Outcome of operative therapy of hepatic metastatic stomach carcinoma: a retrospective analysis.

BACKGROUND: In general, hepatic metastasis from stomach carcinoma has an unfavorable prognosis. In addition, there are often further metastases in other organs, such as peritoneal carcinomatosis. The major aim of the present study was to investigate a potential curative surgical approach in these patients. MATERIAL AND METHODS: Thirty-one patients with hepatic metastases from stomach cancer were treated in the University Clinic Erlangen-Nürnberg. The data were collected retrospectively from 1972 to 1977 and prospectively since 1978 at the Erlangen Cancer Registry. The time frame of this retrospective analysis from patients who had surgical resection of hepatic metatases from gastric cancer was from 1972 to 2008. The median age of the patients was 65 years, and the ratio of men to women was 2:1. RESULTS: Atypical or anatomical resections of segments were possible in 21 cases. Larger operations, such as hemihepatectomy (right/left), were performed in 10 patients. The postoperative complication rate was 29%, and the hospital mortality was 6%. The five-year survival rate was 13%; R0 resection was achieved in 23 patients. We also found a significant difference in the 5-year survival rate between synchronous and metachronous metastases (0 vs. 29%; p < 0.001) and R0 resected patients (p = 0.002). Patients with solitary metastases had a significantly better median survival than patients with multiple metastases (21 vs. 4 months; p < 0.005.) CONCLUSIONS: The overall survival in our study was 13%; therefore gastric cancer with liver metastases is not in every case a palliative situation. It seems that patients with liver metastases benefit from resection, especially if the metastases are metachronous (p < 0.001) and solitary, provided that a curative R0 resection has been achieved. An interdisciplinary approach with neoadjuvant chemotherapy appears useful. Additional controlled studies should be conducted.

Duodeno-pancreatic neuroendocrine tumours.

Duodeno-pancreatic neuroendocrine tumours (DP-ETs) are increasingly diagnosed today due to the widespread use of modern imaging methods. Duodeno-pancreatic endocrine tumours should be treated by radical surgical resection, which offers a high chance for cure when the disease is localized. A high index of suspicion is required in these patients for the presence of a multiple endocrine neoplasia type syndrome. We present four patients with DP-ET surgically treated at our department between 2000 and 2004. Histological/immunohistochemical diagnosis was somatostatin-producing tumour in the first patient, oncocytic endocrine tumour positive for neurone-specific enolase and focally for chromogranin in the second patient, glucagonoma and pancreatic polypeptide-producing endocrine pancreatic tumour in the third patient, and gastrin, somatostatin, calcitonin, insulin and adrenocorticotropic hormone (ACTH)-producing tumour in the fourth. The second patient died 6.5 years following surgery due to disseminated disease.

CD8+ lymphocytes/ tumour-budding index: an independent prognostic factor representing a 'pro-/anti-tumour' approach to tumour host interaction in colorectal cancer.

BACKGROUND: The tumour-host interaction at the invasive front of colorectal cancer, including the epithelial-mesenchymal transition and its hallmark 'tumour budding', is an important area of investigation in terms of prognosis. The aim of this study was to determine the prognostic impact of a 'pro-/anti-tumour' approach defined by an established 'pro-tumour' (tumour budding) and host-related 'anti-tumour' factor of the adaptive immunological microenvironment (CD8+ lymphocytes). METHODS: Double immunostaining for CK22/CD8 on whole tissue sections (n=279; Cohort 1) and immunohistochemistry for CD8+ using tissue microarrays (n=191; Cohort 2) was carried out. Tumour buds, CD8+ and CD8+ T-lymphocytes : tumour buds indices were evaluated per high-power field. RESULTS: In Cohort 1, a low-CD8+/ buds index was associated with lymph node metastasis (P<0.001), vascular invasion (P=0.009), worse survival in univariate (P<0.001) and multivariable (P<0.001) analysis, and furthermore in lymph node-negative patients (P=0.002). In Cohort 2, the CD8+/ buds index was associated with T stage (P<0.001), N stage (P=0.041), vascular invasion (P=0.005) and survival in patients with TNM stage II (P=0.019), stage III (P=0.004), and adjuvantly untreated (P=0.009) and treated patients (P<0.001). CONCLUSION: The CD8+ lymphocyte : tumour-budding index is an independent prognostic factor in colorectal cancer and a promising approach for a future prognostic score for patients with this disease.

