[The role of plasmapheresis in prevention of complications after thoracoscopic thymectomy in patients with myasthenia combined with thymic hyperplasia]. / Rol' plazmafereza v profilaktike oslozhnenii videotorakoskopicheskoi timektomii u patsientov s miasteniei v sochetanii s giperplaziei vilochkovoi zhelezy.

Surgical indications for thymectomy include thymus tumour of different genesis as well as myasthenia. Minimally invasive methods such as thorascopy and robot-assisted thymectomy have been widely used lately as well as standard surgical methods namely sternotomy and thoracotomy. Regardless the type of access in myasthenia patients specific crisis conditions of respiratory failure can appear in postoperative period that usually requires mechanical ventilation. This study was aimed to estimate the efficacy of pre- and postoperative plasmapheresis in prevention of specific myasthenia-associated complications.

[The program of accelerated rehabilitation after esophagoplasty (fast track surgery) in esophageal cancer surgery].

Esophagectomy with simultaneous plasty in patient with esophageal cancer is still associated with a high incidence of postoperative complications and long-stay patient in the clinic. The purpose of our report is to inform the use of the program of accelerated rehabilitation after esophagectomy in a prospective study of 13 patients during the period from 2010 to 2011 year and the role of the anesthesiologist in its implementation. Methods aimed at the preoperative examination, minimally invasive surgery, thoracic epidural anesthesia/analgesia with local anesthetics as a component of anesthesia and postoperative analgesia, early extubation and mobilization of the patient with the implementation of breathing exercises, early enteral feeding, and the planned short postoperative stay in resuscitation and hospital were used. Postoperative complications were observed in 3 (23/1%) patients: one patient (7/7%) had right-side pneumonia, two patients (15/4%) had right-side pneumothorax requiring emergency re drainage. The average intensive care stay was 2 (1-4) days, postoperative hospital stay--9 (7-12) days. Further monitoring of the patients did not show any long-term complications. The results confirm that it is possible to optimize the healing perioperative process in patients after esophagectomy with simultaneous plasty by using of accelerated rehabilitation program without the risk of increasing the frequency of postoperative complications. it will provide the reduction of length of hospital stay. In view of multifaceted and controversial issue the following researches in this direction are necessary.

[Surgery for cardio-esophageal cancer].

The experience of surgery of 369 patients with cardio-esophageal cancer treated in the Kazan Republic Clinical Oncology Center is presented. The patients are divided into 3 groups respective of the type of adenocarcinoma (classification by J.R. Siewert). Thus, the first group consists of 45 (12.1%) patients, the second--172 (46.6%) and the third--152 (41.3%) patients. Each group is divided into subgroups according to the performed operation: transhiatal esophagoplasty with esophagogastroanastomosis on the neck, transthoracal esophagoplasty (operations by Lewis and Gerlock) with intrapleural esophadogastroanastomosis and gastrectomies with high resection of esophagus. High productivity of the differentiated approach to surgical treatment of cardio-esophageal cancer depending on the type of adenocarcinoma is shown. Such approach allows the surgical treatment to be more radical, to reduce quantity of the early and remote complications and to raise the survival. So, it is revealed that performance of transhiatal and transthoracal esophagoplasty is possible in cases of type I adenocarcinoma. Gastrectomies in cases of type II adenocarcimoma are of poor prognosis.

[SOME ASPECTS OF DIAGNOSIS AND COMPREHENSIVE TREATMENT OF BARRETT'S ESOPHAGUS].

OBJECTIVE: Assess the value of routine endoscopy in the diagnosis of Barrett's esophagus (BE) in patients with gastroesophageal reflux disease (GERD) and to show the feasibility of a comprehensive treatment algorithm that includes antireflux surgery as an essential component. MATERIALS AND METHODS: The study was conducted on a sample of 171 patients with Barrett's esophagus who underwent antireflux surgery. In evaluating the operating characteristics of endoscopy were recruited another 675 patients with GERD without BE. On the diagnostic phase was used endoscopy with double chromoscopy and biopsy followed by histological examination. At the stage of treatment, patients received conservative therapy by PPl after which underwent antireflux surgery and argon-plasma coagulation (in some cases). RESULTS: Endoscopy of the esophagus with a double chromoscopy in identification BE in patients with GERD, has a moderate sensitivity (71.9%, 95% Cl 64.6%-78.5%) and high specificity (100%, 95% Cl 99.5%-100%). A comprehensive treatment approach that includes antireflux surgery as an essential component has allowed to achieve excellent and satisfactory immediate results of treatment in 88.9% of patients (95% Cl 83.2%-93.2%). Excellent and satisfactory long-term results were achieved in 89.5 % of patients (95% Cl 83.9%-93.6 %). CONCLUSION: The results indicate the need for biopsy and histological examination in all patients with GERD, who has no suspicion of BE according to endoscopy, and prove high efficiency of complex treatment algorithm that includes antireflux surgery as an essential component.

