Assessing the clinical utility of Wnt pathway markers in colorectal cancer.

PURPOSE: ß-catenin and AXIN2 play an important role in the Wnt signaling pathway. The aim of this study was to investigate ß-catenin and AXIN2 expression in colorectal cancer (CRC) and relate these findings with patients' clinicopathological features and prognosis. METHODS: 57 consecutive patients with surgically treated CRC were included in this study. Quantitative PCR and immunohistochemistry (IHC) analyses were performed to characterize the expression of the aforementioned markers in CRC tissues. RESULTS: ß-catenin overexpression in the nucleus was associated with advanced N stage CRCs (p=0.04). Multivariate Cox regression analysis showed that ß-catenin overexpression is an independent prognostic factor for overall survival (OS). A positive correlation between ß-catenin location and AXIN2 mRNA was observed. CONCLUSIONS: Nuclear ß-catenin is a valuable prognostic factor. AXIN2 is a component of the "Destruction Complex" and also a Wnt target gene. However, the clinical importance of AXIN2 expression in CRC remains unclear.

Epidemiological and clinicopathological characteristics of BRCA-positive and BRCA-negative breast cancer patients in Greece.

PURPOSE: BRCA mutation carriers can benefit from targeted clinical interventions. On the other hand, families with evident aggregation of breast cancer (BC) cases and a BRCA-negative genetic test can still be considered as of elevated risk, since the underlying genetic factor remains unidentified. In the present study, we compared clinical and demographic characteristics between BRCA1 mutation carriers (BRCA1mut) and non-carriers (non-BRCA1) in a Greek group of BC patients (n=321). METHODS: Data were collected and analyzed from 321 women with BC, with 131 patients screened for pathogenic mutations in the high-penetrant genes BRCA1 and BRCA2. Collected data included demographics, pedigrees, tumor histopathology and immunohistochemistry findings. RESULTS: In BRCA1mut patients, their mothers and grand- mothers were diagnosed at a younger age compared to non-BRCA1-carriers. Additionally, BRCA1mut patients were diagnosed with mainly estrogen receptor (ER) negative (p<0.001), Her-2 negative (p<0.05) and triple negative (p<0.01) tumors. The youngest generation was diagnosed with familial breast cancer (FBC) 9.7 years earlier than their mothers (p<0.001). Age at BC diagnosis negatively correlated with the nuclear grade of breast tumors (r=-0.3, p<0.05). Among parous individuals, the number of full-term pregnancies significantly correlated with the age at BC onset (r=0.19, p<0.05). CONCLUSION: Despite their similarities, FBC cases with identified BRCA1 mutations exhibit a clearly distinct profile. We have identified an anticipation effect in FBC patients, with significantly reduced age at diagnosis in younger generations. Increased parity seems to prevent early BC onset. This is the first study comparing clinical and demographic characteristics of FBC BRCA1mut and non-carriers in a Greek cohort.

The effect of U-74389G on pancreas ischemia-reperfusion injury in a swine model.

BACKGROUND: Oxidative stress is a crucial factor in the pathophysiology of acute pancreatitis and its systemic complications. Lazaroids are a novel class of antioxidants that potently protect pancreatic acinar cells against oxidant attack. The aim of our study was to evaluate the therapeutic potential of 21-aminosteroid U-74389G in pancreatic injury after ischemia and reperfusion of the organ in a swine model. MATERIALS AND METHODS: Twelve pigs (weighing 28-35 kg) were randomized into the following two experimental groups: group A (control group, n = 6): ischemia of pancreas (30 min) followed by reperfusion for 120 min; and group B (n = 6): ischemia of pancreas (30 min), U-74389G intravenous injection (10 mg/kg) in the inferior vena cava, and reperfusion for 120 min. Tissue and blood sampling was conducted at 0, 30, 60, 90 and 120 min after reperfusion. Repeated measures analysis of variance was performed for the evaluation of differences between the two groups. RESULTS: Histopathologic evaluation did not reveal a statistically significant difference concerning hemorrhage (P = 0.193), leukocyte infiltration (P = 0.838), acinar necrosis (P = 0.183), and vacuolization (P = 0.185) in the pancreatic tissue between the two groups; nevertheless, edema seemed to be more pronounced in the U-74389G group (P = 0.020). Serum metabolic data in the control and therapy groups were not significantly different; accordingly, tissue malondialdehyde levels (P = 0.705) and tumor necrosis factor α values (P = 0.863) did not differ between the two groups. CONCLUSIONS: On the basis of the histologic data and the absence of reduction in the malondialdehyde and tumor necrosis factor α levels, it is concluded that the administration of U-74389G does not seem to exert a sizable therapeutic effect in attenuating pancreatic damage from ischemia-reperfusion injury.

