Role of lymphatic vessel density in colorectal cancer: prognostic significance and clinicopathologic correlations.

BACKGROUNDS AND AIMS: Over the past decades the identification of several molecules that are expressed specifically in the lymphatic endothelial cells has resulted in marked advances in the field of lymphangiogenesis. We aimed to measure LVD in colorectal cancer patients and to compare it with microvascular density (MVD) - a marker of angiogenesis - and patients' clinicopathological parameters and survival, as the measurement of lymphatic vessel density (LVD) has been documented in various tumor types, including colorectal cancer. PATIENTS AND METHODS: Fifty one patients who had undergone surgical resection for stage I-III colorectal cancer entered this study. LVD and MVD were determined immunohistochemically with the use of D2-40 and CD34 antibody respectively. The evaluation of LVD was performed by both visual and computer-aided image analysis. RESULTS: The majority of lymphatic vessels were located in the peritumoral areas rather than within the tumor. The results obtained from the image analyzer correlated significantly with the data obtained using visual counting with light microscopy. Both visual and image analysis LVD failed to correlate with patients' age and gender and tumor location, stage, grade, MVD count and survival. CONCLUSIONS: The biologic role of the lymphatic vasculature in tumor progression remains controversial. The present study failed to associate LVD with outcome markers and prognosis and further studies would be required to verify our results.

Prognostic value of EZH2, paxillin expression and DNA ploidy of breast adenocarcinoma: correlation to pathologic predictors.

PURPOSE: The objective of this study was to examine the association of EZH2 and paxillin expression and DNA ploidy status with pathological parameters of breast cancer, aiming to correlate tumor phenotype with its malignant behavior. METHODS: EZH2 and paxillin expression and DNA ploidy were evaluated in imprint smear samples obtained from 105 breast tumors after surgical removal. RESULTS: Increased expression of paxillin was associated with p53 expression (p=0.005), Ki-67 expression (p=0.018) and EZH2 expression (p<0.0001). EZH2 expression correlated with estrogen receptor (ER) and progesterone receptor (PR) status (p=0.01 and p=0.035, respectively), and expression of p53 and Ki-67 (p=0.007 and p<0.0001, respectively). Aneuploid tumors were significantly correlated with poor differentiation (p=0.000), stage of disease (p=0.000), size of the primary tumor (p=0.015), presence of nodal metastasis (p=0.001), ER status (p=0.008), cerbB2 status (p=0.012), and expression of Ki-67 (p=0.001) and EGFR (p=0.018). Multivariate analysis of ploidy results using paxillin and EZH2 expression as dependent variables revealed that aneuploid tumors were associated with disease stage and grade of differentiation, cerbB2 expression and EZH2 expression. CONCLUSION: Our results show that aneuploid tumors, EZH2 expression and paxillin expression correlate with more aggressive phenotype of breast cancer.

Procalcitonin in patients with colorectal cancer.

PURPOSE: Bacterial translocation (BT) is common in colon cancer patients and may be associated with increased occurrence of septic complications as well as with adverse oncologic outcomes. The aim of the present study was to correlate the BT detectable through peritoneal lavage culture or identified by abnormal inflammatory parameters with the clinicopathologic parameters and the short-term prognosis in a prospective series of patients. METHODS: Fifty-four consecutive patients with histologically proven colorectal cancer were included in this prospective study. White blood cells (WBC), erythrocyte sedimentation rate (ESR) and serum levels of procalcitonin (PCT) and C-reactive protein (CRP) were determined and cultures from peritoneal lavage were collected immediately after laparotomy. RESULTS: Positive PCT was detected in 31 (55.3%) patients while positive cultures were obtained in 6 (11%) patients. Significant positive correlation of PCT with inflammation markers was noticed. Patients with distant metastases had higher serum PCT levels than patients without distant metastases (p=0.01). Borderline statistical significance was found between PCT and tumor grade (p=0.09). PCT was not correlated with the cultures of the lavage or the outcome. CONCLUSION: PCT is an adequate inflammatory marker, able to preoperatively discriminate patients with bacterial systemic inflammatory reaction due to BT. However, the clinical consequence of BT may be minimal as is shown by the lack of association of PCT or positive peritoneal lavage cultures with time to discharge, complications and short-term survival.

