A rare case of clear-cell carcinoid of appendix.

The carcinoids are the most frequent type of tumors arising from the appendix. In the majority of cases, these tumors are asymptomatic and usually are discovered after appendectomy. Definitive diagnosis relies on pathological examination of the resected appendix, size of the tumor being critical for the further management. Clear-cell change in neuroendocrine tumors (NETs) has rarely been described in the appendix. We choose to present a clear-cell carcinoid subtype of appendiceal NET to raise awareness on this potentially curable and rare condition that can be overlooked. We highlight the importance of the pathological exam and the morphological and immunohistochemical behavior of the tumor in confirming the diagnosis and aiding in the treatment decision making. Also, important entities should be considered in the process of differential diagnosis such as goblet-cell carcinoid or renal-cell÷ovarian carcinoma.

Hydatid Cyst of the Calf - a Rare Pathology that May Be Overlooked.

Hydatid disease is caused by an infestation with the tapeworm Echinococcus. Each parasite can produce thousands of eggs with oncospheres that can migrate to the liver or lungs and rarely to other sites, including muscles. The aim of this case study is to describe a rare case of a patient with an atipical hydatid cyst location and to raise awareness of this condition. We present the case of a 28-year-old female patient admitted in our clinic with a lump in her right calf who underwent surgical excision, hydatid cyst being suspected due to the aspect of the thin cyst wall membrane, confirmed by hystopathological examination. The post-operative course was uneventful and the patient was discharged five days later with medical treatment with albendazole. In conclusion, hydatid disease must be kept in mind as a differential diagnosis when facing a muscle cystic mass, even though it is very rare, and a good medical and surgical management may determine a permanent cure.

Severe Unresponsive Hypoglycemia Associated with Neuroendocrine Tumor of Unknown Primary Site - 18 Years after Rectal Cancer Surgery. Case Report.

INTRODUCTION: Neuroendocrine tumors are derived from cells that have the unique ability to synthesize, store and secrete a variety of metabolically active substances, peptides and amines, characteristic of the tissue of origin, which can cause distinct clinical syndromes. MATERIAL AND METHODS: We present the case of a 58-year-old patient diagnosed and surgically treated in January 1996 for stage III inferior rectal cancer, who was readmitted after 18 years presenting persistent diarrheic syndrome and asthenia. Investigations performed (abdominal CT) showed multiple liver metastases, initially suspected as being related to the rectal cancer. Biopsy of liver metastases and pathological and immunohistochemical analysis demonstrated the neuroendocrine origin (moderately differentiated neuroendocrine tumor). Seven months after the identification of liver metastases and after initiation of oncological therapy with Interferon and Somatostatin, the patient presented severe hypoglycemia (serum glucose 13-70 mg/dl) proved to be due to insulin-like factors (serum insulin level 64.9 ìU/ml) secreted by metastases. Due to the aggressive evolution of neuroendocrine tumor, with multiple episodes of severe hypoglycemia, resistant to treatment, the patient died approximately one month after the occurrence of hypoglycemic episodes. CONCLUSION: Despite comprehensive tests (abdominal CT scan, colonoscopy, bone scintigraphy and PET/CT), the primary site of the neuroendocrine tumors remained unknown.

Management of Acute Pancreatitis in the Early Stage.

Acute pancreatitis (AP) is a potential fatal disease with an overall mortality around 5%. The current treatment for AP relies on supportive medical therapy, sometimes associated with endoscopic procedures and/or surgical interventions. In this review we discuss the recent concepts regarding the fluid therapy, pain management, antibiotic prophylaxis, apheresis for hypertriglyceridemia-induced AP, timing and indications for ERCP and cholecystectomy in biliary AP. For each component, the importance and the impact of early phase treatment is presented in terms of benefits and risks.

Environmental drivers of ectomycorrhizal communities in Europe's temperate oak forests.

