Parecoxib's effects on anastomotic and abdominal wound healing: a randomized Controlled trial.

BACKGROUND: Current evidence regarding the effects of selective cyclooxygenase inhibitors on gastrointestinal anastomoses is controversial. An experimental randomized control study was conducted in our institution to histopathologically evaluate the consequences of parecoxib, on intestinal and abdominal wound healing. METHODS: Twenty-four adult Wistar rats underwent laparotomy, ascending colon transection, and hand-sewn anastomosis. They were randomized to receive either parecoxib (0.5 mg/kg twice daily) or 0.9% normal saline by intraperitoneal injection postoperatively. Animals were euthanatized either on the third or the seventh postoperative day. Semiquantitative methods were used to evaluate both intestinal and abdominal wounds for inflammatory cell composition, angiogenesis, fibroblasts, granular tissue, collagen deposition, epithelization, and presence of necrosis, exudate, and abscess formation. Results are presented as (parecoxib: median [IQR] versus control: median [IQR], P-value). RESULTS: No macroscopic anastomotic leakage or wound dehiscence was observed. Intestinal anastomoses in the parecoxib group, showed significantly decreased epithelization (2 [1] versus 3 [1], [P = 0.004]) and collagen deposition (2 [0] versus 3 [1], [P = 0.041]). No difference was observed in angiogenesis (3 [1] versus 2.5 [1], [P = 0.158]). Abdominal wall specimens appeared to demonstrate decreased epithelization (2 [2] versus 4 [0.5], [P = 0.0004]) in the treatment group. No difference between the two groups was identified regarding collagen deposition (2.5 [1] versus 2 [0.5], [P = 0.280]) and angiogenesis (2.5 [1] versus 2 [1], [P = 0.633]). Necrosis was significantly more present in the parecoxib group in both specimen types, (3.5 [1] versus 2.5 [1], [P = 0.017]) and (3 [1] versus 1 [0.5], [P < 0.0001]). CONCLUSIONS: The present study shows that despite the absence of clinical adverse effects, parecoxib can impair anastomotic and abdominal wound healing on a histopathological level.

Prognostic significance of EGFR and COX-2 expression in colorectal cancer and their association. A study in Greek population.

PURPOSE: Colon cancer is one of the most common malignancies. Various prognostic markers have been proposed and individualized treatment strategies have been adapted according to tumor molecular and genetic characteristics. The purpose of the present study was to retrospectively analyze a possible association between the expression of COX- 2 and EGFR and clinical and histopathological factors of patients undergoing colon surgery in a Greek population. METHODS: Data from our department's prospectively collected database were retrieved for a total of 100 consecutive colectomies that were performed in our department. We examined patient age, sex, tumor stage and location of the tumor. Histological data were also retrieved concerning major tumor diameter, histological grade and immunohistochemical expression of cyclooxygenase (COX)-2 and epithermal growth factor receptor (EGFR). RESULTS: There was no difference between tumors of different differentiation in the expression of EGFR (p=0.146), while there was statistically significant difference in the expression of COX-2 between these groups (p=0.001). There was no difference between these patients in the expression of EGFR (p=0.136), while a statistically significant difference was found in the expression of COX-2 between the same patient groups (p<0.005). CONCLUSION: These data are quite important in order to certify that colorectal cancer molecular and genetic diversity between different study populations is not a confounding factor in the application and clinical implementation of trending individualized decision making in oncological treatments.

Immunohistochemical expression patterns of S100, synaptophysin, chromogranin A and neuron specific enolase in predicting malignant behaviour in paragangliomas.

