Laminin Immunostaining in Biopsies as a Useful Biomarker of Early Invasion in Actinic Cheilitis and Differential Diagnosis Between Actinic Cheilitis and Lip Cancer: New Insights.

BACKGROUND: Squamous cell carcinoma of the lip (LSCC) and oral cavity can be life-threatening if not diagnosed early. Precancerous lesions like actinic cheilitis (AC), can transform into LSCC. Laminin is a fundamental component for basement membrane (BM) and its integrity may prevent neoplastic invasion. Therefore, laminin immunostaining of BM may be useful in identifying early invasion in actinic cheilitis and thus in the differential diagnosis between AC and invasive LSCC or high-grade epithelial dysplasia (ED). MATERIALS AND METHODS: Biopsies from 46 patients with oral lesions were histologically analyzed and immunohistochemically stained for laminin-1. RESULTS: AC was diagnosed in 34 patients and LSCC in 12 patients, including 3 patients with AC and concomitant high-grade ED/in situ carcinoma. Laminin-1 immunostaining revealed intense and linear expression of the BM in AC with low-grade ED. Loss of laminin expression was observed in LSCC. Intracellular laminin expression in parabasal cells was noted in AC with high-grade ED/in situ carcinoma. CONCLUSION: Laminin immunostaining could be useful in identifying AC cases suspected of early invasion. It could also contribute to the histopathological differential diagnosis between AC with low- and high-grade ED and between AC and invasive LSCC. The findings of this study provide new insights into the mechanism involved in the progression process of AC into LSCC, encouraging preclinical studies that may document the stochastic role of laminin in this process.

Hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in cartilage tumors.

Neoangiogenesis has been demonstrated in chondrosarcoma. Anti-angiogenic therapies are being tested in clinical trials for chondrosarcomas. Studies of the underlying mechanisms have been performed almost exclusively in cell lines. We immunostained 20 samples of chondrosarcoma and 20 samples of enchondromas with antibodies against hypoxia-inducible factor 1-alpha (HIF-1-alpha) and vascular endothelial growth factor (VEGF). The immunohistochemical staining of HIF-1-alpha and VEGF were highly correlated. Enchondromas were HIF-1-alpha and VEGF negative, whereas all chondrosarcoma exhibited HIF-1-alpha and VEGF immunostaining. HIF-1-alpha/VEGF double positive cases were almost exclusively chondrosarcomas with a high tumor grade. We suggest that HIF-1-alpha is a marker of malignancy in chondrosarcomas that correlates with tumor neo-angiogenesis. Our findings also suggest that a HIF-1-alpha/VEGF angiogenic pathway may exist in chondrosarcoma in vivo as in other malignant tumors. The inclusion of novel inhibitors to HIF-1-alpha and other factors may optimize anti-angiogenic interventions in chondrosarcoma.

Smad4 and epithelial-mesenchymal transition proteins in colorectal carcinoma: an immunohistochemical study.

Epithelial-mesenchymal transition (EMT) plays an important role in cancer metastasis. During EMT, tumor cells acquire the capacity to migrate and invade the stroma. Activation of the transforming growth factor-b (TGF-b) signaling pathway is of major importance for the initiation of EMT. Smad4, an essential protein of this pathway, is known to complex with multiple transcription factors (e.g. Snail-1, Slug, Twist-1), in various types of cancer, promoting the repression or activation of target genes. The role of Smad4 in colorectal cancer (CRC) is not straightforward so far. In the present study forty eight resected CRC tumor specimens were immunohistochemically examined in order to assess the expression of Smad4 and its association with E-cadherin, Snail-1, Slug, Twist-1 protein expression and with various pathological parameters. Smad4 was found to be positively correlated with Snail-1, Slug and Twist-1 expression (p < 0.001). On the other hand it was negatively correlated with the expression of E-cadherin (p < 0.001). Furthermore, lymphatic invasion could be clearly associated with Smad4 expression, a finding complying with the metastatic ability of EMT cells. In conclusion, Smad4 could be considered as a central component of EMT transition in human colorectal cancer that combines with transcriptional factors to reduce E-cadherin and alter the expression of the epithelial phenotype.