Ectomycorrhizal fungi are major ecological players in temperate forests, but they are rarely used in measures of forest condition because large-scale, high-resolution, standardized and replicated belowground data are scarce. We carried out an analysis of ectomycorrhizas at 22 intensively monitored long-term oak plots, across nine European countries, covering complex natural and anthropogenic environmental gradients. We found that at large scales, mycorrhizal richness and evenness declined with decreasing soil pH and root density, and with increasing atmospheric nitrogen deposition. Shifts in mycorrhizas with different functional traits were detected; mycorrhizas with structures specialized for long-distance transport related differently to most environmental variables than those without. The dominant oak-specialist Lactarius quietus, with limited soil exploration abilities, responds positively to increasing nitrogen inputs and decreasing pH. In contrast, Tricholoma, Cortinarius and Piloderma species, with medium-distance soil exploration abilities, show a consistently negative response. We also determined nitrogen critical loads for moderate (9.5-13.5 kg N/ha/year) and drastic (17 kg N/ha/year) changes in belowground mycorrhizal root communities in temperate oak forests. Overall, we generated the first baseline data for ectomycorrhizal fungi in the oak forests sampled, identified nitrogen pollution as one of their major drivers at large scales and revealed fungi that individually and/or in combination with others can be used as belowground indicators of environmental characteristics.

Inhibition of renin angiotensin axis may be associated with reduced risk of developing venous thromboembolism in patients with atherosclerotic disease.

BACKGROUND: Arterial and venous thrombosis may share common pathophysiology involving the activation of platelets and inflammatory mediators. A growing body of evidence suggests prothrombotic effect of renin angiotensin system (RAS) including vascular inflammation and platelet activation. We hypothesized that the use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) plays a role in protecting against venous thromboembolism (VTE) in patients atherosclerosis. METHODS: We conducted a retrospective study, reviewing 1,100 consecutive patients admitted to a teaching hospital with a diagnosis of either myocardial infarction or ischemic stroke from 2005 to 2010. Patients who had been treated with anticoagulation therapy before or after the first visit were excluded. The occurrence of VTE during the follow up period, risk factors for VTE on admission, and the use of ACEIs or ARBs during the follow up period were recorded. RESULTS: The mean age of the entire study population was 68.1 years. 52.0% of the patients were female and 76.5% were African American. 67.3% were on RAS inhibitors. The overall incidence of VTE was 9.7% (n = 107). Among the RAS inhibitor users, the incidence of VTE events was 9.0% (54/603) for the ACEI only users, 7.1% (8/113) for the ARB only users, and 0% (0/24) for the patients taking combination of ACEI and ARB. Among patients on RAS inhibitors, 8.4% (62/740) developed a VTE, compared with 12.5% (45/360) in the nonuser group [HR (hazard ratio), 0.58; 95% CI (confidence interval), 0.39-0.84; P<0.01]. Even after controlling for factors related to VTE (smoking, history of cancer, and immobilization, hormone use) and diabetes, the use of RAS inhibitors was still associated with a significantly lower risk of developing VTE (AHR, 0.59; 95% CI, 0.40-0.88; P = 0.01). CONCLUSIONS: The use of RAS inhibitors appears to be associated with a reduction in the risk of VTE.

Association between common allergic symptoms and cancer in the NHANES III female cohort.

BACKGROUND: Previous epidemiological studies have investigated the association between allergic symptoms and cancer occurrence. However, the role of allergy in cancer has been elusive, especially for the female population. METHODS: We examined the relationship between cancer prevalence and common allergic symptoms of rhinoconjunctivitis (RC) and wheezing (WZ) among NHANES III female participants. RESULTS: Among 4600 people, 36.3% (n = 1669) did not have any allergic symptoms (NO), while 47.6% (n = 2188) reported RC, and 16.2% (n = 743), WZ. The proportion of cancer among NO groups was 5.43% (91/1669), among RC group, 7.63% (167/2188), and among WZ group, 11.23% (83/743) (RC group- OR 1.44 with 95% CI 1.00-2.08; p = 0.05 while for WZ group- OR 2.20 with 95%CI 1.27-3.80; p = 0.01). After adjusting for all the possible confounding variables including age, smoking, or COPD, having symptoms of RC (AOR 1.49 with 95%CI 1.12-2.36; p = 0.01) or WC (AOR 2.08 with 95%CI 1.11-3.89; p = 0.02) demonstrated consistent strong association with cancer. Among nonsmokers (n = 2505, 54.5%) only symptoms of RC showed association with cancer (AOR 1.51 with 95%CI 1.00-2.28; p = 0.05). Among former or current smokers (n = 2094, 45.5%), only symptoms of WZ demonstrated association with cancer (AOR 2.38 with 95%CI 1.16-4.87; p = 0.02). Among different types of cancers, odds of having breast cancer among participants with symptoms of RC or WZ were approximately twice the odds of having breast cancer among participants without any of these symptoms. AOR for RC group was 1.89 with 95%CI 1.04-3.42 and p = 0.04 while AOR for WC group was 2.08 with 95%CI 0.90-4.78 and p = 0.08. CONCLUSIONS: In summary, we found associations between common allergic symptoms like rhinitis/conjunctivitis and wheezing and prevalence of cancer, specifically between rhinitis/conjunctivitis and breast cancer that were not found in previous studies. Larger prospective studies are required to validate our findings.

