Does the efficacy of regorafenib differ in chemotherapy refractory metastatic colorectal cancer patients who had mucinous pathology compared to those who had non-mucinous pathology?

Purpose: To investigate the importance of mucinous histopathology on the assessment of tumor response in patients with metastatic colorectal cancer (mCRC) receiving regorafenib. Materials and method: All patients diagnosed with histologically confirmed mCRC in 2 oncology centers between 2013 and 2018 were retrospectively analyzed. Among 678 patients diagnosed with mCRC, 103 patients were treated with regorafenib. Ninety-four of these patients who had used at least 2 cycles of regorafenib and evaluable for treatment response were included in the analysis. Histopathologically, 18 patients with mucinous adenocarcinoma and 76 patients with nonmucinous adenocarcinoma were compared in terms of response rate and survival durations. Results: Median follow-up duration of 6 months, median age of the patients was 61 (34-77) years. While 19.1% of the patients had mucinous histology, 80.9% had nonmucinous histology. The overall response rate was significantly lower in the mucinous subgroup than the nonmucinous subgroup (5.6% vs 43.4%, respectively, P = 0.003). Similarly, both progression-free survival (3.0 vs 4.0 months, respectively, P = 0.011) and overall survival duration were shorter in the mucinous subgroup (3.0 vs 7.0 months, P = 0.016, respectively) compared with the nonmucinous subgroup. Conclusion: The histological subgroup may predict tumor response in mCRC patients receiving regorafenib. Its efficacy on nonmucinous histology had significantly more favorable than mucinous subtype.     

Percutaneous transluminal angioplasty for total coronary occlusion: The effect of restenosis on left ventricular function

The study was undertaken to evaluate the effect of restenosis on global and regional left ventricular function after percutaneous transluminal coronary angioplasty (PTCA) for total coronary occlusion. Thirty-one consecutive patients with total coronary occlusion treated successfully with PTCA and had follow-up angiography at 3–6 months formed the study group. Nineteen patients had restenosis (16 males, mean age 48±10 years) and 12 had no restenosis (11 males, mean age 53±10 years). In the LAD group there were increases in anterobasal (35.9±8.5% vs 43.1±5.7%, p=0.05) and apical (24.1±6.8% vs 31.7±2.9%, p=0.03) segment motion scores in patients without restenosis after PTCA. Global ejection fractions (63.1±14.5% vs 68.9±12.4%, p=0.09) and anterolateral (28.7±11.3% vs 39.7±10.2%, p=0.09) segment scores increased, but did not reach statistical significance. In the LAD restenosis group anterobasal (41.5±14.3% vs 34.3±12.6%, p=0.001), apical (21.1±15.0% vs 17.8±10.9%, p=0.05) and anterolateral (32.7±19.6% vs 26.6±13.8%, p=0.03) segment motion scores decreased but the decrease in the global ejection fraction (60.3±18.5% vs 58.6±17.4, p=0.38) was not significant. In the RCA+LCX group there was a significant increases in global ejection fraction (69.0±7.5% vs 74.2±7.6%, p=0.03) and posterobasal (23.8±7.8 vs 34.4±8.0, p=0.04) segment motion scores in patients without restenosis. The wall motion scores were unchanged in patients with restenosis in the RCA+LCX group. It was concluded that restenosis after a successful PTCA for total coronary occlusion may deteriorate segmental wall motion and treatment modalities with increased patency rates should be used for total coronary occlusions.     

Coronary Flow Velocity Reserve and Carotid Intima Media Thickness in Patients with Autosomal Dominant Polycystic Kidney Disease: From Impaired Tubules to Impaired Carotid and Coronary Arteries

