide BPC 157, suggested as an acting mediator of the dopamine brain-gut axis) were included in the dopamine gastric ulcer story. We attempt to resolve dopamine agonists/antagonists issue with the dopamine significance in the stress (cysteamine as a prototype of the duodenal stress ulcer), and cytoprotection (cysteamine in small dose as a prototype of the cytoprotective agents; cysteamine duodenal ulcer in gastrectomized rats). Thereby, along with dopamine agonists' beneficial effects, in special circumstances, dopamine antagonists having their own ulcerogenic effect may act as "mild stress (or)" or "small irritant" counteracting subsequent strong alcohol or stress procedure-induced severe lesions in this particular tissue. Finally, in the conclusion, as a new improvement in further therapy, we emphasized the advantages of the dopamine agents' application in lower gastrointestinal tract therapy.

Stable Gastric Pentadecapeptide BPC 157 and Striated, Smooth, and Heart Muscle.

First, we review the definitively severed myotendinous junction and recovery by the cytoprotective stable gastric pentadecapeptide BPC 157 therapy, its healing that might combine both transected and detached tendon and transected muscle, ligament and bone injuries, applied alone, as native peptide therapy, effective in rat injury, given intraperitoneally or in drinking water or topically, at the site of injury. As a follow up, we reviewed that with the BPC 157 therapy, its cytoprotective ability to organize simultaneous healing of different tissues of and full recovery of the myotendinous junction might represent the particular muscle therapy against distinctive etiopathology muscle disabilities and weakness. In this, BPC 157 therapy might recover many of muscle disabilities (i.e., succinylcholine, vascular occlusion, spinal cord compression, stroke, traumatic brain injury, severe electrolyte disturbances, neurotoxins, neuroleptics, alcohol, serotonin syndrome and NO-system blockade and tumor-cachexia). These might provide practical realization of the multimodal muscle-axis impact able to react depending on the condition and the given agent(s) and the symptoms distinctively related to the prime injurious cause symptoms in the wide healing concept, the concept of cytoprotection, in particular. Further, the BPC 157 therapy might be the recovery for the disabled heart functioning, and disabled smooth muscle functioning (various sphincters function recovery). Finally, BPC 157, native and stable in human gastric juice, might be a prototype of anti-ulcer cytoprotective peptide for the muscle therapy with high curing potential (very safe profile (lethal dose not achieved), with suited wide effective range (µg-ng regimens) and ways of application).

Novel laser activated photoacoustic streaming for removing pulp remnants from round root canals after single file reciprocating instrumentation.

BACKGROUND: This study evaluated the efficacy of a new laser-assisted irrigation system, the shock wave enhanced emission photo-acoustic streaming (SWEEPS) technique in removing pulp tissue from single-rooted premolars. METHODS: Freshly extracted mandibular premolars with round root canals (n = 40), scanned using cone beam computed tomography, were randomly divided into control and four experimental (according to the irrigation technique used) groups (n = 8/group). Groups 1, 2, and 3 were instrumented using Reciproc Blue (RB25/0.06) followed by final irrigation protocol (FIP), activated by SWEEPS, ultrasonically activated irrigation (UAI), and conventional irrigation (CI), respectively. In these groups, 7 mL 3% NaOCl in total was used during instrumentation; for FIP, 3% NaOCl (60 s), ethylenediaminotetraacetic acid (60 s), and 3% NaOCl (30 s). In group 4, SWEEPS activation of 3% NaOCl for 6 × 30 s alone was performed. The untreated control group specimens were processed for histological evaluation of remaining pulp tissue (RPT) in each canal third. The results were analyzed using the Mann-Whitney U test (α = 0.05). RESULTS: Significant differences were observed between the control group and the experimental groups (p<0.05). In the middle third, the UIA and SWEEPS showed similar efficacy (p = 0.171), superior to CI and SWEEPS without instrumentation (p<0.05). In the apical third, SWEEPS was the most efficient (p = 0.002), and UIA and CI showed no difference (p = 0.643). CONCLUSION: SWEEPS was superior to UIA and CI in removing RPT in the apical region of round canals after single instrument root canal preparation; SWEEPS without instrumentation was inefficient in removing pulp tissue.