Status of the Southern Carpathian forests in the long-term ecological research network.

Air pollution, bulk precipitation, throughfall, soil condition, foliar nutrients, as well as forest health and growth were studied in 2006-2009 in a long-term ecological research (LTER) network in the Bucegi Mountains, Romania. Ozone (O(3)) was high indicating a potential for phytotoxicity. Ammonia (NH(3)) concentrations rose to levels that could contribute to deposition of nutritional nitrogen (N) and could affect biodiversity changes. Higher that 50% contribution of acidic rain (pH < 5.5) contributed to increased acidity of forest soils. Foliar N concentrations for Norway spruce (Picea abies), Silver fir (Abies alba), Scots pine (Pinus sylvestris), and European beech (Fagus sylvatica) were normal, phosphorus (P) was high, while those of potassium (K), magnesium (Mg), and especially of manganese (Mn) were significantly below the typical European or Carpathian region levels. The observed nutritional imbalance could have negative effects on forest trees. Health of forests was moderately affected, with damaged trees (crown defoliation >25%) higher than 30%. The observed crown damage was accompanied by the annual volume losses for the entire research forest area up to 25.4%. High diversity and evenness specific to the stand type's structures and local climate conditions were observed within the herbaceous layer, indicating that biodiversity of the vascular plant communities was not compromised.

B1 versus B2 Dukes stage rectal cancer: prospective evaluation of 87 patients in a single institution and quest for re-evaluation of the current protocol.

BACKGROUND/AIMS: Current protocols indicate surgery as single modality of therapy for B1 stage rectal cancer and surgery with adjuvant therapy for B2 stage. The aim of our study was to analyze the five-year survival rate for patients with surgically treated B1 and B2 rectal cancer and to assess the impact of adjuvant therapy on overall survival. METHODOLOGY: Our epidemiological clinical study was based on a prospective analysis of 87 cases of B1 (n=32) and B2 (n=55) rectal cancers operated between 2000 and 2003. Survival evaluation was done through a prospective cohort followup study. RESULTS: There were 33 female and 54 males with a median age of 60 years (IQR 39-74). Tumor location was low rectum for 23 patients (26.4%), medium rectum for 30 patients (34.5%) and high rectum at 34 patients (37.9%). We performed Miles operation in 42 cases, Dixon resection in 26 cases and Hartmann operation in 18 patients. There was no difference in the number and type of postoperative complications between groups. There were no local recurrences in the B1 stage group but 7 cases (12.7%) in the B2 stage group. Distant metastases were recorded in 8 patients (25%) in the B1 group and 2 patients (3.6%) in the B2 group. The survival rate at 5 years (S5) was better for the B2 stage S5=69.9% than B1 stage S5=53.5% (p=0.001). CONCLUSIONS: Patients with B1 stage rectal cancer might benefit from adjuvant/neoadjuvant therapy.

Influence of tumor cell culture supernatants on macrophage functional polarization: in vitro models of macrophage-tumor environment interaction.

AIMS AND BACKGROUND: Macrophages are heterogeneous cells with extensive functional plasticity; they can change their functional profiles repeatedly in response to environmental changes anywhere between their extreme phenotypical programs (labeled as M1 and M2 polarization, respectively). In terms of antitumoral immune response, M1 macrophages are considered to be beneficial, while M2 macrophages supposedly promote tumor progression. Tumor-associated macrophages (TAMs) represent a major leukocyte population present in many tumors. Although many studies indicate that TAMs elicit several M2-associated protumoral functions, including promotion of angiogenesis, matrix remodeling and suppression of adaptive immunity, their role regarding tumor progression is still controversial. The aim of the present study was to develop an appropriate in vitro model to study the effect of tumor-secreted soluble factors on the functional phenotype of macrophages. METHODS AND STUDY DESIGN: THP-1 human monocytic line cells and peripheral blood mononuclear cells from healthy volunteers were used for macrophage differentiation; primary tumor cell culture supernatants or tumor cell line supernatants were employed along with various cytokines, growth factors and other stimuli to design different model variants and to better mimic the in vivo tumor microenvironment. RESULTS: The cytokine secretion patterns of these macrophages suggest that primary tumor cell culture supernatants are able to switch the macrophage phenotype or to induce functional polarization of macrophages toward a mixed M1/M2 phenotype. Conclusions. These data support the hypothesis that TAM behavior is modulated by the tumor microenvironment itself.

