[Endoscopic treatment of Mirizzi syndrome]. / Endoskopicheskoe lechenie sindroma Mirizzi.

Mirizzi syndrome is a complication of cholelithiasis occurring in 0.25-6% of cases [1]. Clinical pattern includes jaundice due to prolapse of a large calculus into the common bile duct following cholecystocholedochal fistula. Ultrasound, CT, MRI, MRCP data, as well as some pathognomonic signs provide preoperative diagnostics of Mirizzi syndrome. In most cases, treatment of this syndrome requires open surgery. We report successful endoscopic treatment of a patient with long-standing bile stone disease complicated by Mirizzi syndrome. Postoperative complications of surgery performed in acute period of disease and further staged treatment using retrograde access are illustrated. Endoscopic treatment demonstrated minimally invasive management of disease presenting diagnostic and technical difficulties.

[Endoscopic treatment of duodenal duplication cyst]. / Endoskopicheskoe lechenie duplikatsionnoi kisty dvenadtsatiperstnoi kishki.

Duodenal duplication cyst (DDC) is a rare form of intestinal malformation (2-12% of all gastrointestinal duplications). There are many difficulties in diagnosis and management of DDC. We present a case of successful endoscopic transluminal treatment of DDC in a 30-year-old female. She complained of epigastric pain, nausea and vomiting, weight loss of 5 kg over the past 3 months. Laparoscopic cholecystectomy for gallstone disease was performed 18 months prior to admission. Examination revealed a cyst 52×60?35 mm in descending part of duodenum. There was a calculus inside the cyst. Transluminal endoscopic cyst fenestration was performed. Histological examination confirmed DDC. According to control duodenoscopy data, cyst was collapsed. The patient remains asymptomatic three months after surgery. DDC is a rare disease of gastrointestinal tract, which should be differentiated first with choledochocele Todani type III and intraluminal duodenal diverticulum. Endoscopic treatment may be an adequate alternative to traditional interventions in some cases.

[X-ray-negative pancreatic dust stones in patients with chronic pancreatiti]. / Rentgenonegativnyi virsungolitiaz u bol'nykh khronicheskim pankreatitom.

Diagnosis of chronic pancreatitis is not associated with any difficulties in patients with CT signs of pancreatic duct stones as a rule. However, 'classical' picture of chronic pancreatitis is usually absent in case of predominant protein matrix in the calculi. Two cases of X-ray-negative pancreatic dust stones in patients with protein stones of the pancreatic duct are reported.

Combination of laparoscopy and endoscopy as an option for treatment patients with gastric neuroendocrine tumors.

BACKGROUND: Neuroendocrine tumors (NETs) are relatively rare neoplasms with the increasing survival due to the development of early diagnostics. There is no universal position in treatment and follow up of small (~20 mm) gastric NETs. CLINICAL CASES: Two female patients 51 and 66 y.o. with multiple gastric NETs <2 cm were observed in our department. In both cases treatment was performed by combination of two minimally invasive technologies: laparoscopy and gastroscopy. According to the localization of tumors in one case intraluminal gastric resection controlled by laparoscopy was performed. In the second case laparoscopic gastric resection with gastroscopy assistance was done. DISCUSSION: There are two positions for surgical treatment of small NETs: to operate as the typical premalignant neoplasm or to make submucosa resections. We demonstrated combination of laparoscopy and gastroscopy as feasible approach with minimal risk of complications.

Effect of the Anti-C1s Humanized Antibody TNT009 and Its Parental Mouse Variant TNT003 on HLA Antibody-Induced Complement Activation-A Preclinical In Vitro Study.

The classic pathway (CP) of complement is believed to significantly contribute to alloantibody-mediated transplant injury, and targeted complement inhibition is currently considered to be a promising approach for preventing rejection. Here, we investigated the mode of action and efficacy of the humanized anti-C1s monoclonal antibody TNT009 and its parental mouse variant, TNT003, in preclinical in vitro models of HLA antibody-triggered CP activation. In flow cytometric assays, we measured the attachment of C1 subcomponents and C4/C3 split products (C4b/d, C3b/d) to HLA antigen-coated flow beads or HLA-mismatched aortic endothelial cells and splenic lymphocytes. Anti-C1s antibodies profoundly inhibited C3 activation at concentrations >20 µg/mL, in both solid phase and cellular assays. While C4 activation was also prevented, this was not the case for C1 subcomponent attachment. Analysis of serum samples obtained from 68 sensitized transplant candidates revealed that the potency of inhibition was related to the extent of baseline CP activation. This study demonstrates that anti-C1s antibodies TNT009 and TNT003 are highly effective in blocking HLA antibody-triggered complement activation downstream of C1. Our results provide the foundation for clinical studies designed to investigate the potential of TNT009 in the treatment or prevention of complement-mediated tissue injury in sensitized transplant recipients.