PURPOSE: The purpose of this study was to evaluate the role of immunohistochemical markers in the prediction of malignancy in paragangliomas. METHODS: Our institute's patient records between 1990-2012 were retrieved in order to identify patients who were treated for paragangliomas. Size and location of the tumour, existence of concurrent metastatic disease, patient demographics and survival were recorded. Haematoxylin-eosin stained slides were reviewed and all tumours were stained specifically for neuron specific enolase (NSE), chromogranin, synaptophysin and S100 protein positivity. Positivity and expression patterns of the above markers were evaluated and compared between malignant and benign tumours. Malignant behaviour was defined when patient had concurrent or subsequent lymph node involvement, local recurrence and/or metastases. RESULTS: A total of 22 patients with a diagnosis of paraganglioma were treated in our institutes. Female to male ratio was 1.75: 1. The mean age was 43.5 and 51.6 years for women and men, respectively. In 5 patients the tumors had malignant clinical behavior. Their mean size was 3.65 cm for benign and 4.56 cm for malignant neoplasms. NSE expression was diffuse in 47.1% and 0% for benign and malignant tumors, respectively (p=0.10). S100 expression in the periphery of the tumour was typical in 88.2% and 0% for benign and malignant tumors, respectively (p<0.001). CONCLUSION: Immunohistochemical profile from the combination of NSE, synaptophysin chromogranin and S100 staining patterns can serve as a cheap and valuable tool for correctly distinguishing between malignant and benign paragangliomas with high diagnostic accuracy.

The effects of hemorrhagic shock secondary to hepatectomy in a swine model.

BACKGROUND: Ischemia-reperfusion injury caused by severe hemorrhagic shock and subsequent resuscitation leads to deterioration of hepatic homeostasis and possibly to liver failure. The present study focuses on determining whether there is a different biological response to hemorrhagic shock by different sources of hemorrhage, hepatic hemorrhage (HH) versus peripheral hemorrhage. METHODS: Twenty-one male swine (Sus scrofa domesticus) were randomly allocated in three groups as follows: sham group (S, n = 5), central venous hemorrhage group, (CVH) (n = 8), and HH group (n = 8). Hepatectomy of the left liver lobe was carried out in groups CVH and HH, and the animals were subjected to controlled bleeding from the internal jugular vein and the traumatic liver surface, respectively. After 10 min of hemorrhage, shock was maintained for 30 min at mean arterial pressure levels of 30 mm Hg-40 mm Hg and resuscitation was initiated with crystalloids and colloids. Hemodynamic parameters and fluid balance were monitored throughout the 6 h of total duration of the experiment. Blood samples were collected at 0-, 40-, and 360-min time points for transaminases, albumin, and interleukin-6 measurement. Hepatic tissue was harvested at the end of the experiment for oxidative marker and proliferation analysis. RESULTS: Although blood loss was comparable between the two groups, the amount of fluids needed for resuscitation was higher for the HH group. Inflammatory response, measured by interleukin-6, was found higher in HH group. Oxidative stress markers did not reveal statistically significant difference between the two groups. Liver hemorrhage decreased hepatocellular proliferation measured by proliferating cell nuclear antigen. CONCLUSIONS: Our study provides evidence that HH entails worse consequences for the hepatocytes than systemic hemorrhage. Higher needs for resuscitation fluids, decreased proliferation, and augmented inflammatory response when HH takes place are findings with possible clinical importance in liver surgery and trauma.

A case of postmenopausal androgen excess.

Ovarian steroid cell tumors are very rare but potentially life-threatening neoplasms. They represent less than 0.1% of all ovarian tumors, typically present in premenopausal women and frequently manifest with virilization. Signs of hyperandrogenism may appear in postmenopausal women due to tumorοus and non-tumorοus adrenal and ovarian causes as well due to the normal aging process. In any case, steroid cell tumor should be suspected in postmenopausal women who present with rapid progressive androgen excess symptoms. This report describes a case of a 67-year-old postmenopausal woman with signs of hyperandrogenism, where an ovarian steroid cell tumor was diagnosed and treated by laparoscopic bilateral salpingo-oophorectomy and synchronous hysterectomy.

Expression of gonadal steroid receptors in the ovaries of post-menopausal women with malignant or benign endometrial pathology: a pilot study.

