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Trastuzumab emtansine (T-DM1) is a human epidermal growth factor receptor 2 (Her2) - targeted antibody-drug conjugate that is approved for patients previously treated with trastuzumab and a taxane for Her2-positive advanced breast cancer and those who have progressed within 6 months of completion of adjuvant chemotherapy, as well as for patients with residual invasive Her2-positive disease after the completion of adjuvant chemotherapy. Peripheral neuropathy is a common adverse event; however, ocular events have also been described. With the current report we present the case of a 67-year old woman who developed transient grade 2-3 blurred vision after the first T-DM1 infusion, which was complicated with grade 2 diplopia causing vertigo after the second infusion. After extended investigation, this symptomatology was attributed to central neurotoxicity, and gradually resolved after T-DM1 discontinuation.

Small cell carcinomas (SCCs) are poorly differentiated neuroendocrine tumors that arise predominantly in the lung and gastrointestinal tract (GIT). Neuroendocrine carcinomas can occur in a variety of extrapulmonary sites throughout the body, including breast, larynx, GIT, prostate, urinary bladder, ovary and cervix. This is a case report of a 55-year-old Asian female patient with metastatic high-grade neuroendocrine carcinoma of unknown origin that responded notably to off-label nivolumab maintenance treatment after first-line carboplatin - etoposide chemotherapy and radiation. After 2 years of nivolumab after platinum-based chemotherapy results from PET-CT showed no residual disease and we proceeded to mastectomy.

Pancreatic trauma is rare compared to other abdominal solid organ injuries, accounting for 0.2%-0.3% of all trauma patients. Moreover, this type of injury may frequently be overlooked or not readily appreciated on initial clinical examinations and investigations. The organ injury scale determines the severity of the trauma. Nonetheless, there are conflicting recommendations for the best strategy in severe cases. Overall, conservative management of induced severe traumatic pancreatitis is adequate. Modern imaging modalities such as ultrasound scanning and computed tomography scanning can detect injuries in fewer than 60% of patients. However, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) have diagnostic accuracies approaching 90%-100%. Thus, management options include ERCP and stent placement or distal pancreatectomy in cases of complete gland transection and wide drainage only for damage control surgery, which can prevent mortality but increases the risk of morbidity. In the majority of cases, surgical intervention is not required and should be reserved for only severe grade III to grade V injuries.

Purpose/aim: To examine with immunohistochemical assay MTA1 protein expression levels in pancreatic cancer tissues defining its prognostic value.The specimens derived from 51 patients who underwent surgery. The levels of MTA1 protein were compared with the age of the patients, their survival, and prognosis. Also, we studied clinical and histopathological factors such as the degree of tumor differentiation and its stage in correlation with MTA1 protein levels. In parallel, there was correlation between the expression of the ΜΤΑ1 protein and the aforementioned factors regarding survival rate. Furthermore, we independently correlated the patient's survival in relation to whether they had undergone adjuvant chemotherapy or not.It has been found to be low, moderate, or high expression of MTA1 levels in 48 out of 51 cancer tissues. Specifically, 49.0% of patients had low expression, 33.3% moderate, and 11.8% high expression of MTA1. Regarding the expression of MTA1 protein in correlation with various clinical and histopathological factors, a statistically significant correlation was observed with the degree of differentiation (p = 0.0068) and with the stage of the disease (p = 0.0173), but not with survival (p = 0.0740) or the age of them (p = 0.1547). Finally, it was found that overexpression of the MTA1protein is a prognostic factor for shorter survival in patients with pancreatic cancer (average 4.67 ± 0.95 months).MTA 1 protein may constitute an important prognostic marker in pancreatic cancer and could improve prognosis and treatment.