Serum interleukin-6 is elevated in symptomatic carotid bifurcation disease.

INTRODUCTION: The levels of circulating proinflammatory cytokines may express the extent of the inflammatory response and their participation in plaque progression and rupture needs to be evaluated. We aimed to investigate differences in circulating levels of proinflammatory cytokines and in plaque infiltration by macrophages between patients undergoing carotid endarterectomy for symptomatic and asymptomatic carotid atherosclerotic disease. METHODS: One hundred nineteen patients (91 men and 28 women; mean age 66 +/- 8 years; range 42-83 years) who underwent carotid endarterectomy for significant (>70%) carotid bifurcation stenosis were enrolled in this study. Patients were characterized as symptomatic (n = 62) or asymptomatic (n = 57) after neurological examination. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, serum amyloid A (SAA), and high-sensitivity C-reactive protein (hs-CRP) were evaluated. Macrophage infiltration of the plaque was assessed quantitatively from endarterectomy specimens using the monoclonal antibody CD68. RESULTS: Serum IL-6 levels were significantly higher in patients with symptomatic compared with those with asymptomatic carotid disease (3.3 [2.0-6.5] pg/ml vs 2.5 [1.9-4.1] pg/ml, P = 0.02). TNF-alpha, IL-1beta, SAA, and hs-CRP levels did not differ significantly between the two groups. Symptomatic patients had also more intense macrophage accumulation in the carotid plaque compared with asymptomatic patients (0.6 +/- 0.1% vs 0.4 +/- 0.1%, P < 0.001). Although there were correlations between the levels of the different inflammatory markers, there were no correlation between any of them and the extent of plaque macrophage infiltration. CONCLUSION: Patients with symptomatic carotid atherosclerotic disease have elevated serum IL-6 levels compared with asymptomatic patients. Symptomatic patients have also more intense macrophage infiltration of the atherosclerotic plaque suggesting that inflammatory process may contribute to the destabilization of the carotid plaque.

Prognostic significance of p53 and Ki67 proteins expression in Greek gastric cancer patients.

AIM: The variability of prognosis of gastric cancer (GC) within a pathological stage necessitates the identification of subgroups of patients with a more aggressive disease. The role of p53 and Ki67 expression in gastric carcinoma is far from being fully established. The aim of the present study was to evaluate the expression of p53 and Ki67 in gastric cancer and correlate the findings with several clinicopathological features and prognosis. MATERIALS AND METHODS: Tissue samples from 93 patients treated by gastric resection for gastric carcinoma between 1996 and 2001 were used. Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53 and Ki67. The results were correlated with clinicopathological features and survival. RESULTS: Stronger expression of p53 was related with tumor size greater than 5 cm and advanced stage. Stronger expression of Ki67 correlated with higher ratio of the number of metastatic lymph nodes to the total number of dissected lymph nodes (metastatic lymph node [MLN] ratio) and advanced stage. Moreover, p53 and Ki67 overexpression, tumor size greater than 5 cm, MLN ratio, depth of invasion, lymph node metastasis, stage III and IV and infiltrative macroscopic appearance were adverse prognostic factors. The levels of p53 and Ki67, the MLN ratio, the tumor size (above 5 cm) and the stage of the disease were identified as independent prognostic factors of survival. CONCLUSIONS: In gastric cancer, the expression of p53 and Ki67 provides significant information about prognosis. The routine evaluation of p53 and Ki67 levels could be a useful tool in identification of patient with more aggressive disease and contribute to a better therapeutic approach.

The role of liquid-based cytology in the investigation of thyroid lesions.