Clinical role of HER-2/neu expression in colorectal cancer.

PURPOSE: To evaluate the HER-2/neu expression and its relationship with clinicopathological parameters and prognosis in colorectal cancer patients. METHODS: A total of 51 colorectal cancer patients who underwent resection with curative intent from January 2005 to March 2006 were included in this study. Patients were regularly followed up and survival data were obtained as of as April 2011. HER-2/neu protein expression was evaluated from tissue samples from the primary tumor using a semiquantitative standardized immunohistochemical staining kit. Staining intensity was scored as faint (1+), weak to moderate (2+) and moderate to strong (3+). RESULTS: Forty-nine (96.1%) patients showed 1+ staining, 2 (3.9%) 2+, while no case was strongly positive (3+) for HER-2/neu. No apparent association was noted between HER-2/neu expression and patients' age, gender, tumor location, tumor grade, stage and survival. CONCLUSION: Moderate (2+) overexpression of HER-2/neu was detected in a small proportion of colorectal cancer patients. Considering the low rate of HER-2/neu overexpression in colorectal cancer, studies with larger sample sizes using standardized tests are essential to understanding the biologic role of HER-2/neu in this disease.

Constipation-predominant irritable bowel syndrome associated to hyperprolactinemia.

Irritable bowel syndrome (IBS) is considered to be a physical disorder that mainly affects the bowel and is clinically characterized by lower abdominal pain or discomfort, diarrhea, constipation (or alternating diarrhea/constipation), gas, bloating, and nausea. According to recent studies, it appears that there is an association with increased prolactin levels in patients suffering from IBS. We report a rare case of regression of IBS symptoms (constipation type) in a 16-year-old female adolescent after receiving cabergoline for treating hyperprolactinemia due to pituitary macroadenoma. Our hypothesis is that increased prolactin levels, for instance due to a pituitary adenoma, may suppress prolactin-releasing peptide release and lead to a reverse feedback interaction, consequently resulting in oversecretion of cholecystokinin, inducing the development of IBS.

Sugammadex, a promising reversal drug. A review of clinical trials.

According to published data, sugammadex, rapidly reverses (2-5 min) shallow and profound NM block induced by rocuronium and vecuronium, without being connected with serious adverse events. It is accepted that in order to reverse shallow block, the suggested dose of sugammadex comes up to 2 mg/kg. Profound level of NM block demands 4 mg/kg in order to defy few responses at the post titanic count. Doses of sugammadex lower than 1 mg/kg may lead to rebound of rocuronium's effect. Higher doses of sugammadex (12 16 mg/g) are used in rescue reversal. In children and adolescents the 2 mg/kg dose is both effective and well tolerated, while, to date, data regarding infants are scarce. In patients with renal failure, 2 mg/kg of sugammadex resulted in a mean time to recovery of TOF ratio to 0.9 in 2 min, which was quicker than the time of reversal by acetylcholinesterase inhibitors. Investigations in cardiac patients undergoing noncardiac surgery suggest that 2 and 4 mg/kg of sugammadex are both safe and effective. Compared with neostigmine, sugammadex has no need to use muscarinic antagonists and therefore is not associated with variations in heart rate. Trials indicate that sugammadex acts faster than edrophonium and neostigmine. Sugammadex is a promising, well tolerated agent that enables fast reversal in different depths of NM block -shallow and profound- and in different patients populations. After completion of trial probation and settlement of issues concerning estimated cost and cost impact, it is believed to play a leading part in future anesthesiology.

The value of TOP2A, EZH2 and paxillin expression as markers of aggressive breast cancer: relationship with other prognostic factors.