DEPARTMENT BEFORE DEPARTMENT: HOW WAS THE DEPARTMENT OF PATHOLOGY ESTABLISHED AT THE SCHOOL OF MEDICINE UNIVERSITY OF ZAGREB / ZAVOD PRIJE ZAVODA: KAKO JE OSNOVAN ZAVOD ZA PATOLOGIJU MEDICINSKOG FAKULTETA SVEUCILISTA U ZAGREBU

The authors of the paper aim to present the foundation of the Department of Pathology at the University of Zagreb. The first years of the Department of Pathology, from 1918 to 1922, will be analysed in the paper. The emphasis is on the construction of the Department and the difficulties encountered at the same time. Also, persons who were crucial for the establishment of the Department of Pathology will be discussed. So far, the literature has mostly stated that the initiator of the Department of Pathology was Sergej Saltykow, a pathologist of Russian descent. Although Saltykow's role is unquestionable, the aim is to present more persons who have more or less contributed to the establishment of the Department. Thus, more will be said about Vaclav Neumann, Dorde Joanovic, Walter Berlinger and others. Besides, the paper will provide a brief context focusing on the establishment of the School of Medicine and pathology in Zagreb before the foundation of the Department of Pathology. The Pathoanatomic Service of The Public Health Divisions in the City of Zagreb and Ljudevit Jurak, the first head of this institution, should certainly be pointed out. The Pathoanatomic Service played a key role in the development of forensic medicine and pathology in Croatia. In addition to available literature, the paper is based on archival materials found in the School of Medicine University of Zagreb archive.

Stable Gastric Pentadecapeptide BPC 157 as a Therapy for the Disable Myotendinous Junctions in Rats.

(1) Aim: The stable gastric pentadecapeptide BPC 157 is known to heal transected muscle, tendon, and ligament. Thereby, in this study, we investigated the effect of BPC 157 on the dissection of the quadriceps tendon from the quadriceps muscle in rats. (2) Materials and Methods: Myotendinous junction defect, which cannot heal spontaneously in rats, as evidenced with consistent macro/microscopic, biomechanical, functional assessments, eNOS, and COX-2 mRNA levels and oxidative stress and NO-levels in the myotendinous junctions. BPC 157 (10 µg/kg, 10 ng/kg) regimen was given (i) intraperitoneally, first application immediately after surgery, last 24 h before sacrifice; (ii) per-orally, in drinking water (0.16 µg/mL, 0.16 ng/mL, 12 mL/rat/day), till the sacrifice at 7, 14, 28 and 42 postoperative days. (3) Results: These BPC 157 regimens document prominent therapy effects (macro/microscopic, biomechanical, functional much like eNOS and COX-2 mRNA levels and counteracted oxidative stress and NO-levels in the myotendinous junctions), while controls have a poor presentation. Especially, in rats with the disabled myotendinous junction, along with full functional recovery, BPC 157 counteracts muscle atrophy that is regularly progressive and brings muscle presentation close to normal. Accordingly, unlike the perilous course in controls, those rats, when receiving BPC 157 therapy, exhibit a smaller defect, and finally defects completely disappear. Microscopically, there are no more inflammatory infiltrate, well-oriented recovered tissue of musculotendon junction appears in BPC 157 treated rats at the 28 days and 42 days. (4) Conclusions: BPC 157 restores myotendinous junction in accordance with the healing of the transected muscle, tendon, and ligament.

Robert's Intragastric Alcohol-Induced Gastric Lesion Model as an Escalated General Peripheral and Central Syndrome, Counteracted by the Stable Gastric Pentadecapeptide BPC 157.

We redefined Robert's prototypical cytoprotection model, namely the intragastric administration of 96% alcohol in order to generate a general peripheral and central syndrome similar to that which occurs when major central or peripheral veins are occluded in animal models. With this redefinition, we used Robert's model to examine the cytoprotective effects of the stable gastric pentadecapeptide BPC 157. The intragastric administration of alcohol induced gastric lesions, intracranial (superior sagittal sinus) hypertension, severe brain swelling and lesions, portal and vena caval hypertension, aortal hypotension, severe thrombosis, inferior vena cava and superior mesenteric vein congestion, azygos vein failure (as a failed collateral pathway), electrocardiogram disturbances, and heart, lung, liver and kidney lesions. The use of BPC 157 therapy (10 µg/kg or 10 ng/kg given intraperitoneally 1 min after alcohol) counteracted these deficits rapidly. Specifically, BPC 157 reversed brain swelling and superior mesenteric vein and inferior vena caval congestion, and helped the azygos vein to recover, which improved the collateral blood flow pathway. Microscopically, BPC 157 counteracted brain (i.e., intracerebral hemorrhage with degenerative changes of cerebral and cerebellar neurons), heart (acute subendocardial infarct), lung (parenchymal hemorrhage), liver (congestion), kidney (congestion) and gastrointestinal (epithelium loss, hemorrhagic gastritis) lesions. In addition, this may have taken place along with the activation of specific molecular pathways. In conclusion, these findings clarify and extend the theory of cytoprotection, offer an approach to its practical application, and establish BPC 157 as a prospective cytoprotective treatment.

