Adipose Tissue Hypertrophy, An Aberrant Biochemical Profile and Distinct Gene Expression in Lipedema.

BACKGROUND: Lipedema is a common adipose tissue disorder affecting women, characterized by a symmetric subcutaneous adipose tissue deposition, particularly of the lower extremities. Lipedema is usually underdiagnosed, thus remaining an undertreated disease. Importantly, no histopathologic or molecular hallmarks exist to clearly diagnose the disease, which is often misinterpreted as obesity or lymphedema. MATERIALS AND METHODS: The aim of the present study is to characterize in detail morphologic and molecular alterations in the adipose tissue composition of lipedema patients compared with healthy controls. Detailed histopathologic and molecular characterization was performed using lipid and cytokine quantification as well as gene expression arrays. The analysis was conducted on anatomically matched skin and fat tissue biopsies as well as fasting serum probes obtained from 10 lipedema and 11 gender and body mass index-matched control patients. RESULTS: Histologic evaluation of the adipose tissue showed increased intercellular fibrosis and adipocyte hypertrophy. Serum analysis showed an aberrant lipid metabolism without changes in the circulating adipokines. In an adipogenesis gene array, a distinct gene expression profile associated with macrophages was observed. Histologic assessment of the immune cell infiltrate confirmed the increased presence of macrophages, without changes in the T-cell compartment. CONCLUSIONS: Lipedema presents a distinguishable disease with typical tissue architecture and aberrant lipid metabolism, different to obesity or lymphedema. The differentially expressed genes and immune cell infiltration profile in lipedema patients further support these findings.

Carnitine modulates crucial myocardial adenosine triphosphatases and acetylcholinesterase enzyme activities in choline-deprived rats.

Choline is an essential nutrient, and choline deficiency has been associated with cardiovascular morbidity. Choline is also the precursor of acetylcholine (cholinergic component of the heart's autonomic nervous system), whose levels are regulated by acetylcholinesterase (AChE). Cardiac contraction-relaxation cycles depend on ion gradients established by pumps like the adenosine triphosphatases (ATPases) Na(+)/K(+)-ATPase and Mg(2+)-ATPase. This study aimed to investigate the impact of dietary choline deprivation on the activity of rat myocardial AChE (cholinergic marker), Na(+)/K(+)-ATPase, and Mg(2+)-ATPase, and the possible effects of carnitine supplementation (carnitine, structurally relevant to choline, is used as an adjunct in treating cardiac diseases). Adult male albino Wistar rats were distributed among 4 groups, and were fed a standard or choline-deficient diet for one month with or without carnitine in their drinking water (0.15% w/v). The enzyme activities were determined spectrophotometrically in the myocardium homogenate. Choline deficiency seems to affect the activity of the aforementioned parameters, but only the combination of choline deprivation and carnitine supplementation increased myocardial Na(+)/K(+)-ATPase activity along with a concomitant decrease in the activities of Mg(2+)-ATPase and AChE. The results suggest that carnitine, in the setting of choline deficiency, modulates cholinergic myocardial neurotransmission and the ATPase activity in favour of cardiac work efficiency.

Increased levels of VEGF-C and macrophage infiltration in lipedema patients without changes in lymphatic vascular morphology.

Lipedema is a chronic adipose tissue disorder characterized by the disproportional subcutaneous deposition of fat and is commonly misdiagnosed as lymphedema or obesity. The molecular determinants of the lipedema remain largely unknown and only speculations exist regarding the lymphatic system involvement. The aim of the present study is to characterize the lymphatic vascular involvement in established lipedema. The histological and molecular characterization was conducted on anatomically-matched skin and fat biopsies as well as serum samples from eleven lipedema and ten BMI-matched healthy patients. Increased systemic levels of vascular endothelial growth factor (VEGF)-C (P = 0.02) were identified in the serum of lipedema patients. Surprisingly, despite the increased VEGF-C levels no morphological changes of the lymphatic vessels were observed. Importantly, expression analysis of lymphatic and blood vessel-related genes revealed a marked downregulation of Tie2 (P < 0.0001) and FLT4 (VEGFR-3) (P = 0.02) consistent with an increased macrophage infiltration (P = 0.009), without changes in the expression of other lymphatic markers. Interestingly, a distinct local cytokine milieu, with decreased VEGF-A (P = 0.04) and VEGF-D (P = 0.02) expression was identified. No apparent lymphatic anomaly underlies lipedema, providing evidence for the different disease nature in comparison to lymphedema. The changes in the lymphatic-related cytokine milieu might be related to a modified vascular permeability developed secondarily to lipedema progression.