This pilot study aimed to investigate the expression of estrogen (ER) and progesterone receptors (PR), as well as their subtypes [alpha (ERα), beta (ERß)], in the ovaries of postmenopausal women with benign or malignant endometrial pathology. Twenty postmenopausal women (age 66.2 ± 7.4 years) were included, diagnosed with benign (n = 10) or malignant [(serous/papillary (n = 4), endometrioid (n = 6)] endometrial lesions. Higher ERß and PR ovarian expressions were observed comparing women with endometrioid versus non-endometrioid endometrial carcinoma (p = 0.022 and p = 0.029, respectively). Age, age at menarche and presence of hypertension were negatively associated with ERs and PR expression. The expression of ERα and ERß was inversely correlated with menopausal age, which was not verified for PR. No significant association was observed between ERs or PR expression and benign or malignant endometrial pathology. Higher expression of ERß and PR in the postmenopausal ovary is associated with the presence of a less aggressive type of endometrial cancer, comparing women with endometrioid versus non-endometrioid lesions. The expression pattern of ovarian receptors did not differ regarding the development of benign or malignant endometrial lesions. Larger observational studies are necessary to confirm the significance of our findings.

A 12-year experience at a tertiary hospital on patients with multiple primary malignant neoplasms.

PURPOSE: The incidence of multiple primary malignant neoplasms (MPMN) has dramatically increased. The purpose of this retrospective study was to present the 12-year experience at a University Hospital in patients with MPMN and to investigate the role of genetic factors in their pathogenesis. METHODS: The medical records of 7516 cancer patients, treated in our Institution from 2000 to 2012, were reviewed. Diagnosis of MPMN was based on the Warren and Gates' criteria. RESULTS: Among 7516 patients, 39 (0.5%) (10 men, mean age 70.0±6.98 years, and 29 women, mean age 64.7±8.24 years) presented with MPMN. Eighty-two percent of them developed 2 primary malignant neoplasms (PMNs), whereas 3 PMNs were developed in 7 patients. Breast cancer was the most common cancer type diagnosed among female patients (59%); 14 and 3 had 2 and 3 PMNs, respectively. Eight had a family history of breast cancer while in 3 genetic testing revealed mutations in BRCA1 and BRCA2 genes. The second most common type of malignancy was colorectal cancer (24%); 5 developed 2 PMNs, whereas 2 developed 3 PMNs. Five patients had a family history of colorectal cancer. Colon cancer was the most frequent neoplasm among male patients (50%; 3 developed 2 and 2 3 PMNs. In 2 patients the family history was positive for colorectal cancer. CONCLUSIONS: Although many factors may contribute to MPMN development, positive family history and inherent mutations significantly predispose to MPMN appearance. Thus, management of MPMN patients should be based on a detailed family history and genetic testing.

Uncommon benign lesions of the adrenal glands mimicking sinister pathologies: report of 8 cases.

PURPOSE: To present series of patients with large rare primary lesions of the adrenal glands that were operated in our department. The initial indication for surgery was decided based on their impressive similarity to other more sinister adrenal pathologies. METHODS: The clinical records of the department and histopathology reports, covering the 1986-2015 period were assessed. Rare adrenal pathologies that preoperatively were clinically mimicking other adrenal tumors were included. RESULTS: In total, 8 patients (age range 20-75 years) with rare tumors of the adrenal glands were found. Seven patients had a preoperative indication for adrenalectomy due to the possibility of malignancy. In one patient surgery was undertaken due to the possible diagnosis of adrenal hemorrhagic cyst. Among these patients 4 had a histopathologic diagnosis of hemangiomas, one of a lymphangiomatous cyst and 3 of myelolipomas. CONCLUSION: Rare benign tumors of the adrenal glands can present as very large lesions that can be either diagnosed incidentally or due to atypical symptoms. Though unusual, they should be considered in the differential diagnostic approach of adrenal lesions, because they share common clinical and radiological characteristics with more sinister and frequent lesions such as malignant tumors and also hematomas.

Proposal for a 10-high-power-fields scoring method for the assessment of tumor budding in colorectal cancer.