Dose-related effect of statins in venous thrombosis risk reduction.

BACKGROUND: Atherosclerosis and venous thromboembolism share similar pathophysiology based on common inflammatory mediators. The dose-related effect of statin therapy in venous thromboembolism remains controversial. This study investigated whether the use of antiplatelet therapy and statins decrease the occurrence of venous thromboembolism in patients with atherosclerosis. METHODS: We conducted a retrospective cohort study reviewing 1795 consecutive patients with atherosclerosis admitted to a teaching hospital between 2005 and 2010. Patients who had been treated with anticoagulation therapy were excluded. Patients who either used statins for <2 months or never used them were allocated to the nonuser group. RESULTS: The final analysis included 1100 patients. The overall incidence of venous thromboembolism was 9.7%. Among statin users, 6.3% (54/861) developed venous thromboembolism, compared with 22.2% (53/239) in the nonuser group (hazard ratio [HR] 0.24; P <.001). After controlling for confounding factors, statin use was still associated with a lower risk of developing venous thromboembolism (HR 0.29; P <.001). High-dose statin use (average 50.9 mg/day) (HR 0.25; P <.001) lowered the risk of venous thromboembolism compared with standard-dose statins (average 22.2 mg/day) (HR 0.38; P <.001). Dual antiplatelet therapy with aspirin and clopidogrel decreased occurrence of venous thromboembolism (HR 0.19; P <.001). Interestingly, combined statins and antiplatelet therapy further reduced the occurrence of venous thromboembolism (HR 0.16; P <.001). CONCLUSIONS: The use of statins and antiplatelet therapy is associated with a significant reduction in the occurrence of venous thromboembolism with a dose-related response of statins.

Serum levels of adipokines resistin and leptin in patients with colon cancer.

Adipose tissue displays characteristics of an endocrine organ releasing a number of adipocyte-specific factors known as adipocytokines. It has been recently suggested that adipocytokines may play a role in pathogenesis and progression of certain cancers, in particular in colorectal cancer. The aim of this study was to investigate the association between several blood adipocytokine levels and clinicopathological characteristics of colon cancer patients undergoing surgery. The study group comprised of 29 patients who underwent surgical resection for colon cancer at Emergency University Hospital Bucharest and 27 healthy volunteers. The serum levels of adipocytokines were measured using multianalyte xMap profiling technology (Luminex). Resistin levels were significantly higher in colon cancer patients while leptin serum levels were significantly lower as compared to controls. Leptin levels decreased gradually with tumor stage and aggressiveness. Taken together, these results of this study suggest that adipokines, in particular resistin and leptin may be involved in development and progression of colon cancer.

Primary cell culture of human adenocarcinomas--practical considerations.

Cell culture is one of the major tools for oncology research, being an excellent system in which to study the biochemistry and molecular biology associated with individual cancer types and to understand cancer cell physiology. Progress in understanding the biology of any type of carcinoma has been impeded by the inability to culture adequately malignant cells from most epithelial tissues. The ultimate in vitro tumor model would completely reflect the in vivo tumor microenvironment in function and mechanism. Unfortunately, such a model does not currently exist. Homogeneous cell lines that can be continuously propagated on plastic surfaces have been extensively used as a surrogate for tumor environment; however they are very different from the in vivo tumor cells. Model systems involving primary culture represent the situation most closely related to the original tissue although they have a number of disadvantages over cell lines, such as the limited ability to repeat studies with a well characterized culture system that can be used in multiple laboratories. The primary culture may contain many types of stromal and infiltrating cell types potentially complicating the interpretation of data. Yet, their properties better reflect the cellular interactions present in intact tissue. The present article reviews the critical steps in obtaining, routine maintenance and cryopreservation of primary tumor cell cultures, based on information from literature and personal experience on the subject. The article also includes an updated protocol for primary tumor cell isolation and culture.