A real-world study focused on the long-term efficacy of mycophenolate mofetil as first-line treatment of autoimmune hepatitis.

BACKGROUND: Front-line therapy with mycophenolate mofetil (MMF) in autoimmune hepatitis (AIH) has shown high on-treatment remission rates. AIM: To study prospectively in a real-world fashion the long-term outcome of a large group of consecutive treatment-naïve AIH patients. METHODS: Between 2000 and 2014, 158 patients were recruited but only 131 were eligible for treatment (109 MMF/prednisolone; 22 prednisolone ± azathioprine). Long-term data on outcome after drug withdrawal were evaluated. Patients stopped treatment after having achieved complete response (normal transaminases and IgG) for at least the last 2 years. RESULTS: At diagnosis, 31.6% of patients had cirrhosis and 72.8% insidious presentation. A total of 102 of 109 (93.6%) responded initially to MMF within 2 (1-18) months. A total of 78 of 109 (71.6%) had complete response on treatment and 61 of 78 (78.2%) maintained remission off prednisolone. MMF-treated patients had increased probability of complete response compared to those receiving azathioprine (P = 0.03). Independent predictors of complete response were lower ALT at 6 months (P = 0.001) and acute presentation (P = 0.03). So far, treatment withdrawal was feasible in 40/109 patients and 30 (75%) are still in remission after 24 (2-129) months. Remission maintenance was associated with longer MMF treatment (P = 0.005), higher baseline ALT (P < 0.02), lower IgG on 6 months (P = 0.004) and histological improvement. CONCLUSIONS: Mycophenolate mofetil proved to be an efficient first-line treatment for AIH, achieving so far the highest rates of remission maintenance off treatment (75%) ever published for at least a median of 2 years, although the remission criteria used were strict. However, the risk of potential bias and overestimation of intervention benefits from MMF cannot be completely excluded as this is a real world and not a randomised controlled trial.

Mutation profile of KRAS and BRAF genes in patients with colorectal cancer: association with morphological and prognostic criteria.

KRAS and BRAF mutations are well-recognized molecular alterations during colorectal carcinogenesis, but there is little agreement on their effect on tumor characteristics. Therefore, we aimed to evaluate the distribution of the most common KRAS and BRAF mutations in Greek patients with colorectal cancer and their possible associations with clinical histopathological parameters. In this study, 322 and 188 colorectal carcinomas were used for the mutation analysis of KRAS (exon 2) and BRAF (exon 15) genes, respectively. The mutational status of both genes was evaluated by polymerase chain reaction and sequencing analysis. Although the overall frequency of KRAS mutations (36.6%) seemed to be similar to those reported for other populations, the rate of point mutations at codon 13 was significantly lower (12%) in Greek patients with colorectal cancer and associated with male gender (P < 0.05). Tumors with G>T codon 12 transversions and G>C transitions showed more frequent lymph node metastasis (P < 0.05, P < 0.005, respectively). The rate of KRAS mutations gradually decreased with increasing histological grade (P < 0.05), as opposed to BRAF mutations, which were strongly associated with poorly differentiated tumors (P < 0.005). Additionally, we found that the histological features of preexisting adenoma were associated with the absence of BRAF mutations, in contrast to KRAS (P < 0.05). Our data suggested that there seems to be a correlation between morphological criteria and discrete genetic pathways in colorectal carcinogenesis. Moreover, ethnic or geographic factors may have an impact on genetic background of colorectal carcinomas, and specific types of KRAS mutations may influence the metastatic potential of colorectal tumors.

Expression profile of the GA733 gene family in colorectal cancer: correlation with clinicopathological parameters.