Although tumor budding is linked to adverse prognosis in colorectal cancer, it remains largely unreported in daily diagnostic work due to the absence of a standardized scoring method. Our aim was to assess the inter-observer agreement of a novel 10-high-power-fields method for assessment of tumor budding at the invasive front and to confirm the prognostic value of tumor budding in our setting of colorectal cancers. Whole tissue sections of 215 colorectal cancers with full clinico-pathological and follow-up information were stained with cytokeratin AE1/AE3 antibody. Presence of buds was scored across 10-high-power fields at the invasive front by two pathologists and two additional observers were asked to score 50 cases of tumor budding randomly selected from the larger cohort. The measurements were correlated to the patient and tumor characteristics. Inter-observer agreement and correlation between observers' scores were excellent (P<0.0001; intraclass correlation coefficient=0.96). A test subgroup of 65 patients (30%) was used to define a valid cutoff score for high-grade tumor budding and the remaining 70% of the patients were entered into the analysis. High-grade budding was defined as an average of ≥10 buds across 10-high-power fields. High-grade budding was associated with a higher tumor grade (P<0.0001), higher TNM stage (P=0.0003), vascular invasion (P<0.0001), infiltrating tumor border configuration (P<0.0001) and reduced survival (P<0.0001). Multivariate analysis confirmed its independent prognostic effect (P=0.007) when adjusting for TNM stage and adjuvant therapy. Using 10-high-power fields for evaluating tumor budding has independent prognostic value and shows excellent inter-observer agreement. Like the BRE and Gleason scores in breast and prostate cancers, respectively, tumor budding could be a basis for a prognostic score in colorectal cancer.

Loss of Raf-1 kinase inhibitor protein (RKIP) is strongly associated with high-grade tumor budding and correlates with an aggressive phenotype in pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Raf-1 kinase inhibitor protein (RKIP) has emerged as a significant metastatic suppressor in a variety of human cancers and is known to inhibit Ras/Raf/MEK/ERK signaling. By suppressing the activation of the NFkB/SNAIL circuit, RKIP can regulate the induction of epithelial-mesenchymal transition (EMT). The aim of this study was to evaluate RKIP expression and to determine its association with clinicopathological features, including EMT in form of tumor budding in pancreatic ductal adenocarcinoma (PDAC). METHODS: Staining for RKIP was performed on a multipunch Tissue Microarray (TMA) of 114 well-characterized PDACs with clinico-pathological, follow-up and adjuvant therapy information. RKIP-expression was assessed separately in the main tumor body and in the tumor buds. Another 3 TMAs containing normal pancreatic tissue, precursor lesions (Pancreatic Intraepithelial Neoplasia, PanINs) and matched lymph node metastases were stained in parallel. Cut-off values were calculated by receiver operating characteristic (ROC) curve analysis. RESULTS: We found a significant progressive loss of RKIP expression between normal pancreatic ductal epithelia (average: 74%), precursor lesions (PanINs; average: 37%), PDAC (average 20%) and lymph node metastases (average 8%, p<0.0001). RKIP expression was significantly lower in tumor buds (average: 6%) compared to the main tumor body (average 20%; p<0.005). RKIP loss in the tumor body was marginally associated with advanced T-stage (p=0.0599) as well as high-grade peritumoral (p=0.0048) and intratumoral budding (p=0.0373). RKIP loss in the buds showed a clear association with advanced T stage (p=0.0089). CONCLUSIONS: The progressive loss of RKIP seems to play a major role in the neoplastic transformation of pancreas, correlates with aggressive features in PDAC and is associated with the presence of EMT in form of tumor budding.

Synchronous gastric adenocarcinoma and gastrointestinal stromal tumor (GIST) of the stomach: a case report.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms of the gastrointestinal tract (1%), and stomach is the most common location involved. However, the co-existence of gastric adenocarcinoma and GIST is very rare. A case of an 80-year-old male with a simultaneous presentation of a gastric adenocarcinoma and GIST is presented. Various hypotheses have been proposed in order to explain this rare simultaneous development, but even though it's cause has not been proven yet.

Metastatic neoplasms of the ovaries: a clinicopathological study of 97 cases.