Kallikrein-related peptidases in cancers of gastrointestinal tract: an inside view of their role and clinical significance.

Human tissue kallikrein (KLK1) and is related peptidases (KLK2-KLK15) are a family of 15 homologous serine proteases, participating in numerous processes of normal physiology. Considering the irreversible impact of proteases on substrates, the tissue-dependent regulation of KLKs activity becomes crucial for their beneficial role in normal homeostasis. Moreover, KLKs expression is strongly regulated at the transcriptional and post-transcriptional level by steroid hormones and miRNAs, respectively. Deregulation of KLKs expression, secretion and/or activation has been observed in most human malignancies and there is a trend to identify their role in the multi-complex process of cancer development. The identification of extracellular matrix (ECM) proteins, cell-surface receptors, cell-surface adhesion molecules and growth factors among substrates, clearly support the driving role of KLK abnormal expression and function during tumorigenesis and cancer progression. KLKs have also clinical utility in cancer diagnosis and monitoring like KLK 3 (PSA) in prostate cancer. In this review, we tried to summarize the existing literature about the role of KLKs in gastrointestinal cancers as well as to emphasize their clinical significance for patients' prognosis.

Fibrinolytic and coagulation pathways after laparoscopic and open surgery: a prospective randomized trial.

BACKGROUND: Tissue injury poses increased risk for postoperative thromboembolic complications. Laparoscopic surgery, by causing limited tissue injury, is associated with lower risk for thromboembolism than is open surgery. We conducted a prospective randomized study in order to detect potentially existing differences in activation of coagulation and fibrinolytic pathways between open and laparoscopic surgery. METHODS: Forty patients with chronic cholelithiasis were randomly assigned to undergo open (group A) or laparoscopic cholecystectomy (group B). Blood samples were taken preoperatively, at the end of the procedure, and at 24 and 72 h postoperatively. Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), platelets (PLT), soluble fibrin monomer complexes (F.S. test), fibrin degradation products (FDP), D-dimers (D-D), and fibrinogen (FIB) were measured and compared within each group and between groups: Thrombin-antithrombin complexes (TAT) and prothrombin fragments (F1 + 2) were measured at 24 and 72 h postoperatively. RESULTS: Demographics were comparable between groups. Immediately postoperatively, TAT and F1 + 2 were significantly higher in group A (p < 0.05). They also increased significantly postoperatively as compared with preoperative levels within each group (p < 0.05). D-dimers were significantly higher in group A (p < 0.01) immediately postoperatively. D-dimers also increased significantly postoperatively in group B as compared with preoperative levels (p < 0.001). FIB decreased slightly in both groups at 24 h postoperatively but there was a significant increase in group A (p < 0.01). Soluble fibrin monomer complexes (SFMC) were detected twice in group A and only once in group B. FDP levels over 5 µg/ml were detected more often in group A (p < 0.05). There was not any case of thromboembolism or abnormal bleeding. CONCLUSIONS: Open surgery leads to higher activation of the clotting system than do laparoscopic procedures. Although of a lower degree, hypercoagulability is still observed in patients undergoing laparoscopic surgery and therefore routine thromboembolic prophylaxis should be considered.

Capsule endoscopy retention as a helpful tool in the management of a young patient with suspected small-bowel disease.

Capsule endoscopy is an easy and painless procedure permitting visualization of the entire small-bowel during its normal peristalsis. However, important problems exist concerning capsule retention in patients at risk of small bowel obstruction. The present report describes a young patient who had recurrent episodes of overt gastrointestinal bleeding of obscure origin, 18 years after small bowel resection in infancy for ileal atresia. Capsule endoscopy was performed, resulting in capsule retention in the distal small bowel. However, this event contributed to patient management by clearly identifying the site of obstruction and can be used to guide surgical intervention, where an anastomotic ulcer is identified.

Acute mechanical bowel obstruction: clinical presentation, etiology, management and outcome.

