Polo-like kinase 1 expression is a prognostic factor in human colon cancer

AIM: To clarify the expression patterns and prognostic implications of the mitotic regulator Polo-like kinase 1(PLK1) in colon cancer.METHODS: Expression of PLK1 was investigated by immunohistochemistry (158 cases) and immunoblotting in tissue of colon adenomas and adenocarcinomas. PLK1expression patterns were correlated with clinicopathological parameters and patient prognosis. In addition, expression of PLK1 was evaluated by immunoblot and PCR in colon carcinoma cell lines, and coexpression of PLK1 with the proliferation marker Ki-67 was investigated.RESULTS: Weak PLK1 expression was observed in normal colon mucosa and adenomas. In contrast, 66.7% of carcinomas showed strong expression of PLK1.Overexpression of PLK1 correlated positively with Dukes stage (P＜0.001), tumor stage (P = 0.001) and nodal status (P＜0.05). Additionally, PLK1 expression was a prognostic marker in univariate survival analysis (P＜0.01) and had independent prognostic significance (RR = 3.3, P = 0.02)in patients with locoregional disease. Expression of PLK1 mRNA and protein was detected in all cell lines investigated. Coexpression of PLK1 and Ki-67 was observed in the majority of colon cancer cells, but a considerable proportion of cells showed PLK1 positivity without Ki-67expression.CONCLUSION: PLK1 is a new prognostic marker for colon carcinoma patients and may be involved in tumorigenesis and progression of colon cancer. Strategies focusing on PLK1 inhibition in vivo might therefore represent a promising new therapeutic approach for this tumor entity.

Current clinical approach to achalasia

Idiopathic achalasia is a rare primary motility disorder of the esophagus. The classical features are incomplete relaxation of a frequently hypertensive lower esophageal sphincter (LES) and a lack of peristalsis in the tubular esophagus. These motor abnormalities lead to dysphagia, stasis, regurgitation, weight loss, or secondary respiratory complications. Although major strides have been made in understanding the pathogenesis of this rare disorder, including a probable autoimmune mediated destruction of inhibitory neurons in response to an unknown insult in genetically susceptible individuals, a definite trigger has not been identified. The diagnosis of achalasia is suggested by clinical features and conf irmed by further diagnostic tests, such as esophagogastroduodenoscopy (EGD), manometry or barium swallow. These studies are not only used to exclude pseudoachalasia, but also might help to categorize the disease by severity or clinical subtype. Recent advances in diagnostic methods, including high resolution manometry (HRM), might allow prediction of treatment responses. The primary treatments for achieving long-term symptom relief are surgery and endoscopic methods. Although limited high-quality data exist, it appears that laparoscopic Heller myotomy with partial fundoplication is superior to endoscopic methods in achieving long-term relief of symptoms in the majority of patients. However, the current clinical approach to achalasia will depend not only on patients' characteristics and clinical subtypes of the disease, but also on local expertise and patient preferences.

Osteoclast-like giant cell tumors of the pancreas and liver

Osteoclast-like giant cell tumors (OGCT) are rare abdominal tumors, which mainly occur in the pancreas. The neoplasms are composed of two distinct cell populations and frequently show an inhomogenous appearance with cystic structures. However, due to the rarity of these tumors, only very limited clinical data are available. Imaging features and sonographic appearance have hardly been characterized. Here we report on two cases of osteoclast-like giant cell tumors, one located within the pancreas, the other within the liver, in which OGCTs are extremely rare. Both patients were investigated by contrast sonography, which demonstrated a complex, partly cystic and strongly vascularized tumor within the head of the pancreas in the first patient and a large, hypervascularized neoplasm with calcifications within the liver in the second patient. The liver OGCT responded well to a combination of carboplatin, etoposide and paclitaxel. With a combination of surgical resection, radiofrequency ablation and chemotherapy, the patient’s survival is currently more than 15 mo, making him the longest survivor with an OGCT of the liver to date.

Effective treatment of gastrointestinal bleeding with thalidomide- Chances and limitations

For more than 50 years bleeding from gastrointestinal angiodysplasias has been treated by hormonal therapy with estrogens and progesterons. After a randomized study finally demonstrated that hormones have no effect on bleeding events and transfusion requirements, therapy has switched to endoscopic coagulation. However, angiodysplasias tend to recur over months to years and endoscopy often has to be repeated for long time periods. Thalidomide, which caused severe deformities in newborn children in the 1960 s, is now increasingly used after it was shown to suppress tumor necrosis factor alpha, inhibi t angiogenesis and to be also effective for treatment of multiple myeloma. In 2011 thalidomide was proven to be highly effective for treatment of bleeding from gastrointestinal angiodysplasias in a randomized study. Further evidence by uncontrolled studies exists that thalidomide is also useful for treatment of bleeding in hereditary hemorrhagic telangiectasia. In spite of this data, endoscopic therapy remains the treatment of choice in many hospitals, as thalidomide is still notorious for its teratogenicity. However, patients with gastrointestinal bleeding related to angiodysplasias are generally at an age in which women have no child-bearing potential. Teratogenicity is therefore no issue for these elderly patients. Other side-effects of thalidomide like neurotoxicity may limit treatment options but can be monitored safely.

Angiogenesis and vascular malformations:Antiangiogenic drugs for treatment of gastrointestinal bleeding

Treatment of gastrointestinal bleeding in patients with angiodysplasias and Osler’s disease (hereditary hemorrhagic teleangiectasia) is clinically challenging. Frequently, vascular malformations occur as multiple disseminated lesions, making local treatment an unfavorable choice or impossible. After local therapy, lesions often recur at other sites of the intestine. However, as there are few therapeutic alternatives, repeated endoscopic coagulations or surgical resections are still performed to prevent recurrent bleeding. Hormonal therapy has been employed for more than 50 years but has recently been shown to be ineffective. Therefore, new therapeutic strategies are required. Understanding of the pathophysiology of angiogenesis and vascular malformations has recently substantially increased. Currently, multiple inhibitors of angiogenesis are under development for treatment of malignant diseases. Experimental and clinical data suggest that antiangiogenic substances, which were originally developed for treatment of malignant diseases, may also represent long-awaited specif ic drugs for the treatment of vascular malformations. However, antiangiogenics display significantly different actions and side-effects. Although antiangiogenics like thalidomide seem to inhibit gastrointestinal bleeding, other substances like bevacizumab can cause mucosal bleeding. Therefore differential and cautious evaluation of this therapeutic strategy is necessary.