[Role of splenectomy in the treatment of myelofibrosis].

AIM: To evaluate the clinical and hematologic efficiency of splenectomy (SE) in patients with myelofibrosis (MF) resistant to conventional traditional treatment. SUBJECTS AND METHODS: Case histories were retrospectively analyzed in 52 MF patients who had been followed up at the Hematology Research Center, Ministry of Health of the Russian Federation, in 2004 to 2012 and undergone therapeutic SE (47 patients with primary myelofibrosis, 4 with postpolycythemia myelofibrosis, and 1 with postthrombocythemia myelofibrosis). The mean age was 47 years at diagnosis and 53 years before surgery. The patients younger than 50 years of age constituted 60%. Massive and giant splenomegaly was detected in 37 (71%) patients. The spleen weighing 0.9 to 2.9 and 3 to 7 kg was removed in 15 (29%) and 35 (67%) patients, respectively. In 2 cases, the weight of the removed spleen was as much as 10 and 11 kg. RESULTS: By the moment of SE, the disease duration averaged 76 (from 1 to 240) months. Twenty-one (40%) patients developed perioperative complications, including bleeding (15%), thrombosis (11.5%), and infectious complications (13.5%). There were no deaths from surgical interventions in the intra- and early postoperative periods. In more than 80% of the patients after SE, their general condition improved and the symptoms of intoxication disappeared; in the majority of patients, the therapeutic effect lasted about 2 years. In the follow-up period, 33 (63%) patients died; the time to death averaged 27 (1-84) months following SE. The causes of death were blast transformation in 27 (82%) patients and comorbidity in 6 (18%); 19 (37%) patients with an average post-SE follow-up of 37 (4-72) months continued hydroxyurea treatment. The median survival after SE was equal to 3 years; the median overall survival was 11 years. CONCLUSION: SE is effective palliative care with an acceptable level of occurring complications for individual patients with MF. Contraindications to SE as blast crisis and severe comorbidities should be strictly taken into account.

[Investigation of ß-endorphin concentrations in patients with hemophilia].

UNLABELLED: AIM. To study changes in the plasma concentration of beta-endorphin (beta-E) in patients with hemophilia A and B (in the presence of bleeding and in the absence of hemorrhagic syndrome) and in whole blood and plasma donors before and after donation and to investigate the factors associated with (beta-E) concentration changes. SUBJECTS AND METHODS: The prospective study of beta-E concentration changes (and related factors) enrolled 38 persons: 12 patients with hemophilia after acute blood loss, 11 patients with hemophilia without hemorrhagic syndrome, and 15 whole blood and plasma donors. beta-E concentrations were measured by enzyme immunoassay. RESULTS: In blood loss, the patients with hemophilia were found to have elevated serum beta-E concentration: 9.6 pg/ml (95% confidence interval (CI), 6.1 to 13.0 pg/ml) versus 5.2 pg/ml (95% CI, 1.4 to 8.9 pg/ml). After donation, the concentration of 3-E in the group of donors was higher than before donation: 7.3 pg/ml (95% CI, 4.9 to 9.7 pg/ml) versus 4.7 pg/ml (95% CI, 3.2 to 6.3 pg/ml). In the group of patients with hemophilia, the elevation of 3-E concentrations is steady-state (lasted at least 10 days); at this time, the beta-E value variability (estimated by mean square deviation) increased as compared with that in remission: 7.7 pg/ml (95% CI, 5.5 to 13.1 pg/ml) versus 2.4 pg/ml (95% CI, 1.7 to 4.4 pg/ml). The above differences are statistically significant (p = 0.05). CONCLUSION: In blood loss, there is an increase in plasma beta-E concentrations in the patients with hemophilia and donors. The increase in beta-E concentrations and the variability of its values were greater in the patients with hemophilia and blood loss than in the donors. The beta-E concentration elevation accompanying hemorrhage is characterized by steadiness in the patients with hemophilia.

[Spleen removal in hematological patients with splenomegaly].

By large and giant volume of the spleen the mainstay of the surgery remains the open splenectomy. Splenomegaly stipulates certain difficulties and dangers of the procedure, mainly because the lack of the free space in the abdominal cavity. The maximally wide access, preliminary preparation and ligation of the splenic artery in situ and thorough separation of the spleen and pancreatic tail provide the safety and success of the operation. 374 splenectomies on the reason of the splenomegaly were analyzed. The standardization of the technique allowed the 2.5 times reduction of the postoperative complication rate (from 26.9 to 10.8%); the 1.8 times reduction of the intraoperative complication rate and the 17% reduction of the intraoperative blood loss. The postoperative pancreatitis was registered 4 times rare; the intraabdominal bleeding - 2 times rare and the frequency of the subphrenic abscess was 1.5 times lesser.