Background:Improvement of the management of pancreatic cancer requires a better understanding of the genetic and molecular changes responsible for the development of the disease. The family of p21-activated kinases (PAKs) and especially PAK1 appears to mediate many cellular processes that contribute to the development and progression of pancreatic cancer, but the clinical relevance of PAK1 expression with the disease still remains unclear. Aim of the study was to assess the clinical value and the potential prognostic significance of PAK1 in pancreatic adenocarcinoma.Methods:We investigated the relationship between the PAK1 expression and the clinical and histopathologic characteristics of pancreatic cancer patients and the potential significance of PAK1 on survival. We examined tissue samples from 51 patients operated for pancreatic cancer. PAK1 expression was investigated with immunohistochemistry and correlated to clinicopathological parameters.Results:PAK1 was detected in all tumor samples and high expression was found in most patients. High PAK1 expression was also associated with younger age and well-differentiated tumors, but no association was found between PAK1 expression and Tumor-Node-Metastasis stage as well as deceased or alive status on follow-up. Moderate to high PAK1 expression favored higher 6-month and 1-year survival and low PAK1 expression 2-year survival but without statistical significance.ConclusionsOur results indicate that PAK1 could potentially be used as a prognostic marker in pancreatic cancer. Further studies could clarify whether utilization of PAK1 in therapeutic protocols for the treatment of pancreatic cancer will render them more effective.

The aim of this study was to evaluate the sensitivity and specificity of aortic arch calcification for detection of severe coronary atherosclerosis in patients suffering from coronary artery disease (CAD), with or without type 2 diabetes.This study included 107 type 2 diabetic patients (68 men) with a mean age of 62.4 +/- 10.7 years and a mean diabetes duration of 14.2 +/- 5.9 years and 104 patients (63 men) with a mean age of 64.5 +/- 9.3 years who did not have diabetes. All patients had CAD, documented by coronary arteriography. Severe CAD was defined as atherosclerosis of the left main branch or atherosclerosis of three coronary arteries or atherosclerosis of the proximal part of the left anterior descending artery. Aortic arch calcification was assessed by means of posteroanterior chest X-rays, studied by a radiologist kept blind to the result of coronary arteriography.In type 2 diabetic patients, diagnosis of aortic arch calcification had 65.6% sensitivity and 86.9% specificity for detection of severe CAD. In patients without diabetes, diagnosis of aortic arch calcification had 47.7% sensitivity and 96.7% specificity for detection of severe CAD.Aortic arch calcification has a high specificity for detection of severe coronary atherosclerosis in patients with CAD. Sensitivity is higher in patients with type 2 diabetes, while specificity is slightly higher in non-diabetic patients.

To evaluate mean platelet volume (MPV) in type 2 diabetic versus non-diabetic patients, as well as to investigate the associations between MPV and diabetic complications.This study included 416 patients divided into two groups. Group A comprised 265 type 2 diabetic patients (131 men) with a mean age of 67.4 +/- 9.5 years and a mean diabetes duration of 14.5 +/- 5.7 years. Group B comprised 151 non-diabetic patients (74 men) with a mean age of 68.6 +/- 9.1 years. MPV (blood samples anticoagulated with sodium citrate) was measured in two blood cell counters (Sysmex SF 3000 and Cell-Dyn 3700).MPV was significantly higher (P = 0.01) in group A (14.2 +/- 2.2 fl) than in group B (7.1 +/- 1.2 fl). In group A MPV was significantly higher (P = 0.043) in patients with retinopathy (15.8 +/- 1.3 fl) than in patients without retinopathy (10.9 +/- 1.1 fl) and also significantly higher (P = 0.044) in patients with microalbuminuria (15.6 +/- 1.2 fl) than in patients without microalbuminuria (10.1 +/- 1.2 fl). No association, however, was found in group A between MPV and age, gender, duration of diabetes, insulin dependency, BMI, HbA1c, coronary artery disease or dyslipidaemia.MPV is higher in type 2 diabetic patients than in non-diabetic patients. Among type 2 diabetic patients MPV is higher in those who have microvascular complications (retinopathy or microalbuminuria).

Lateral cervical cysts containing squamous cell carcinoma is a diagnostic and therapeutic challenge for the clinician since they usually represent a cystic metastasis from an occult carcinoma. Various imaging modalities or even blind biopsies will help identify the primary tumour. If the primary tumour is identified, an appropriate treatment decision can be made that incorporates both the primary tumour and the cervical node. If the primary remains unidentified, the neck is treated with a modified or radical neck dissection, depending on the extent of metastatic disease, and radiation therapy is administered to Waldeyer's ring and both necks. We present in this paper, a case with a large cervical cyst where histology showed the presence of a poorly differentiated squamous cell carcinoma in the wall of the cyst. A diagnostic evaluation of the patient was negative. Blind biopsies of the right tonsil revealed occult squamous cell carcinoma. The patient was treated by combined chemo/radiotherapy and she is doing well nine months following excision of the mass. The relevant literature is briefly reviewed.

