Gas in the Portal Vein: An Emergency or Just Hot Air?

We report the case of a 87-year-old woman admitted to our Emergency Department for mild abdominal pain associated with vomiting. An abdominal X-ray showed gas present in the portal venules of the left hepatic lobe, a finding associated with numerous surgical and medical conditions. The patient was successfully managed with conservative treatment. Isolated intrahepatic gas is a rare radiologic finding; emergency surgery should be performed only when there are signs of associated acute intestinal infarction.

In vitro anti-angiogenic effects of Hemidesmus indicus in hypoxic and normoxic conditions.

ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of the roots of Hemidesmus indicus is widely used in the Indian traditional medicine for many purposes and poly-herbal preparations containing Hemidesmus are often used by traditional medical practitioners for the treatment of cancer. In the context of anticancer pharmacology, anti-angiogenic therapy has become an effective strategy for inhibiting new vessel formation and contrast tumor growth. These considerations are supported by the evidence that most tumors originate in hypoxic conditions and limitation of oxygen diffusion stimulates the formation of tumor abnormal microvasculature. Aim of this study was to evaluate the in vitro anti-angiogenic potential of Hemidesmus indicus (0.31-0.93 mg/mL) on human umbilical vein endothelial cells and delineate the main molecular mechanisms involved in its anti-angiogenic activity both in normoxia and hypoxia. MATERIALS AND METHODS: The decoction of Hemidesmus indicus was subjected to an extensive HPLC phytochemical characterization. Its in vitro anti-angiogenic potential was investigated in normoxia and hypoxia. Cell proliferation, apoptosis induction, and inhibition of endothelial cell migration and invasion were analyzed by flow cytometry. The endothelial tube formation assay was evaluated in matrix gel. The capillary tube branch points formed were counted using a Motic AE21 microscope and a VisiCam videocamera. The regulation of key factors of the neovascularization process such as VEGF, HIF-1α and VEGFR-2 was explored at mRNA and protein level by real time PCR and flow cytometry, respectively. RESULTS: Treatment with Hemidesmus resulted in a significant inhibition of cell proliferation and tube formation in both normoxia and hypoxia. Hemidesmus differently regulated multiple molecular targets related to angiogenesis according to oxygen availability. In normoxia, the inhibition of VEGF was the main responsible for its anti-angiogenic effect; the angiogenesis inhibition induced in hypoxia was regulated by a more complex mechanism involving firstly HIF-1α inhibition, and then VEGF and VEGFR-2 down-regulation. Additionally, the inhibition of endothelial cell migration and invasion by Hemidesmus was more pronounced in normoxia than in hypoxia, possibly due to the physiological enhanced induction of invasion characteristic of hypoxia. CONCLUSIONS: Our results indicate that Hemidesmus might represent a promising therapeutic strategy for diseases in which the inhibition of angiogenesis could be beneficial, such as cancer. The antiangiogenic activity of Hemidesmus is based on multiple interactions with critical steps in the angiogenic cascade. VEGF expression stimulated by HIF-1α as well as endothelial cell migration and differentiation represent important targets of Hemidesmus action and might contribute to its cancer therapeutic efficacy that is presently emerging and offer a scientific basis for its use in traditional medicine.

Hemidesmus indicus induces apoptosis as well as differentiation in a human promyelocytic leukemic cell line.

ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of the roots of Hemidesmus indicus is widely used in the Indian traditional medicine for the treatment of blood diseases, dyspepsia, loss of taste, dyspnea, cough, poison, menorrhagia, fever, and diarrhea. Poly-herbal preparations containing Hemidesmus are often used by traditional medical practitioners for the treatment of cancer. The aim of this study was to investigate the cytodifferentiative, cytostatic and cytotoxic potential of a decoction of Hemidesmus indicus's roots (0.31-3 mg/mL) on a human promyelocytic leukemia cell line (HL-60). MATERIALS AND METHODS: The decoction of Hemidesmus indicus was characterized by HPLC to quantify its main phytomarkers. Induction of apoptosis, cell-cycle analysis, levels of specific membrane differentiation markers were evaluated by flow cytometry. The analysis of cell differentiation by nitroblue tetrazolium (NBT) reducing activity, adherence to the plastic substrate, α-napthyl acetate esterase activity and morphological analysis was performed through light microscopy (LM) and transmission electron microscopy (TEM). RESULTS: Starting from the concentration of 0.31 mg/ml, Hemidesmus indicus induced cytotoxicity and altered cell-cycle progression, through a block in the G0/G1 phase. The decoction caused differentiation of HL-60 cells as shown by NBT reducing activity, adherence to the plastic substrate, α-naphtyl acetate esterase activity, and increasing expression of CD14 and CD15. The morphological analysis by LM and TEM clearly showed the presence of granulocytes and macrophages after Hemidesmus indicus treatment. CONCLUSIONS: The cytodifferentiating, cytotoxic and cytostatic activities of Hemidesmus indicus offers a scientific basis for its use in traditional medicine. Its potent antileukemic activity provides a pre-clinical evidence for its traditional use in anticancer pharmacology. Further experiments are worthwhile to determine the in vivo anticancer potential of this plant decoction and its components.

Surgical therapy for adenocarcinoma of the cardia: modalities of recurrence and extension of resection.

In order to define the optimal extent of resection for cancer of the cardia, we considered 116 patients operated upon with five different surgical techniques. The procedures were: transabdominal total gastrectomy associated with distal esophagectomy in 38 patients; transabdominal total gastrectomy and left thoracotomic esophageal resection at the inferior pulmonary vein level in 26 patients; transabdominal total gastrectomy and right thoracotomic esophageal resection at the azygos vein level in 27 patients; transabdominal total gastrectomy and transhiatal lower third esophagectomy in 18 patients; transhiatal total esophagectomy and upper third gastrectomy with cervical esophago-gastroplasty in seven patients. Grading, staging, neoplastic lymphangitis, satellite intramural metastases, infiltration of the resection margin, site of recurrence, and survival were analyzed. N+ was the single independent prognostic factor for survival. A poorly differentiated grading was related to T (P = 0.0009), N (P = 0.001), satellite growth (P = 0.05), and infiltration of the resection margin (P = 0.0001). Recurrence was local in 26% and distant in 74% of patients. The modalities of recurrence were not related to the aggressiveness parameters and the surgical technique. Infiltration of the esophageal resection margin was related to the type of operation (P = 0.005) and survival (P = 0.02), but it was not related to the site of recurrence. Transabdominal total gastrectomy and the right thoracotomic esophageal resection procedure achieved free margins and control of the lymph nodal metastatic spread. Transabdominal total gastrectomy and right thoracotomic esophageal resection at the azygos vein level provides a radical oncologic resection, particularly in poorly differentiated tumors. However, surgery alone cannot cure the majority of adenocarcinomas of the cardia.

Role and new perspectives of transforming growth factor-alpha (TGF-alpha) in adenocarcinoma of the gastro-oesophageal junction.

The incidence of gastro-oesophageal junction (GEJ) adenocarcinoma is increasing in Western countries and prognosis is poor since metastasis is most often present at diagnosis. We examined samples from 87 resected type II GEJ adenocarcinomas, 30 of these with endoscopic diagnostic biopsy material, to evaluate transforming growth factor alpha (TGF-a) expression and p53 overexpression by immunohistochemistry and in situ hybridization (for TGF-alpha), in relation to biological and clinical behaviour. TGF-alpha messenger RNA (mRNA) and protein were detectable in neoplastic cells in 56% and 64% cases respectively. TGF-alpha mRNA was detected in intra- and peritumoral lymphocytes and those of metastatic lymph nodes. TGF-alpha protein expression was significantly associated with tumour progression (P= 0.025) and lymph node metastasis (P < 0.05). The strong TGF-alpha expression found in neoplastic cells inside blood and lymphatic vessels and in metastatic localizations suggests that TGF-a-positive GEJ adenocarcinomas could have a more aggressive biological phenotype. The expression of TGF-alpha mRNA and protein in both inflammatory and neoplastic cells indicates that TGF-alpha is directly synthesized by both cell compartments. Finally, since TGF-alpha expression was associated with lymph node metastasis, its detection in preoperative perendoscopic biopsies might identify patients with more aggressive tumours who may need additional therapy, including neo-adjuvant treatment.

