Cardiovascular complications in patients with pheochromocytoma: A mini-review

Phaeochromocytomas are rare neuroendocrine tumours secreting high levels of catecholamines, able to exert serious metabolic and cardiovascular effects. The serious and potentially lethal cardiovascular complications of these tumours are due to the potent effects of secreted catecholamines, especially noradrenaline, the main transmitter released from sympathetic nerve terminals. Hypertension, tachycardia, pallor, headache and anxiety, usually dominate the clinical presentation. Occasionally, patients with predominantly epinephrine-secreting tumours present hypotension or even shock. Other cardiovascular complications of pheochromocytoma include ischaemic heart disease, acute myocardial infarction, cardiac arrhythmias, heart failure due to toxic cardiomyopathy, or pulmonary edema. Catecholamines have been shown to influence the extracellular matrix with collagen deposition and subsequent fibrosis in the arterial wall and in the myocardium. These morphofunctional changes of the myocardium and of arterial wall can be emphasized by ultrasound imaging. Indeed, ultrasound imaging of the myocardium and arterial wall not only identifies wall thickness but also contains information on texture that may be revealed by acoustic tissue characterization. The latter can be quantified through videodensitometric analysis of echographic images or through ultrasonic integrated backscatter signal analysis. This paper reviews cardiovascular complications in patients with pheochromocytoma and utility of the new ultrasound technique as backscatter signal. It is useful for evaluating preclinical pathological morphofunctional changes of the myocardium and arterial wall, characterized by increased collagen content in pheochromocytoma patients. The recognition of early catecholamine-induced alterations in patients with pheochromocytoma, is important to prevent at least morbidity and mortality, before surgical treatment.     

Pain and pain generation in pancreatic cancer

Background  Pain can be a frequent symptom during the natural history of a patient with pancreatic cancer. An increase in incidence with disease progression and the presence of unbearable pain may preclude a curative resection. Materials and methods  Even in those patients with resectable pancreatic cancer, the presence of pain has an impact on prognosis. To date, we do not really know why some patients develop pain. Results  Perineural cancer cell invasion is one of the most intriguing characteristics of this neoplasia and may in some cases explain the pain sensation. In addition, so-called “neurogenic inflammation” might also play a role in pain generation in pancreatic cancer, just like in chronic pancreatitis. Conclusion  In conclusion, understanding the mechanisms of pain in pancreatic cancer could help patients because what counts is not only 5-year survival but also median survival with good quality of life.     

Platelet-Derived Growth Factor-Receptor α Strongly Inhibits Melanoma Growth In Vitro and In Vivo

Cutaneous melanoma is the most aggressive skin cancer; it is highly metastatic and responds poorly to current therapies. The expression of platelet-derived growth factor receptors (PDGF-Rs) is reported to be reduced in metastatic melanoma compared with benign nevi or normal skin; we then hypothesized that PDGF-Rα may control growth of melanoma cells. We show here that melanoma cells overexpressing PDGF-Rα respond to serum with a significantly lower proliferation compared with that of controls. Apoptosis, cell cycle arrest, pRb dephosphorylation, and DNA synthesis inhibition were also observed in cells overexpressing PDGF-Rα. Proliferation was rescued by PDGF-Rα inhibitors, allowing to exclude nonspecific toxic effects and indicating that PDGF-Rα mediates autocrine antiproliferation signals in melanoma cells. Accordingly, PDGF-Rα was found to mediate staurosporine cytotoxicity. A protein array-based analysis of the mitogen-activated protein kinase pathway revealed that melanoma cells overexpressing PDGF-Rα show a strong reduction of c-Jun phosphorylated in serine 63 and of protein phosphatase 2A/Bα and a marked increase of p38γ, mitogen-activated protein kinase kinase 3, and signal regulatory protein α1 protein expression. In a mouse model of primary melanoma growth, infection with the Ad-vector overexpressing PDGF-Rα reached a significant 70% inhibition of primary melanoma growth (P < .001) and a similar inhibition of tumor angiogenesis. All together, these data demonstrate that PDGF-Rα strongly impairs melanoma growth likely through autocrine mechanisms and indicate a novel endogenous mechanism involved in melanoma control.     

Histone deacetylase inhibitors as a new weapon in the arsenal of differentiation therapies of cancer

Absent or altered differentiation is one of the major features of cancer cells. Histone deacetylases (HDACs) play a central role in the epigenetic regulation of gene expression. Aberrant activity of HDACs has been documented in several types of cancers, leading to the development of HDAC inhibitors (HDACi) as anti-tumor drugs. In vitro and in vivo experimental evidences show that HDACi are able to resume the process of maturation in undifferentiated cancer cells, justifying their introduction as differentiating agents in several clinical trials. Modulation of cell fate by HDACi is observed at several levels, including the stem cell compartment: HDACi can act both on cancer stem cells, and with the rest of the tumor cell mass, leading to complex biological outputs. As a note of caution, when used as single agent, HDACi show only a moderate and limited biological response, which is augmented in combinatorial therapies with drugs designed against other epigenetic targets. The optimal employment of these molecules may be therefore in combination with other epigenetic drugs acting against the set of enzymes responsible for the set-up and maintenance of epigenetic information.     

Induction of labor in women with oligohydramnios.

