Percutaneous Cryoablation for the Treatment of Medically Inoperable Stage I Non-Small Cell Lung Cancer

BACKGROUND: To evaluate the midterm results of percutaneous cryoablation for medically inoperable stage I non-small cell lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Between January 2004 and June 2010, 160 patients underwent computer tomography guided percutaneous cryoablation for lung tumors at our institution. Of these patients, histologically proven stage I lung cancer patients with more than one year of follow-up, were retrospectively reviewed. All of these patients were considered to be medically inoperable with Charlson comorbidity index of 3 or greater. Follow-up was based primarily on computed tomography. There were 22 patients with 34 tumors who underwent 25 sessions of cryoablation treatment. Complications were pneumothoraces in 7 treatments (28%, chest tube required in one treatment), and pleural effusions in 8 treatments (31%). The observation period ranged from 12-68 months, average 29±19 months, median 23 months. Local tumor progression was observed in one tumor (3%). Mean local tumor progression-free interval was 69±2 months. One patient died of lung cancer progression at 68 months. Two patients died of acute exacerbations of idiopathic pulmonary fibrosis which were not considered to be directly associated with cryoablation, at 12 and 18 months, respectively. The overall 2- and 3-year survivals were 88% and 88%, respectively. Mean overall survival was 62±4 months. Median overall survival was 68 months. The disease-free 2- and 3-year survivals were 78% and 67%, respectively. Mean disease-free survival was 46±6 months. Pulmonary function tests were done in 16 patients (18 treatments) before and after cryoablation. Percentage of predicted vital capacity, and percentage of predicted forced expiratory volume in 1 second, did not differ significantly before and after cryoablation (93±23 versus 90±21, and 70±11 versus 70±12, respectively). CONCLUSIONS/SIGNIFICANCE: Although further accumulation of data is necessary regarding efficacy, cryoablation may be a feasible option in medically inoperable stage I lung cancer patients

HP1 Recruits Activity-Dependent Neuroprotective Protein to H3K9me3 Marked Pericentromeric Heterochromatin for Silencing of Major Satellite Repeats

H3 lysine 9 trimethylation (H3K9me3) is a histone posttranslational modification (PTM) that has emerged as hallmark of pericentromeric heterochromatin. This constitutive chromatin domain is composed of repetitive DNA elements, whose transcription is differentially regulated. Mammalian cells contain three HP1 proteins, HP1α, HP1β and HP1γ These have been shown to bind to H3K9me3 and are thought to mediate the effects of this histone PTM. However, the mechanisms of HP1 chromatin regulation and the exact functional role at pericentromeric heterochromatin are still unclear. Here, we identify activity-dependent neuroprotective protein (ADNP) as an H3K9me3 associated factor. We show that ADNP does not bind H3K9me3 directly, but that interaction is mediated by all three HP1 isoforms in vitro. However, in cells ADNP localization to areas of pericentromeric heterochromatin is only dependent on HP1α and HP1β. Besides a PGVLL sequence patch we uncovered an ARKS motif within the ADNP homeodomain involved in HP1 dependent H3K9me3 association and localization to pericentromeric heterochromatin. While knockdown of ADNP had no effect on HP1 distribution and heterochromatic histone and DNA modifications, we found ADNP silencing major satellite repeats. Our results identify a novel factor in the translation of H3K9me3 at pericentromeric heterochromatin that regulates transcription