Background and objectives: Cardiovascular problems are a major cause of morbidity and mortality in patients with autosomal dominant polycystic kidney disease. Endothelial dysfunction, an early and reversible feature in the pathogenesis of atherosclerosis, is associated with increased vascular smooth muscle tone, arterial stiffening, and increased intima-media thickness. Coronary flow velocity reserve is a noninvasive test showing endothelial function of epicardial coronary arteries and coronary microcirculatory function. The aim of the study was to investigate the carotid intima-media thickness and coronary flow velocity reserve in patients with autosomal dominant polycystic kidney disease.Design, setting, participants, & measurements: Thirty normotensive patients with autosomal dominant polycystic kidney disease (10 male, 20 female) with well-preserved renal function and 30 healthy subjects (12 male, 18 female) were included in the study. Coronary flow velocity reserve was measured at baseline and after dipyridamole infusion by echocardiography. Coronary flow velocity reserve was calculated as the ratio of hyperemic to baseline diastolic peak velocities.Results: Carotid intima-media thickness was significantly higher in patients than in control subjects (0.80 ± 0.29 versus 0.54 ± 0.14 mm, respectively; P < 0.001). Moreover, coronary flow velocity reserve was significantly lower in patients than in control subjects (1.84 ± 0.39 versus 2.65 ± 0.68, respectively; P < 0.001).Conclusions: Normotensive patients with autosomal dominant polycystic kidney disease with well-preserved renal function have significantly increased carotid intima-media thickness and significantly decreased coronary flow velocity reserve compared with healthy subjects. These findings suggest that atherosclerosis starts at an early stage in the course of their disease in patients with autosomal dominant polycystic kidney disease.Autosomal-dominant polycystic kidney disease (ADPKD) is a hereditary renal disease that occurs in 1 of 400 to 1000 individuals (1,2). Cardiovascular problems are a major cause of morbidity and mortality in patients with ADPKD (3). Hypertension, a common finding in patients with ADPKD, often occurs before the onset of renal insufficiency and is associated with faster progression to ESRD and increased cardiovascular mortality (4,5). Activation of the renin-angiotensin-aldosterone system (RAAS) caused by cyst expansion and local ischemia has been proposed to play an important role in the development of hypertension in ADPKD (6). The RAAS is stimulated at an early stage of ADPKD, even before the onset of hypertension and clinical findings (7,8). Likewise, increased left ventricular mass indexes and biventricular diastolic dysfunction have been reported before the development of hypertension in patients with ADPKD with well-preserved renal function (9–16). Moreover, endothelial dysfunction (ED), which is an early manifestation of vascular injury, occurs in both normotensive and hypertensive patients with ADPKD, before the onset of renal failure (17).Coronary flow velocity reserve (CFVR) represents the capacity of the coronary circulation to dilate after an increase in myocardial metabolic demands (18). Although CFVR was measured invasively until recently, it can be evaluated noninvasively by using Doppler and vasodilator stress, such as dipyridamole or adenosine (19). By using this method, impairment of CFVR can be assessed before development of angiographically detectable stenosis in epicardial coronary arteries. The aim of this study was to investigate the CFVR in patients with ADPKD, with well-preserved renal function.     

Status of the disabled in Turkey. A theoretical approach to the perception of the disabled in Turkey

Purpose.?Although the ratio of the disabled population is higher in Turkish society than the average value in the world, studies in this issue have been limited to statistical surveys and no firm theoretical bases on investigation of the perception of disability in the perspective of Turkish society have been established. Reliable theses on the form and manners of Turkish society's responses to disability have not been put forward, yet. Therefore, existence of the sociology of disability in Turkey, which is a relatively new field also for western societies, cannot be stated. The purpose of the study is to evaluate the perception of disability and responses to the disabled in Turkish society in the light of the findings of research, which was conducted in 2002, into the disabled in Turkey.

Method.?Theoretical assessment is carried out from the perspective of two viewpoints: The structural-functional and interactional theses.

Conclusion.?It is concluded that the interactional thesis sets a better ground for explanation of the circumstances of the disabled and response of the society to them in Turkey.     

No Strong Association Between HER-2/neu Protein Overexpression and Gene Amplification in High-grade Invasive Urothelial Carcinomas

The generation of urothelial carcinoma is caused by the accumulation of various molecular changes, as in most malignancies. There are conflicting data about the status of HER-2/neu oncogene in urothelial carcinomas. The aim of this study was to determine the status of HER-2/neu oncogene in high-grade invasive urothelial carcinoma of urinary bladder both in protein and DNA level. We evaluated HER-2/neu protein overexpression by immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH) and real-time quantitative PCR in paraffin-embedded samples of high-grade invasive urothelial carcinoma obtained from 36 patients. Polysomy 17 was also assessed by FISH. Immunohistochemically, HER-2/neu protein overexpression was observed in 22 (61.1%) tumors (ten tumors with score 3+ and 12 with score 2+). Fourteen of 36 tumors (38.9%) were evaluated as negative (score 0 or 1+). Complete concordance between FISH and the PCR was seen in all of the samples scored as 0 and 1+ by IHC. HER-2/neu gene amplification was observed in three of 27 (11.1%) tumors by FISH (nine samples were non-informative) and in eight of 36 (22.2%) tumors by the PCR. The complete concordance between HER2-2/neu protein overexpression and gene amplification was seen only in three of 27 tumors. Polysomy 17 was seen in nine tumors (33.3%). The results indicated that, in contrast to breast cancer, there was no strong association between HER-2/neu overexpression and gene amplification in invasive urothelial carcinomas, and polysomy 17 was higher in tumors showing HER-2/neu overexpression.     