Background: The indications and benefits of laparoscopic cholecystectomy (LC) in patients with liver cirrhosis and symptomatic cholelithiasis have not been satisfactorily documented. The aim of this study was to investigate its efficacy and safety in such patients. Methods: Medical records of 38 patients with liver cirrhosis (stages Child-Pugh A and B) who underwent LC were retrospectively reviewed. Demographic characteristics and other parameters including initial presentation, conversion rate, complication rate, mortality, and duration of hospital stay were investigated and compared with noncirrhotic patients' parameters in our database. Results: Cirrhotic patients who underwent LC were older than noncirrhotic patients (P=0.021). Both the conversion rate (15.78%) and the duration of hospital stay were increased in the cirrhotic group, but without significant differences. Major complications occurred more often in the cirrhotic group (P=0.027), increasing morbidity; however, the mortality was zero. Conclusions: LC can be safely performed in Child-Pugh A and B cirrhotic patients with symptomatic gallstone disease, with acceptable complication and conversion rates. The increased risk for a major complication, however, demands more attention than usual.

The aim of this study was to investigate the potential role of ankle-brachial index (ABI) as a marker of microvascular disease in patients with type 2 diabetes mellitus.This study included 126 type 2 diabetic patients (64 male and 62 female) with an age of 66.6+/-5.3 years (mean+/-SD) and diabetes duration of 13.2+/-4.1 years. ABI was measured with a Doppler device. The exclusion criterion was the medial arterial calcification. Patients were also examined for microalbuminuria, retinopathy and peripheral neuropathy.ABI was significantly lower in patients with microalbuminuria than in those without microalbuminuria (0.91+/-0.17 vs 1.05+/-0.13, P=0.004), in patients with retinopathy than in those without retinopathy (0.91+/-0.18 vs 1.06+/-0.1, P=0.005), as well as in patients with neuropathy than in those without neuropathy (0.94+/-0.17 vs 1.06+/-0.11, P=0.001). Sensitivity and specificity of ABI0.9 were 48.8% and 87.9% respectively for microalbuminuria, 39.1% and 93% respectively for retinopathy and 47% and 90.7% respectively for neuropathy. In multiple regression analysis, significant predictor of microalbuminuria was diabetes duration (P=0.0014), significant predictor of retinopathy was diabetes duration (P=0.001), while significant predictors of neuropathy were diabetes duration (P=0.001), male sex (P=0.001) and presence of retinopathy (P=0.047).ABI is significantly lower in patients with than in those without microvascular complications of type 2 diabetes. An ABI0.9 has a low to modest sensitivity, but a high specificity for the diagnosis of these complications. Our results suggest a potential role for ABI as a surrogate marker of microvascular complications in type 2 diabetic patients.

Summary Objective To investigate the potential effect of gliclazide on serum ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) levels in poorly controlled type 2 diabetic patients. Patients and methods The study included 104 patients, randomly divided into two groups. Group A comprised 53 patients (26 men) treated with gliclazide with a mean age of 67.5±9.9 years, a mean diabetes duration of 13.4±5.4 years and a mean HbA 1c of 8.6±1.1%. Group B comprised 51 patients (25 men) treated with glibenclamide with a mean age of 66.4±10.9 years, a mean diabetes duration of 13.2±6.1 years and a mean HbA 1c of 8.4±1.3%. A third group of 30 healthy controls (15 men) with a mean age of 63.3±10.4 years was also included. Serum levels of ICAM-1 and VCAM-1 were measured at the beginning of the study and after six months of treatment. Results Pretreatment serum ICAM-1 and VCAM-1 levels did not differ between groups A and B, while they were significantly higher (P=0.0001) than in healthy controls. No significant difference in HbA 1c , body mass index, blood pressure control and lipid profile between the two groups was observed after the sixth month of treatment. In group A, serum ICAM-1 levels after six months of treatment were significantly reduced from 623.12±61.17 ng/ml to 370.14±49.92 ng/ml (P=0,01), while no reduction was found in VCAM-1 levels. In group B, no reduction was found in serum ICAM-1 and VCAM-1 levels after the end of the study. Conclusions Our results suggest that gliclazide treatment reduces serum ICAM-1 levels in poorly controlled type 2 diabetic patients. This reduction is independent of the hypoglycaemic action of gliclazide.