[The value of monitoring of qualitative content of onco-antigens in serum in diagnostics of malignant tumors].

The results of monitoring of qualitative content of 8 onco-antigens (CK, CA-242, CA-19-9, CA-125, REA, AFP, SCC, NSE) in serum of 414 patients are presented. The examination of 62 patients with tumors of different localization was carried our in dynamics before and after treatment. The monitoring of concentration of onco-antigens in serum permitted to apply early diagnostics of malignant process to 9 out of 28 patients with unclear clinical symptomatic. The technique informativeness is demonstrated in pre-clinical diagnostic and prognosis of course of oncological diseases. The possibility of transitory increase of concentration of certain onco-antigens under non-oncologic diseases returning to normal values after application of corresponding pharmaceutical treatment is revealed. The broader implementation of this technique into practice of public health is recommended.

[Nine-year experience in the treatment of patients with diffuse large B-cell lymphosarcoma].

AIM: To ascertain indications to standard (CHOP-21/R-CHOP-21) and intensive (mNHL-BFM-90) treatment in patients with diffuse large B-cell lymphosarcoma (DLBCL) with involvement of lymphoid organs. MATERIAL AND METHODS: The trial, performed from January 2002 to December 2010, enrolled 139 DLBCL patients with affected lymph nodes (LN), tonsils, spleen, bone marrow (BM). The diagnosis was made according to WHO criteria. The patients were examined according to the protocol of lymphoproliferative diseases. Biopsy material from all 139 patients was studied immunohistochemically on paraffin blocks (LN, tonsils, spleen, BM) using a wide panel of antibodies. The same examinations of BM were made in all 18 cases of BM involvement. Cytogenetic examination was performed in 106 patients: 48 standard cytogenetic tests, 139 - FISH for t (14;18) as well as rearrangement of locus 3q27. Patients with a poor prognosis (n = 86, 61.8%) received intensive therapy according to mNHL-BFM-90 program. The signs of a poor prognosis were the following: massive tumor (tumor size more than 7.5 cm), invasion into the adjacent organs or tissues, stage III-IV disease by Enn-Erbor, high concentration of LDG. Patients without a poor prognosis (n = 53, 38.2%) received standard treatment CHOP-21 (n = 28) or R-CHOP-21 (n = 25). RESULTS: A complete remission without recurrences was achieved in all 53 patients without signs of unfavourable prognosis (100%). Overall 5-year survival was 96%, 2 patients died in remission of other causes. Of 86 patients with a poor prognosis a complete remission was achieved in 64 (74.4%) patients. Overall and recurrence-free 5-year survival was 65 and 86%, respectively. CONCLUSION: Standard treatment provided long-term complete remission in all the patients without poor prognosis. Intensive (mNHL-BFM-90) treatment produced the best results in generalized lesion without BM involvement. Overall 5-year survival was 84% in these patients and 12% in patients with BM involvement.

[Hereditary spherocytic hemolytic anemia in an adult with the formation of ectopic foci of extramedullary hemopoiesis in the chest].

The paper describes a rare case of formation of paravertebral extramedullary hemopoietic foci in microspherocytic anemia or Minkovsky-Shoffar disease in an adult. Therapeutic splenectomy has led to regression of extramedullary hemopoietic foci, which supports that there is a direct relationship of the above formations to the specific features of the etiology and pathogenesis of microspherocytic anemia.

[A case of hemolytic-uremic syndrome with development of catastrophic antiphospholipid syndrome: diagnosis and clinical tactics].

The paper describes a case of practically simultaneous development of the hemolytic-uremic syndrome (HUS) and the catastrophic antiphospholipid syndrome (CAPS) complicated by mesenteric vessel thrombosis and small bowel necrosis. Multimodality treatment comprising volume plasmapheresis, fresh frozen plasma transfusion, hemodialysis, anticoagulant and disaggregant therapy could relieve thrombogenic events, such as pulmonary artery thromboembolism and intestinal necrosis.

[Acute abdominal syndrome in blood system diseases].

AIM: To define an optimal diagnostic and therapeutic algorithm when the acute abdominal syndrome occurs in hematological patients. MATERIALS AND METHODS: The results of 145 emergency surgeries made in 2006-2008 for acute abdominal syndrome were studied in patients with blood system diseases. RESULTS: Clinical manifestations of acute abdominal syndrome emerge in 1-1.4% of all the patients treated at the Hematology Research Center, Russian Academy of Medical Sciences. There is a need for surgery in 0.5-0.7% of all the patients admitted. In this group of patients, annual postoperative mortality is 12-16%. CONCLUSION: The routine algorithm for a diagnostic search in hematological patients with acute abdominal syndrome can lead to both hyperdiagnosis and unwarranted surgery, and incorrect choice of expectant policy as well.

