Primary Renal Vein Aneurysm Rupture: Case Report of a Catastrophic Entity.

BACKGROUND: Renal vein aneurysms (RVAs) are uncommon entities, which are usually incidental findings or may cause mild nonspecific symptoms. Modern radiological imaging, mainly multislice computed tomography (CT), has substantially contributed to a prompt and accurate diagnosis. Treatment may range from watchful waiting to aneurysmorraphy, aneurysmectomy, and nephrectomy. Potential complications include thrombosis, pulmonary embolism, pressure to other structures, and rupture. CASE: A 58-year-old male patient was admitted at the emergency department with abdominal pain. He underwent an emergency CT scan which showed a huge retroperitoneal hematoma around the right kidney, while soon afterward he had a hypovolemic shock, less than an hour after a temporary loss of consciousness after an acute emotional distress episode. He underwent an emergency laparotomy and a right nephrectomy because of an RVA. Interestingly, his postoperative course was uneventful and his six-month follow-up was normal. DISCUSSION: This report presents the rupture of an RVA for the first time, which was successfully treated through nephrectomy by general surgeons in a secondary hospital. This is a catastrophic event which may be lethal, in case prompt diagnosis and surgical intervention delay. Due to the rarity of the disease, its etiology and optimal treatment remain to be clarified.

Pathophysiological and clinical aspects of the diagnosis and treatment of bezoars.

Bezoars are intraluminal conglomerates of indigestible foreign materials that accumulate in the gastrointestinal (GI) tract. They consist of vegetable or fruit fibers, hairs or other substances; accordingly, bezoars are classified as phytobezoars, trichobezoars, pharmacobezoars, etc. Although sometimes asymptomatic, bezoars may cause serious symptoms, such as abdominal discomfort or pain, dysphagia, hematemesis, or even life-threatening entities (GI bleeding, obstruction or perforation). Current technological applications have contributed to the diagnostic and therapeutic approach to these masses, mainly through endoscopic techniques able to diagnose, fragment and extract bezoars, as well as laparoscopic and other surgical modalities that may be used to treat serious complications. Although bezoars were described centuries ago and the term was officially introduced in the mid nineties by Quain, they are still a demanding pathological entity. Their pathophysiology, accurate and prompt diagnosis, as well as successful and minimally invasive treatment, remain under investigation and see continuous progress. Current advances in these challenging areas are discussed in this review, which attempts to present an in-depth study of bezoars along with the well-established modalities and techniques.

Surgical and Endoscopic Treatment of a Double Phytobezoar Causing Ileus and Jaundice: A Case Report.

Bezoars are rare conditions of mechanical intestinal occlusion. Among the various types of bezoars, phytobezoars and trichobezoars are the most common types. Symptoms are usually indistinguishable from other more common entities; therefore, it may be difficult to reach a correct diagnosis. Computed tomography (CT) scan is the preferred diagnostic method. Treatment may include surgery, lavage with Coca-Cola or hydrolytic solutions, and endoscopic mechanical or electrical disintegration. The present case report aimed to describe an uncommon symptomatic double phytobezoar (ileal and gastric), which was successfully treated surgically and endoscopically. The patient, an 83-year-old woman, was admitted to the General Hospital of Drama (Drama, Greece) after suffering from abdominal pain for 3 days. Physical examination revealed abdominal distention and pain mainly in the right quadrants. The CT scan revealed an intestinal phytobezoar which was subsequently removed surgically with a longitudinal enterotomy. On the third postoperative day, the patient presented jaundice and a new CT scan showed a second phytobezoar impacted into the duodenal bulb, which was missed during the initial diagnosis. The gastric phytobezoar was fragmented endoscopically using a polypectomy snare with high flow electric current (70-80 Watts) and its pieces were removed orally. The patient had no complications during the hospital stay and was discharged on the eighth postoperative day. Three months later, the follow-up gastroduodenoscopy and CT scan revealed no signs or symptoms of any gastrointestinal mass. The present case report is the first presentation of a double gastrointestinal phytobezoar that caused ileus and temporary jaundice. Moreover, a successful single-session mechanical-electrical fragmentation of a large gastric phytobezoar is described for the first time.

Natural history of hepatic metastases from colorectal cancer--pathobiological pathways with clinical significance.

Colorectal cancer hepatic metastases represent the final stage of a multi-step biological process. This process starts with a series of mutations in colonic epithelial cells, continues with their detachment from the large intestine, dissemination through the blood and/or lymphatic circulation, attachment to the hepatic sinusoids and interactions with the sinusoidal cells, such as sinusoidal endothelial cells, Kupffer cells, stellate cells and pit cells. The metastatic sequence terminates with colorectal cancer cell invasion, adaptation and colonisation of the hepatic parenchyma. All these events, termed the colorectal cancer invasion-metastasis cascade, include multiple molecular pathways, intercellular interactions and expression of a plethora of chemokines and growth factors, and adhesion molecules, such as the selectins, the integrins or the cadherins, as well as enzymes including matrix metalloproteinases. This review aims to present recent advances that provide insights into these cell-biological events and emphasizes those that may be amenable to therapeutic targeting.