[The ruptures of the trachea with the intubation tube in patients with esophagus cancer].

Postintubation tracheal ruptures is a rare but serious complication with high risk for the patient's life. The preliminary diagnosis is usually made after occurrence of subcutaneous emphysema, blood spitting, respiratory insufficiency, pneumothorax and/or pneumomediastinum. The suspected rupture of the trachea should be verified by fiber-optic bronchoscopy. The decision about necessity of surgical or conservative treatment is based on the compilation of clinical, radiologic and endoscopic data. We present 9 cases (7 women and 2 men) of postintubation tracheal ruptures, occurred during the esophageal (6), lung (2) and mammary gland (1) surgery.

[Thymectomy and antibodies to acetylcholine receptors (AChR) in patients with myasthenia gravis in the early postoperative period].

Thymectomy and removal of the hyperplastic thymus have been performed in 21 patients with myasthenia. In 14 patients, thymectomy is performed through thoracoscopic access (TA), while in 7 cases through thoracotomic access (TT). The serum levels of antibodies to acetylcholine receptors (AChR) determined before and after surgery were increased in both groups of patients. Thus, thymectomy, regardless of the degree of clinical improvement in early post operative period, significantly increases the level of anti-AChR antibodies in the serum of patients in the early postoperative period compared to baseline. These changes may reflect the immune response to a stressful situation related to the traumatic surgery. It should be noted that the level of anti-AChR antibodies was significantly higher in a group of TT that may be related with a larger volume of the removed tissue.

Adaptive licensing: taking the next step in the evolution of drug approval.

Traditional drug licensing approaches are based on binary decisions. At the moment of licensing, an experimental therapy is presumptively transformed into a fully vetted, safe, efficacious therapy. By contrast, adaptive licensing (AL) approaches are based on stepwise learning under conditions of acknowledged uncertainty, with iterative phases of data gathering and regulatory evaluation. This approach allows approval to align more closely with patient needs for timely access to new technologies and for data to inform medical decisions. The concept of AL embraces a range of perspectives. Some see AL as an evolutionary step, extending elements that are now in place. Others envision a transformative framework that may require legislative action before implementation. This article summarizes recent AL proposals; discusses how proposals might be translated into practice, with illustrations in different therapeutic areas; and identifies unresolved issues to inform decisions on the design and implementation of AL.

[An integrated approach to diagnosis and treatment of Barrett's esophagus].

Barrett's oesophagus is a condition when the oesophagus adenocarcinoma risk increases. There are different ways of diagnostic and treatment for this disease abroad and our country. We offer a complex method for Barrett's oesophagus treatment. Our method reveals Barrett's oesophagus effectively. We also take antireflux treatment and Barrett's epithelium elimination using miniinvasive surgery with drugs therapy. We have experience of curing 48 patients from Barrett's oesophagus. Considering obtained results our tactic for clinical practice is recommended.

[Endoscopic diagnosis and complex treatment of Barrett's esophagus complicated by hernia of esophageal foramen of the diaphragm].

A protocol is suggested of complex diagnosis and treatment of Barrett's esophagus using sparing endoscopic removal of Barrett's epithelium in combination with surgery and medicinal antireflux therapy. Eighty-three patients were diagnosed and treated for hernia of esophageal foramen of the diaphragm and gastro-esophageal reflux complicated by Barrett's esophagus. Ninety-two percent of patients receiving our four-component treatment were cured; no recurrent esophageal adenocarcinoma was reported during the 56.7 +/- 2.4 month follow-up. Conversely, in patients receiving three-component treatment, efficacy was 56%; esophageal adenocarcinoma was reported in 3 (12%).

[Laparoscopic surgeries in the treatment of hiatal hernias]. / Laparoskopicheskie operatsii v lechenii gryzh pishchevodnogo otverstiia diafragmy.

Immediate and long-term results of treatment of 132 patients with hiatal hernias are analyzed. Indications for surgery are determined. Complications during and after laparoscopic antireflux surgeries are analyzed.

12/15-Lipoxygenase gene disruption attenuates atherogenesis in LDL receptor-deficient mice.