GA733-1/-2/-3 genes have been detected in various types of cancer, although their role has not been fully clarified. GA733-2 and GA733-1 have been correlated with lymph node metastases in laryngeal cancer and liver metastases, respectively. Only a few studies have elucidated the mechanisms regulating GA733-1/-2 expression and their effect on colorectal cancer. Therefore, the expression pattern and the role of the aforementioned molecules in colorectal carcinogenesis were evaluated in this study. Tissue samples were obtained from 40 patients with colorectal cancer with no liver metastases. GA733-1/-2 mRNA levels were evaluated by quantitative real-time polymerase chain reaction. GA733-1/-2 gene expression in noncancerous/cancerous tissues was also correlated with clinicopathological parameters. The GA733-1 mRNA levels were very low; however, the GA733-1 mRNA transcripts were higher in cancerous tissues than in normal tissues (median ratio, 0.004391/0.00093; range, 0.000001- 0.025139/0.000001-0.007761), respectively (P = 0.012). GA733-2 gene expression was higher in noncancerous tissues than in cancerous tissues (median ratio 273.31/115.64; range, 65.24-1,486.41/11.58-1,189.14; P = 0.0000195). Lower GA733-2 expression in cancer tissues appeared to correlate with lymph node metastases (P < 0.05). GA733-1 gene expression was significantly higher in cancerous samples; conversely, the GA733-2 mRNA levels were higher in noncancerous tissues, and were significantly correlated with lymph node perforation in colorectal cancer (P < 0.05). Therefore, GA733-1/-2 mRNA expression levels appear to be a potential predictive marker of tumorigenesis.

Dissatisfaction with male sexual performance and female sexual dysfunction in women with type 1 diabetes.

Although partnership issues are thought to be implicated in female psychology and sexual life, no data exist on the relationship between dissatisfaction with male sexual performance and female sexual dysfunction (FSD) in women with type 1 diabetes mellitus (DM-1). We studied 70 women with uncomplicated DM-1 and 100 nondiabetic women using Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS) and a Likert Scale to evaluate sexual function, sexual distress and the degree of satisfaction derived from the male partner's sexual performance. Compared with healthy controls, DM-1 women had significantly worse sexual function, higher sexual distress and higher FSD frequency. No significant difference in dissatisfaction with partner's sexual performance was found between diabetic and control group (CG). Moreover, dissatisfied diabetic and control women were comparable in sexual functioning, sexual distress and FSD frequency. In the CG, dissatisfied women had significantly worse total FSFI score compared with the satisfied ones. In addition, dissatisfaction with male sexual performance led to significantly worse FSDS score and higher FSD frequency in both diabetic and CGs. Therefore, our findings reveal a negative association between dissatisfaction with male partner's sexual performance and female sexual functioning, regardless of the presence of diabetes.

Aurora B kinase in Hodgkin lymphoma: immunohistochemical pattern of expression in neoplastic Hodgkin and Reed-Sternberg cells.

Aurora B is a member of the chromosomal passenger complex, which is essential for proper completion of mitosis and cell division (cytokinesis). Inappropriate chromosomal segregation and cytokinesis due to deregulated expression of chromosome passenger proteins may lead to aneuploidy and cancer including lymphomas. According to our knowledge there are extremely limited studies investigating the immunohistochemical expression of Aurora B in tumor specimens of Hodgkin lymphoma. Our purpose was to characterize the expression of Aurora B in biopsies of Hodgkin lymphomas, and to evaluate the pattern of immunoreactivity in neoplastic Hodgkin and Reed-Sternberg cells (RS cells). We examined Aurora B immunoreactivity in paraffin sections of 15 samples of Hodgkin lymphomas, obtained from 15 patients, 8 men and 7 women. Ten were of nodular sclerosis type and five were of mixed cellularity. Our results showed immunoexpression of Aurora B in mononuclear lymphoid cells as well as in bi- and multinucleated RS cells. In addition, positive neoplastic cells in mitosis were observed, whereas a subpopulation without evidence of immunoreaction was also detected in each case. Taken together our results point to a possible association between Aurora B expression and mitotic deregulation in Hodgkin lymphoma, which may provide novel targets for treatment.