The corticotropin releasing factor system in the liver: expression, actions and possible implications in hepatic physiology and pathology.

The corticotropin-releasing factor (CRF) system plays a crucial regulatory role in the adaptation to exogenous and endogenous stress stimuli, as well as homeostasis. Apart from the central nervous system (CNS), the members of this neuropeptide family extend their actions in the periphery, where they may affect various body systems independently, stimulating peripheral CRF receptors via vagal and/or autocrine/paracrine pathways. Here, we review all findings concerning the expression and role of the CRF system in human liver, but also in other species. Direct and indirect regulatory data are also analyzed in order to draw conclusions about possible physiological/pathophysiological implications. Although data supporting any clinical significance are still limited and further research in the field is necessary, scientific interest in the CRF system is particularly active, with multiple ongoing clinical studies evaluating the activity of CRF ligands in medical conditions involving other organs. Thus, new knowledge with therapeutic potential appears to be steadily accumulating.

Traumatic appendicitis in minor blunt abdominal injury.

Trauma has been reported as a cause of appendicitis on several cases in the literature. The present study reports the relationship between blunt abdominal trauma (BAT) of injury severity score less than 4 and appendicitis. A 17-year-old girl developed appendicitis after a minor BAT. An ecchymosis at the right lower quadrant misled the diagnosis, which was made 1 day later. Laparotomy revealed an inflamed appendix, a few enlarged mesenteric lymph nodes, contusion, as well as punctuated bleeding sites of the caecum. Moreover, based on a brief literature review, the different pathophysiological mechanisms and the difficulties of diagnosis of this entity are discussed. It is suggested that appendicitis should be considered as a possibility in the setting of right lower quadrant pain following minor BAT, when there is clinical suspicion of an inflammatory process within the right iliac fossa.

Liver regeneration and its impact on post-hepatectomy metastatic tumour recurrence.

Hepatic resection remains the primary potentially curative therapeutic modality for liver metastases. The regenerative process that occurs postoperatively is a complex phenomenon, orchestrated by molecular cascades involving growth factors, cytokines, proteolytic enzymes and other proteins. Unfortunately, some of these molecules, such as hepatocyte growth factor, tumour growth factor beta and matrix metalloproteinases also promote tumour growth and may contribute to the recurrence of liver metastasis. The reactivation of dormant micrometastases or the intrahepatic accumulation of circulating malignant cells has been suggested as the responsible mechanism, although not clearly understood. Current clinical and experimental research has developed inhibitors of several regenerative molecules, attempting to treat tumour reappearance within the liver. Despite the considerable progress of the last decade, multiple queries remain to be clarified concerning liver regeneration, as well as its impact on post-hepatectomy tumour recurrence. This review describes the responsible molecular pathways and the clinical importance of post-hepatectomy liver regeneration, and investigates how the regenerative process may promote metastatic tumour recurrence.

Corticotropin-releasing hormone receptors mediate opposing effects in cholestasis-induced liver cell apoptosis.

CRH receptors are expressed in human and rat liver. The current study investigated the biological role of the CRH system in the hepatocellular apoptotic process and aimed to reveal the responsible molecular mechanisms. Using a rat experimental model of common bile duct surgical ligation leading to obstructive jaundice and cholestasis, liver apoptosis was induced in the hepatic parenchyma as confirmed by the elevated expression of the early apoptotic neoepitope M30. This effect was reversed by administration of the nonselective CRH antagonist astressin but not by the selective CRH(2) antagonist astressin2B, suggesting that antagonism of the endogenous CRH(1) blocked the cholestasis-induced apoptotic mechanism. No effect was observed in the noncholestasis controls. In our experimental model, early and late apoptosis-preventing markers were induced in parallel to apoptosis; elevated gene transcript levels of the anti-apoptotic bcl-2 were found by real-time PCR in the first postoperative day and increased serum hepatocyte growth factor levels were measured by ELISA in the third postoperative day. Selective CRH(2) antagonism reversed the elevated expression of bcl-2 and hepatocyte growth factor, suggesting that this receptor type mediated antiapoptotic actions of the endogenous CRH system, opposing the preapoptotic ones mediated by CRH(1). In conclusion, the present study indicated that the CRH neuroendocrine system regulates cholestasis-induced apoptosis in the hepatic parenchyma via receptor-specific pathways. These data may contribute to better understanding of the CRH biology and its pathophysiological significance in the periphery.

Role of Kupffer cells in the outgrowth of colorectal cancer liver metastases.