Continuous peritoneal lavage in severe post abortion peritonitis

The authors report on 7 cases of severe postabortum peritonitis treated with hysterectomy and postoperative perinoteal lavage. The technique consisted of placing the tubes subhepatically, parietocolic on the right, Douglas cul-de-sac on the right, supramesocolic on the midline, in the splenic recess, parietocolic on the left, and Douglas cul-de-sac on the left. Each of the left. Each of the 2-way tubes was irrigated clockwise every hour with a 0.9% sodium chloride solution, at room temperature, in a volume of 24 liters/24 hours at a rate of 1 liter/hour. The lavage lasted for 24-72 hours. Improvement of the toxicoseptic phenomena was obtained within this interval, with rapid resumption of diuresis and natural nutrition. Peritoneal lavage is an efficient procedure, completing the surgical intervention as demonstrated by survival of all patients, with a small number of complications and a brief period of postoperative hospitalization. (author's)     

A laboratory training model for interhemispheric-transcallosal approach to the lateral ventricle

Laboratory training models are essential for developing and refining surgical skills before clinical application of microneurosurgery. Our aim is to train residents of neurosurgery to be familiar with a basic microneurosurgical technique in access to the lateral ventricle via a transcallosal approach. The training material consists of a 2-year-old fresh cadaveric cow cranium. A four-step approach was designed to simulate microneurosurgical dissection along the falx to visualize cingulated gyri, callosomarginal and pericallosal arteries in order to perform callosotomy and access to the lateral ventricle, and finally to the foramen of Monroe. We conclude that the model perfectly simulates standard microneurosurgical steps in interhemispheric-transcallosal approach to the lateral ventricle and to the area of the foramen of Monroe.     

A case of isolated Nocardia asteroides brain abscess in a kidney transplant recipient

Because of the immunosuppressive drugs used after organ transplantation, there is an increased rate of certain infections and malignancies. Nocardia brain abscess is a rare condition, seen most commonly among immunocompromised patients. It may be confused with intracranial tumors and requires long-term combined antibiotic therapy after drainage. CASE REPORT: A patient who underwent renal transplantation because of end-stage renal disease of unknown origin was shown to have a nocardial brain abscess while she was taking immunosuppressive drugs. The patient was given combined antibiotics and the abscess drained surgically. After 2 months, antibiotic therapy was continued with one drug. Neither a complication nor clinical or radiological sequelae occurred in this patient. CONCLUSIONS: When central nervous system findings are observed in renal transplant recipients, nocardial brain abscess must be considered in the differential diagnosis. Recommended treatment duration is 6 to 12 months with frequent imaging.     

Expression of cyclin D1 in normal,hyperplastic and neoplastic endometrium and its correlation with Ki-67 and clinicopathological variables

Methods We investigated cyclin D1 expression in proliferative endometrium, endometrial hyperplasia and endometrioid adenocarcinoma, and examined the correlation of cyclin D1 expression with Ki67 as a cell proliferation associated marker. Immunohistochemical expression of cyclin D1 and Ki67 were studied in 30 cases with endometrial carcinoma, 14 cases with atypical hyperplasia, 15 cases with simple hyperplasia and 30 cases with proliferative endometrium.Results One out of 30 patients (3.3%) with proliferative endometrium, 1 out of 14 patients (7.1%) with atypical hyperplasia, and 8 out of 30 patients (26.6%) with endometrial carcinoma were found to have immunoreactivity to cyclin D1. All cases of simple hyperplasia had negative staining for cyclin D1. A positive immunoreaction for Ki67 was obtained in all cases. Statistically significant difference was found in cyclin D1 immunoreactivity between both proliferative endometrium and adenocarcinoma, and simple hyperplasia and adenocarcinoma (p<0.05). In patients with adenocarcinoma, cyclin D1 immunoreactive cases had higher mean Ki67 values compared with the non-immunoreactive ones (p<0.05). Ki67 and cyclin D1 immunoreactivity had no impact on overall survival. Univariate analysis revealed a significant relationship between survival and grade and stage (p<0.01). Cyclin D1 expression was not correlated with age, depth of myometrial invasion, lymphovascular space involvement, grade, lymph node metastasis and stage.Conclusion Cyclin D1 expression in endometrial carcinoma is higher than proliferative endometrium and simple hyperplasia. These findings support that cyclin D1 may play a role in endometrial carcinogenesis.     

The chick embryo chorioallantoic membrane as a model system for the study of tumor angiogenesis, invasion and development of anti-angiogenic agents

Angiogenesis, the formation of new blood vessels, is essential for tumor growth, progression and metastasis. The development of agents that target tumor vasculature is ultimately dependent on the availability of appropriate preclinical screening assays. The chorioallantoic membrane (CAM) assay is well established and widely used as a model to examine angiogenesis, and anti-angiogenesis. This review 1) summarizes the currently used angiogenesis assays and the importance of CAM model among them; 2) summarizes the current knowledge about the development and structure of the CAM's capillary bed; 3) reports findings regarding the role played by molecular signaling pathways in angiogenesis process; 4) discusses the use, advantages and limitations of the CAM as a model for studying tumor angiogenesis and invasiveness, as well as development of angiogenic and/or anti-angiogenic agents; 5) discusses the importance of standardization of the major methodologies for all aspects of the use of the CAM in angiogenesis-related studies; 6) and finally, summarizes major findings regarding the agents developed by the use of CAM model in the study of tumor angiogenesis, invasion and development of anti-angiogenic agents.