Objective An association between type 2 diabetes mellitus and inflammation has been described in several studies. The aim of this study was to search for the presence of low-grade inflammation in a special group of insulin-treated patients with type 2 diabetes, and to investigate a possible correlation between inflammation and obesity, glucose homeostasis and insulin requirement (IU insulin/kg body weight, BW). Methods We studied 85 subjects with type 2 diabetes that were receiving insulin treatment (group A) and 32 receiving sulfonylurea treatment (group B), and 57 subjects without diabetes (group C). Interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and the soluble TNF-α receptors sTNFR-60 and sTNFR-80 were measured in serum samples taken from all patients. Results The mean serum cytokine levels in group A vs. group B were: IL-6, 8.54 ± 11 vs. 2.71 ± 1.9 pg/ml ( p = 0.000); TNF-α, 14.33 ± 24 vs. 5.12 ± 15 pg/ml ( p = 0.016); sTNFR60, 3.9 ± 2.8 vs. 2.36 ± 1.4 ng/ml ( p = 0.000); and sTNFR80, 11.9 ± 7 vs. 9.4 ± 6 ng/ml ( p = 0.080). The mean serum cytokine levels in group A vs. group C were: IL-6, 8.54 ± 11 vs. 4.74 ± 7 pg/ml ( p = 0.017); TNF-α, 14.33 ± 24 vs. 5.94 ± 3.4 pg/ml ( p = 0.003); sTNFR60, 3.9 ± 2.8 vs. 2.54 ± 1.4 ng/ml ( p = 0.000); and sTNFR80, 11.9 ± 7 vs. 10.85 ± 8 ng/ml ( p = 0.470). A positive association between waist circumference and IL-6 ( r = 0.165, p = 0.030) and sTNFR-60 ( r = 0.276, p = 0.000) was detected. A significant correlation coefficient was observed between haemoglobin A1c (HbA1c) and both IL-6 ( r = 0.278, p = 0.000) and sTNFR-60 ( r = 0.293, p = 0.000), when the groups were studied as one. No correlation between inflammation and units of insulin/kg BW was found. In conclusion, low-grade chronic inflammation, as estimated by the relative levels of inflammatory cytokines, was present in patients with type 2 diabetes that were receiving insulin treatment, with significantly higher cytokine levels recorded compared to sulfonylurea-treated patients. In addition, an association between inflammation and both obesity and glucose homeostasis was detected.

To investigate the correlation between liver echogenicity and serum C-peptide levels in type 2 diabetic patients treated with oral hypoglycaemic agents.The study included 231 type 2 diabetic patients (114 men) with a mean age of 64.3 +/- 6.9 years and a mean diabetes duration of 8.5 +/- 3.2 years. Liver echogenicity was graded by ultrasound examination as follows: Grade 0 (normal liver texture), grade 1 (slight increase of liver echogenicity), grade 2 (moderate increase of liver echogenicity with impaired visualization of intrahepatic vessels and right hemi-diaphragm), grade 3 (marked increase of liver echogenicity with very poor visualization or non-visualization of intrahepatic vessels and right hemi-diaphragm). Serum C-peptide was measured both in fasting state (Fasting C-peptide, FCP) and after glucagon administration (Glucagon-stimulated C-peptide, GCP).FCP (median; interquartile range) showed a significant difference (p=0.041) between patients with grade 0 (1.9 ng/dl; 1.1-2.7 ng/dl),grade 1 (2.7 ng/dl; 1.9-3.7 ng/dl), grade 2 (4.1 ng/dl; 2.6-5.1 ng/dl) and grade 3 (6.2 ng/dl; 4.6-7.5 ng/dl) liver echogenicity. GCP (median; interquartile range) also differed significantly (p=0.04) between patients with grade 0 (2.6 ng/dl; 1.8-3.3 ng/dl), grade 1 (4.3 ng/dl; 3.3-5 ng/dl), grade 2 (5.8 ng/dl; 4.6-6.9 ng/dl) and grade 3 (8.3 ng/dl; 6.6-9.5 ng/dl) liver echogenicity. In multiple regression analysis, both FCP and GCP showed significant (p0.05) positive correlations with waist circumference, triglycerides, WHR and liver echogenicity.In type 2 diabetic patients treated with oral hypoglycaemic agents, liver echogenicity shows a significant positive correlation with serum C-peptide levels, both in fasting state and after glucagon administration.