OBJECTIVE: This study investigates the role of liquid-based cytology by ThinPrep technique in the detection of thyroid lesions. METHODS: In all, 252 specimens from 157 patients for pre-operative evaluation of thyroid nodules, prepared by the ThinPrep, were examined. In all cases thyroidectomy followed the initial cytological evaluation. All cytological diagnoses were correlated to the histological ones. RESULTS: According to our findings, a sensitivity of 87.80%, a specificity of 99.50%, a positive predictive value of 97.30%, a negative predictive value of 97.56% and an overall accuracy of 97.52% were observed in fine needle aspiration cytology in correlation to the histological diagnosis after thyroidectomy. CONCLUSIONS: ThinPrep technique is a valid method for the pre-operative cytological diagnosis of thyroid nodules, offering the possibility of ancillary techniques, such as immunocytochemical and molecular methods and can, therefore, be potentially complementary to histological evaluation for further investigation of follicular lesions.

Immunohistochemical expression of bcl-2 in UICC stage I and III colorectal carcinoma patients: correlation with c-erbB-2, p53, ki-67, CD44, laminin and collagen IV in evaluating prognostic significance.

BACKGROUND: The objective of this study was to evaluate the expression of bcl-2 in UICC stage I and stage III (Dukes's stage B and C) colorectal adenocarcinoma and to examine its association with clinicopathological features, c-erbB-2, p53, ki-67, CD44, laminin and collagen IV and long term outcome. METHODS: Paraffin embedded specimens from 61 patients with UICC stage I (Dukes's stage B) and 39 patients with UICC stage III (Dukes's stage C) colorectal adenocarcinoma who were treated with surgery were assessed. We determined by immunohistochemistry the expression of bcl-2, c-erB-2, p53, ki-67, CD44, laminin and collagen IV with 5 year follow up. RESULTS: Cytoplasmic staining of the bcl-2 gene product was seen in the tumour cells of 27 cases (27%). Expression of bcl-2 protein was unrelated to patient sex, age, tumour site or tumour grade, but was related to tumour stage (p = 0.012). No significant association was demonstrated between bcl-2 and c-erbB-2, p53 or CD44. However, there was very strong evidence of correlation between bcl-2 staining and ki-67, laminin and collagen IV. There was a trend towards increased survival in patients whose tumours expressed bcl-2 protein. When a correlation between bcl-2 and the other markers had been made the positive expression of bcl-2 was beneficial. CONCLUSIONS: The results from this study would suggest that expression of bcl-2 appear to be useful in selecting a group of colorectal cancer patients with a better prognosis.

Prognostic evaluation of CD44 expression in correlation with bcl-2 and p53 in colorectal cancer.

To investigate the expression of CD44 in colorectal cancer and examine its association with clinicopathological features, bcl-2, p53 and long-term outcome, paraffin-embedded tumour specimens from 61 patients with Dukes stage B (AJCC/UICC stage I) and 39 patients with Dukes stage C (AJCC/UICC stage III) colorectal adenocarcinoma were assessed by immunohistochemistry. The expression of CD44, bcl-2 and p53 were correlated with 5-year follow-up. Low CD44 expression was present in 30%, moderate in 30% and extensive in 40% of cases. It was not related to patient sex and age but was related to tumour differentiation, stage and tumour site. No association was demonstrated between CD44 and bcl-2. However, there was significant evidence of an association between CD44 and p53 in 66 cases in which p53 was previously assessed. There was a trend towards increased survival in patients whose tumours expressed lower levels of CD44 protein. When entered into multivariate analysis model, which also included bcl-2 and p53, CD44 staining emerged as an indicator of poor prognosis in colorectal cancer patients.

Does gentamicin induce acute renal failure by increasing renal TXA2 synthesis in rats?

Acute renal failure (ARF) induced with large doses of Gentamicin (GM) (an aminoglycoside) was associated with increased urinary TXB (TXA) excretion which provoked a decrease of the ratios of urinary PGE2/TXB2 and 6-keto-PGF1 alpha (PGI2)/TXB2 excretions. Furthermore, as indicated by light microscopy most of the epithelial cells lining the proximal tubules show obvious lesions varying from swelling of their cytoplasm to complete necrosis. Either the inhibitor, OKY-O46, of TXA-synthetase, or volume expansion (VE) with isotonic saline (IS) of the experimental animals diminished urinary TXB excretion which provoked 1) augmentation of the ratios of urinary PGE/TXB and 6-keto-PGF1 alpha/TXB excretions, 2) elevation of creatinine clearance (Ccr) and 3) diminution of proteinuria (PU). This protection against ARF-by OKY-O46 and VE can a can be seen in microscopic sections where necrosis of proximal tubules is almost absent. Only a few proximal tubules show swelling of their epithelial cells and some focal areas of tubule necrosis. We suggest that the metabolites of arachidonic acid (AA), TXA2 a (potent vasoconstrictor agent) and prostaglandins (PGE2 and PGI2), (potent vasodilator factors), play an important role in the development (TXA2) or in the prevention (PGs) of ARF induced by this antibiotic.