Radiofrequency ablation of lung tumours

Pulmonary radiofrequency ablation (RFA) has become an increasingly adopted treatment option for primary and metastatic lung tumours. It is mainly performed in patients with unresectable or medically inoperable lung neoplasms. The immediate technical success rate is over 95%, with a low periprocedural mortality rate and 8–12% major complication rate. Pneumothorax represents the most frequent complication, but requires a chest tube drain in less than 10% of cases. Sustained complete tumour response has been reported in 85–90% of target lesions. Lesion size represents the most important risk factor for local recurrence. Survival data are still scarce, but initial results are very promising. In patients with stage I non-small-cell lung cancer, 1- and 2-year survival rates are within the ranges of 78–95% and 57–84%, respectively, with corresponding cancer-specific survival rates of 92% and 73%. In selected cases, the combination of RFA and radiotherapy could improve these results. In patients with colorectal lung metastasis, initial studies have reported survival data that compare favourably with the results of metastasectomy, with up to a 45% 5-year survival rate. Further studies are needed to understand the potential role of RFA as a palliative treatment in more advanced disease and the possible combination of RFA with other treatment options

Research of lipid exchange diffusion of medium-age patients with chronic pancreatitis with diabetes mellitus

Chronic pancreatitis refers to diseases in which both excretoric and incretoric sections of the pancreas are damaged, which in later stages leads to the development of concomitant diabetes mellitus (DM), which are not sufficiently studied in this pathology. This article presents a study of lipid metabolism in patients with chronic middle-aged pancreatitis with concomitant diabetes. It has been proved that the presence of DM significantly complicated the clinical course of chronic pancreatitis (CP) in the ballistic system M - ANNHEIM, which correlated with changes in the program (r=0,67; p<0,001), the criteria for ultrasound (r=0,54; p<0,01), the level of glycosylated hemoglobin (r=0,66; p<0,001). In patients with CP with concomitant diabetes the severity of the disease was more pronounced than in patients with CP: the average severity (C) predominated in 69,56% of patients in group 2, with 26,32% of the 1st, and cases of severe and severe severity. A direct reliable correlation between all the atherogenic indicators of the lipidogram and the age of the patients and the duration of the course of the CP were found, which makes it possible to assume the age and duration of the CP by factors of the deepening of the dyslipidemia. In patients with CP in combination with DM and dyslipidemia, the lower index of fecal α-elastase level was established in comparison with the CP group: (157,15 ± 7,36) versus (112,86 ± 2,98), respectively (p<0,001) which proved a deepening of dyslipidemia in the development of excretory insufficiency of the pancreas

