[Possible use of the growing liver biological set for hepatic recovery after toxic damage (an experimental study)]. / Vozmozhnosti biologicheskoi kombinatsii, poluchennoi iz rastushchei pecheni, dlia ee vosstanovleniia pri toksicheskom povrezhdenii (éksperimental'noe issledovanie).

The lack of acceptable pharmacological approaches for restoration of the injured liver is associated with complex of mechanisms involved in hepatic regeneration and with difficulty of the target selection. The aim of this research was to study the hepatoprotective function of the extract from both the growing and regenerating liver containing a natural set of factors crucial for the hepatic restoration. Extracts from both regenerating liver of rats after 70% hepatic resection and the growing liver of neonatal pigs were obtained using own original technique. The set of resultant extracts was named as the hepatic regeneration set (HRS). HRS fractionation was carried out using the Toyopearl HW-50S sorbent. The efficiency of HRS and its fractions was estimated using a model of the mouse liver thioacetamide injury and monitoring hepatic enzyme activity in blood serum. The activities of AST and ALT in intact animals were 50 U/l and 80 U/l, respectively; after thioacetamide administration they increased to 2059±212 U/l and 4280±440 E/l, respectively (p<0.05). Treatment of injured animals with HRS from the rat regenerating liver resulted in a significant decrease of transaminase activities to 924±148 U/l (AST; p<0.05) and 1633±308 U/l (ALT; p<0.05). A similar effect was observed after treatment with HRS from the neonatal pig liver: the AST decreased to 937±138 U/l (p<0.05), while ALT activity decreased to 1710±237 U/l (p<0.05). HRs fractionation resulted in identification two active fractions characterized by much higher (8-29) hepatotropic effect that that of the whole extract. These fractions contained peptide/protein components with the range of molecular mass of 3-60 kDa (fraction 1) and 3-25 kDa (fraction 2a). Fraction 1 also contained some polynucleotides in fraction 1. Subsequent studies of these fractions exceeding the hepatotropic effect of original HRS is clearly needed to identify their individual components by immunochromatography methods, ELISA, MRM mass spectrometry and quantitative PCR.

[The classification of obstructive jaundice severity].

It was analyzed the results of examination and surgical treatment of 338 patients with obstructive jaundice. The patients were operated in 2004-2012 years. 148 patients had benign jaundice and 190 patients had malignancy genesis of jaundice. It was determined laboratory data (bilirubin total, protein total, prothrombin index) as well as complications of obstructive jaundice (cholangitis, renal failure, hepatic encephalopathy, gastrointestinal bleeding, sepsis) indicating to the severity of obstructive jaundice and it was taken into consideration the malignant origin of jaundice. The selected attributes were assigned marks from 1 to 3. Each complication as well as factor of malignancy was evaluated two times higher than mark of bilirubin. The grade of jaundice severity (A, B, C) was determined by combination of the marks that identified the attributes. It was analyzed the influence of prothrombin index and blood serum protein on the results of severity grade formation of obstructive jaundice with the postoperative results (lethality, complications). It was done for simplification of classification. The absence of significant differences in assessing of the severity obstructive jaundice class with and without attributes of a "total protein" and "prothrombin index". To simplify the classification and to get more reliable information about the difference of postoperative results between the grades (A, B, C) are possible by exception of total protein attributes and prothrombin index.

[Rate of biliary ducts' decompression by the tumorous obstructive jaundice].

Results of biliary decompression were analyzed in 185 patients with malignant obstructive jaundice. Among them 85 patients underwent nasobiliary drainage, 37 - percutaneous transhepatic bile drainage and 63 - cholecystectomy. Dynamics in biochemical indices of blood serum, cholangiomanometry and jaundice response to decompression according to T. Shimizu et K.Yoshida's formula in our modification were evaluated for estimation of bile flow rate. It is ascertained that application of nasobiliary drainage leads to low-rate decompression, percutaneous transhepatic bile drainage and cholecystectomy - to high-rate decompression. Low-rate decompression enables to decrease significantly the frequency of "fast decompression syndrome" and complications, particularly augmenting of liver dysfunction, multiple organ failure and lethality in post-decompression period related to them.