Experimental isolation and preservation of solid organs before transplantation: effects of pretreatment using four different molecules.

OBJECTIVES: In transplantation surgery, the ischaemic organ and reperfusion impairment after cold storage remains a considerable risk factor for impaired function and potential failure of the grafted organ. Substantial logistical efforts have been undertaken to reduce the cold ischaemic time because the demand for available transplant organs and the periods of cold ischaemia are increasing. METHODS: Four molecules were investigated (erythropoietin, sildenafil, lazaroid [U74389G], octreotide) in individual intravenous infusions 1 hour before the organ was harvested. This study was performed in 30 healthy landrace/large-white pigs (male; >10 weeks old; average weight, 22 ± 2 kg) in groups of six. The organs were studied at harvest, and at 8 and 24 hours post-harvest. RESULTS: The lazaroid molecule increased malondialdehyde (MDA) levels in the liver and pancreas at 8 hours. Hepatic lazaroid molecules improved liver histology at 8 and 24 hours. For kidneys, erythropoietin had a positive effect at 24 hours post-harvest. For the pancreas, octreotide showed better performance. In the lungs, there was less interstitial oedema with erythropoietin and lazaroid compared with the control group at 8 hours post-harvest. CONCLUSION: All molecules had a positive effect and decreased ischaemia/reperfusion graft injury. Thus, pretreatment before organ harvest has a beneficial role.

Humoral Factors From Musculoskeletal Polytrauma Patients Impair Antibacterial Responses Of Neutrophils In vitro.

Polytrauma is associated with increased risk of sepsis, but the risk for implant infection is less clear. Neutrophil antibacterial responses are significantly reduced in polytrauma patients (n= 9, ISS≥15) for at least 5 days compared to healthy controls. Reduced neutrophil activity could influence implant infection in addition to sepsis.

Massive ovarian oedema: a misleading clinical entity.

BACKGROUND: Massive ovarian oedema is a rare non-neoplastic clinicopathologic entity has a higher incidence in women during their second and third life decade. The oedema can be presented in one or both ovaries as a result of partial intermittent torsion of the ovarian pedicle that interferes to the venal and lymphatic drainage of the ovary. CASE PRESENTATION: We present a clinical case of a 16 year old with massive ovarian oedema and we performed a review of the literature. The pathophysiology of this entity is very complex. We tried to perform a complete review of the literature and focus on the complexity of this entity as far as its pathophysiological backround is concerned and as far as its clinical presentation is concerned. CONCLUSIONS: In conclusion, massive ovarian oedema is a rare, multi disease mimicking clinical entity, with an acute or progressive clinical presentation. It has also to be a part of our differential diagnosis in cases of acute abdominal pain and we have to try to treat her conservatively, in order to preserve fertility.

Gastrointestinal stromal tumor mesenchymal neoplasms: the offspring that choose the wrong path.

Gastrointestinal stromal tumors (GISTs) are relatively rare neoplasms of the gastrointestinal tract originating from the pluripotential mesenchymal stem cells, which differentiate into interstitial Cajal cells. They are usually located in the upper gastrointestinal track. These tumors are typically defined by the expression of c-KIT (CD117) and CD34 proteins in the tumor cells. A small percentage of these tumors is negative for c-KIT. The neoplasms are positive for platelet-derived growth factor α (PDGFα) mutations. In addition to PDGFRα mutations, wild-type c-KIT mutations can also be present. The therapeutic approach to locally developed gastrointestinal stromal tumors is surgical resection, either with open or laparoscopic surgery. In case of systemic disease, molecular pharmacologic agents such as imatinib and sunitinib are used for treatment. These agents block the signaling pathways of neoplastic-cell tyrosine kinases, interfering in their proliferation and causing apoptosis.

