Multifocal and multicentric breast cancer: is breast conserving surgery acceptable?

PURPOSE: The purpose of our study was to evaluate the significance of multifocal (MF) and multicentric (MC) breast cancer in the diagnosis and treatment of this condition. METHODS: This retrospective study was a combination of clinical and laboratory data. The patient population consisted of 274 women operated on with Madden mastectomy for breast cancer. Assessed were the following parameters: age, menstrual status, histopathological parameters, HER-2 status, estrogen receptor (ER) and progesterone receptor (PR) status, disease stage, quadrant(s) in which breast cancer was detected and axillary lymph nodes status. RESULTS: Of 274 patients 206 (85%) has unifocal disease, 41 (15%) suffered of MF (n=27; 9.9%)/MC (n=14; 5.1%) disease. MC disease was associated with metastatic axillary lymph nodes in 92.9% of the cases. MF/MC cases were primarily dependent on histology. MF/MC cancer was best related to the lobular type (85.7% of the cases), while ductal histological type was characteristic of unifocal tumors. CONCLUSION: Quadrantectomy as a form of conservative breast surgery is acceptable in cases of MF tumors, because all tumor foci can be removed. We suggest radical surgical treatment in all cases of suspected MC tumors because they are most often associated with metastasis to the axillary lymph nodes. Lobular histology characterizes MC breast cancer.

Cisplatin monotherapy with concurrent radiotherapy versus combination of cisplatin and 5-fluorouracil chemotherapy with concurrent radiotherapy in patients with locoregionally advanced cervical carcinoma.

PURPOSE: To compare the efficacy, toxicity and survival of cisplatin monotherapy with concurrent radiotherapy ver-sus combination of cisplatin and 5-fluorouracil (5-FU) with concurrent external beam radiotherapy (EBRT) in patients with locoregionally advanced cervical carcinoma FIGO stages IIB-IV. METHODS: 134 patients with locoregionally advanced, histologically confirmed carcinoma of the uterine cervix were analysed. The first group of patients (n=70; 52.24%) started concomitant chemotherapy on the second day of radiotherapy with single-agent cisplatin 40 mg/m(2) given 2 h before radiotherapy, once a week for 6 courses. The second group of patients (n=64; 47.76%) started concomitant chemotherapy on the second day of radiotherapy with cisplatin 75 mg/m(2). Treatment was continued with 96-h infusion of 5-FU 4 g/m(2) (1 g/ m(2) per day for 5 consecutive days). The patients were irradiated by EBRT followed by intracavitary brachytherapy (ICB). RESULTS: 24- and 42-month survival in the first group were 71.9 and 57.81% and 52.5 and 35.4% in the second group, respectively (p=0.012). Mean time to progression in the first group was 24 months and in second group it was 15.9 months (p=0.012). After 2 years progression was noted in 38.3% of the first and in 62.9% of second group patients (p=0.003). After 40 months 60 patients were without relapse, 35 (57.81%) patients in the first group and 25 (37.147percnt;) patients in the second group (p=0.018). CONCLUSION: Treatment with combined cisplatin and 5-FU with concurrent EBRT was more efficient in comparison to cisplatin monotherapy with concurrent radiotherapy in patients with locoregionally advanced cervical carcinoma, in terms of 12- and 24-month overall survival and disease relapse after 2 years.

Synthesis and biological properties of C12,13-cyclopropyl-epothilone A and related epothilones.

BACKGROUND: The epothilones are natural substances that are potently cytotoxic, having an almost identical mode of action to Taxoltrade mark as tubulin-polymerization and microtubule-stabilizing agents. The development of detailed structure-activity relationships for these compounds and the further elucidation of their mechanism of action is of high priority. RESULTS: The chemical synthesis of the C12,13-cyclopropyl analog of epothilone A and its C12,13-trans-diastereoisomer has been accomplished. These compounds and several other epothilone analogs have been screened for their ability to induce tubulin polymerization and death of a number of tumor cells. Several interesting structure-activity trends within this family of compounds were identified. CONCLUSIONS: The results of the biological tests conducted in this study have demonstrated that, although a number of positions on the epothilone skeleton are amenable to modification without significant loss of biological activity, the replacement of the epoxide moiety of epothilone A with a cyclopropyl group leads to total loss of activity.

Type I fiber atrophy and internal nuclei. A form of centronuclear myopathy?

A 6-year-old boy had a myopathy characterized by central nuclei with type I muscle fiber atrophy and preponderance. Study of the family members demonstrated no abnormalities with the exception of an unusually high incidence of centrally located muclei in the muscle biopsy specimen of the mother. A review of the literature disclosed a limited number of cases with identical morphological abnormalities, suggesting that they constitute a form of centronuclear myopathy with some distinctive clinical features.

Ischemic Charcot foot: different disease with different treatment?

AIM: Aim of the study was to describe the presence of peripheral arterial disease in combination with Charcot neuroarthropathy in diabetic patients, and to evaluate the role of revascularization supporting surgical and orthopedic treatment. METHODS: We retrospectively collected and analyzed data of all diabetic patients affected by Charcot neuroarthropathy in combination with critical limb ischemia, which arrived to our care for the presence of foot lesions and underwent endovascular revascularization, followed by surgical and orthopedic treatment between January 2010 and January 2012. The primary end point was to assess the limb salvage rate. The secondary end point was to evaluate the healing time of the lesions. RESULTS: Ten diabetic patients (10 men; mean age 69.1±8.5 years), affected by ischemic Charcot neuroarthropathy underwent endovascular revascularization, surgical debridement and orthopedic correction. The limb salvage rate was 90%, avoiding major amputation in 9 patients. In one patient (10%) the infection could not be controlled and below-the-knee amputation was carried out. The required time to heal the lesion was in mean 197.4±22.4 days, after revascularization, surgical and orthopedic treatment. CONCLUSION: Patients with Charcot foot deformity can be affected by critical limb ischemia and revascularization therapy is necessary, to support surgical and orthopedic treatment, avoiding amputation and leading to limb and foot salvage.