[Postoperative biliary complications after liver resections].

Postoperative biliary complications (BC) after liver resections carried out from 1990 to 2009 were analyzed in 216 patients. Among them - 139 women and 77 men aged 15-79 years (mean age 49,8±0,9 years). Complications in early postoperative period were observed in 110 patients (50,9%); among them BC - in 27 patients (12,2%), bilomas - in 6, external biliation - in 14, abscesses - in 7. Lethal outcomes were not observed. Average duration of hospital stay amounted 41,3±12 days. Relationship between frequency of BC and age, malignancy of neoplasm and extent of liver resection was estimated. All patients were cured using low invasive techniques. Recurrent operations were not carried out.

[Intraoperative injuries of bile ducts].

125 patients with injuries of bile ducts were observed from 1988 to 2008 years. Minor injuries (ducts in the bed of the gall bladder) were registered in 64 patients. Magistral bile ducts were injured in 61 cases. Analysis revealed 3 key points of the successful treatment of of such patients: type of the injury (cut, dissection, side wound), localization of the defect (intra- and extrahepatic ducts) and participation of a highly qualified surgeon.

[The role of biliary decompression and correction of dysbiosis in the treatment of obstructive jaundice].

The article providing in-depth analysis of pathogenesis of obstructive jaundice shows that this disease is manifest not only as changes at the hepatic level (cholestasis, cholehemia, cholangitis, cholangio- and lymphovenous shunts, hepatic encephalopathy) but also as marked dysbiotic disturbances due to anacholia and toxic metabolites that cause bacterial translocation and endotoxemia complicating liver insufficiency. Based on the literary data and original observations, a new scheme for the treatment of obstructive jaundice is proposed including simultaneous correction of both components of hepatoenteric turnover, also, it permits to improve the outcome of the postoperative period.

[Relationship of tumor necrosis factor alpha expression with activation of sphingomyelinase and lipid peroxidation after removal of cholestatic factor].

The goal of this work was to study the expression of tumor necrosis factor alpha (TNFalpha), sphingomyelin cycle activation, and lipid peroxidation (LPO) processes after the removal of a cholestatic factor in the liver subjected to different durations of cholestasis. Restored bile flow after a 9-day hepatic cholestasis normalized sphingomyelinase (SMase) activity and levels of TNFalpha and LPO products. The removal of a cholestatic factor after a 12-day cholestasis did not normalize the studied parameters: SMase activity and the levels of TNFalpha and LPO products remained much higher compared to control. A significant positive correlation between TNFalpha expression, SMase activity, and LPO rate has been revealed. The obtained data indicate that hepatocyte apoptosis after bile outflow restoration in late cholestasis can be due to the activation of the sphingomyelin cycle, LPO, and TNFalpha expression. The synergistic interaction can sharply increase the proapoptotic capacity of each of these factors since TNFalpha activates SMase and LPO, SMase activity depends on the LPO rate, while ceramide, an SMase-produced secondary messenger of apoptosis, can induce oxidative stress.

[Chronic pancreatitis: resective and decompressive procedures].

PURPOSE: Definition of resective and decompressive operations in chronic pancreatitis. MATERIALS AND METHODS: A retrospective analyses of surgical management of 51 chronic pancreatitis patients is carried out. 24 patients underwent longitudinal pancreaticojejunostomy (PA), 27--pancreatic head ( PH) resective procedures: Beger--5, modified Frey (PH intraparenchimatose resection-- IR, supposing removal of fibrous masses from the ventral and greater part of the dorsal PH)--22. According to the character of the PH lesion the patients were divided in 3 groups: head dominant (13), total (11) and cystic pancreatitis (20). RESULTS: One early postoperative death developed after reoperation for adhesive intestinal ileus in patient with PA. No mortality was noted after IR. Remote results in terms of 4.8+/-0,7 years were studied in 32 (71%) patients underwent PA and IR. IR lead to good and satisfactory results. After PA poor results came to 5 (29.5%). CONCLUSIONS: Combination of PH IR and PA is indicated in head dominant and total chronic pancreatitis patients. In cases of pseudocysts and dilation of the main pancreatic duct (>6-7 cm) decompressive variant of procedure cysto-pancreato-jejunostomy is preferable.