Colorectal cancer is one of the commonest malignancies in the "developed" world. The liver constitutes the main host organ for its distant metastases which, when present, augur a bad prognosis for the disease. Kupffer cells (KCs) are macrophages that constantly reside within the liver and form an effective first line defence against multiple harmful agents which reach the hepatic sinusoids via the portal circulation. KCs remove chemical compounds and dead or damaged cells, eliminate bacteria and protect against invading tumour cells. They may play a crucial tumouricidal role, exerting cytotoxic and cytostatic functions through the release of multiple cytokines and chemokines. Subsequently, colorectal metastasising cells are destroyed either by KC-performed phagocytosis or via the stimulation of other immune cells which migrate into the sinusoids and act accordingly. On the contrary, KC products, including cytokines, growth factors and matrix-degrading enzymes may promote liver metastasis, supporting tumour cell extravasation, motility and invasion. Current research aims to exploit the antineoplastic properties of KCs in new therapeutic approaches of colorectal cancer liver metastasis. Numerous agents, such as the granulocyte macrophage-colony stimulating factor, interferon gamma, muramyl peptide analogues and various antibody based treatments, have been tested in experimental models with promising results. Future trials may investigate their use in everyday clinical practice and compare their therapeutic value with current treatment of the disease.

The engagement of selectins and their ligands in colorectal cancer liver metastases.

he colonization of the liver by colorectal cancer (CRC) cells is a complicated process which includes many stages, until macrometastases occur. The entrapment of malignant cells within the hepatic sinusoids and their interactions with resident non-parenchymal cells are considered very important for the whole metastatic sequence. In the sinusoids, cell connection and signalling is mediated by multiple cell adhesion molecules, such as the selectins. The three members of the selectin family, E-, P- and L-selectin, in conjunction with sialylated Lewis ligands and CD44 variants, regulate colorectal cell communication and adhesion with platelets, leucocytes, sinusoidal endothelial cells and stellate cells. Their role in CRC liver metastases has been investigated in animal models and human tissue, in vivo and in vitro, in static and shear flow conditions, and their key-function in several molecular pathways has been displayed. Therefore, trials have already commenced aiming to exploit selectins and their ligands in the treatment of benign and malignant diseases. Multiple pharmacological agents have been developed that are being tested for potential therapeutic applications.

Neuropeptide and sigma receptors as novel therapeutic targets for the pharmacotherapy of depression.

Among the most prevalent of mental illnesses, depression is increasing in incidence in the Western world. It presents with a wide variety of symptoms that involve both the CNS and the periphery. Multiple pharmacological observations led to the development of the monoamine theory as a biological basis for depression, according to which diminished neurotransmission within the CNS, including that of the dopamine, noradrenaline (norepinephrine) and serotonin systems, is the leading cause of the disorder. Current conventional pharmacological antidepressant therapies, using selective monoamine reuptake inhibitors, tricyclic antidepressants and monoamine oxidase inhibitors, aim to enhance monoaminergic neurotransmission. However, the use of these agents presents severe disadvantages, including a delay in the alleviation of depressive symptoms, significant adverse effects and high frequencies of non-responding patients. Neuroendocrinological data of recent decades reveal that depression and anxiety disorders may occur simultaneously due to hypothalamus-pituitary-adrenal (HPA) axis hyperactivity. As a result, the stress-diathesis model was developed, which attempts to associate genetic and environmental influences in the aetiology of depression. The amygdala and the hippocampus control the activity of the HPA axis in a counter-balancing way, and a plethora of regulatory neuropeptide signalling pathways are involved. Intervention at these molecular targets may lead to alternative antidepressant therapeutic solutions that are expected to overcome the limitations of existing antidepressants. This prospect is based on preclinical evidence from pharmacological and genetic modifications of the action of neuropeptides such as corticotropin-releasing factor, substance P, galanin, vasopressin and neuropeptide Y. The recent synthesis of orally potent non-peptide micromolecules that can selectively bind to various neuropeptide receptors permits the onset of clinical trials to evaluate their efficacy against depression.

The corticotropin-releasing factor system in inflammatory bowel disease: prospects for new therapeutic approaches.

Mounting evidence suggests that stress is implicated in the development of inflammatory bowel disease (IBD), via initial nervous disturbance and subsequent immune dysfunction through brain-gut interactions. The corticotropin-releasing factor (CRF) system, being the principal neuroendocrine coordinator of stress responses, is involved in the inflammatory process within the gastrointestinal tract, via vagal and peripheral pathways, as implied by multiple reports reviewed here. Blocking of CRF receptors could theoretically exert beneficial anti-inflammatory effects in colonic tissues. The recently synthesised small-molecule CRF(1) antagonists or alternatively non-peptide CRF(2) antagonists when available, may become new reliable options in the treatment of IBD.

The role of cell adhesion molecules in the progression of colorectal cancer and the development of liver metastasis.

Cell adhesion molecules (CAMs) play a significant role in the metastatic potential of colorectal cancer and thus mediate the prognosis of this common malignancy. The downregulation of cadherins and catenins facilitates tumour cell detachment from the primary site, while the expression of selectins, integrins and members of the immunoglobulin superfamily may support neoplastic progression, intravasation and malignant cell attachment to foreign tissue, leading to the development of metastases. The liver is the main host organ of colorectal metastatic lesions. The process of hepatic invasion originates in the sinusoids, where non-parenchymal cells interact with metastasising ones, through the expression of numerous CAMs, following complex molecular pathways. Concurrently, the selective expression of cell adhesion molecules on different organs and endothelia, in conjunction with the presence of dissimilar adhesion ligands on various colorectal cancer cell lines, suggest that CAMs may also mediate the selection of the host organ, for the development of distant colorectal metastases.