Surgical approaches of endobronchial neoplasms.

Endobronchial tumors are a rare entity that presents with different pathological findings. The interventional pulmonologist, but also the thoracic surgeon have at their disposal the same techniques for diagnosis, however; the two modalities differentiate in the treatment approach. Diagnosis evaluation should include lymph node evaluation. Minimal invasive techniques under local or general anesthesia are usually preferred by the interventional pulmonologists, whereas in the surgical approach of the thoracic surgeons the general anesthesia is necessary. A more extensive surgical approach either lobotomy or pneumonectomy should be performed in cases with positive intrapulmonary lymph nodes. Carinal reconstruction should be performed skillfully to get a negative proximal margin whenever needed. In the current manuscript we will present the methods of patient evaluation and surgical techniques for the management of these lesions.

Pelvic schwannoma in the right parametrium.

Neurilemomas are benign usually encapsulated nerve sheath tumors derived from the Schwann cells. These tumors commonly arise from the cranial nerves as acoustic neurinomas but they are extremely rare in the pelvis and the retroperitoneal area (less than 0.5% of reported cases), unless they are combined with von Recklinghausen disease (type 1 neurofibromatosis). We report the case of a 58-year-old female with pelvic schwannoma, 6.5 × 5.5 cm in size, in the right parametrium. This is the first case reported in the literature. Based on the rarity of this tumor and in order to ensure optimum treatment and survival for our patient, we performed laparotomy with total abdominal hysterectomy and en-block tumor excision. A frozen section was taken during the surgery before complete resection of the mass, which was ambiguous. Because of the possibility of malignancy, complete excision of the mass was performed, with pelvic blunt dissection. Histological examination showed a benign neoplasm, originating from the cells of peripheral nerve sheaths; diagnosis was a schwannoma. There were degenerative areas, including cystic degeneration, hemorrhagic infiltrations, ischemic foci with pycnotic cells, and collagen replacement. Pelvic schwannomas are rare neoplasms that can be misdiagnosed. Laparoscopy is a safe and efficient option for approaching benign pelvic tumors and might offer the advantage of better visualization of structures due to the magnification in laparoscopic view, especially in narrow anatomic spaces.

Heart dysfunction induced by choline-deficiency in adult rats: the protective role of L-carnitine.

Choline is a B vitamin co-factor and its deficiency seems to impair heart function. Carnitine, a chemical analog of choline, has been used as adjunct in the management of cardiac diseases. The study investigates the effects of choline deficiency on myocardial performance in adult rats and the possible modifications after carnitine administration. Wistar Albino rats (n=24), about 3 months old, were randomized into four groups fed with: (a) standard diet (control-CA), (b) choline deficient diet (CDD), (c) standard diet and carnitine in drinking water 0.15% w/v (CARN) and (d) choline deficient diet and carnitine (CDD+CARN). After four weeks of treatment, we assessed cardiac function under isometric conditions using the Langendorff preparations [Left Ventricular Developed Pressure (LVDP-mmHg), positive and negative first derivative of LVDP were evaluated], measured serum homocysteine and brain natriuretic peptide (BNP) levels and performed histopathology analyses. In the CDD group a compromised myocardium contractility compared to control (P=0.01), as assessed by LVDP, was noted along with a significantly impaired diastolic left ventricular function, as assessed by (-) dp/dt (P=0.02) that were prevented by carnitine. Systolic force, assessed by (+) dp/dt, showed no statistical difference between groups. A significant increase in serum BNP concentration was found in the CDD group (P<0.004) which was attenuated by carnitine (P<0.05), whereas homocysteine presented contradictory results (higher in the CDD+CARN group). Heart histopathology revealed a lymphocytic infiltration of myocardium and valves in the CDD group that was reduced by carnitine. In conclusion, choline deficiency in adult rats impairs heart performance; carnitine acts against these changes.