OBJECTIVE: To present the clinicopathological features of metastatic ovarian neoplasms with emphasis in the diagnostic challenge. METHODS: This is a retrospective study including 97 patients with pathological diagnosis of metastatic ovarian neoplasms, examined during the decade 2000-2009. The gross, microscopical and immunohistochemical characteristics as well as the clinical data (age of the patients, origin of the neoplasm, symptoms, treatment options) and 5-year survival rates were examined. RESULTS: The mean age of the patients is 55 years (range 26-78 years). 62.89% of the tumors were metastatic from extragenital organs (from stomach 21.65%, breast 15.46%, colon 15.46%, appendix 3.09%, pancreas 2.06%, lung 1.03% and kidney 1.03%, sarcoma 1.03% melanoma 1.03%) and 37.11% tumors originated from the genital tract. The 3-year survival rates ranged from 25.39% for metastatic ovarian neoplasms originating outside the genital tract up to 29.41% for those originating from the genital tract. Tumor immunohistochemistry is a helpful aid in the differential diagnosis mainly between primary mucinous ovarian tumors and metastatic colon cancers and in the recognition of metastatic breast cancers and other neoplasms of the GI tract. CONCLUSION: The management of metastatic ovarian neoplasms should include specific immunohistochemical methods in order to identify the primary neoplasm site. The differential diagnosis of a pelvic mass should always include metastatic neoplasms of the ovaries.

Recurrent pulmonary embolism due to giant hepatic hamangioma treated with hepatectomy under vascular exclusion.

Giant hepatic hemangiomas are benign tumors that measure more than 4 cm and are usually asymptomatic. Pulmonary embolism (PE) is an extremely rare manifestation of giant hepatic hemangiomas. We report a case of a 44-year-old woman who suffered of recurrent pulmonary emboli that, after thorough work up, were attributed to thrombi formation inside a giant hepatic hemangioma. A right hepatectomy under vascular exclusion was performed and the hemangioma, measuring 17 cm, was resected. Two years later the patient remains asymptomatic. The report highlights the value of investigating giant liver hemangiomas in case of PE. In such cases, the hemangioma should be resected preferably under occlusion of the venous outflow of the liver to avoid PE intraoperatively.

Combination of right nephrectomy and total pancreaticoduodenectomy for Von Hippel-Lindau disease.

CONTEXT: Von Hippel-Lindau disease is an inherited syndrome of multiorgan neoplasia caused by a germline mutation in the von Hippel-Lindau gene and can include central nervous system tumors, renal cell carcinomas and benign pancreatic cystic tumors. CASE REPORT: We report the case of a 56-year-old patient who had a past history of cerebellar hemangioblastoma and presented with abdominal pain. Imaging revealed renal tumors and multiple pancreatic tumors which caused duodenal and pancreatic duct compression. The patient was treated with a combination of radical right nephrectomy, total pancreaticoduodenectomy and splenectomy. Pathology identified a multifocal unilateral clear cell renal carcinoma which interestingly coexisted with multiple large pancreatic serous microcystic adenomas with infiltration of the fibrous capsule. CONCLUSION: In past cases of von Hippel-Lindau disease, pancreatic adenomas with malignant transformation have not been reported. In our case, the infiltration of the fibrous capsule by parenchymal cells may indicate malignant transformation.

Abscess formation mimicking disease progression, in a patient with metastatic renal cell carcinoma during sunitinib treatment.

BACKGROUND: Renal cell carcinoma (RCC) represents approximately 3% of all adult cancers and is more common in males. Systemic treatment for RCC has improved following the introduction of tyrosine kinase inhibitors, such as sunitinib. The molecular targets of sunitinib are receptor tyrosine kinases (RTKs). Moreover, sunitinib has an additional anti-angiogenic effect through its inhibition of the vascular endothelial growth factor receptor activation. CASE PRESENTATION: We present a case of intra-abdominal abscess formation mimicking disease progression, in a patient with metastatic renal cell carcinoma during sunitinib treatment. CONCLUSION: In the advancing era of molecular therapy of solid tumours, sunitinib has demonstrated significant efficacy in the post-cytokine setting treatment of metastatic renal cancer. Concurrently, however, increasing evidence has emerged to indicate that this class of drugs exert profound immunomodulatory effects on T cells and play major roles in immune tumor surveillance.

The combined effect of erythropoietin and granulocyte macrophage colony stimulating factor on liver regeneration after major hepatectomy in rats.