Protective, elective lung irradiation in non-metastatic Ewing's sarcoma.

Ewing's sarcoma in childhood is a disease from family of the peripheral primitive neuroectodermal tumours. For a period of 16 y (1984-2000), 34 children with Ewing's sarcoma were treated and followed in our department. Twenty-seven of these patients were without distant metastases. Complex treatment was applied to all these patients-chemotherapy VACA (vincristine, actinomycin D, cyclophosphamide, adriamycin), local radiotherapy to a total dose of 50-56 Gy +/- surgery. After, a local tumour control was achieved in 11 children with non-metastatic Ewing's sarcoma, elective whole lung irradiation to a total dose of 12-15 Gy was applied. Our experience in these 11 patients with non-metastatic Ewing's sarcoma, in whom elective lung irradiation was applied, showed significant reduction in the lung metastases, improved free of disease survival and overall survival. The achieved good treatment results necessitate extending this treatment approach through defining the risk groups of patients, suitable for elective lung radiotherapy combined with chemotherapy in non-metastatic Ewing's sarcoma.

Nosocomial transmission of measles among healthcare workers, Bulgaria, 2010.

This report describes 326 cases of nosocomial transmission of measles with 286 cases among non-healthcare workers who acquired the disease in a hospital setting. Between October 2009 and April 2010, 40 healthcare workers from seven different regions in Bulgaria have contracted the disease.

An ongoing measles outbreak in Bulgaria, 2009.

After seven years without indigenous transmission of measles in Bulgaria, an increasing number of cases have been reported since 15 April 2009. By 19 June, the total number of notifications reached 84. To date, 64 were confirmed as measles cases and 15 cases, for whom laboratory results are pending, have been classified as probable. The present measles outbreak affects mostly the Roma population living in the north-eastern part of the country. The most affected age groups are young children below 1 year of age and children 1 to 9 years of age. An immunisation campaign was started in the affected administrative regions, targeting all persons from 13 months to 30 years of age who had not received the complete two-dose MMR vaccination.

An update on an ongoing measles outbreak in Bulgaria, April-November 2009.

Earlier this year, an outbreak of measles was detected in Bulgaria, following an eight-year period without indigenous measles transmission, and continues to spread in the country. By the end of 48 week of 2009 (first week of November), 957 measles cases had been recorded. Most cases are identified among the Roma community living in the north-eastern part of the country. Measles has affected infants, children and young adults. The vaccination campaign that started earlier in the year in the affected administrative regions continues, targeting all individuals from 13 months to 30 years of age who have not received the complete two-dose regimen of the combined measles-mumps-rubella (MMR) vaccination.

Long term survival in five rare cases with multiple primary neuroblastomas.

PURPOSE: Multiple primary neuroblastomas are a very uncommon disorder in infancy. The tumors may arise simultaneously in different parts of the sympathetic nervous system. The purpose of this paper was to present 5 new cases with multifocal neuroblastomas. This is a representative study based on the largest clinical material in Bulgaria. PATIENTS AND METHODS: The records of children treated for neuroblastoma during a 26 year-period (1979-2005) were reviewed and analysed retrospectively. RESULTS: Out of 193 children treated for neuroblastoma and followed in our department, 5 (2.6%) had multifocal lesions. All were boys aged from 2 months to 4 years at the time of diagnosis, and all were treated successfully with radical surgery. Four children were also administered chemotherapy with vincristine, cyclophosphamide and epirubicin; one of them received postoperative radiotherapy as well. All 5 patients are alive and disease-free for a period ranging from 7 to 26 years. CONCLUSION: The excellent prognosis of those rare cases with multiple primary neuroblastomas elucidates questions concerning the tumor's biological behavior and the role of different factors affecting cell differentiation, tumor growth and dissemination.

Radiotherapy of craniopharyngioma in childhood; single institution experience.