OBJECTIVE: To prospectively evaluate the outcome of labor induction in women with oligohydramnios at term. METHODS: This was a prospective case-control study which included 120 consecutive patients with Amniotic Fluid Index (AFI) < or =5 undergoing labor induction. One hundred and sixteen patients with normal amniotic fluid matched for gestational age (+/- 3 days) and Bishop-score served as controls. Inclusion criteria were: requirement of labor induction, singleton pregnancy, nulliparity, Bishop score <5, gestational age > or =266. Preinduction treatment included the use of up to 3 successive doses of dinoprostone intracervical gel (0.5 mg). Vaginal dinoprostone (2 mg) and/or oxytocin were then applied to induction labor, if necessary. RESULTS: The rate of cesarean section in AFI < or = 5 group (38.3%) was not significantly different to that in control group (34.2%). The interval from induction to vaginal delivery was not significantly different for AFI < or =5 group (1499 +/- 895 min.) and control group (1398 +/- 852 min.). The changes in Bishop score evaluated at 6th and 12th hour after dinoprostone were not significantly different in control and AFI< or =5 group. More women in the latter group (11.7% vs 3.3%, Chi Square:4.86, p = 0.027) required the use of drugs in order to manage tachysystole/hyperstimulation allowing a OR = 3.83 (95%C.I. = 1.13-14.27). The length of stay at hospital was 4.2 +/- 1.8 days for AFI < or =5 group and 4.3 +/- 1.3 for control group. CONCLUSIONS: Oligohydranmios at term did not influence the outcome of induction of labour in nulliparous women with unfavorable cervix.     

Subarachnoid haemorrhage of unknown origin

Summary This study concerns 64 patients with angiographically negative subarachnoid haemorrhage (SAH) hospitalized in the period 1970–1982. Requisites for inclusion in the study were adequate angiographic demonstration of the carotid and vertebrobasilar systems and no clinical signs of spinal SAH or spontaneous intracerebral haematoma. The clinical data on the 64 cases confirm the close similarity, except for the prognostic factors, between angiographically negative SAH and SAH secondary to rupture of an intracranial saccular aneurysm. The study underlines the benign character of the clinical course and of the medium and long-term prognosis of the condition under study. In view of this, the hypothesis advanced sometime ago relating angiographically negative SAH to the rupture of microaneurysms (Ø<2 mm) of the large cerebral arteries with subsequent complete repair of the artery wall, or to the spontaneous thrombosis of intracranial saccular aneurysms, with the possibility of subsequent recanalization and risk of fresh rupture, would appear to be a reasonable one.     

Interpleural analgesia after thoracotomy

We examined the effects of the following variables on interpleural analgesia after thoracotomy: addition of epinephrine to local anesthetic, thoracostomy drainage, two-catheter placement, and location of catheter tips. Twenty patients were randomized to have one catheter (paravertebral tip location) or two catheters (paravertebral and lateral thoracic wall tip locations). Interpleural catheters were sutured to the parietal pleura by the surgeon at time of wound closure. Patients were then randomly assigned to receive 20 mL of 0.5% bupivacaine with 1:200,000 epinephrine through the single catheter or 10 mL of 0.5% bupivacaine with or without 1:200,000 epinephrine through each of the two catheters while supine. Bupivacaine concentrations in whole blood and in thoracostomy drainage fluid were assayed by gas chromatography. Actual content of bupivacaine in the drainage fluid was calculated. Degree of analgesia was assessed by verbal numerical pain scores over the first 4 h and opioid demand thereafter. Addition of epinephrine to bupivacaine did not influence the degree of analgesia. Approximately 30%-40% of any administered dose of bupivacaine was lost via the thoracostomy tube over a 4-h period. There was no correlation between the true initial dose (100 mg minus thoracostomy drainage) and Cmax. Use of two catheters resulted in significantly less opioid requirements after an initial 8-h period. Failure to achieve adequate interpleural analgesia in postthoracotomy patients may be related to loss of anesthetic via thoracostomy drainage, presence of extravasated blood and tissue fluid in the pleural space, and possibly sequestration and channeling of flow of local anesthetic by restricted motion of an operated lung.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gd-BOPTA/Dimeg: experimental disease imaging.

The novel tissue-specific contrast agent, Gd-BOPTA/Dimeg, was tested in MR imaging of experimental focal liver disease and of acute myocardial ischemia in rats. Directly implanted liver tumors and blood-borne metastases were used as models for focal liver disease and occlusion of the lower anterior descending coronary artery as model for acute ischemia. The studies with implanted tumors, at a dose level of 250 mumol/kg, showed a very high (370%) and persistent (greater than 2 h) increase in the tumor-liver contrast-to-noise ratio (CNR), owing to selective enhancement of normal liver parenchyma signal intensity. While all blood-borne metastases showed a similar late CNR enhancement, some of them experienced early contrast loss due to transient signal intensity enhancement. In myocardial imaging, Gd-BOPTA/Dimeg produced a signal intensity enhancement in normal myocardium and an injured area-normal area CNR enhancement which were both much stronger and more persistent than those produced by Gd-DTPA/Dimeg.     

Acute cholecystitis associated with calculosis of the biliary tract in a high-risk patient. Combined emergency surgical and peroperative endoscopic treatment]

Patient age (over 65), and lithiasis of the common bile duct are two factors which increase the morbidity and mortality rate in emergency surgery for biliary lithiasis. Normally, calculi in the CBD can be cleared by means of supraduodenal or transduodenal access. In both cases, however, complications are frequent in high risk patients. Treatment of gallstones can be modified to achieve a reduction in the morbidity and mortality rate. This study presents an initial survey of 4 elderly patients, presenting with acute gallbladder disease and CBD stones, treated with surgical cholecystectomy and contemporary perioperative endoscopic papillotomy and CBD clearance. The underlying rationale and the good initial results support this combined surgical and endoscopic approach.