Stable Gastric Pentadecapeptide BPC 157 Therapy for Monocrotaline-Induced Pulmonary Hypertension in Rats Leads to Prevention and Reversal.

Background. Monocrotaline selectively injures the lung's vascular endothelium and induces pulmonary arterial hypertension. The stable gastric pentadecapeptide BPC 157 acts as a prototype cytoprotective agent that maintains endothelium, and its application may be a novel therapy. Besides, BPC 157 prevents and reverses thrombosis formation, maintains platelet function, alleviates peripheral vascular occlusion disturbances, and has anti-arrhythmic and anti-inflammatory effects. Monocrotaline-induced pulmonary arterial hypertension in rats (wall thickness, total vessel area, heart frequency, QRS axis deviation, QT interval prolongation, increase in right ventricle systolic pressure and bodyweight loss) can be counteracted with early or delayed BPC 157 therapy. Methods and Results. After monocrotaline (80 mg/kg subcutaneously), BPC 157 (10 µg/kg or 10 ng/kg, days 1-14 or days 1-30 (early regimens), or days 14-30 (delayed regimen)) was given once daily intraperitoneally (last application 24 h before sacrifice) or continuously in drinking water until sacrifice (day 14 or 30). Without therapy, the outcome was the full monocrotaline syndrome, marked by right-side heart hypertrophy and massive thickening of the precapillary artery's smooth muscle layer, clinical deterioration, and sometimes death due to pulmonary hypertension and right-heart failure during the 4th week after monocrotaline injection. With all BPC 157 regimens, monocrotaline-induced pulmonary arterial hypertension (including all disturbed parameters) was counteracted, and consistent beneficial effects were documented during the whole course of the disease. Pulmonary hypertension was not even developed (early regimens) as quickly as the advanced pulmonary hypertension was rapidly attenuated and then completely eliminated (delayed regimen). Conclusions. Thus, pentadecapeptide BPC 157 prevents and counteracts monocrotaline-induced pulmonary arterial hypertension and cor pulmonale in rats.

BPC 157 Therapy and the Permanent Occlusion of the Superior Sagittal Sinus in Rat: Vascular Recruitment.

We show the complex syndrome of the occluded superior sagittal sinus, brain swelling and lesions and multiple peripheral organs lesions in rat. Recovery goes centrally and peripherally, with the stable gastric pentadecapeptide BPC 157, which alleviated peripheral vascular occlusion disturbances, rapidly activating alternative bypassing pathways. Assessments were gross recording, venography, ECG, pressure, microscopy, biochemistry. The increased pressure in the superior sagittal sinus, portal and caval hypertension, aortal hypotension, arterial and venous thrombosis, severe brain swelling and lesions (cortex (cerebral, cerebellar), hypothalamus/thalamus, hippocampus), particular veins (azygos, superior mesenteric, inferior caval) dysfunction, heart dysfunction, lung congestion as acute respiratory distress syndrome, kidney disturbances, liver failure, and hemorrhagic lesions in gastrointestinal tract were all assessed. Rats received BPC 157 medication (10 µg/kg, 10 ng/kg) intraperitoneally, intragastrically, or topically to the swollen brain at 1 min ligation-time, or at 15 min, 24 h and 48 h ligation-time. BPC 157 therapy rapidly attenuates the brain swelling, rapidly eliminates the increased pressure in the ligated superior sagittal sinus and the severe portal and caval hypertension and aortal hypotension, and rapidly recruits collateral vessels, centrally ((para)sagittal venous collateral circulation) and peripherally (left superior caval vein azygos vein-inferior caval vein). In conclusion, as shown by all assessments, BPC 157 acts against the permanent occlusion of the superior sagittal sinus and syndrome (i.e., brain, heart, lung, liver, kidney, gastrointestinal lesions, thrombosis), given at 1 min, 15 min, 24 h or 48 h ligation-time. BPC 157 therapy rapidly overwhelms the permanent occlusion of the superior sagittal sinus in rat.

Comparison of Androgen Receptor, VEGF, HIF-1, Ki67 and MMP9 Expression between Non-Metastatic and Metastatic Stages in Stromal and Tumor Cells of Oral Squamous Cell Carcinoma.