Uric acid induces caspase-1 activation, IL-1ß secretion and P2X7 receptor dependent proliferation in primary human lymphocytes.

BACKGROUND: Urate through Nacht Domain, Leucine-Rich Repeat, and pyrin domain-containing protein 3 (NALP3) dependent caspase-1 activation stimulates macrophages to secrete inteleukin-1ß (IL-1ß). Purinergic receptor P2X7 plays a role in the urate induced NALP3 activation. Urate also enhances adaptive immunity indirectly through its effect on antigen presenting cells. In this study, the direct effect of urate on primary human lymphocytes was evaluated. METHODS: Lymphocytes were cultured with or without monosodium urate crystals in the presence or not of a P2X7 inhibitor. Caspase-1 activity was assessed colorimetrically in cell lysates and IL-1ß was measured in supernatants with ELISA. Whole lymphocyte viability and proliferation, as well as T-cell proliferation were assessed by means of 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay and of flow cytometry respectively. RESULTS: Urate induced caspase-1 activation and IL-1ß release by lymphocytes. It also induced proliferation of whole lymphocytes and T-cells as well. P2X7 inhibitor abrogated lymphocyte proliferation. CONCLUSIONS: Urate, a well defined danger signal, stimulates directly human lymphocytes in a P2X7 dependent way. The subsequent IL-1ß secretion could enhance inflammation, whereas expansion of lymphocyte clones could facilitate a subsequent adaptive immune response.

Review article: autoimmune hepatitis -- current management and challenges.

BACKGROUND: Autoimmune hepatitis (AIH) is a disease of unknown aetiology characterised by interface hepatitis, hypergammaglobulinaemia, circulating autoantibodies and a favourable response to immunosuppression. AIM: To review recent advancements in understanding aetiopathogenesis, clinical, serological and histological features, diagnostic criteria and treatment strategies of AIH. METHODS: Published studies on AIH extracted mainly from PubMed during the last 15 years. RESULTS: Autoimmune hepatitis has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations are variable ranging from no symptoms to severe acute hepatitis and only seldom to fulminant hepatic failure. Autoimmune attack is perpetuated, possibly via molecular mimicry mechanisms, and favoured by the impaired control of regulatory T-cells. A typical laboratory finding is hypergammaglobulinaemia with selective elevation of IgG, although in 15-25% of patients - particularly children, elderly and acute cases - IgG levels are normal. Liver histology and autoantibodies, although not pathognomonic, still remain the hallmark for diagnosis. Immunosuppressive treatment is mandatory and life-saving; however, to meet strict response criteria, the conventional therapy with prednisolone with or without azathioprine is far from ideal. CONCLUSIONS: Autoimmune hepatitis remains a major diagnostic and therapeutic challenge. The clinician, the hepato-pathologist and the laboratory personnel need to become more familiar with different expressions of the disease, interpretation of liver histology and autoimmune serology. According to the strict definition of treatment response issued by the 2010 AASLD guidelines, many patients are nonresponders to conventional treatment. Newer immunosuppressive agents targeting pathogenetic mechanisms can improve patient management, which needs to be tailored on a case-by-case basis.

Open inguinal hernia repair with the use of polyglycolic acid/trimethylene carbonate mesh: gross and pathologic assessment of the inguinal area at reoperation for recurrence.