[Causes, diagnosis and surgical treatment of strictures of lobar and segmental hepatic ducts].

Causes of strictures of lobar and segmental ducts after their injuries during open and laparoscopic cholecystectomy in 53 patients were analyzed. For correction of bile outflow precision non-wireframe (n=22) and wireframe (n=20) anastomoses were used. In 10 patients a combined anastomosis was established. In 1 patient the external drainage of hepatic ducts was performed. After surgery 3 patients died. 1-15 year long-term results were studied in 48 (96%) patients. Good results were achieved in 29 (60.5%), satisfactory -- in 13 (27%) patients. Recurrences of the strictures were diagnosed in 6 patients. It is concluded that dynamic control is necessary in patients operated on for bile ducts injuries. Underestimation of remittent cholangitis leading to biliary cirrhosis worsens prognosis of the disease.

[Changes in sphingomyelinase activity, tumor necrosis factor alpha level, and lipid peroxidation rate in the course of development of cholestatic liver injury].

Changes in sphingomyelinase activity, tumor necrosis factor alpha expression, and lipid peroxidation rate in the course of development of cholestatic liver injury have been studied. The same type phase shifts in the parameters analyzed were observed, which included a marked decrease at the early stages of cholestasis (days 3-6) and a pronounced increase at the later stages (days 12-16), i.e., under the conditions of developed pathology. There is a significant positive linear correlation between tumor necrosis factor alpha expression, sphingomyelinase activity, and lipid peroxidation rate during cholestatic injury. The changes detected may reflect balance between the effects of the two major bile components--bilirubin, which is accumulated in the liver at the early stages of cholestasis, and bile acids, whose influence dominates at the later stages of pathologic process. Our results indicate that tumor necrosis factor alpha overexpression, the sphingomyelin cycle activation, and lipid peroxidation intensification may cause apoptosis of hepatocytes at the late stages of cholestasis.

[Diagnosis and treatment of different types of high scar strictures of the hepatic ducts]. / Diagnostika i lechenie razlichnykh tipov vysokikh rubtsovykh striktur pechenochnykh protokov.

Results of treatment of 224 patients with scar strictures of the hepatic ducts (BSDH) are presented. Based on Bismuth's classification of BSDH E.I. Galperin (2002) proposed own one. According to this classification there were 17 (7,6%) patients with type "+2" (stump of common hepatic duct - CHD more than 2 cm), 26 (11,6%) - with type "+1" (stump of CHD 1 - 2 cm), 72 (32,2%) - with "0" type (stump of CHD less than 1 cm), 54 (24,1%) - with "-1" type (upper fornix of CHD confluence is not affected), 35 (17,4%) - with "-2" type (CHD confluence is destroyed), 20 (8,9%) - with "-3" type (strictures of segmental ducts). There were greater number of previous surgeries in the patients with "-1" and "-2" types (p<0,05). Jaundice and secondary biliary liver cirrhosis were seen more frequently in types "0" - "-3". Hepaticojejunostomy was the surgery of choice. For approach to unaltered wall of hepatic ducts (HD) section of lobar ducts in types "+1", "0", excision of portal plate and partial resection of IV hepatic segment (31 patients) in "-1" - "-3" types were used. Exchangeable transhepatic drainage (ETD) was applied in 31 patients due to impossibility to excise scar tissues completely. In early postoperative period 9 (4%) patients died due to purulent cholangitis (7 patients) and insufficiency of anastomosis (2 patients). Long-term results were evaluated in 180 (80,4%) patients from 1 to 14 (6,6+/-3,9) years of follow-up. Thirteen surgeries were performed for repeated strictures. The main cause of restrictures was inadequate resection of scar tissues and unreasonable refusal of ETD (7 patients). Developed surgical technique in different types of strictures permits to reduce postoperative lethality and the rate of restrictures.