OBJECTIVES: Oral squamous cell carcinoma (OSCC) is the most common oral malignancy with low survival as it is very often diagnosed at an advanced stage, which is why the accurate profiling of the tumor is essential. The aim of this study was to, for the first time, compare in OSCC the frequency of AR, VEGF, MMP9, HiF1beta and Ki67 between the non-metastatic and metastatic disease. MATERIALS AND METHODS: In the study, 96 non-metastatic and 91 metastatic OSCC patients were analysed for AR, VEGF, MMP9, HiF1beta and Ki67 levels by immunohistochemistry. RESULTS: All of the tested biomarkers significantly differed between non-metastatic and metastatic disease. A significant association was found between >/=20% AR positive epithelium cells in cytoplasm, Ki67 and VEGF in cancer stroma. Ki67, HiF1beta, VEGF and MMP9 were significantly associated with TNM stages. CONCLUSION: Our results show for the first time an interplay between AR, VEGF, MMP9, HiF1beta and Ki67 in OSCC which may contribute to better diagnostics and therapy selection.

Stable Gastric Pentadecapeptide BPC 157 Therapy of Rat Glaucoma.

Cauterization of three episcleral veins (open-angle glaucoma model) induces venous congestion and increases intraocular pressure in rats. If not upgraded, one episcleral vein is regularly unable to acquire and take over the whole function, and glaucoma-like features persist. Recently, the rapid upgrading of the collateral pathways by a stable gastric pentadecapeptide BPC 157 has cured many severe syndromes induced by permanent occlusion of major vessels, veins and/or arteries, peripherally and centrally. In a six-week study, medication was given prophylactically (immediately before glaucoma surgery, i.e., three episcleral veins cauterization) or as curative treatment (starting at 24 h after glaucoma surgery). The daily regimen of BPC 157 (0.4 µg/eye, 0.4 ng/eye; 10 µg/kg, 10 ng/kg) was administered locally as drops in each eye, intraperitoneally (last application at 24 h before sacrifice) or per-orally in drinking water (0.16 µg/mL, 0.16 ng/mL, 12 mL/rat until the sacrifice, first application being intragastric). Consequently, all BPC 157 regimens immediately normalized intraocular pressure. BPC 157-treated rats exhibited normal pupil diameter, microscopically well-preserved ganglion cells and optic nerve presentation, normal fundus presentation, normal retinal and choroidal blood vessel presentation and normal optic nerve presentation. As leading symptoms, increased intraocular pressure and mydriasis, as well as degeneration of retinal ganglion cells, optic nerve head excavation and reduction in optic nerve thickness, generalized severe irregularity of retinal vessels, faint presentation of choroidal vessels and severe optic nerve disc atrophy were all counteracted. In conclusion, we claim that the reversal of the episcleral veins cauterization glaucoma appeared as a consequence of the BPC 157 therapy of the vessel occlusion-induced perilous syndrome.

Mitochondrial ROS Induce Partial Dedifferentiation of Human Mesothelioma via Upregulation of NANOG.

The expression of pluripotency factors is a key regulator of tumor differentiation status and cancer stem cells. The purpose of this study was to examine the expression of pluripotency factors and differentiation status of human mesothelioma and the role of mitochondria in their regulation. We tested the expression of OCT4/POU5F1, NANOG, SOX2, PI3K-AKT pathway and BCL2 genes and proteins in 65 samples of human mesothelioma and 19 samples of normal mesothelium. Mitochondrial membrane potential, reactive oxygen species (ROS) generation and expression of pluripotency factors were also tested in human mesothelioma cell line. Human mesothelium and mesothelioma expressed SOX2, NANOG, PI3K and AKT genes and proteins and POU5F1 gene, whereby NANOG, SOX2 and phosphorylated (activated) AKT were upregulated in mesothelioma. NANOG protein expression was elevated in less differentiated samples of human mesothelioma. The expression of genes of PI3K-AKT pathway correlated with pluripotency factor genes. Mesothelioma cells had functional, but depolarized mitochondria with large capacity to generate ROS. Mitochondrial ROS upregulated NANOG and mitoTEMPO abrogated it. In conclusion, human mesothelioma displays enhanced expression of NANOG, SOX2 and phosphorylated AKT proteins, while elevated NANOG expression correlates with poor differentiation of human mesothelioma. Mitochondria of mesothelioma cells have a large capacity to form ROS and thereby upregulate NANOG, leading to dedifferentiation of mesothelioma.

