[The Russian consensus on the diagnosis and treatment of chronic pancreatitis: Enzyme replacement therapy]. / Rossiiskii konsensus po diagnostike i lecheniiu khronicheskogo pankreatita: zamestitel'naia fermentnaia terapiia.

Pancreatology Club Professional Medical Community, 1A.S. Loginov Moscow Clinical Research and Practical Center, Moscow Healthcare Department, Moscow; 2A.I. Evdokimov Moscow State University of Medicine and Dentistry, Ministry of Health of Russia, Moscow; 3Kazan State Medical University, Ministry of Health of Russia, Kazan; 4Kazan (Volga) Federal University, Kazan; 5Far Eastern State Medical University, Ministry of Health of Russia, Khabarovsk; 6Morozov City Children's Clinical Hospital, Moscow Healthcare Department, Moscow; 7I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russia, Saint Petersburg; 8Siberian State Medical University, Ministry of Health of Russia, Tomsk; 9M.F. Vladimirsky Moscow Regional Research Clinical Institute, Moscow; 10Maimonides State Classical Academy, Moscow; 11V.I. Razumovsky State Medical University, Ministry of Health of Russia, Saratov; 12I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, Moscow; 13S.M. Kirov Military Medical Academy, Ministry of Defense of Russia, Saint Petersburg; 14Surgut State Medical University, Ministry of Health of Russia, Surgut; 15City Clinical Hospital Five, Moscow Healthcare Department, Moscow; 16Nizhny Novgorod Medical Academy, Ministry of Health of Russia, Nizhny Novgorod; 17Territorial Clinical Hospital Two, Ministry of Health of the Krasnodar Territory, Krasnodar; 18Saint Petersburg State Pediatric Medical University, Ministry of Health of Russia, Saint Petersburg; 19Rostov State Medical University, Ministry of Health of Russia, Rostov-on-Don; 20Omsk Medical University, Ministry of Health of Russia, Omsk; 21Russian Medical Academy of Postgraduate Education, Ministry of Health of Russia, Moscow; 22Novosibirsk State Medical University, Ministry of Health of Russia, Novosibirsk; 23Stavropol State Medical University, Ministry of Health of Russia, Stavropol; 24Kemerovo State Medical University, Ministry of Health of Russia, Kemerovo; 25N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia, Moscow; 26A.M. Nikiforov All-Russian Center of Emergency and Radiation Medicine, Russian Ministry for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters, Saint Petersburg; 27Research Institute for Medical Problems of the North, Siberian Branch, Russian Academy of Sciences, Krasnoyarsk; 28S.P. Botkin City Clinical Hospital, Moscow Healthcare Department, Moscow; 29Tver State Medical University, Ministry of Health of Russia, Tver The Russian consensus on the diagnosis and treatment of chronic pancreatitis has been prepared on the initiative of the Russian Pancreatology Club to clarify and consolidate the opinions of Russian specialists (gastroenterologists, surgeons, and pediatricians) on the most significant problems of diagnosis and treatment of chronic pancreatitis. This article continues a series of publications explaining the most significant interdisciplinary consensus statements and deals with enzyme replacement therapy.

Relationship between parameters of lipid peroxidation during obstructive jaundice and after bile flow restoration.

Restoration of bile flow after 9-day cholestasis in rat liver normalized the content of lipid peroxidation products. The removal of the cholestatic factor after 12-day cholestasis was not followed by recovery of these parameters. We showed that measurement of serum concentration of lipid peroxidation products in patients with cholelithiasis during the preoperative period holds promise for selection of the optimum time for surgical treatment and prediction of the risk of postoperative complications.

Role of tumor necrosis factor alpha and sphingomyelin cycle activation in the induction of apoptosis by ischemia/reperfusion of the liver.