Expression of prolactin receptors in human liver during cholestasis of different etiology and secondary liver cancer.

Indirect immunoperoxidase assay and computer analysis of photographic images revealed more intensive expression of prolactin receptors in hepatocytes of women compared to men. The intensity of expression was maximum in secondary liver cancer, high in obstructive jaundice of different etiology, and less pronounced in cholelithiasis. The expression of prolactin receptors in cholangiocytes was higher than in hepatocytes and was maximum during obstructive jaundice of different etiology. Cells of secondary tumors were characterized by low expression, while distant hepatocytes most intensively expressed prolactin receptors.

[Diagnosis and surgical treatment of pancreonecrosis]. / Diagnostika i khirurgicheskoe lechenie pankreonekroza.

Actual problems of diagnosis and treatment of pancreonecrosis (PN) are discussed. Results of treatment of 154 patients hospitalized with sterile necrosis SN (n = 133) and infected PN (n = 21) were analyzed. SN became infected in 49 patients. The diagnostic methods were as follows: USE, CT, biochemical examinations of blood, urine and exudate. Percutaneous puncture contrast retroperitoneography (PPCR) was developed. It is demonstrated that modern diagnostic methods and PPCR permit one to diagnose PN, detect location, zone of retroperitoneal fat's necrosis and characterize its infection. The size of lesion of retroperitoneal fat in patients with sterile PN (n = 133) does not determine severity of the patients' condition and early lethality, but increases the risk of infection and makes worse prognosis of the disease. In laparoscopic sanation of the abdominal cavity for fermentative peritonitis, compared with laparotomic one, infection developed less rarely (10.2 and 40%, p < 0.01) and lethality decreased. Lethality in repeated mini-invasive surgeries through burso- and retroperitoneostomas performed in 34 patients with infected pancreonecrosis was 17.6% that is lower than one in repeated relaparotomies (n = 21, lethality 47.8%).

[Selective-occlusive method of drug administration in the treatment of experimental liver tumors]. / Selektivno-okkliuzionnyi metod vvedeniia preparatov pri lechenii éksperimental'nykh opukholei pecheni.

263 experimental studies on 184 rats were carried out. Hepatic tumors were provoked by intraparenchymatous implantation of 0.1 ml 20% tumoral suspension of mucous cancer (RS-I). Treatment was realized on 10-12 day after vaccination. Photodynamic therapy with "Photosense" (PS) and laser irradiation (670 nm, 50-100 Dj, 4-13 mm), and also catalytic therapy (CT) with "Teraftal" (TF) and ascorbic acid (AA) were used. FS and TF were administered by developed selective-occilisive method (SOM). Rapid accumulation of drugs in occluded lobe of liver was revealed in SOM, that permitted to decrease administered dose of TF in 16.5 times. There was no growth of tumor after FDT unlike control group. Same results were obtained after CT with SOM, but there was further growth of tumor after systemic administration of drugs. Developed SOM of drugs administration in FDT and CT lead to good results in treatment of experimental hepatic tumors.

[Treatment of extrahepatic bile ducts injuries due to laparoscopic cholecystectomy]. / Lechenie povrezhdenii vnepechenochnykh zhelchnykh protokov, poluchennykh pri laparoskopicheskoi kholetsistéktomii.