The aim of the present study was to evaluate the gravity of aortic arch calcification in adult Greek patients.A total of 1027 patients (498 men, 529 women) were included. Aortic arch calcification was assessed by means of posteroanterior chest X-rays. These were studied by two radiologists blinded to the patients' medical records. Calcification was graded as follows: grade 0 (no visible calcification), grade 1 (small spots of calcification or single thin calcification of the aortic knob), grade 2 (one or more areas of thick calcification), grade 3 (circular calcification of the aortic knob). All patients were clinically and electrocardiographically examined for coronary artery disease. The other parameters included in the analysis were age, sex, smoking, body-mass index, hypertension, dyslipidemia, diabetes mellitus and history of stroke.Calcification gravity was grade 0 in 421 patients (41%), grade 1 in 308 patients (30%), grade 2 in 216 patients (21%) and grade 3 in 82 patients (8%). In simple regression analysis the gravity of aortic arch calcification was positively correlated with age (p=0.01), diabetes mellitus (p=0.014), hypertension (p=0.022), dyslipidemia (p=0.038) and coronary artery disease (p=0.041). In multiple regression analysis it was associated with age (p=0.019), diabetes mellitus (p=0.02) and hypertension (p=0.03).Gravity of aortic arch calcification in adult Greek patients may easily be assessed on routine chest X-rays and is positively correlated with coronary artery disease, as well as important cardiovascular risk factors (age, diabetes mellitus, hypertension and dyslipidemia).

Amifostine (AMF) promotes in vitro growth and survival of hematopoietic progenitors. In this study we evaluated the efficacy of AMF in the treatment of anemia in patients with low-risk myelodysplastic syndromes (MDS) and the possible predicting value for response to AMF therapy of two types of in vitro clonogenic assays. Two different doses of AMF, 300 mg/m(2) (group A, 11 patients) or 400 mg/m(2) (group B, 16 patients), were studied. AMF was given three times weekly for 3 weeks, i.v., followed by 2 weeks off therapy. Patients were evaluated after two cycles of treatment. Partially or nonresponding patients of group A received 400 mg/m(2) AMF and were reevaluated. An increase of hemoglobin (Hb) values of more than 2 g/dl and a 100% decrease in transfusion requirements for at least 6 weeks were defined as a complete response (CR) while an increase of Hb values of 1-2 g/dl or a 50% decrease in transfusion requirements was considered as a partial response (PR). In group A, two out of 11 (18.1%) patients achieved a CR with the initial dose and one of the nine that received 400 mg/m(2) AMF achieved a PR. In group B, three out of 16 (18.7%) patients achieved a PR; the overall response rate in both groups was 22.2%. In group A, bone marrow progenitor assay was performed pre- and post-amifostine treatment. Erythroid burst-forming units (BFU-E) were increased in six out of 11 (54.5%) patients, and this increase preceded the rise in Hb levels in three of them. In group B, a clonogenic assay was performed in 11 out of 16 patients before AMF treatment. In vitro results after pretreatment with 500 M amifostine confirmed the response of two MDS patients that achieved a PR. No response in vitro was observed in all eight nonresponding patients and in one PR patient. The lack of response in the clonogenic assays predicted for nonresponse to treatment with a predictive power of 91.8%. We conclude that 300 mg/m(2) is an adequate initial treatment for low-risk MDS patients and both clonogenic assays have a strong predicting value for response to treatment.