The signal transduction pathways triggering apoptotic mechanisms after ischemia/reperfusion may involve TNF-alpha secretion, ceramide generation, and initiation of lipid peroxidation. In the present study involvement of the TNF-alpha, sphingomyelin cycle, and lipid peroxidation in the initiation of apoptosis induced in liver cells by ischemia and reperfusion was investigated. Wistar rats were subjected to total liver ischemia (for 15, 30 min, and 1 h) followed by subsequent reperfusion. Ischemia caused sharp decrease of neutral sphingomyelinase activity. Activity of acidic sphingomyelinase initially decreased (during 15-30 min ischemia) but then increased (after 1 h of ischemic injury). Reperfusion of the ischemic lobe of the liver caused increase in neutral sphingomyelinase activity and decrease in acidic sphingomyelinase activity. A small amount of TNF-alpha detected by immunoblotting analysis was accumulated in the ischemic area of liver rapidly and the content of this cytokine dramatically increased after the reperfusion. TNF-alpha is known to induce free radical production. We found that the accumulation of TNF and increase of sphingomyelinase activity during the development of ischemic/reperfusion injury coincided with increase in content of lipid peroxidation products (conjugated dienes) and DNA degradation detected by gel electrophoresis. Recently it was shown that superoxide radicals are used as signaling molecules within the sphingomyelin pathway. This suggests the existence of cross-talk between the oxidation system and the sphingomyelin cycle in cells, which may have important implications for the initial phase and subsequent development of post-ischemic injury.

Role of endogenous TNF-alpha and sphingosine in induced DNA synthesis in regenerating rat liver after partial hepatectomy.

Cytokine-stimulated metabolism of sphingomyelin results in the accumulation of ceramide and sphingosine which play a part in the regulation of cell proliferation, differentiation, and reception, as well as in oncogenesis. Formation of TNF-alpha (a member of the cytokine family), accumulation of sphingosine, and DNA synthesis (measured by immunoblotting, HPLC, and [3H]thymidine incorporation, respectively) were studied in rat liver after partial hepatectomy. The content of TNF-alpha was found to increase during 12 h following hepatectomy. The maximum of sphingomyelinase activity and accumulation of sphingosine precede the maximum of DNA synthesis. Sphingosine is known to inhibit protein kinase C. On the other hand, it stimulates the metabolism of phosphatidylinositol, thus causing accumulation of diacylglycerol and inositol-1,4,5-triphosphate, which in turn activate protein kinase C. Hence, the release of TNF-alpha in regenerating liver may modulate DNA synthesis through the accumulation of sphingosine which is involved in regulation of protein kinase C activity and of phosphatidylinositol turnover.

Results of pancreatic blood shunting into the systemic blood flow in insulin-dependent diabetics.

A new surgical method of treating patients with unstable insulin-dependent diabetes (IDD) has been developed--that of surgically shunting pancreatic blood into the systemic blood flow with the purpose of creating a more optimal interaction of subcutaneously administered insulin and pancreas-secreted glucagon. The long term results of the operation depend on the patency of a splenorenal anastomosis. This has been studied by following up 137 patients over periods from half a year to three years. Anastomotic patency was determined by renal and splenic venography and celiacy arteriography, which revealed a patent anastomosis in 114 patients, and an obliterated one in 23. Patients with patent anastomoses showed a lowering of glycosylated hemoglobin (HbA1c) from 13.3 +/- 0.3% to 9.3 +/- 0.6%, p < 0.05, a decrease of the injected insulin dose from 0.97 +/- 0.04 to 0.72 +/- 0.03 U/kg, p < 0.05, disappearance or considerable abatement of pain in the lower extremities, and of hypoglycemia. Improvement of clinical status was accompanied by an increase of glucagon in the systemic blood stream from 60.8 +/- 10.1 to 91.5 +/- 9.4 pg/ml, p < 0.05, a rise of tissue oxygen pressure, pO2, from 49.2 +/- 2.4 to 58.1 +/- 1.9 mm Hg, p < 0.05. In patients with oblivious anastomoses postoperative HbA1c levels did not change from preoperative values: 12.9 +/- 0.4% and 12.8 +/- 0.7%, p < 0.05, respectively; the insulin dose remained the same--0.91 +/- 0.07 U/kg and 0.85 +/- 0.07 U/kg, p < 0.05, no rise of the systemic blood glucagon content was noted, and former complaints continued. The suggested method is not an alternative for insulin therapy, but considerably enhances its potential.

[Cicatricial strictures of the hepatic ducts and area of their junction (stricture 0)]. / Rubtsovye striktury pechenochnykh protokov i oblasti ikh sliiania (striktura 0).