PURPOSE: Our group tried to test the hypothesis of using a totally absorbable material for open inguinal hernia repair. However, the increased incidence of recurrences alleviated our initial enthusiasm regarding the technique. The purpose of the present study was to attain both gross and microscopic data that could at least in part justify the hernia repair failure from a patient included in our initial pilot study and was re-operated for recurrence. METHODS: A 65-year-old male patient was diagnosed clinically with a recurrence 24 months after open inguinal hernia repair with the use of polyglycolic acid/trimethylene carbonate mesh. The patient was operated for the recurrence upon our group on July 2012. The gross appearance of the inguinal area as well as the degree of chronic inflammation provoked by the used mesh as depicted by the pathologic analysis of specimens obtained intraoperatively were assessed. RESULTS: An open tension-free repair with the use of a non-absorbable mesh under spinal anesthetic was undertaken. Intraoperatively, after the division of the external oblique aponeurosis, only minor fibrotic reaction was observed a finding that was additionally confirmed pathologically. CONCLUSION: Polyglycolic acid/trimethylene carbonate mesh used for inguinal hernia repair was associated with a minimal inflammatory host reaction in the inguinal area at 3 years verified both grossly and microscopically.

Oxidative stress and reduced antioxidative status, along with endothelial dysfunction in acromegaly.

Acromegaly is characterized by high cardiovascular morbidity and mortality. Oxidative stress and endothelial dysfunction are underlying mechanisms of atherosclerosis.The aim of this study was to evaluate the blood redox status and endothelial function by means of nitric oxide (NO) levels in patients with acromegaly. Total antioxidant capacity (TAC), catalase activity and glutathione concentration (GSH), as measures of antioxidative capacity, total oxidized glutathione (GSSG) and thiobarbituric acid reactive substances (TBARS), as indices of oxidative stress, and NO levels were assessed in 15 patients with acromegaly (age 55.4±10.5 years; 6 males) and 15 age- and sex-matched controls (age 58.4±8.1 years; 7 males). Active disease was present in 12 patients: 11 on current pharmacotherapy and 1 newly diagnosed. Three acromegalics were in remission after successful treatment. Acromegalics as compared with controls had significantly lower levels of catalase activity (8.2±5.8 vs. 51.3±29.1 mmol/ml/min, p<0.001), GSH (0.97±0.54 vs. 1.41±0.35 mmol/l, p=0.006), GSSG (0.27±0.19 vs. 2.04±1.32 mmol/l, p=0.002) and NO levels (6.0±3.1 vs. 43.0±29.8 mmol/l, p<0.001), but higher TBARS (16.3±8.9 vs. 10.1±10.8, nmol/ml, p=0.019). After adjustment for confounders, differences in catalase activity, NO levels and TBARS remained significant (p=0.004, p<0.001 and p=0.025, respectively). No association between IGF-I/GH and oxidative stress markers was noticed, except for a positive correlation between nadir GH and GSSG (r²=0.563, p=0.036). Acromegaly is associated with increased levels of oxidative stress coupled by diminished antioxidant capacity and endothelial dysfunction indicated by the presence of decreased NO levels.

Open inguinal hernia repair with the use of polyglycolic acid/trimethylene carbonate absorbable mesh: a critical update of the long-term results.

PURPOSE: Our group evaluated on a pilot basis open inguinal hernia repair with the use of a fully absorbable mesh aiming to take mesh inguinal hernia repair one step forward. The purpose of the present study was to assess the long-term results of the proposed technique. METHODS: Patients that were included in our previous report were followed up at 3 years after the initial operation. RESULTS: Ten patients underwent open inguinal hernia repair with the use of an absorbable polyglycolic acid/trimethylene carbonate mesh. 3 years after the procedure, from the total of ten patients, two were lost to follow-up (20 %). Three patients (37.5 %), one with direct and two with indirect hernia, were diagnosed clinically with a recurrence at the follow-up of 3 years. Recurrences were developed nearly 2 years--median 24 months (range 18-30)--after the initial operation. Among patients without recurrence none complained about chronic pain, foreign body sensation or numbness. On the other hand, chronic pain was a constant complain in the recurrence patient group. CONCLUSIONS: The results of the 3-year follow-up in the given patient sample alleviate the initial enthusiasm regarding the use of an absorbable mesh for inguinal hernia repair as an attractive alternative and causes skepticism about the generalized use of the procedure in its certain form.

Long-term results after laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair under spinal anesthesia.