Clinical and surgical relevance of the progressive phases of intrathoracic migration of the gastroesophageal junction in gastroesophageal reflux disease.

OBJECTIVE: The pathophysiologic influence of progressive intrathoracic migration of the gastroesophageal junction axial to the esophagus on gastroesophageal reflux disease was investigated. METHODS: A radiologic-manometric study was performed on hiatal insufficiency, concentric hiatus hernia, and short esophagus, the three radiologic steps of intrathoracic gastroesophageal junction migration, and on healthy volunteers. The distances between inferior and superior margins of the lower esophageal sphincter and the diaphragm were measured. Endoscopic, manometric, and pH-metric evaluations were performed after barium swallow in 38 patients with severe gastroesophageal reflux disease and sliding hiatus hernia with intraabdominally reducible gastroesophageal junction, in 35 patients with hiatal insufficiency, in 40 with concentric hiatus hernia, and in 19 with short esophagus. RESULTS: The distance from the lower esophageal sphincter inferior margin to the diaphragm was different in healthy volunteers (-2.6 +/- 0.9 cm [standard deviation]) versus that in patients with hiatal insufficiency (-1.0 +/- 0.7 cm; p = 0.02), concentric hiatus hernia (-0.8 +/- 1.0 cm; p = 0.02), and short esophagus (4.0 +/- 2.5 cm; p = 0.0002), and in patients with short esophagus versus hiatal insufficiency (p = 0.0002) and concentric hiatus hernia (p = 0.0002). Lower esophageal sphincter tone was reduced between healthy volunteers (19 +/- 9.1 mm Hg [standard deviation]) and patients with sliding hiatus hernia (12 +/- 7.2 mm Hg;p = 0.02), hiatal insufficiency (10 +/- 5.9 mm Hg; p = 0.0001), concentric hiatus hernia (7 +/- 3.1 mm Hg; p = 0.00002), and short esophagus (7 +/- 3.7 mm Hg; p = 0.00003) and between concentric hiatus hernia versus sliding hiatus hernia (p = 0.007). Acid gastroesophageal reflux total time percent was increased between healthy volunteers (2.4% +/- 1.8% [standard deviation]) and patients with sliding hiatus hernia (12.8% +/- 7.8%;p = 0.02), hiatal insufficiency (17.2% +/- 15.8%; p = 0.0001), concentric hiatus hernia (24.0% +/- 19.6%;p = 0.00002), and short esophagus (26.1% +/- 19.6%;p = 0.00002) and between sliding hiatus hernia versus concentric hiatus hernia (p = 0.002) and short esophagus (p = 0.01). CONCLUSIONS: Permanent gastroesophageal junction orad migration axial to the esophagus has greater pathophysiologic relevance on gastroesophageal reflux disease than sliding hiatus hernia with an intraabdominally reducible gastroesophgeal junction. Hiatal insufficiency, concentric hiatus hernia, and short esophagus are markers of progressively increasing irreversible cardial incontinence and therefore indications for surgical therapy.

Effects of conjugated equine oestrogens and oestriol on blood clotting, plasma lipids and endometrial proliferation in post-menopausal women.

The effects on blood-clotting factors, plasma lipids and endometrial proliferation of two types of oral oestrogen therapy (a) cyclical therapy with 0.625 mg/day conjugated equine oestrogens for 3 wk followed by 1 wk without treatment, and (b) continuous therapy with 2 mg/day oestriol) were investigated in a 5-mth study involving 22 post-menopausal women. Assays were performed in order to measure blood-clotting factors (activity of the factor II-VII-X complex, anti-thrombin III, euglobulin lysis time) and plasma lipids (total cholesterol, triglycerides, lipoprotein electrophoresis) before treatment and after 3 and 4 mth of treatment. The only significant change found to have occurred was a decrease in the beta: alpha lipoproteins ratio; this was greater in the group treated with conjugated equine oestrogens, but was also statistically significant in the group treated with oestriol. Endometrial proliferation was investigated indirectly by means of the medroxyprogesterone acetate (MPA) test before treatment and after 5 mth of treatment. The response to MPA at the end of 5 mth of treatment in patients previously unresponsive, showed endometrial proliferation to have occurred during treatment with conjugated equine oestrogens but not during treatment with oestriol.