BACKGROUND: Human 15-lipoxygenase (LO) and its murine analogue 12/15-LO are capable of directly oxidizing esterified fatty acids in lipoproteins and phospholipids. Because these oxidized products possess atherogenic properties, it was suggested that LOs may be involved in enhancing atherogenesis. Previous in vivo tests of the role of LOs in atherogenesis animal models, however, have yielded conflicting results. METHODS AND RESULTS: Aiming to study the role of the 12/15-LO in murine atherogenesis, we crossed LDL-receptor-deficient mice (LDL-R(-/-)) with 12/15-LO-knockout mice and evaluated plaque formation 3 to 18 weeks after initiation of a high-fat diet. Atherosclerotic lesions were considerably reduced in the LDL-R/12/15-LO-double-knockout mice compared with LDL-R(-/-) mice at 3, 9, 12, and 18 weeks, at the aortic root as well as throughout the aorta. The cellular composition of plaques from mice deficient in 12/15-LO did not differ with respect to macrophage and T-lymphocyte content compared with plaques from 12/15-LO littermates. CONCLUSIONS: 12/15-LO plays a dominant role in promoting atherogenesis in LDL-R(-/-) mice.

[Diagnosis and treatment of breast cancer with central and medial localization using video-assisted thoracoscopic parasternal lymphadenectomy]. / Diagnostika i lechenie raka molochnoi zhelezy tsentral'noi i medial'noi lokalizatsii s ispol'zovaniem videotorakoskopii.

Since extended mastectomy after Urban involves an unjustifiably high level of trauma, this method has limited application. We have evolved a procedure of video-assisted thoracoscopic parasternal lymphadenectomy (VATPL). On completion of the experimental part using cadavers to work out the rationale for extent of surgery, clinical trials started. A total of 120 operations in patients aged 27-73 were performed (left-sided--64, right-sided--56), with the number of lymph nodes removed in each case ranging 1-10. Metastases were detected in 23 (19.2%), isolated lesions (metastases to parasternal lymph nodes alone)--6 (5.0%). With volume of removed tissue being identical, the findings on level of pain, amount of narcotic analgetics, hospital stay duration, intra- and postoperative complication incidence and cardiointervalography and pneumotachometry for VATPL patients were significantly better than for those treated by traditional (open-chest) procedure. It is concluded that VATPL is a highly effective and low-traumatizing diagnostic method. It may be recommended as an operation of choice for parasternal lymph collector involvement of central or medial localization.

[Stereotaxic biopsy of non-palpable breast neoplasms with the ABBI system (USSC)]. / Stereotakticheskaia biopsiia nepal'piruemykh obrazovanii molochnoi zhelezy s primeneniem ABBI system (USSC).

The study was concerned with application of the stereotactic automated surgical biopsy breast with the ABBI (USSC) device for verification of non-palpable breast lumps. It included 13 females, aged 34-72 (mean age--54) and lasted 6 months (1999). Microcalcinates were detected in 3 (22.8%), local cordlike tissue structures--3 (22.8%), focal shadows--7 (53.2%). Lesion size: (5 mm (16%), 5.1-10 mm (25%) and 10.1-20 mm (59%). Malignancy was diagnosed in 3 cases (22.8%), dia. 7-10 mm; atypical ductal hyperplasia--2 (8.3%), and miscellaneous benign pathology--53.2%. Adequate removal of lesions was histologically confirmed in all cases. The procedure was carried out with ambulatory monitoring, under local anesthesia, and lasted 1.5 hrs. No complications were reported. The cosmetic results were good; no analgetics were dispensed. The ABBI system proved an effective means of stereotactic surgical biopsy of the breast because it removed the entire radiologically-suspicious site as a complete tissue preparation. It provided all histological data without crushing or segmenting the preparation. Since tissue texture and, particularly, the preparation edges remained intact, the latter could be examined too, if needed. All this ruled out inaccurate interpretation, repeat biopsy and unjustified lumpectomies.

[Biopsy of non-palpable tumors of the breast]. / Biopsiia nepal'piruemykh obrazovanii molochnoi zhelezy.

14 biopsies were performed in patients with non-palpable tumors of the breast with stereotaxic automated system (ABBI) and disposable "pistol-needle" ("Auto-Suture") whose needle-harpoon penetrates into pathologic focus under local anesthesia (four fold digital stereotaxic control guarantees the precision of biopsy). Non-palpable breast cancer in the tissue areas of 4, 7 and 11 mm in horizontal section was diagnosed in 3 patients. Biopsy was performed outpatiently, there were no complications. The procedure is like a diagnostic sectoral resection of the breast.

[Parasternal lymph node excision in breast cancer]. / Parasternal'naia limfadenéktomiia pri rake molochnoi zhelezy.