INTRODUCTION: The immunocytochemical expression of topoisomerase II alpha (TOP2A), enhancer of zeste homologue 2 (EZH2) and paxillin has recently gained increasing attention. Although previous studies have commented on the clinical usefulness of these markers, their role remains controversial. AIM: The purpose of the study was to investigate the expression of TOP2A, EZH2 and paxillin in relation to classic prognostic parameters and their significance as prognostic markers in imprints of resected breast carcinomas. METHODS: Imprint smears from 55 patients who underwent surgical treatment for primary carcinoma in our department between 2005 and 2006 were studied immunocytochemically with the use of TOP2A, EZH2 and paxillin antibodies. RESULTS: The expression of TOP2A correlated with higher histologic grade, tumor size and negative PR expression. High intensity staining for EZH2 expression was associated with higher histologic grade, negative ER and PR expression and positive Ki-67 expression. The expression of paxillin showed no correlation with estrogen/progesterone and HER2 expression nor with tumor grade and stage. CONCLUSION: Our data indicate that TOP2A and EZH2 expression are related to a more aggressive tumor phenotype. The expression of paxillin failed to correlate with any of the studied clinicopathologic factors. Further studies are needed to verify these results.

Analysis of clinical and molecular associations of triple negative breast cancers in node-negative patients.

INTRODUCTION: Therapeutic modalities in node-negative breast cancer patients remain a matter of controversy. Various prognostic factors have been proposed to help select those patients that would most likely benefit from adjuvant therapy. In view of this notion the triple negative phenotype (hormone receptors and HER2 negative tumors) has gained increasing attention. AIM: To evaluate the clinicopathologic characteristics of triple negative (TN) tumors in node-negative invasive breast carcinomas. METHODS: We retrospectively analyzed the archival pathology tissues of 160 patients with node-negative invasive carcinomas, diagnosed and treated in two surgical departments in Greece from 1999 to 2006. Statistical analysis was used to examine the association between TN tumors and other clinicopathological factors. RESULTS: Triple negative breast cancers correlated with higher histologic grade, mitotic activation index and Ki-67 expression (p < 0.05). Moreover TN tumors were correlated with negative staining for bcl-2 (p < 0.05). CONCLUSION: In node-negative breast cancer patients, triple negativity is associated with aggressive biologic behavior. Further studies are required to better understand the clinical implications of these findings.

Struggling with a Gastric Volvulus Secondary to a Type IV Hiatal Hernia.

Type IV hiatal hernias are characterized by herniation of the stomach along with associated viscera such as the spleen, colon, small bowel, and pancreas through the esophageal hiatus. They are relatively rare, representing only about 5%-7% of all hernias, and can be associated with severe complications. We report a 71-year-old veteran wrestler who presented to our department with a type IV paraesophageal hernia containing a gastric volvulus and treated successfully with emergency operation.

Differences in colorectal cancer patterns between right and left sided colorectal cancer lesions.

PURPOSE: Colorectal carcinomas that arise proximal (right) or distal (left) to the splenic flexure exhibit different clinical and biological characteristics. Although various hypotheses have been proposed to explain these differences, their origin remains unclear. In this study we investigated the clinicopathologic differences between left and right colon tumors and comment on the possible explanatory theories behind them. METHODS: This study included a total of 388 retrospectively collected cases of colorectal cancer, surgically treated from 1999 to 2004. Differences of patients' demographic data and tumor micro- and macroscopic characteristics between left and right-sided tumors were investigated and analysed. RESULTS: Patients with right-sided colon cancer were significantly older (mean age 70 vs. 68 years; p<0.05) and had more lymph nodes examined than patients with left colon tumors (mean number of nodes 18.9 vs. 12.6; p<0.05). There was a lower proportion of T1 stage right-sided tumors (3.1 vs. 5%) and a higher proportion of stage T2-4 (96.9 vs. 95%) compared with left-sided tumors (p<0.001 for x2 test of all T stages). Furthermore, right-sided tumors had a higher mean width and depth (4.3 vs. 3.8 cm and 1.8 vs. 1.6 cm, respectively; p<0.05). Finally, there was a higher percentage of poorly differentiated right colon tumors (41.4 vs. 17.5%; p<0.001). CONCLUSION: Right-sided colon tumors affect older patients and are diagnosed at more advanced disease stages. The underlying mechanisms that provoke these differences remain unclear. Further studies are needed in order to better understand the true nature of these differences and their possible clinical implications.