BACKGROUND: Laparoscopic transabdominal preperitoneal (TAPP) repair is indicated for recurrent and bilateral inguinal hernias and traditionally is performed under general anesthesia. However, the feasibility of performing TAPP under spinal anesthesia has been recently reported by our team. AIM: To assess the long-term results of TAPP repair under spinal anesthesia for primary inguinal hernia. MATERIALS AND METHODS: Between January 2006 and October 2009, 94 consecutive patients with primary unilateral inguinal hernia were submitted to laparoscopic transabdominal preperitoneal repair under spinal anesthesia. We looked at the immediate postoperative outcome as well as the long-term outcome, mainly recurrences and incidence of chronic pain. RESULTS: One patient experienced a scrotal hematoma, one patient a trocar site infection, two patients were diagnosed with an operation-related orchitis, while 31 patients (33 %) developed symptoms of urinary retention. At a median follow-up of 35 months (range 14-59), four patients (4.3 %) were diagnosed with a recurrence, while 89 % of patients reported satisfied from the procedure in the long-term. Chronic pain was not encountered in any of the patients studied. Four patients (4.3 %) reported an intermitted foreign body sensation and/or rigidity and two patients (2.1 %) numbness in the operated inguinal area. CONCLUSION: Laparoscopic TAPP hernia repair under spinal anesthesia is associated with satisfactory short- and long-term results. Use of regional anesthesia instead of the traditional general anesthesia does not seem to adversely affect the quality of repair, and moreover, it offers the patient an attractive anesthetic alternative.

Development of GC-MS/MS method with programmable temperature vaporization large volume injection for monitoring of 17ß-estradiol and 2-methoxyestradiol in plasma.

Monitoring of estradiol and its metabolites in biological samples is essential for the accurate diagnosis of a number of endocrine diseases. In this study, a sensitive, precise and specific GC-MS/MS method for the quantification of 17ß-estradiol (17-BE) and its main metabolite, 2-methoxyestradiol (2-MEOE), in plasma was developed and validated. Plasma concentrations of these steroids are currently investigated as diagnostic markers for pre-eclampsia, a systematic disorder of pregnancy and a leading cause of maternal and fetal morbidity and mortality worldwide. The method comprised treatment of the plasma sample by protein precipitation and subsequent isolation of steroids by solid phase extraction, derivatization of steroids by trifluoroacetic anhydride and GC-MS/MS analysis of the derivatized steroids. The large volume (10 µL) injection with the assistance of a Programmed Temperature Vaporization (PTV) injector in solvent split mode allowed a substantial increase in the sensitivity of the method. The ion trap MS was operated in optimized Product Ion Scan. By increasing the damping gas flow in the ion trap from the conventional 0.3 mL min(-1) to 2 mL min(-1), ion fragmentation was reduced and the instrument response was enhanced substantially. As a result, mass spectra with predominant molecular ions were acquired and molecular ions of the steroids of interest were used as precursor ions thus increasing specificity of the method. Under optimized GC-MS/MS conditions in product ion mode, the Limit of Detection (LOD) of the analyzed steroids ranged from 18.4 pg mL(-1) for 17-BE to 5.5 pg mL(-1) for 2-MEOE (S/N=3). The instrument response was linear in the investigated concentration range from 0.1 to 10 ng mL(-1) with R(2)>0.99 for 17-BE and 2-MEOE. The intra-batch accuracy obtained for quality control samples at the concentration levels of 0.1, 1, 3, 7 ng mL(-1) ranged from 94.9% to 109.9% for 17-BE and from 99.9% to 104.5% for 2-MEOE.

Associations of estrogen receptor alpha and beta gene polymorphisms with sex steroid levels and body fat content in men.