The management of the advanced colorectal cancer: management of the pulmonary metastases.

Pulmonary metastases from colorectal cancer present as systemic manifestation of the disease. As a general principle, the presence of metastases predispose to a poor prognosis. However, the application of some criteria of "operability" permitted the surgical resection resulting in prolonged survival (reported 5-year survival up to 50%), in better quality of life and in the cure of some patients. When the primary tumor site is controlled, and the metastatic disease is limited in lungs without extrapulmonary location (except for resectable or resected hepatic lesion) surgical removal is indicated. As significant prognostic factors in metastasectomies have been reported the synchronous or metachronous caracter of the metastases, the disease free survival, the complete removal of the metastases, the thoracic lymph node invasion, the CEA level before metastasectomy and 1 month after, the solitary vs. multiple pulmonary metastatic locations, the induction chemotherapy, the histological type and differentiation grade, as well as the vascular emboli in histopathological examination. Thorough preoperative evaluation of the patient includes oncological assessment and respiratory functional tests. Alternatively, when the patient is not a good surgical candidate, radiofrequency ablation is an option. Many surgical accesses have been validated, as posterolateral or lateral or even posterior thoracotomy, sternotomy, clamshell incision, and thoracoscopic techniques that offer the advantages of less pain, fast recovery, and less morbidity. Though thoracoscopic metastasectomies have been questioned concerning to the completeness of metastatic removal, no statistical difference in survival has been revealed in many series comparing thoracotomy to thoracoscopic techniques. As a conclusion, there are many advances in the management of pulmonary metastases from colorectal cancer during last decade, the results have been essentially optimized, the role of surgery has been established, and the multimodality approach has been recognized as the cornerstone of a successful outcome.

Extrapelvic endometriosis: a rare entity or an under diagnosed condition?

Endometriosis is a clinical entity characterized by the presence of normal endometrial mucosa abnormally implanted in locations other than the uterine cavity. Endometriosis can be either endopelvic or extrapelvic depending on the location of endometrial tissue implantation. Despite the rarity of extrapelvic endometriosis, several cases of endometriosis of the gastrointestinal tract, the urinary tract, the upper and lower respiratory system, the diaphragm, the pleura and the pericardium, as well as abdominal scars loci have been reported in the literature. There are several theories about the pathogenesis and the pathophysiology of endometriosis. Depending on the place of endometrial tissue implantation, endometriosis can be expressed with a wide variety of symptoms. The diagnosis of this entity is neither easy nor routine. Many diagnostic methods clinical and laboratory have been used, but none of them is the golden standard. The multipotent localization of endometriosis in combination with the wide range of its clinical expression should raise the clinical suspicion in every woman with periodic symptoms of extrapelvic organs. Finally, the therapeutic approach of this clinical entity is also correlated with the bulk of endometriosis and the locum that it is found. It varies from simple observation, to surgical treatment and treatment with medication as well as a combination of those. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1968087883113362.

Advanced bronchoscopic techniques in diagnosis and staging of lung cancer.

The role of advanced brochoscopic diagnostic techniques in detection and staging of lung cancer has steeply increased in recent years. Bronchoscopic imaging techniques became widely available and easy to use. Technical improvement led to merging in technologies making autofluorescence or narrow band imaging incorporated into one bronchoscope. New tools, such as autofluorescence imagining (AFI), narrow band imaging (NBI) or fuji intelligent chromo endoscopy (FICE), found their place in respiratory endoscopy suites. Development of endobronchial ultrasound (EBUS) improved minimally invasive mediastinal staging and diagnosis of peripheral lung lesions. Linear EBUS proven to be complementary to mediastinoscopy. This technique is now available in almost all high volume centers performing bronchoscopy. Radial EBUS with mini-probes and guiding sheaths provides accurate diagnosis of peripheral pulmonary lesions. Combining EBUS guided procedures with rapid on site cytology (ROSE) increases diagnostic yield even more. Electromagnetic navigation technology (EMN) is also widely used for diagnosis of peripheral lesions. Future development will certainly lead to new improvements in technology and creation of new sophisticated tools for research in respiratory endoscopy. Broncho-microscopy, alveoloscopy, optical coherence tomography are some of the new research techniques emerging for rapid technological development.