The value of proliferation indexes in breast cancer.

INTRODUCTION: During the past several years, the Ki-67 antigen has gathered great interest in its role as a prognostic marker. Nevertheless, despite the large number of published papers, the role of Ki-67 in clinical practice remains controversial. AIM: To evaluate the association between Ki-67 immunoreactivity and other clinicohistopathological parameters. METHODS: We retrospectively analyzed the archival pathology tissues of 356 patients, diagnosed and treated in our department, from 2002 to 2006. Statistical analysis was used to examine the association between Ki-67 expression and other clinicopathological factors. RESULTS: The expression of Ki-67 was correlated with the mitotic count, tumor grade and size and p53, HER2 and EGFR expression. Furthermore Ki-67 expression was significantly related with nodal status and inversely associated with hormonal expression. Moreover, invasive carcinomas appeared to have greater proliferation values than in situ carcinomas, while invasive ductal carcinomas were correlated with higher Ki-67 expression compared to lobular cancers. CONCLUSION: The expression of Ki-67 appears to be a valuable method of proliferation measurement that could prove helpful in clinical practice. Further research is warranted in order to standardize the methodology and to reach uniformity in regard with the optimal cut-off value.

The role of sonography in the diagnosis of cystic lesions of the breast.

INTRODUCTION: Breast sonography is appropriate in the initial assessment of a women younger than 30 years with a palpable lump and in the adjunctive evaluation of mammographic masses, and palpable abnormalities not seen mammographically. MATERIAL AND METHODS: A total of 269 patients underwent breast examination with ultrasound due to the presence of bilateral or unilateral palpable lesions. Women under 40 years old were submitted to US examination only while patients older than 40 years underwent US breast assessment and conventional mammography. RESULTS: Mammography had an accurancy of 57.3% and confirmed diagnosis in 113 out of 197 patients; in 57 patients (28.4%) it identified the lesion but could not determine the diagnosis. False-positive results for malignancy were detected in 23 patients (11.7%) and there were no false-negative results. Ultrasound assessment had an accuracy in diagnosis reaching 87.3%, 172 cases out of 196. (87.3% vs 57.3% p < 0.05); false-positive results were identified in 17 cases (8.6%). CONCLUSION: Sonography demonstrates a better diagnostic significance than mammography in the early detection of cystic breast carcinoma.

Gastrointestinal stromal tumors of the rectum: report of five cases.

We report on five patients (three males and two females), with a median age of 66.2 years (range, 58-73 years) who were admitted in our department from April 1998 until January 2004 with the diagnosis of rectal gastrointestinal stromal tumor (GIST). Their main symptoms were rectal bleeding, constipation and abdominal discomfort. Two patients were treated by an abdominoperineal resection of the rectum. One patient received palliative surgical treatment and adjuvant therapy with imatinib for metastatic disease. Another patient presented with complete rectal prolapse, and was treated with Delorme's procedure. The subsequent pathological examination of the resected specimen showed positive resection margins and was given adjuvant therapy with imatinib. Finally, one case was considered inoperable. However, after nine months of treatment with imatinib, the magnetic resonance imaging (MRI) scan revealed a significant reduction in the tumor size, and the patient was treated with abdominoperineal excision of the rectum. All cases have been proved to be immunohistochemically positive for the CD117 and the CD34 stain. During the follow-up period (mean duration 3.7 years), one patient died of progressive disease while the other four had no sign of recurrence.

Primary hydatidosis of the gluteus muscles: report of three cases.