ДИСЛІЛІДЕМІЯ ТА ЧИННИКИ ЇЇ ПОГЛИБЛЕННЯ ПРИ КОМОРБІДНОСТІ ХРОНІЧНОГО ПАНКРЕАТИТУ І ЦУКРОВОГО ДІАБЕТУ

A chronic pancreatitis (CP) behaves to the diseases at that both secretory and incretory departments of pancreas are damaged, that on the late stages results in development of concomitant diabetes mellitus (DM), that at this pathology is studied not enough. The study of lipid exchange for patients with chronic pancreatitis is presented in this article with concomitant DM. It is well-proven, the presence of DM for certain complicated clinical motion of CP on the ball system M-ANNHEIM, that correlated with the changes of analysis of coprogram (r=0,67; р&lt;0,001), criteria of ultrasonic research (r=0,54; р&lt;0,01), level of haemoglobin A1C (r=0,66; р&lt;0,001).For the patients of CP with concomitant DM the degree of weight of disease was more expressed, than at CP without incretory insufficiency: the middle degree of weight prevailed for the 69,56% patients of 2-th group against 26,32% 1-th, the cases of the expressed and heavy degree of weight appeared. Direct reliable cross-correlation connection is educed between all atherogenic indexes of deepening of violation and age of patients and duration of motion of CP that allows to consider age and duration of CP the factors of deepening of violation of lipid exchange. For the patients of CP in combination with DM and violation of lipid exchange is set for certain more subzero index of level of sullage α-elastase by comparison to a group CP:  (157,15±7,36) against (112,86±2,98) accordingly (p&lt;0,001), that led to deepening of violation of lipid exchange at aggravating exocrine insufficiency of pancreas of CP.Хронический панкреатит относится к заболеваниям, при которых повреждаются как секреторные, так и инкреторные отделы поджелудочной железы, что на поздних стадиях приводит к развитию сопутствующего сахарного диабета (СД), которые при этой патологии изучены недостаточно.     В данной статье представлено изучение липидного обмена у больных хроническим панкреатитом с сопутствующим СД. Доказано, что наличие СД достоверно усложняло клиническое течение хронического панкреатита (ХП) по бальной системе M-ANNHEIM, который коррелировал с изменениями копрограммы (r=0,67; р&lt;0,001), критериями ультразвукового исследования (r=0,54; р&lt;0,01), уровнем гликозилированного гемоглобина (r=0,66; р&lt;0,001). У больных ХП с сопутствующим СД степень тяжести заболевания была более выражена, чем при ХП без инкреторной недостаточности: средняя степень тяжести (С) преобладала у 69,56% пациентов 2-й группы против 26,32% 1-й, появились случаи выраженной и тяжелой степени тяжести. Выявлена прямая достоверная корреляционная связь между всеми атерогенными показателями липидограммы и возрастом больных и длительностью течения ХП, которая позволяет считать возраст и длительность ХП факторами углубления дислипидемии. У больных  ХП в сочетании с СД и дислипидемией установлен достоверно более низкий показатель уровня фекальной α-эластазы в сравнении с группой ХП: (157,15±7,36) против (112,86±2,98) соответственно (p&lt;0,001),  что доказало углубление дислипидемии при прогреccировании ВСН ПЖ.Наявність цукрового діабету (ЦД) достовірно ускладнювала клінічний перебіг хронічного панкреатиту (ХП) за бальною системою M-ANNHEIM, який корелював зі змінами копрограми (r=0,67; р&lt;0,001), критеріями ультразвукового дослідження (r=0,54; р&lt;0,01), рівнем глікозильованого гемоглобіну (r=0,66; р&lt;0,001). У хворих з ХП з супутнім ЦД ступінь тяжкості захворювання був більш вираженим, ніж при ХП без інкреторної недостатності: середній ступінь тяжкості (С) переважав у 69,56% пацієнтів 2-ої групи проти 26,32% 1-ої, з’явились випадки вираженого та важкого ступеня тяжкості. Виявлено прямий достовірний кореляційний зв'язок між усіма атерогенними показниками ліпідограми та віком хворих і тривалістю перебігу ХП, що дозволяє вважати вік і тривалість ХП чинниками поглиблення дисліпідемії. У хворих на ХП у поєднанні з ЦД із дисліпідемією встановлено достовірно нижчий показник рівня фекальної α-еластази порівняно із групою ХП: 157,15±7,36 проти 112,86±2,98 відповідно, (p&lt;0,001), що довело поглиблення дисліпідемії при прогресуванні ЗСН ПЗ

Optimization of the complex therapy of chronic pancreatitis with metabolic syndrome

The most common reasons of chronic pancreatitis are alcohol abuse, biliary tract and liver diseases, stomach and duodenum, hyperlipidemia, which is often associated with metabolic syndrome. The aim: to study the effectiveness of using medicine omega-3 polyunsaturated fatty acids in standard therapy to the correction of lipids and prooxidant-antioxidant disorders in patients with chronic pancreatitis and metabolic syndrome. Materials and methods: The study included 90 patients with chronic pancreatitis with metabolic syndrome. They were divided into two groups: I group (45 patients) received standard treatment; II group (45 patients) along with baseline therapy received medication omega-3 polyunsaturated fatty acids (Omacor) for 2 capsules (1680 mg) for one month. Results: After treatment the lipid blood spectrum and prooxidant-antioxidant status have improved. Conclusions: Adding to the complex therapy of patients with chronic pancreatitis and the metabolic syndrome of the medicine omega-3 polyunsaturated fatty acids helps to improve the lipid and prooxidation-antioxidant status more significantly compared with standard baseline therapy