AIM: To identify and analyze the clinical presentation, management and outcome of patients with acute mechanical bowel obstruction along with the etiology of obstruction and the incidence and causes of bowel ischemia, necrosis, and perforation. METHODS: This is a prospective observational study of all adult patients admitted with acute mechanical bowel obstruction between 2001 and 2002. RESULTS: Of the 150 consecutive patients included in the study, 114 (76%) presented with small bowel and 36 (24%) with large bowel obstruction. Absence of passage of flatus (90%) and/or feces (80.6%) and abdominal distension (65.3%) were the most common symptoms and physical finding, respectively. Adhesions (64.8%), incarcerated hernias (14.8%), and large bowel cancer (13.4%) were the most frequent causes of obstruction. Eighty-eight patients (58.7%) were treated conservatively and 62 (41.3%) were operated (29 on the first day). Bowel ischemia was found in 21 cases (14%), necrosis in 14 (9.3%), and perforation in 8 (5.3%). Hernias, large bowel cancer, and adhesions were the most frequent causes of bowel ischemia (57.2%, 19.1%, 14.3%), necrosis (42.8%, 21.4%, 21.4%), and perforation (50%, 25%, 25%). A significantly higher risk of strangulation was noticed in incarcerated hernias than all the other obstruction causes. CONCLUSION: Absence of passage of flatus and/or feces and abdominal distension are the most common symptoms and physical finding of patients with acute mechanical bowel obstruction, respectively. Adhesions, hernias, and large bowel cancer are the most common causes of obstruction, as well as of bowel ischemia, necrosis, and perforation. Although an important proportion of these patients can be nonoperatively treated, a substantial portion requires immediate operation. Great caution should be taken for the treatment of these patients since the incidence of bowel ischemia, necrosis, and perforation is significantly high.

Effects of lazaroid U-74389G on intestinal ischemia and reperfusion injury in porcine experimental model.

BACKGROUND: The readmission of molecular oxygen into an ischemic tissue promotes the oxidation of resuscitated tissue with certain pathophysiologic mechanisms. MATERIALS AND METHODS: Twenty four pigs (male or female) were randomized in this study. The animals were allocated to four groups with an equal number (n = 6) in each group: (1) control group-ischemia for 30 min and reperfusion for 60 min. (2) control group-ischemia for 30 min and reperfusion for 120 min. (3) ischemia for 30 min and immediate iv injection of lazaroid U-74389G and reperfusion for 60 min. (4) ischemia for 30 min and immediate iv injection of lazaroid U-74389G and reperfusion for 120 min. RESULTS: We investigated further the role of an antioxidant molecule such as U-74389G and we concluded that there is statistically significant relation in MDA (malondialdeyde), TNF -α (tumor necrosis factor-α) measurement in tissue, while the histological score in the groups that the lazaroid was administered was improved. CONCLUSIONS: In many emergency clinical situations, such as reperfusion of the intestine, the role of U-74389G can be protective.

Development of the Greek version of the University of Washington quality of life questionnaire for patients with head and neck cancer.

The University of Washington quality of life (UW-QOL) questionnaire, created in 1993 to evaluate health related quality of life, has been widely used in English-speaking populations and translated and validated in other languages. The aim of the present study was to carefully translate and psychometrically validate the UW-QOL questionnaire in Greek. The revised version of the questionnaire was obtained by forward and backward translation of the original English version, according to internationally accepted guidelines. Validation was performed in 120 patients with head and neck cancer treated in a Greek Anticancer Institute in Athens, during their follow-up visits. Eligible patients completed the Greek version of the questionnaire and two other previously validated quality of life questionnaires (EORTC QLQ H&N35 and C-30). Related data and the patients' demographics were extracted from the patient's notes. Strong internal consistency (mean Cronbach α value of 0.83) was shown, with good construct validity. Statistically significant differences were noted between tumour staging and treatment modality and global quality of life. Strong correlation was shown between previously validated EORTC questionnaires and the translated UW-QOL questionnaire. In conclusion, the Greek version of the UW-QOL questionnaire appears to be culturally appropriate and psychometrically valid.

Intracystic hemorrhage in a mediastinal cystic adenoma causing parathyrotoxic crisis.

BACKGROUND: We report a case of intracystic hemorrhage in a mediastinal cystic parathyroid adenoma causing parathyrotoxic crisis. METHODS AND RESULTS: A 30-year-old man presented with a large neck mass, dyspnea, and abdominal pain. The patient's serum calcium and parathormone levels were elevated. Radiography showed a right tracheal deviation, ultrasonography identified a thyroid nodular goiter extending to the mediastinum with a large (4.0 cm x 5.6 cm) cystic mass adjacent to the lower left thyroid pole. After IV fluid, pamidronate, and furosemide were administered, the patient underwent total thyroidectomy, and excision of the cyst and a small mass (2 cm x 2 cm) adjacent to the upper right thyroid lobe. Histopathologic examination revealed a double parathyroid adenoma and identified the mediastinal lesion as a cystic adenoma with intracystic hemorrhage. CONCLUSIONS: Intracystic hemorrhage in a functional mediastinal cystic parathyroid adenoma is an extremely rare cause of parathyrotoxic crisis. Aggressive medical treatment should be immediately instituted, and surgery should be performed as soon as hypercalcemia is controlled.

Adenocarcinoma of the third and fourth portion of the duodenum: a case report and review of the literature.