[Splenectomy in programmed therapy of aplastic anemia].

AIM: To define efficacy of splenectomy (SE) in current programmed therapy of aplastic anemia (AA). MATERIALS AND METHODS: SE efficacy was analysed in 2 stages: a retrospective study of efficacy of surgery as monotherapy (1986-1996) (74 AA patients) and of SE in programs of immunosuppressive therapy (IST) (1991-2002). Program treatment of AA patients was conducted on the base of IST algorithm developed in Hematological Research Center after many year investigations. RESULTS: SE as monotherapy improved AA course in 73.3% patients with non-severe AA (NAA) and 18.2% patients with severe AA (SAA). Three and five year survival in NAA postsplenectomy patients was 80%. One-year survivors after surgery were likely to survive long. Overall survival of SAA after SE was significantly less (p < 0.0001): 3-year survival - 6%. SE efficacy in programs including antilymphocytic globulin (ALG) and cyclosporin A (CsA) was studied in 69 AA patients. A 85.5% response was registered to program treatment including ALG, CsA and SE, being 81% in SAA and 1% in NAA patients. Efficacy of SE in combination with CsA at the first stage NAA treatment (a 30% positive response) was much inferior to ALG+CsA (68% response). At stage two treatment SE improved treatment results in most of SAA patients. Long-term survival in SAA patients after program treatment with SE is 60%. CONCLUSION: SE in the program of combined therapy in adult AA patients including CsA is an alternative to ALG in NAA patients. In SAA, SE can be included in the program at the first stage in ALG intolerance or in the absence of the drug, at the second stage--to overcome resistance to conducted therapy.

[First experience with the modified program NHL-BFM-90 application in adult patients with primary diffuse large B-cell gastric lymphosarcoma with unfavourable prognosis].

AIM: To assess efficacy of a modified program NHL-BFM-90 in adult patients with primary diffuse large B-cell gastric lymphosarcoms (PDLBGL) with unfavourable prognosis. MATERIAL AND METHODS: Modified courses of NHL-BFM-90 were conducted in 5 patients aged 27-67 years from January 2004 to September 2005. Four patients received chemotherapy of the first line, in one patient block therapy followed monotherapy with chlorambucil and a CHOEP course. All the patients were in a severe clinical condition and had several initial factors of unfavourable prognosis: size of the tumor more than 10 cm; stage IE and more advanced; B-symptoms; proliferative activity above 70%. The program NHL-BFM-90 was modified because of the patients' age. Chemotherapy was conducted according to the middle arm of the original program NHL-BFM-90, but methotrexate was introduced in a dose 1 g/m2 for 12 hours, while leukovorin was given 18 hours after the start of methotrexate injection. In two cases the blocks were enhanced with rituximab, 2 patients had doxorubicin in block A, in one case block C was enhanced with methotrexate. A total of 23 modified blocks NHL-BFM-90 were performed: one patient was given 6 blocks, two patients--5, one patient--4 blocks and one patient--3 blocks. RESULTS: Four patients after block 2 and one patient after block 3 of polychemotherapy NHL-BFM-90 achieved remission of the disease of 6 to 22 months duration which still continues. Infectious complications related to hematological toxicity arose more frequently at the latest courses of chemotherapy. CONCLUSION: Treatment according to the modified program NHL-BFM-90 in adult patients with PDLBGL and unfavourable prognosis is highly effective. For a mean follow-up of 10.2 months no recurrences occurred. The number of courses can be reduced to decrease accumulated hematological toxicity and in case of rapid achievement of remission.

[Possibilities of early diagnosis of tumors].

AIM: To study diagnostic significance of blood serum cancer antigens levels in patients who subsequently develop pulmonary cancer (PC) and gastrointestinal cancer (GIC). MATERIAL AND METHODS: ELISA was used to study expression of tumor antigens (CEA, NSE, CA19-9, CA242, AFP) in the blood serum of 27 PC and 31 GIC patients; 22 patients with lymphatic tumors and 32 patients with pulmonary and gastrointestinal inflammation served control. After removal of the tumor the same antigens including cytokeratines (CK) and differentiated leukocytic markers were studied immunocytochemically in the tumor cells with relevant monoclonal antibodies. RESULTS: Sera of patients with verified afterwards cancer contained elevated concentrations of the antigens: NSE and CEA in PC, CA19-9, CA242 in GIC. The expression of these antigens including CK was found also in tumor cells of these patients. Atypical cells of lymphatic tumors had hemopoietic markers in the absence of CK. In inflammation and in lymphatic tumors, tumor antigens levels remained normal. CONCLUSION: The test for tumor antigens levels in the serum may be used for early (preoperative) diagnosis of cancer, especially in tumors with difficult access or if they are asymptomatic.