PURPOSE: To present the effect of radiotherapy after subtotal excision of craniopharyngioma in childhood and the problems associated with the side-effects after radiotherapy of that rare benign tumor in children. PATIENTS AND METHODS: The study included 8 children with craniopharyngioma, treated with subtotal excision followed by radiotherapy. The median period of observation was 4 years. Radiotherapy was delivered with Co60 telegammatherapeutic machine (Rokus), with daily radiation dose (DRD) of 1.5-1.8 Gy to a total radiation dose (TRD) of 50-56 Gy. RESULTS: All 8 treated children achieved local tumor control (LTC) which was verified with dynamic observations by computed tomography (CT) and magnetic resonance imaging (MRI). In 50% of the cases the eye changes (vision, papillae, perimetric vision) were normalized, and in the remainder an improvement was noted. No child developed neurological or psychical disturbances and no memory or concentration problems ever appeared. From them 50% are very good students. CONCLUSION: Radiotherapy is the main method for achieving a long-term LTC after subtotal excision for craniopharyngioma in childhood. The radiation dose used was well tolerated by brain structures and no late neurological sequelae were observed in our patients.

Desmoid-type fibromatosis in childhood: report of 3 cases with review of the literature.

During the last 20 years we observed 3 cases with the rare condition of desmoid fibromatosis in childhood. This benign tumor with infiltrating potential has therapeutic difficulties for the achievement of a stable local tumor control (LTC). In this paper we present our experience with the therapeutic manipulations applied to our patients and go through the relevant literature on desmoids tumors.

Conservative treatment of invasive lobular breast cancer.

PURPOSE: To assess the efficacy of breast conserving surgery (BCS), followed by postoperative radiation treatment (RT), chemotherapy and/or hormonotherapy in patients with early invasive lobular breast cancer (ILC). PATIENTS AND METHODS: 48 patients with TNM stages I and II ILC of the breast were treated conservatively by BCS (quadrantectomy) and axillary dissection to levels I and II, followed by RT and adjuvant chemotherapy or hormonal treatment. In patients with pN0 the remaining breast with scar and chest were treated by RT, with a total radiation dose (TRD) of 50 Gy. In cases with pN1 the axilla was included to the described field with TRD 50 Gy. In patients with high risk factors (pT2, tumor necrosis, infiltration of the subcutaneous fat and of lymph and/or blood vessels) the tumor bed was boosted up to a TRD of 60 Gy. The 5 and 10- year cancer-specific and recurrence-free survival were calculated according to the Kaplan-Meyer life-table method. RESULTS: With a median observation period of 6.5 years (range 1.5-11.5 years) 2 (4.1%) patients developed local recurrence and 2 (4.1%) distant metastases. Ten-year cancer- specific and recurrence-free survival are 97% and 90%, respectively. CONCLUSION: The obtained good treatment results proved that the conservative treatment strategy in cases with ILC of the breast is a correct therapeutic choice.

[Local treatment of axillae and its impact on survival in patients with early breast cancer (EBC) after breast conservative surgery (BCS)]. / Lokalno lechenie na aksilata i negovoto vliianie v'rkhu prezhivaemostta na patsientite s ranen rak na mlechnata zhleza operatsiia (RMZh) sled zapazvashta g'rdata operatsiia (ZGO).

Following a shut survey showing the influence of the local therapeutic approaches (operative and radiation) for axillaries region on the distant survival, dissemination and lethality in patients with early BC after BCS, the author presents her treatment results. It is pointed out that BC is a systemic disease in some criteria taking in a consideration. In this aspect no significant influence of the local therapeutic methods is found. Furthermore a long-term follow up is still met to prove that a less extensive local treatment methods lead to irreversible consequences: increasing the local recurrences, distant dissemination and lethality.

[Factors influencing the cosmetic outcome in early breast cancer patients following salvage surgery and radioisotope teletherapy]. / Faktori, vliiaeshti v'rkhu kozmetichnite rezultati pri patsientki s ranen rak na mlechnata zhleza sled konservativna khirurgiia i telegamaterapiia.

It is the purpose of the report to analyze the factors exerting effect on the cosmetic outcome in breast cancer patients (I-II clinical stage), following organ-salvaging operation in conjunction with telegammatherapy. Assessment of the cosmetic results in 100 female patients with early mammary gland cancer is done 5 years after complex treatment (conservative surgery, postoperative radiotherapy, and chemo- and/or hormonotherapy when indicated). The influence of eight factors on the cosmetic outcome attained is evaluated through correlative statistical analysis, namely: breast size, scope of the surgical intervention, number of lymph nodes dissected, type of operative cicatrix, dose exposure of the entire mamma, homogeneity of radiation dose distribution in tre entire mammary gland, dose exposure of the tumor bed and adjuvant therapy. The analysis performed points to the important practical implications of three of the factors: size of operative intervention (axillary dissection range), breast volume and homogeneity of the irradiation dose in the entire breast.