Adjuvant chemotherapy and radiotherapy in the treatment of non-small cell lung cancer (NSCLC).

Lung cancer is one of the most common human malignancies and remains the leading cause of cancer related deaths worldwide. Many recent technological advances led to improved diagnostics and staging of lung cancer. With development of new treatment options such as targeted therapies there might be improvement in progression free survival of patients with advanced stage non-small cell lung cancer (NSCLC). Improvement in overall survival is still reserved for selected patients and selected treatments. One of the mostly investigated therapeutic options is adjuvant treatment. There are many open issues in selection of patients and administration of appropriate adjuvant treatment.

Video assisted thoracoscopic plication of the left hemidiaphragm in symptomatic eventration in adulthood.

Diaphragmatic eventration is a rare congenital developmental defect of the muscular portion of the diaphragm, which appears attenuated and membranous, maintaining its normal attachments and its anatomical continuity. It has been attributed to abnormal myoblast migration to the septum transversum and the pleuroperitoneal membrane. Eventration can be unilateral or bilateral, partial or complete. It is more common in males, and involves more often the left hemidiaphragm. Eventration results in diaphragmatic elevation (cephalad displacement). Most adults are asymptomatic and the diagnosis is incidentally made by chest radiography. The commonest symptom in the adults is dyspnoea, while orthopnoea, mild hypoxemia, tachypnoea, respiratory alkalosis, palpitations, and non specific gastrointestinal symptoms may be present. Surgery is indicated only in the presence of symptoms. The established surgical treatment is diaphragmatic plication. Various techniques and approaches have been employed. We present a simple surgical technique of a 3-port video assisted thoracoscopic plication of the left hemidiaphragm in the adult.

Early hemi-diaphragmatic plication through a video assisted mini-thoracotomy in postcardiotomy phrenic nerve paresis.

New symptom onset of respiratory distress without other cause, and new hemi-diaphragmatic elevation on chest radiography postcardiotomy, are usually adequate for the diagnosis of phrenic nerve paresis. The symptom severity varies (asymptomatic state to severe respiratory failure) depending on the degree of the lesion (paresis vs. paralysis), the laterality (unilateral or bilateral), the age, and the co-morbidity (respiratory, cardiac disease, morbid obesity, etc). Surgical treatment (hemi-diaphragmatic plication) is indicated only in the presence of symptoms. The established surgical treatment is plication of the affected hemidiaphragm which is generally considered safe and effective. Several techniques and approaches are employed for diaphragmatic plication (thoracotomy, video-assisted thoracoscopic surgery, video-assisted mini-thoracotomy, laparoscopic surgery). The timing of surgery depends on the severity and the progression of symptoms. In infants and young children with postcardiotomy phrenic nerve paresis the clinical status is usually severe (failure to wean from mechanical ventilation), and early plication is indicated. Adults with postcardiotomy phrenic nerve paresis usually suffer from chronic dyspnoea, and, in the absence of respiratory distress, conservative treatment is recommended for 6 months -2 years, since improvement is often observed. Nevertheless, earlier surgical treatment may be indicated in non-resolving respiratory failure. We present early (25(th) day postcardiotomy) right hemi-diaphragm plication, through a video assisted mini-thoracotomy in a high risk patient with postcardiotomy phrenic nerve paresis and respiratory distress. Early surgery with minimal surgical trauma, short operative time, minimal blood loss and postoperative pain, led to fast rehabilitation and avoidance of prolonged hospitalization complications. The relevant literature is discussed.

Lost in time pulmonary metastases of renal cell carcinoma: complete surgical resection of metachronous metastases, 18 and 15 years after nephrectomy.