Comparative analysis of the results of videothoracoscopic parasternal lymphadenectomy and standard mastectomy by Urban--Holdin is presented. In November 1995 to December 1999 205 videothoracoscopic parasternal lymphadenectomies were performed (96--on the left, 104--on the right). Central and medial location of breast cancer was indication for this operation. Age of the patients ranged from 23 to 73 years. Surgery was performed under intravenous anesthesia in the conditions of artificial lung ventilation with separate lung intubation. Mastectomy was performed as the first stage. Further, thoracoports were introduced into pleural cavity in the 5th intercostal space along medioclavicular and mediaxillar lines and in the 4th intercostal space along anterior axillar line. Parietal pleurotemy was performed parallely to internal thoracic vessels, parasternal fat and lymph nodes were removed en-block. Parasternal lymph nodes were involved in 40 (19.5%) patients. The spirometry, cardiomonitoring which were used pre-, intra-, postoperatively demonstrated that parasternal thoracoscopic lymphadenectomy is less traumatic and effective as diagnostic method than mastectomy by Urban--Holdin. Parasternal thoracoscopic lymphadenectomy can be recommended as a method of choice in medial and central breast cancer.

Applied genomics: integration of the technology within pharmaceutical research and development.

Multiple novel technologies have recently been developed to improve the analysis of genetic sequences, to rapidly assess RNA or protein levels in relevant tissues, and to validate function of potential new drug targets. The challenge facing pharmaceutical research is one of effective integration of these new technologies in ways that can maximally affect the discovery and development pipeline. Although database mining and transcriptional profiling clearly have increased the number of putative targets, the current focus is to assign function to new gene targets in a high-throughput manner. This requires a restructuring of the classical linear progression from gene identification, functional elucidation, target validation and screen development. New approaches are called for that can make this process non-linear and high-throughput.

Overexpression of 15-lipoxygenase in vascular endothelium accelerates early atherosclerosis in LDL receptor-deficient mice.

To study the possible role of the human lipid-oxidizing enzyme 15-lipoxygenase (15-LO) in atherosclerosis, we overexpressed it specifically in the vascular wall of C57B6/SJL mice by using the murine preproendothelin-1 promoter. The mice overexpressing 15-LO were crossbred with low density lipoprotein (LDL) receptor-deficient mice to investigate atherogenesis. High levels of 15-LO were expressed in the atherosclerotic lesion in the double-transgenic mice as assessed by immunohistochemistry. The double-transgenic, 15-LO-overexpressing, LDL receptor-deficient mice (LDLR-/-/15LO) developed significantly larger atherosclerotic lesions at the aortic sinus compared with lesions in the LDL receptor-deficient (LDLR-/-) mice after 3 and 6 weeks (107,000 versus 28,000 microm(2) [P:<0.001] and 121,000 versus 87,000 microm(2) [P:<0.05], respectively) of an atherogenic diet. LDL from the LDLR-/-/15LO mice was more susceptible to oxidation than was the LDL from the control LDLR-/- mice, as shown by a shorter lag period for copper-induced conjugated diene formation. On the other hand, no differences were found in the levels of serum anti-oxidized LDL antibodies between the study groups. There were also no differences with respect to the density of macrophages and T lymphocytes infiltrating the lesions in both experimental groups. Taken together, these results support the hypothesis that 15-LO overexpression in the vessel wall is associated with enhanced atherogenesis.

The effects of N-6 polyunsaturated fatty acid supplementation on the lipid composition and atherogenesis in mouse models of atherosclerosis.

Despite numerous studies, the precise role of dietary n-6 polyunsaturated fatty acids in the pathogenesis of atherosclerosis remains controversial. It has been shown that feeding an n-6-enriched diet resulted in decreased atherosclerosis in African green monkeys and was associated with a reduction in LDL levels. However, other authors reported that n-6 supplementation increased the oxidative stress and the susceptibility of LDL to undergo in vitro oxidation, thus potentially enhancing atherosclerosis. The present study was designed to investigate the effect of dietary supplementation of n-6 polyunsaturated fats (safflower oil), as compared with a saturated fat-rich diet (Paigen), on the blood lipid profile and atherosclerosis in two mouse models. In the first experiment, female C57BL/6 mice (n=23-30 per group) were fed a cholate containing Paigen diet, a safflower oil-rich diet (with cholate), or normal chow for 15 weeks. No significant differences between the high fat diet groups were evident with respect to total cholesterol, LDL, HDL or triglyceride levels. The extent of aortic sinus fatty streaks did not differ significantly between the two groups. In the second experiment, LDL-receptor-deficient (LDL-RD) mice (n=20-30 per group) were randomized into similar dietary regimens. Mice consuming a safflower oil-enriched diet developed significantly less atherosclerosis, in comparison with Paigen diet-fed mice. A reduction in LDL levels, although not of a similar magnitude as the reduction in atherosclerosis, was evident in the safflower oil-fed mice when compared to the Paigen diet-fed littermates. In both mouse models of atherosclerosis, LDL isolated from the plasma of mice on the n-6 polyunsaturated diet was rendered slightly more susceptible to oxidation in vitro, as indicated by a shorter lag period for diene formation. Thus, the effects of n-6 fatty acids on the lipoprotein composition and other potential influences may have contributed to the anti-atherogenic effect in the LDL-RD mouse model.