Suppression of collagen-induced arthritis by continuous administration of IL-4.

The onset of collagen-induced arthritis in DBA/1 mice is accompanied by a predominantly Th1 response, characterized by production of the proinflammatory cytokines IFN-gamma and TNF-alpha, and a predominance of IgG2a anti-collagen Abs. This study has primarily addressed the effects of continuous administration of exogenous IL-4, a Th2 cytokine, on collagen-induced arthritis in terms of time of onset, clinical symptoms, and histologic changes compared with those in untreated controls. The contributions of Th1 and Th2 cell responses were studied by examining anti-CII IgG subclasses, serum IgE levels, and cytokine production by synovial membrane and lymph node cell cultures. Continuous exposure to IL-4 for 28 days significantly delayed the onset of arthritis from 19 to 37 days and suppressed clinical symptoms. Arthritis occurred approximately 13 to 24 days after treatment ceased. Thereafter, the severity and duration of clinical symptoms were similar to those in control animals, although both joint damage and inflammation at the histologic and cellular levels were less severe than those in untreated controls. During IL-4 treatment, anti-collagen Ab levels were reduced (most significantly those of the IgG2a subclass), histology scores were lower, and the most striking effect was a 1000-fold decrease in TNF-alpha secretion by synovial cells. No significant differences in IgE levels were found between controls and IL-4-treated mice. These data suggest that the anti-inflammatory properties of IL-4 are mediated in part by down-regulation of Th1 responses rather than up-regulation of Th2 responses.

[The importance of histological verification in the conservative surgery of breast cancer]. / Znachenie na khistologichnata verifikatsiia pri konservativna khirurgiia na raka na mlechnata zhleza.

The place and significance of the histological verification in the team method of approach in case of conservative breast cancer treatment are discussed. An accent is made on the histological risk factors increasing the recurrence appearance probability that gathers such patients in a high risk group. On the basis of our own material representing breast cancer patients treated in the period 1987-1993 the significance of the histological verification in the treatment approach is estimated. Requirements for comprehensive histological verification being much needed for breast cancer patients are risen for the pathohistologists.

[The conservative treatment of carcinoma in situ of the cervix uteri by the local application of 5-fluorouracil]. / Konservativno lechenie na kartsinom in situ na matochnata shiika s lokalno aplitsirane na 5-fluorouracil.

Local treatment with 5% of 5-Fluorouracil (5-Fu) in the form of globules was carried out on 37 patients with carcinoma in situ of the uterine cervix, established histologically, as the application was performed once daily for a period of 14-20 days. There was a complete correlation between the cytological investigation after the conservative treatment and the histological examination of the operative material from the conization, which was made within 1-2 weeks after local application of 5-Fu. It could be possible to use cytology for objective determination of the therapeutic effect as well as a possible usage of colposcopic-directed biopsy. The conservative treatment with 5-Fu should be the first stage of treatment of these patients, but in the absence of therapeutic effect conization of the uterine cervix should be made, which reduces the risk of spontaneous abortion. The conservative treatment with local application of 5% of 5-Fu is recommended in young women, with not large lesions of carcinoma in situ of the uterine cervix and still at their reproductive age.

Fibronectin and the adhesive properties of rat lymphocytes obtained from different peripheral lymphoid tissues.

A comparative investigation has been carried out on the effect of plasma fibronectin (Fn) on the adhesive properties of normal rat lymphocytes obtained from different lymphoid tissues: blood, spleen, mesenteric and tonsillar lymph nodes. Fn was immobilized on the basis of its ability to bind to gelatin. We established that concentrations of 40-50 micrograms/ml are sufficient for a saturation effect on Fn coating. For spleen cells an adhesion of 55.7 +/- 9.3%, for mesenteric lymph nodes 34.5 +/- 8.7% and for tonsillar cells 33.8 +/- 3.2% was observed. Blood lymphocytes showed the lowest adhesion, 21.3 +/- 4.2%. Compared to the other lymphoid tissues, the spleen cells exhibited a "basal" adherence to surfaces coated with gelatin only: 19.2 +/- 4.1%. T lymphocytes participate to a greater extent in the process, since their number was significantly reduced in cell suspensions after adhesion to both gelatin and gelatin-Fn coated surfaces. The addition of soluble Fn leads to a competitive inhibition of the lymphocyte adhesion to gelatin-Fn coated surfaces. The data demonstrated the important role of Fn for the adhesive interactions of lymphocytes during their functional distribution in the tissues.