OBJECTIVE: Estrogens play an important role in male physiology. We investigated the possible association of four single nucleotide polymorphisms in Estrogen Receptor α ( ESR1) and Estrogen Receptor ß ( ESR2) genes with circulating levels of sex steroids and Sex Hormone Binding Globulin (SHBG) in men. DESIGN AND METHODS: SHBG, total and calculated free testosterone (TT and cal FT), estradiol (E2) and free Estradiol (FE2) were determined in a population-based cohort of 170 apparently healthy Greek men. Body mass index (BMI), waist circumference (WC) and percentage of body fat (%fat) content were measured in all participants. Genotyping for the PVU II and XBA I polymorphisms of the ESR1 gene and for the RSA I and ALU I polymorphisms of the ESR2 gene was performed. RESULTS: PVU II showed an association with E2 levels [median (IQR) pp 58.5 (42.1-73.4) pg/ml vs. Pp 48.8 (42.9-60.1) and PP 57.7 (44-70.5), p=0.032], and with %fat [mean±SD pp 24.6±5.3 vs. Pp 22.4±5.2 and PP 21.2±6.7, p=0.044], after adjustment for age and WC. Furthermore, the effect of PVU II on E2 was independent of %fat (p=0.038). A synergistic effect of the two ESR1 polymorphisms on E2 (p=0.023), FE2 (p=0.03) and %fat (p=0.004) was present. Finally, a synergistic effect of the ESR1 and ESR2 genes on TT (p=0.009), independent of age, WC and %fat also emerged. CONCLUSIONS: Genetic variation in ESR1 is associated with serum estradiol levels and body fat content regulation in men. Furthermore, a synergistic effect of ESR1 and ESR2 genes is exerted on serum testosterone levels.

Comparative study of spatial localization of HER-2 and CEP17 signals and of HER-2/CEP17 ratios, in "thin" and "thick" tissue sections.

One presumed drawback of performing fluorescence in situ hybridization on routine tissue sections for HER-2 status evaluation in breast carcinomas is nuclear truncation. Therefore, HER-2/CEP 17 ratios were compared in routine (4 µm) vs. thicker (15 µm) tissue sections. Additionally, the distances of both signals from the nuclear center were measured by three-dimensional image analysis. HER-2 and CEP 17 signals' number increased in thick sections; however, HER-2/CEP 17 ratios were decreased. This could be attributed to a preferential increase in CEP17 signals explained by their more peripheral localization and apparent "loss" in truncated nuclei. The aforementioned decrease of HER-2 ratios did not alter HER-2 status except in cases in the equivocal category where it changed from equivocal to non-amplified. Thus, at least a subset of the equivocal cases could represent an artifactual increase of HER-2 ratio related to nuclear truncation and loss of peripheral CEP 17 signals in routine sections.

Colorectal cancer surgery in the elderly: limitations and drawbacks.

PURPOSE: The purpose of this study was to evaluate the outcomes of colorectal cancer surgery among the elderly. METHODS: From March 2002 until February 2010, 434 patients who presented to our institution with the initial diagnosis of colorectal cancer and were submitted to open curative colorectal cancer resections or some kind of palliative procedure either elective or emergencies were retrospectively reviewed. A total of 286 of these patients (65.8%) were below 75 years (group A) and 148 (34.2%) above 75 years (group B). RESULTS: A procedure with curative intent was undertaken in 386 patients (88.9%), while forty-eight patients (11.1%) were submitted to a palliative procedure. Regarding the incidence of emergency operations, forty-five patients (15.7%) from group A and forty-four patients (29.7%) from group B were operated due to an emergency (obstructing, perforating or bleeding tumors; P < 0.001). Mean ASA score was 1.74 ± 0.84 and 2.32 ± 0.94 for groups A and B, respectively (P < 0.001). Mean TNM stage was 2.28 ± 1.00 and 2.74 ± 0.98 for groups A and B, respectively (P = 0.0001). Elderly patients exhibited increased incidence of post-operative complications and increased post-operative mortality compared with their younger counterparts (P = 0.002 and 0.001, respectively). CONCLUSION: Colorectal cancer surgery in the elderly is a challenging clinical scenario. Treatment decision adjusted to each individual case is the ideal practice in order to maintain an acceptable balance between curative cancer resections and palliative procedures.