Endocrine function in abetalipoproteinemia: a study of a female patient of Greek origin.

AIM: To investigate the pituary, genitalia, adrenal, thyroid, parathyroid and pancreatic endocrine function of a female patient aged 37 with abetalipoproteinemia at the time of diagnosis and 5 years thereafter (after application of a modified diet). SUBJECT-METHODS: Serum concentrations of cortisol, A4, ACTH, aldosteron, renin, dehydroepiandrosterone sulfate (DHEA-5), progesterone, 17-OH progesterone, testosterone, SH13G, estradiol, luteinizing hormone, follicle stimulating hormone, T3, T4, TSH, FT3, FT4, parathormone, osteocalcin, prolactin, proinsuline, insulin, glucagon, somatomedin-C (Insulin-like Growth Factor-1, IGF-1), IG171-13P3, 25 (OH) Vitamin D3 and 1-25 (OH) 2 Vitamin D3, were measured by radioimmunoassay. Synactlien test, and 24-hour urine cortisol, were also estimated. Serum leptin estimation was carried-out using a sensitive enzymatic technique. Ionized part of serum calcium was measured by the use of a special machine (CORNING), while bone alkaline phosphatase was measured by radioimmunoassay. RESULTS: Serum progesterone and 17-OH-progesterone were reduced in both examinations. Estimation of serum progesterone performed on the 21th day of the menstrual cycle revealed again values below the lowest normal limit. Serum prolactin was increased both in rest and during movement. The levels of both, somatomedin-C (IGF-1) and leptin were below the lowest normal limit. Despite normal serum parathormone, serum-ionized calcium and 25-OH vitamin D were low, while serum bone alkaline phosphatase was increased. Serum proinsulin was increased, and serum insulin was low. Serum thyroid hormone, glucagon, parathormone, FSH, LH, ACTH, testosterone, estradiol and SH13G were normal. The hormonal profile of the patient estimated 5 years later did not differ substantially suggesting that the metabolic improvement due to the adoption of the modified diet had not any significant impact on it. CONCLUSION: Female patients with abetalipoproteinernia have reduced production of progesterone by the corpus luteum and slightly abnormal bone metabolism. The reduced production of progesterone is probably due to the low levels of serum LDL and cholesterol, while reduced serum levels of Leptin and IG17-1 are probably due to the impairment nutritional status. The adoption of a modified diet does not alter the hormonal profile significantly.

Loss of E-cadherin independently predicts the lymph node status in colorectal cancer.

BACKGROUND: The identification of biomarkers that improve risk stratification in patients with colorectal cancer (CRC) is still a challenge. The objective of our study was to identify independent protein markers as predictors of lymph node (N) stage in CRC. METHODS: Tumour specimens from 221 CRC patients were mounted onto a multiple-punch tissue microarray and evaluated for 21 tumour related factors and one host related factor involved in CRC carcinogenesis, namely ß-catenin, E-cadherin, EGFR, pERK, RHAMM, pAKT, pSMAD2, p21, p16, Bcl-2, Ki-67, APAF-1, MST1, RKIP, VEGF, EphB2, MMP7, Laminin5γ2, MUC1, CDX2, caspase-3 as well as intra-tumoural and stromal CD8+ tumour infiltrating lymphocytes (iTILs and sTILs). RESULTS: Node positive cancers showed significant losses for p21 (p = 0.026), Bcl-2 (p = 0.027), APAF-1 (p = 0.033), EphB2 (p = 0.006), E-cadherin (p < 0.001), RKIP (p = 0.019), CD8+ iTILs and sTILs (p < 0.001 and p = 0.008, respectively) and cytoplasmic MST1 (p = 0.014). Based on the area under the receiver operating characteristic curve (AUC) EphB2, E-cadherin, iTILs and sTILs were identified as potential predictors of N stage (AUC values >0.6), but only loss of E-cadherin was an independent predictor in multivariate analysis. CONCLUSIONS: E-cadherin appears to be a strong predictor of N stage in CRC and should be considered in pre-operative and post-operative management of colon and rectal cancer patients.