[Needle biopsy in diagnosing primary mediastinal tumors]. / Puntsionnaia biopsiia v diagnostike pervichnoi mediastal'noi opukholi.

AIM: To assess the potential of biopsies with the thick cutting needle of anterior mediastinum tumor. MATERIAL AND METHODS: Biopsy with the use of the thick cutting needle (Baxter Healthcare Corporation, length 150 mm, thickness 2.5 mm, length of the cutting channel 20 mm) of a primary mediastinal tumor was made in 12 patients. RESULTS: The findings were the following: 8 cases of primary mediastinal B-cell lymphosarcoma, 1 case of T-cell lymphosarcoma with involvement of the mediastinum, 2 cases of thymic carcinoma, 1 case of pituitary tumor. Mediastinal puncture was controlled by ultrasound which secured accurate position of the needle and safe conduction of the puncture. CONCLUSION: Puncture biopsy with the thick cutting needle of anterior mediastinum tumor provides short duration of the diagnostic process and correction of the treatment policy.

[Stimulation of regenerative processes and correction of the functional activity of the liver in its partial resection and toxic lesions]. / Stimuliatsiia protsessov regeneratsii i korrektsiia funktsional'noi aktivnosti pecheni pri ee chastichnoi rezektsii i toksicheskikh porazheniiakh.

The effects of hepatotropic growth factors (HGFs) and phospholipid drugs on the recovery of functions and the regeneration of the rat liver were studied in CC14-induced toxic damage and after partial hepatectomy (PHE). HGFs isolated from the cytoplasmic cells of the regenerating liver, as well as from the liver of the animals given prodigiozan and from the media taken after culturing the explants of the regenerating liver were found to stimulate DNA synthesis and hepatocytic proliferation following PHE and in the cirrhotic liver. Prodigiozan was shown to induce the formation of HGFs not only in the rat liver following PHE, but in the liver of intact animals. It was established that the covalently binding complex of albumin and bilirubin stimulated the synthesis of proteins and DNA in the regenerating liver, but non-covalently binding complex inhibited these processes. When CC14 was administered to the animals, the two complexes enhanced the reparative synthesis of DNA, without changing the level of replicating synthesis, the non-covalently binding complex completely eliminating the single-strand breaks in DNA. Phospholipid agents containing soybean and sunflower phosphatidylcholines increased the synthesis of RNA and albumin, which were decreased due to exposure to CC14 and had the property of stimulating the synthesis of total DNA and considerably enhancing that of mitochondrial DNA.

[Prognostication of risk in surgical treatment of space-occupying formations of the liver]. / Prognozirovanie riska khirurgicheskogo lecheniia ob"emnykh obrazovanii pecheni.

From practice in the surgical management of 230 space-occupying formations of the liver (100 hepatic resections among other operations) a practical method for quantitative appraisal of the degree of the operative risk was elaborated. The method takes into account the relationship between the risk factors of various significance by multiplying the estimated probability of an unfavourable outcome in each of these factors, which is expressed as a risk multiplication coefficient determined for each of the 34 risk factors defined by the author. The factor of minimal and increased risk, unremovable and potentially removable, were determined. The suggested method allows the probability of an unfavourable outcome to be predicted on an individual basis and the therapeutic tactics to be reasonably changed in each specific case.

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.

[Stimulation of DNA and RNA synthesis in the liver of hepatectomized rats by fractions of liver cytosol and conditioned media obtained during cultivation of rat liver explants]. / Stimuliatsiia sinteza DNK i RNK v pecheni gepatéktomirovannykh krys fraktsiiami tsitozolia pecheni i konditsionirovannoi sredy, poluchennoi pri kul'tivirovanii éksplantatov pecheni krys.

Heat resistant fractions stimulating proliferation (PSF) were identified in the fractions of rat liver cytosol after 70% hepatectomy as well as in the medium harvested after cultivation of rat liver explants. The PSF augmented considerably the rate of DNA synthesis, it increased synthesis and transport of rapidly labelled RNA as well as the level of mitotic activity in rat liver tissue resected by 30% and 80%. Role of the PSF in regulation and acceleration of regeneration processes in the residual parts of liver tissue, remained after hepatectomy, is discussed.