BACKGROUND: The liver presents a remarkable capacity for regeneration after hepatectomy but the exact mechanisms and mediators involved are not yet fully clarified. Erythropoietin (EPO) and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) have been shown to promote liver regeneration after major hepatectomy.Aim of this experimental study is to compare the impact of exogenous administration of EPO, GM-CSF, as well as their combination on the promotion of liver regeneration after major hepatectomy. METHODS: Wistar rats were submitted to 70% major hepatectomy. The animals were assigned to 4 experimental groups: a control group (n = 21) that received normal saline, an EPO group (n = 21), that received EPO 500 IU/kg, a GM-CSF group (n = 21) that received 20 mcg/kg of GM-CSF and a EPO+GMCSF group (n = 21) which received a combination of the above. Seven animals of each group were killed on the 1st, 3rd and 7th postoperative day and their remnant liver was removed to evaluate liver regeneration by immunochemistry for PCNA and Ki 67. RESULTS: Our data suggest that EPO and GM-CSF increases liver regeneration following major hepatectomy when administered perioperatively. EPO has a more significant effect than GM-CSF (p < 0.01). When administering both, the effect of EPO seems to fade as EPO and GM-CSF treated rats have decreased regeneration compared to EPO administration alone (p < 0.01). CONCLUSION: EPO, GM-CSF and their combination enhance liver regeneration after hepatectomy in rats when administered perioperatively. However their combination has a weaker effect on liver regeneration compared to EPO alone. Further investigation is needed to assess the exact mechanisms that mediate this finding.

Primary hepatic neuroendocrine tumor with exophytic growth: report of a case with diagnosis by fine needle aspiration biopsy.

BACKGROUND: Primary hepatic neuroendocrine tumor with exophytic growth is a unique entity. CASE: A 74-year-old man presented to our hospital with abdominal discomfort. Diagnostic imaging procedures revealed a 15 x 10-cm mass in the liver with exophytic growth. The tumor was adjacent to the stomach, and clinical suspicion of gastrointestinal stromal tumor of the stomach was very strong initially. The cytologic and immunocytochemical examination of aspirated material showed features similar to those of neuroendocrine tumor. Systemic staging procedures showed no evidence of metastasis or other primary site. The histopathologic results of the excised tumor confirmed the cytologic diagnosis. CONCLUSION: Primary neuroendocrine tumor with exophytic growth is a rare entity and can be diagnosed with cytology and immunocytochemistry.

The influence of total plasma homocysteine and traditional atherosclerotic risk factors on degree of abdominal aortic aneurysm tissue inflammation.

OBJECTIVE: Modulating effects of genetic and environmental risk factors on severity of human abdominal aortic aneurysm (AAA) tissue inflammation remain unclear. We investigated the influence of total plasma homocysteine (tHcy) and traditional atherosclerotic risk factors (ARF) on degree of AAA tissue inflammation. METHODS: Aneurysm specimens were obtained from 89 male patients aged 52 to 83 years, underwent asymptomatic not ruptured AAA (mean diameter 5.5 cm) open repair and graded for degree of histologic inflammation. Multivariate analysis was used to determine the association of tHcy and ARF, with degree of inflammation. RESULTS: Current cigarette smoking, odds ratio (OR) 4.4, 95% confidence interval 1.3 to 15.2, P = .01 and no other ARF, neither tHcy levels OR 0.9 (0.9-1.02), P = .2 were associated with high-grade tissue inflammation. CONCLUSION: These results provide evidence against a major effect of tHcy levels on AAA tissue inflammation, while current cigarette smoking is a significant modulating factor.

A rare coexistence of adrenal cavernous hemangioma with extramedullar hemopoietic tissue: a case report and brief review of the literature.

BACKGROUND: Cavernous hemangiomas of the adrenal gland are rare, benign, non-functioning neoplastic tumors. To our knowledge, 55 cases have been reported in the literature to date. CASE PRESENTATION: We report the first case of a large, non-functioning adrenal cavernous hemangioma that was incidentally found during the preoperative staging workup of a 75 year old woman with left breast adenocarcinoma. Imaging with US, CT scan and MRI showed a heterogeneous 8 cm mass with non-specific radiological features that was located on the left adrenal gland. The mass was surgically excised and pathology revealed an adrenal hemangioma with areas of extramedullar hemopoiesis. CONCLUSION: Although adrenal hemangiomas are rare and their preoperative diagnosis is difficult, they should always be included in the differential diagnosis of adrenal neoplasms.