Risk factors for colorectal polyps: findings from a Greek case-control study.

UNLABELLED: There is a body of evidence showing that several lifestyle and dietary factors are associated with colorectal polyps' formation; however, the magnitude of this association in diverse populations remains unclear. The aim of this study was to investigate this association in a Greek sample. MATERIAL AND METHOD: The study comprised of 52 subjects with histologically confirmed advanced colorectal polyps and 52 healthy controls. Data concerning lifestyle and dietary factors were collected using a validated questionnaire. Logistic regression analysis was used to estimate odds ratios and 95% confidence intervals after adjustment for potential confounders. RESULTS: Physical activity level (95% CI 0.032-0.953, P = 0.044) and consumption of yoghurt (95% CI 0.969-0.996, P = 0.024), cheese (95% CI 0.932-0.996, P = 0.030), fish (95% CI 0.782-0.964, P = 0.008), vegetables (95% CI 0.965-0.998, P = 0.029), and garlic (95% CI 0.005-0.671, P = 0.022) were inversely associated with colorectal polyps. Increasing age (95% CI 1.005-1.231, P = 0.039) and central obesity (95% CI 1.001-1.019, P = 0.025) were strongly associated with their presence. CONCLUSION: Our study indicates that a cluster of modifiable risk factors have significant impact on colorectal polyps' occurrence in Greek population.

Acute idiopathic pancreatitis preceding diagnosis of Crohn's disease. Description of three cases.

UNLABELLED: Acute idiopathic pancreatitis seems to represent a rare extraintestinal manifestation of Crohn's disease usually appearing after the establishment of diagnosis of the intestinal disorder. The aim of this study was to describe the clinicoepidemiological characteristics and clinical course of three patients with Crohn's disease who developed acute idiopathic pancreatitis years before the establishment of diagnosis intestinal disease. DESCRIPTION OF CASES: All patients were suffering from Crohn's disease. In all patients, an extensive work-up aiming to identify an etiological factor involved in the pathogenesis of acute pancreatitis was negative. The main clinical characteristics of the patients were the young age, the mild or moderate degree of severity of pancreatitis, and the concurrent involvement of small and large bowel from Crohn's disease in two of them. There was no preference for either male or female sex. The course of pancreatitis was favorable in all patients. During the follow-up period, ranging from 2 to 8 years, no exacerbation of pancreatitis was noticed. CONCLUSION: This case-series suggests that acute idiopathic pancreatitis could precede diagnosis of Crohn's disease. Clinicians must bear in mind the possibility of the existence of Crohn's disease when they are confronting a young patient with clinical and laboratory features of acute idiopathic pancreatitis.

Coexistence of medullary sponge kidney and ulcerative colitis in the same patient: long-term follow-up.

We describe a female patient with ulcerative colitis since the age of 17, who was accidentally diagnosed as having medullary sponge kidney 3 years after the establishment of diagnosis of inflammatory bowel disease. The diagnosis of renal disease was based on the typical appearance of both kidneys on abdominal ultrasound examination and on IV pyelography findings. All other well-known causes of medullary sponge kidney were excluded on the basis of the relevant laboratory investigation. So far, the patient experienced only one episode of urinary infection but no renal colic. Since the time of diagnosis of ulcerative colitis her renal function tests are perfectly normal. She is under maintenance treatment with mesalazine. The benign nature of the situation was explained to her. She was advised to drink at least one and a half litter of water daily, in order to reduce the risk of nephrolithiasis. The combination of the two disorders in our patient is probably the result of a chance. However, taking into account the potentially dangerous long-term results of medullary sponge kidney, we suggest that patients with ulcerative colitis must have a careful ultrasound examination of both kidneys at least at the time of diagnosis of the bowel disease, in order to exclude the possibility of medullary sponge kidney, as conservative measures could result in avoidance of potentially dangerous complications, such as renal stones and urinary infections.