Pentadecapeptide BPC 157 resolves suprahepatic occlusion of the inferior caval vein, Budd-Chiari syndrome model in rats.

BACKGROUND: Recently, as a possible therapy resolving solution, pentadecapeptide BPC 157 therapy, has been used in alleviating various vascular occlusion disturbances. BPC 157 was previously reviewed as novel mediator of Robert cytoprotection and endothelium protection in the stomach, and gut-brain axis, beneficial therapy in gastrointestinal tract, with particular reference to vascular recruitment, ulcerative colitis and tumor cachexia, and other tissues healing. Here we raised new hypothesis about BPC 157 therapy in the Budd-Chiari syndrome in rats, rapid bypassing of the suprahepatic inferior caval vein occlusion, and rats recovery with the active and effective pharmacotherapy treatment. AIM: To investigate Budd-Chiari syndrome model (inferior caval vein suprahepatic occlusion) resolution, since BPC 157 resolves various rat vascular occlusion. METHODS: We assessed the activated bypassing pathways between the inferior and superior caval veins and portocaval shunt, counteracted caval/portal hypertension, aortal hypotension, venous/arterial thrombosis, electrocardiogram disturbances, liver and gastrointestinal lesions (i.e., stomach and duodenum hemorrhages, in particular, congestion). Rats with suprahepatic occlusion of the inferior vena cava by ligation were medicated at 1 min, 15 min, 24 h, or 48 h post-ligation. Medication consisted of 10 µg/kg BPC 157, 10 ng BPC 157 or 5 mL/kg saline, administered once as an abdominal bath or intragastric application. Gross and microscopic observations were made, in addition to assessments of electrical activity of the heart (electrocardiogram), portal and caval hypertension, aortal hypotension, thrombosis, hepatomegaly, splenomegaly and venography. Furthermore, levels of nitric oxide, malondialdehyde in the liver and serum enzymes were determined. RESULTS: BPC 157 counteracted increased P wave amplitude, tachycardia and ST-elevation, i.e., right heart failure from acute thrombotic coronary occlusion. The bypassing pathway of the inferior vena cava-azygos (hemiazygos) vein-superior vena cava and portocaval shunt occurred rapidly. Even with severe caval ˃ portal hypertension, BPC 157 antagonized portal and caval hypertension and aortal hypotension, and also reduced refractory ascites. Thrombosis of portal vein tributaries, inferior vena cava, and hepatic and coronary arteries was attenuated. In addition, there was reduced pathology of the lungs (severe capillary congestion) and liver (dilated central veins and terminal portal venules), decreased intestine hemorrhagic lesions (substantial capillary congestion, submucosal edema and architecture loss), and increased liver and spleen weight. During the period of ligation, nitric oxide- and malondialdehyde-levels in the liver remained within normal healthy values, and increases in serum enzymes were markedly reduced. CONCLUSION: BPC 157 counteracts Budd Chiari syndrome in rats.

Oral and Vulvar Lichen Sclerosus.

Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of genital and extragenital skin (1). Simultaneous involvement of the oral mucosa is extremely rare, but it may be the only affected area (2). A 55-year-old woman was referred to the Department of Oral Medicine, School of Dental Medicine University of Zagreb due to whitish lesions on the right ventrolateral part of the tongue and buccal mucosa with desquamative gingivitis (Figure 1, a-c). The lesions were asymptomatic but indurated on palpation. Histology was conclusive for oral lichen sclerosus (OLS). The lesions on gingiva were successfully treated with betamethasone ointment, three times a day for two weeks. One year earlier, she had been referred to the Department of Dermatology and Venereology with progressive pruritus and dyspareunia, white patches, obliteration of the labia minora, and stenosis of the introitus (Figure 2). Histology was conclusive for vulvar LS (Figure 3, a and b). She was successfully treated for 5 months with clobetasol propionate 0.05% ointment. The patient was taking levothyroxine to treat hypothyroidism associated with Hashimoto's thyroiditis and was otherwise healthy. Oral LS is clinically characterized by the appearance of white macules, papules, or plaques mostly appearing on labial mucosa but also on buccal, palate mucosa and on the lower lip (2,3). On the genitals, it typically manifests as atrophic white plaques, which may be accompanied by purpura or fissuring (1). While vulvar LS is often associated with pruritus, dyspareunia, and dysuria, OLS is often asymptomatic, although pain, soreness, pruritus, and tightness when opening the mouth can be present (1,2). Oral manifestations of LS, as well as association of anogenital and oral LS, are rarely reported in the literature (4-6). Tomo et al. searched the Medline database for papers reporting oral LS cases with histological diagnosis confirmation from 1957 to 2016 and found only 34 cases of oral LS with histopathologic confirmation of the diagnosis (4). Kakko et al. reported 39 histologically proven cases of OLS (2). Attilli et al. (5) reviewed the clinical and histologic features of 72 cases of LS with oral/genital involvement. They reported that LS was diagnosed with exclusive genital lesions in 45, exclusive lip involvement in 20, and orogenital involvement in only 7 cases (5). Some believe that many cases of clinically diagnosed lichen planus may actually be LS and that isolated oral mucosal LS may not be as rare as is generally thought (2). While vulvar LS can occur at any age with increasing incidence with age, the median age of patients with OLS was 34 years and most of the patients were female (1,2,5). Due to the small number of patients in the literature, treatment recommendations for OLS are not available. In case of symptomatic oral lesions, topical or intralesional corticosteroids are considered to be the first-line treatment (2). First-line treatment for anogenital LS is a potent to very potent topical corticosteroid ointment, and second-line therapies include topical calcineurin inhibitors 1% pimecrolimus and 0.1% and 0.03% tacrolimus (1). For treatment-resistant genital LS, oral retinoids, methotrexate, and possibly local steroid injections for single lesions are mainly applicable for women (1). There is limited evidence for systemic treatments for both conditions. If it is not treated, genital LS is associated with a greater degree of scarring and an elevated risk of progression to squamous cell cancer; however, malignant transformation of OLS has not been reported (1-6). Due to the very rare presentation in the oral cavity, it is important to notice these lesions during a dental exam.

An extremely rare primary sarcoma of the lung with peritoneal and small bowel metastases: a case report.

BACKGROUND: Primary sarcoma of the lung is a very rare malignant tumor accounting for less than 0.5% of all lung tumors and presenting diagnostic and treatment challenge. We describe a case of a patient diagnosed with primary lung undifferentiated pleomorphic sarcoma developing subsequent peritoneal and small bowel metastases, which stand for highly unusual disease presentation. CASE PRESENTATION: A 57-year-old male presented with extensive partially necrotic tumor in the left upper lobe (LUL) of the lung that involved LUL bronchus and extended to the visceral pleura. There was no evidence of nodal or visceral dissemination. After initial presentation, the patient was admitted to the hospital's pulmonology department for further workup. The most likely diagnosis based on biopsy specimen was poorly differentiated sarcoma. Left pneumonectomy with mediastinal lymph node dissection was performed. The final pathohistological diagnosis (PHD) was undifferentiated pleomorphic sarcoma (UPS). Three months after lung surgery, a follow-up CT scan was done which showed a 60-mm obstructive metastatic intraabdominal lesion with small bowel infiltration and further separate peritoneal deposits. Unfortunately, an urgent surgery had to be performed as the patient developed signs of acute abdomen due to bowel perforation. Only 2 months later, the patient passed away at home. CONCLUSIONS: Treatment options of UPS are based on algorithms used in treatment of extremity lesions with well-established role of surgery. However, the role of perioperative chemotherapy remains equivocal with no strong evidence-based data due to the rarity of the disease. Small bowel is an unexpected metastatic site, but of significant clinical relevance.

Morphometric analysis of renal arteries in patients with renal cell carcinoma.

The aim of this study was to analyze morphometric parameters of renal arteries (longest diameter and tunica media thickness) in patients with renal cell carcinoma (RCC), to look into their relationship to tumor necrosis and to compare them with morphometric parameters recorded in a control group. We analyzed archival cases of RCC diagnosed in 2003 that also contained routinely sampled specimens of distal segments of renal artery. The control group consisted of specimens from both renal arteries obtained from 16 patients at routine autopsy during 2004-2005. Autopsy, as well as further histological analysis, did not disclose any malignant disease in the control group. Morphometric analysis of diameter and thickness of the renal artery tunica media was performed using Issa 3.1 software (Vamstek 2002, Zagreb, Croatia). The comparison of tunica media thickness showed that renal arteries from RCC cases were significantly thicker compared to distal parts of renal arteries in the control group (p=0.0002). Although renal artery samples from cases with necrotic tumor areas were thicker than those without tumor necrosis, the difference was not statistically significant. It is concluded that significantly thicker tunica media characterizes renal arteries in the group of patients with RCC when compared with the control group.