BACKGROUND: Hydatid disease caused by the tapeworm Echinococcus granulosus is a worldwide problem especially in sheep and cattle raising countries. AIMS: Muscle involvement is most commonly encountered as recurrence of previously treated disease or concurrently with primary lesions of the liver or lung. Furthermore, the rarity of muscle hydatidosis has unique implications in diagnosis and management. METHODS: We report on three cases of primary echinococcus of the gluteus muscles presented in our clinic during a 10-year period. RESULTS: We have administered albendazole for one cycle of 28 days in two of our patients based on the size and appearance of the cyst. All patients underwent total pericystectomy without cyst rupture. We have not found any recurrences after minimum follow up of 12 months. CONCLUSIONS: Muscle echinococciasis respond well to surgical intervention. Complete and intact removal of the cyst in primary muscular hydatidosis should be considered curative.

Primary insular carcinoid of the ovary.

Primary ovarian carcinoids are very rare tumors that account for less than 5% of all carcinoids and 0.1% of all ovarian malignancies. We present a rare case of a primary, non-functioning, insular carcinoid of the left ovary in a 44-year-old woman originating from the outer surface of a mature cystic teratoma. After an uneventful unilateral salpingo-oophorectomy, the patient had no sign of recurrence with computed tomography and 5-HIAA evaluation at 3-year follow-up. Although rare, primary ovarian insular carcinoid tumors that are confined to the ovary and treated with surgery are expected to have an excellent overall outcome.

Laparoscopic fenestration of multiple giant biliary mucinous cystadenomas of the liver.

Biliary cystadenomas of the liver are rare, cystic neoplasms of the biliary ductal system usually occur in middle aged women. We report a case of synchronous multiple huge biliary mucinous cystadenomas with unique features. This is, according to our knowledge, the first report in the literature about three synchronously occurring hepatobiliary cystadenomas. Cystadenomas have a strong tendency to recur, particularly following incomplete excision, and a potential of malignant transformation. A therapeutic re-evaluation may be necessary when the diagnosis of hepatobiliary cystadenoma is made after the operation and an open liver resection should be considered.

Metastatic breast carcinoma initially presenting as acute cholecystitis: a case report and review of the literature.

INTRODUCTION: The gallbladder is an infrequent site of metastatic malignant disease. Although malignant melanoma, renal cell and cervical carcinoma have been documented, breast carcinoma has rarely been reported to metastasize in the gallbladder. CASE REPORT: We describe such a case that manifested as acute cholecystitis and was incidentally recognized after cholecystectomy, in an otherwise disease-free 46-year-old female who had undergone mastectomy for breast cancer two years before. The patient was subjected to adjuvant chemotherapy, but unfortunately died just a year after diagnosis because of generalized peritoneal seeding of the tumor. DISCUSSION: Metastatic gallbladder involvement is rare, especially in cases of primary breast carcinoma, usually leading to symptoms of abdominal pain, mimicking acute or chronic cholecystitis. Thus, abdominal pain in a patient with a previous history of breast carcinoma should raise suspicion of gallbladder metastasis.

A prospective comparison of ampullectomy with pancreaticoduodenectomy for the treatment of periampullary cancer.

Local surgical treatment of periampullary neoplasms seems attractive in the context of the reduced morbidity and mortality than the more radical treatment options. The aim of our study was to compare local excision (LE) of the ampulla with standard pancreaticoduodenectomy (PD) for the treatment of periampullary cancer in terms of overall survival. Inclusion criteria were primary tumor < or = 2 cm with no evidence of lymph node involvement or distant metastasis on abdominal computed tomography (CT). Between January 2000 and January 2004, 23 patients were enrolled onto this study (9 in the LE group and 14 in the standard PD group). The two groups were homogeneous with respect to age and gender as well as the size and origin of the primary neoplasm. There was no correlation of the survival with age, gender, presence of lymph node metastasis, size of the primary tumor, type of surgery or histologic grade (x(2), p >0.05). However, the origin of the tumor had major impact on survival, with pancreatic tumors having the worst prognosis. Hospital stay was significantly reduced in the LE treated patients. Our results showed that LE for periampullary tumors is a viable option and is well suited for medically unfit patients or those who refuse more radical treatment options.