The department of hepatic surgery of I.M. Sechenov Moscow Medical Academy has gained experience of treatment of 25 patients with injuries of bile ducts inficted in laparoscopic cholecystectomy (LCE). All the patients underwent LCE in other hospitals. 4 patients were hospitalized with recent injuries (within 24 hours after injury) and 21--later. Injuries of the duct in LCE characterized by early clinical manifestation, injury in proximal portion of hepatic duct, technical difficulties of anastomosis creation during the first operation due to thin-walled duct of small diameter. Reconstructive operations yielded good results in 22 patients. Recurrent strictures were revealed in 3 patients who required repeated intervention. There were no lethal outcomes.

[Hepatoprotective action of phosphogliv in surgery of patients with chronic calculous cholecystitis]. / Gepatoprotektornoe deistvie fosfogliva u bol'nykh, operirovannykh po povodu khronicheskogo kal'kuleznogo kholetsistita.

32 patients with chronic calculous cholecystitis were treated by a new preparation. Phosphogliv (on the base of polyunsaturated phospholipids)--5 days before planned surgery and 5 days after. The increase of alanine and asparagine aminotransferases activities and of bilirubin concentration (2-2.5 fold) was observed in all the patients, cirespective of the drug treatment. However, the essential difference between treated and untreated patients was revealed in the course of post-operative period. In the control group asparagine aminotransferase activity and bilirubin level remained high, and alanine aminotransferases activity even more increased. In contrast, both two aminotransferases activities and bilirubin level fell substantially in Phosphogliv group, that may show more active liver regeneration after surgery. Besides, in this group operation did not result even in short-time changes of plasma protein fractions ratios--opposite to control. It may testify on some protective action of Phosphogliv on liver protein-synthesis system. The observed action of new phospholipid preparation Phosphogliv, together with the absence of side effects, allows to recommend it as an adjuvant in the surgery of patients with chronic calculous cholecystitis. Besides, the above results broaden usage field of polyunsaturated phosphatidylcholine as cell membranes repair agent: it appears to be effective not only for liver diseases treatment, but also for soonest overcome of post-surgery liver changes.

[Biliary sepsis: some peculiarities of pathogenesis]. / Biliarnyi sepsis: nekotorye osobennosti patogeneza.

Results of clinical study of 87 biliary sepsis patients and experimental study on 54 rats with obstructive jaundice and cholangitis are presented. Own and literary data are compared. Specific immune and portal haemodynamic changes, provoced by obstructive jaundice are main pathogenic factors defining specific course of biliary sepsis. These changes are: 1) gut bacterial and endotoxin translocation, portal endotoxaemia; 2) reduction of RES and Kupfer cell function and endotoxin break into the systemic circulation; 3) liver parenchyma ischemia and milliary abscess formation; 4) portal blood flow shunting into the general circulation additionally increasing systemic endotoxaemia. These factors determine rapid, even fulminate development of milliary abscesses of the liver and multiorganic failure. The authors suggest that etiologic and pathogenic factors, causing peculiarities of the clinical course should be indicated in the diagnosis of septic patient.

[Changes in the activity of neutral and acidic isoforms of sphingomyelinase in hepatoma-22, regenerating and ischemic liver]. / Izmenenie aktivnosti neitral'noi i kisloi izoform sfingomielinazy v gepatome-22, v regeneriruiushchei i ishemizirovannoi pecheni.

Activity of neutral and acidic sphingomyelinases (N- and A-SMases) were studied in regenerating liver after partial hepatectomy (during 48 hrs after operation), in ischemic liver during 15, 30 min and 1 and 2 hrs ischemia and during following reperfusion (from 5 min up to 2 hrs), in hepatoma- 22 after 15 days of transplantation and in liver of tumor bearing animals. It was shown that activity of N-SMase is increased in hepatoma-22 and in regenerating liver and it is decreased in ischemic liver. Following reperfusion of ischemic liver area activity of enzyme was found to have returned to baseline in dependence on time of ischemia and reperfusion. Activity of A-SMase is decreased in tumor, is not changed in regenerating liver and increased after long time of ischemia. It was supposed that N-SMase is involved in cell proliferation, but A-SMase is connected with cell damage.