A 65-year-old woman presented with abdominal pain, weight loss, fatigue, and microcytic anemia. Esophagogastroduodenoscopy, until the second part of duodenum, was normal. Ultrasound and computed tomography demonstrated a solid mass in the distal duodenum. A repeat endoscopy confirmed an ulcerative, intraluminar mass in the third and fourth part of the duodenum. Segmental resection of the third and fourth portion of the duodenum was performed. Histology revealed an adenocarcinoma. On the 4th postoperative day, the patient developed severe acute pancreatitis leading to multiple organ failure and died on the 30th postoperative day.

Thyroid surgery: comparison between the electrothermal bipolar vessel sealing system, harmonic scalpel, and classic suture ligation.

BACKGROUND: This study was conducted to compare the outcome of total thyroidectomy using the electrothermal bipolar vessel sealing system, the harmonic scalpel, and the classic suture ligation technique. METHODS: This was a retrospective study of prospectively collected data from 382 consecutive total thyroidectomies from September 2004 to August 2006. Patients were divided into 3 groups: group SL patients (n = 90) underwent total thyroidectomy with the classic suture ligation technique, group L (n = 148) with the electrothermal bipolar vessel sealer, and group U (n = 144) with the harmonic scalpel. The main outcomes measured were surgical and hospitalization time, intraoperative and postoperative bleeding, postoperative hypocalcemia, and superior and inferior laryngeal nerves injuries. RESULTS: The 3 groups were similar in terms of demographics, thyroid gland weight and pathology, perioperative complications, and hospital stay. Compared with the classic technique, surgical time was reduced significantly by about 20% when the bipolar vessel sealer or harmonic scalpel was used (93.3 +/- 12.5 vs 74.3 +/- 14.2 and 73.8 +/- 13.8 min, P = .001, and P = .001, respectively). CONCLUSIONS: Both the bipolar vessel sealer and harmonic scalpel are safe, useful, and time-saving alternatives to the traditional suture ligation technique for thyroid surgery. Because no differences were observed regarding these 2 devices, the choice should be made based on the surgeon's preferences and experience.

Management of early and late detected vascular complications following femoral arterial puncture for cardiac catheterization.

INTRODUCTION: latrogenic vascular trauma is more frequent today as a result of the increase in diagnostic and therapeutic femoral catheterizations. Management of related complications is elective or urgent and sometimes needs complex vascular reconstruction. The present study evaluated when and whether conservative, urgent surgical, or elective surgical treatment is appropriate. METHODS: A retrospective analysis was made of 45 consecutive iatrogenic vascular trauma patients, among 10,450 cardiac diagnostic or therapeutic catheterizations. Patients' demographics, type of catheterization, time from catheterization to initial diagnosis, the type of complication (thrombosis, infection, bleeding, pseudoaneurysm, etc.), time from presentation of the complication to definite treatment, diagnostic imaging and decision making, the surgical or conservative management, the length of stay and the clinical outcome were determined and analyzed. RESULTS: We identified and treated 30 early and 15 late (after patient's discharge) arterial complications: 18 pseudoaneurysms, 6 bleedings, 9 hematomas, 5 deep vein thromboses, 3 arteriovenous fistulas, 2 arterial embolisms and 2 arterial thromboses. Eight patients underwent emergency surgical repair, three elective surgical repair and 31 were managed conservatively. Decision making was based only on clinical evaluation in 12 patients, whereas vascular ultrasound was the most frequent diagnostic imaging modality in the remainder. A total of 10 (22.2%) minor secondary complications were identified after the initial management with no limb loss and zero mortality. CONCLUSIONS: Close clinical observation and conservative management of vascular trauma complications resulted in a low incidence of the necessity for surgical repair (25% of cases). Bleeding and acute leg ischemia were the most frequent indication for emergency surgical treatment, whereas the majority of pseudoaneurysms, fistulas and vein thrombosis were successfully treated conservatively. Late vascular complications do occur and add an important morbidity factor to early catheterization complications.

The imprint of radiofrequency in the management of hepatocellular carcinoma.

BACKGROUND: This article reviews the current results of radiofrequency application in the management of hepatocellular carcinoma (HCC) with reference to the comparison between the different surgical modalities. METHOD: An electronic search was performed for studies on the treatment of HCC. RESULTS: Thermoablation by means of radiofrequency (RFA), microwave coagulation therapy (MCT) and laser-induced thermotherapy (LITT) provides tumor necrosis with a low complication rate. These methods are still not predictable and it is difficult to monitor the extent of necrosis in a real-time manner. Combined transarterial embolization and RF ablation is a promising strategy for large HCCs. Radiofrequency-assisted liver resection is unique and has become very popular recently because it permits parenchymal transection with minimal blood loss. CONCLUSION: Many alternative techniques have been applied recently for the management of HCC but their exact roles need to be defined by randomized studies. Advances in technology and refinements in technique may provide an effective and predictable way to ablate liver tumors using radiofrequency devices.