Surgery is the only potentially curative therapeutic approach for renal cell carcinoma (RCC). RCC is resistant to most systemic therapies, including chemotherapy, radiotherapy, and hormonal therapy, having limited response to immunotherapy. Newer agents targeting angiogenesis, recommended in metastatic RCC, offer improved disease free and overall survival, stabilizing the disease, rather than having a curative effect.One of the most common sites of synchronous or metachronous RCC metastases is the lung. The five-year survival after resection of RCC pulmonary metastases ranged between 21% and 83%. Complete metastasectomy improves the prognosis and should be evaluated, despite improved results of newer systemic treatments.In surgically treated metachronous RCC pulmonary metastases, the reported disease free interval varied, but in the majority of cases it did not exceed five years. Surgical resection of RCC pulmonary metastases 15 or more years after nephrectomy is very rare. We report complete surgical resection of metachronous, multiple, unilateral clear cell RCC pulmonary metastases in two patients without enlarged mediastinal lymph nodes or extrapulmonary disease, 15 and 18 years after initial nephrectomy. Both patients had an uneventful recovery, and remain alive and well one year, and five months respectively, after metastasectomy.

Non-Hodgkin lymphoma and GIST: molecular pathways and clinical expressions.

We report the case of a 64-year-old woman with a gastrointestinal stromal tumor and a diffuse large cell lymphoma. For this case, we conducted a literature review in an attempt to correlate these two neoplasms on a molecular basis. Diffuse large cell lymphoma is a subtype of non-Hodgkin lymphomas. The etiologic factor of these lymphomas is considered to be the mutations or allelic losses of the TP53 tumor suppressor gene and the overexpression of the bcl-2 oncogene. Gastrointestinal stromal tumors are mesenchymal tumors, which are typically defined by the expression of c-KIT (CD117) and CD34 genes in the tumor cells. Although there are references to dispersants in the literature about patients with both non-Hodgkin lymphoma and gastrointestinal stromal tumors, there is no common molecular pathway between these two diseases. In conclusion, there is no indication that these two neoplasms are relevant on a molecular basis.

Pegylated liposomal doxorubicin in malignant pleural mesothelioma: a possible guardian for long-term survival.

Malignant pleural mesothelioma is a rare and aggressive malignancy of the pleura correlated with exposure to asbestos, with a medium survival of 11-12 months after diagnosis. A case of a 67-year-old male who had previously worked in the asbestos industry and is a current smoker is reported. The computed tomography evaluation revealed a right pleural mass with pleural thickening, and the pleural biopsy confirmed a diagnosis of malignant pleural mesothelioma. He was treated with chemotherapy consisting of etoposide, paclitaxel, and pegylated liposomal doxorubicin hydrochloride. After completion of chemotherapy, radiologic evaluation confirmed a reduction of pleural thickening and improvement in his symptoms. A complete presentation of each drug formulation and characteristics are also included in this paper. The patient's follow-up is continuing, and computed tomography reveals stable disease 9 years after initial examination.

Management of sigmoid volvulus avoiding sigmoid resection.

Acute sigmoid volvulus is typically caused by an excessively mobile and redundant segment of colon with a stretched mesenteric pedicle. When this segment twists on its pedicle, the result can be obstruction, ischemia and perforation. A healthy, 18-year-old Caucasian woman presented to the emergency department complaining of cramping abdominal pain, distention, constipation and obstipation for the last 72 h, accompanied by nausea, vomiting and abdominal tenderness. The patient had tympanitic percussion tones and no bowel sounds. She was diagnosed with acute sigmoid volvulus. Although urgent resective surgery seems to be the appropriate treatment for those who present with acute abdominal pain, intestinal perforation or ischemic necrosis of the intestinal mucosa, the first therapeutic choice for clinically stable patients in good general condition is considered, by many institutions, to be endoscopic decompression. Controversy exists on the decision of the time, the type of definitive treatment, the strategy and the most appropriate surgical technique, especially for teenagers for whom sigmoid resection can be avoided.