The article deals with experience in the treatment of 187 patients (in 1980-1992) with cicatricial stricture of the hepatic ducts in the region of their coalescence (0 stricture). A high cholecystoenteric anastomosis, was formed, on a transhepatic drain in 117 (group I) and a precision anastomosis in 70 patients (group II). Analysis of the results of the operations showed that in group I patients, the early postoperative period was quite severe with the development of specific complications due to use of a replaceable transhepatic drain (hematobilia, leakage of bile into the subdiaphragmatic space, subdiaphragmatic abscess). Ten patients died (8.5%), a recurrent stricture was encountered in 4 patients. In group II patients, the early postoperative period followed a favorable course, there were no fatal outcomes, only one patient had a recurrent stricture. Experience shows that a high precision cholecystoenteric anastomosis can be formed in cicatricial stricture of the hepatic ducts in the region of their coalescence by means of some methodical manipulations. However, it should not be considered an alternative to operations with framed drainage of the bile-draining anastomosis.

[Role of polypeptides of pancreatic juice in the healing of intestinal anastomosis]. / Rol polipeptidov pancreaticheskogo soka v zazhivlenii kishechnykh anastomozov.

The possibility of using the polypeptide fraction of the pancreatic juice to accelerate healing of an intestinal anastomosis was studied in experiments. It was shown that the pancreatic polypeptides possess the properties of potential growth factors: after a single injection of these substances into the zone of the anastomosis during the operation, the synthesis of DNA and proteins in the tissues of the anastomosed intestinal segments essentially increases, which is evidence of stimulation of cell proliferation. Intensification of the proliferative processes in the tissues of the anastomosis improves the qualitative characteristics of the muscular suture-mechanical strength and biological air-tightness. The use of pancreatic polypeptides for acceleration of healing of an anastomosis formed in peritonitis showed this nontraditional method of protection of the intestinal suture to be very effective.

Extracorporeal immunopharmacotherapy in patients with chronic septic cholangitis.

An immunological examination of patients with septic cholangitis revealed secondary immunodeficiency. Traditional methods of therapy and immunocorrection were ineffective in eight patients with septic cholangitis. They were treated with extracorporeal immunopharmacotherapy using diuciphon. For the accomplishing detoxication, this was used in combination with plasma exchange. The course of treatment consisted of 3 or 4 procedures, within a 3- or 4-day interval. As a result of extracorporeal immunocorrection, patients were observed to have positive immunological indexes, demonstrated by the normalization of the lymphocyte count in 5 of 6 patients, CD3+ and CD4+ in 3 patients, and CD8+ in 4. Four patients had clinical remissions (0.5 year), and 3 patients underwent surgery with no septic postoperative complications.

A new simplified method of selective exposure of hepatic pedicles for controlled hepatectomies.

Our experience of 90 hepatectomies (HE) and examinations of 64 cadaver livers resulted in the elaboration of a simplified technique for the exposure of hepatic pedicles (HP) and the rapid selective ligation without significant normothermal ischemia of the retained parts of the liver. The method comprises 4 consecutive steps: 1) a superficial T-shaped incision of Glisson's capsule at the site of HP projection on the liver's inferior surface, 2) introduction of the surgeon's forefinger into the liver parenchyma, controlled by clamping the hepatoduodenal ligament, the fingertip finding a tubular structure well distinguished by its smooth elastic surface from the friable parenchyma and bending the finger to hook the pedicle, 3) drawing the hooked pedicle downwards through the slit in the capsule and temporarily clamping it, while releasing the hepatoduodenal ligament so as to restore blood supply to the retained parts of the liver, 4) checking for correct ligature position on the HP before its final ligation by matching the actual ischemic area with the intended line of resection and moving the clamp proximally or distally along the exposed pedicle for the release or clamping of lateral branches as necessary. Whereupon resection can be performed by any of the known methods. This method has been used in 8 major HE, allowing to reduce intraoperative blood loss from 2200 +/- 247 ml to 1000 +/- 225 ml and reducing general liver ischemia from 10 minutes and more to 2-3 minutes.

[Treatment of proximal strictures of the great bile duct by endless drainage (author's transl)]. / Chirurgische Behandlung von proximalen Narbenstrikturen der Gallengänge durch transhepatische Ring-Drainage.

The authors describe some technical modifications of endless transhepatic drainage. These permanent drains should be left in place for a period of at least 2 years, in order to prevent the risk of restenosis. The results of 50 patients who underwent endless drainage until 6 years ago are dealt with.