[Comparison of clinical results of anterior cruciate ligament reconstruction using two different procedures].

During the last two decades the "golden standard" in reconstruction of anterior cruciate ligament knee was the middle third of patellar tendon, but now are more used hamstrings tendon autograft. The aim of this work was to compare our results of the artroscopic reconstruction ACL (anterior cruciate ligament) of the knee using two different technics. We were controling 60 patients within the period of two years after operation. Group A was composed of 39 patients which had reconstructed ACL done with bone-patella tendon- bone autografts, in the group B were 21 patients and at them as autographts have been used hamstring tendon. Difference between healthe and the ill knee by the Lachman's test after operation, in the group A was 2,4 mm, but in the group B was 2,2mm (p> 0,05 ). Postoperative middle value of the Lysholm and Gillquist score in the group A was 97,74, in the group B it was 96,67 (p>0,05). IKDC score results are following: Group A- mark A 32 patients (84,6%); mark B 5 (12,8%); mark C 1 (2,6%) and in the group B: mark A 17 patients (81%); mark B 3 (14,28%): mark C 1 (4,72%) (p> 0,05). Postoperative value for the Tegner and Lyscholm score activity in the A group was 8,23, in B group it was 8,81. The reconstruction of ACL with bone- patella tendon-bone grafts gave better results then the reconstruction with the hamstring tendon only according to Tegner score values. In other parameters between those two groups there was no statisticaly significant difference.

Peripheral angioplasty as the first-choice revascularization procedure in diabetic patients with critical limb ischemia: prospective study of 993 consecutive patients hospitalized and followed between 1999 and 2003.

OBJECTIVE: To evaluate the effectiveness of peripheral angioplasty (PTA) as the first-choice revascularisation procedure in diabetic patients with critical limb ischemia (CLI). DESIGN: Prospective study. METHODS: PTA was employed as first choice revascularisation in a consecutive series of diabetic patients hospitalized for CLI between January 1999 and December 2003. RESULTS: PTA was successful performed in 993 patients. Seventeen (1.7%) major amputations were carried out. One death and 33 non-fatal complications were observed. Mean follow-up was 26+/-15 months. Clinical restenosis was observed in 87 patients. The 5 years primary patency was 88%, 95% CI 86-91%. During follow-up 119 (12.0%) patients died at a rate of 6.7% per year. CONCLUSIONS: PTA as the first choice revascularisation procedure is feasible, safe and effective for limb salvage in a high percentage of diabetic patients. Clinical restenosis was an infrequent event and PTA could successfully be repeated in most cases.

[MEDLINE on compact disk as an information source at the Medical School Library in Novi Sad]. / MEDLINE na kompakt disku kao izvor informacija u Biblioteci Medicinskog fakulteta u Novom Sadu.

The transformation of the Library at the Medical Faculty of Novi Sad into a modern information center necessitated the introduction of an up-to-date technology and enforced the use of the latest information sources among which MEDLINE medical database is the most famous one. In the studied period, January 1993-current, 200 searches have been performed on the basis of which the following parameters were analyzed: institution, occupation, and degree of the user, purpose and accuracy of the order, relevant period, number and format of the references, assessment of the search quality and the quality of the library staff services. The analysis proved the initial belief that MEDLINE is a remarkably valuable data base necessary for medical libraries.

Synthesis of epothilones A and B in solid and solution phase.

Epothilones A and B, two compounds that have been recently isolated from myxobacterium Sorangium cellulosum strain 90, have generated intense interest among chemists, biologists and clinicians owing to the structural complexity, unusual mechanism of interaction with microtubules and anticancer potential of these molecules. Like taxol, they exhibit cytotoxicity against tumour cells by inducing microtubule assembly and stabilization, even in taxol-resistant cell lines. Following the structural elucidation of these molecules by X-ray crystallography in 1996, several syntheses of epothilones A and B have been reported, indicative of the potential importance of these molecules in the cancer field. Here we report the first solid-phase synthesis of epothilone A, the total synthesis of epothilone B, and the generation of a small epothilone library. The solid-phase synthesis applied here to epothilone A could open up new possibilities in natural-product synthesis and, together with solution-phase synthesis of other epothilones, paves the way for the generation of large combinatorial libraries of these important molecules for biological screening.

Total synthesis of epothilone E and related side-chain modified analogues via a Stille coupling based strategy.

A Stille coupling strategy has been utilized to complete a total synthesis of epothilone E from vinyl iodide 7 and thiazole-stannane 8h. The central core fragment 7 and its trans-isomer 11 were prepared from triene 15 using ring-closing metathesis (RCM), and were subsequently coupled to a variety of alternative stannanes to provide a library of epothilone analogues 18a-o and 19a-o. The Stille coupling approach was then used to prepare epothilone B analogues from the key macrolactone intermediate 24 which was itself synthesized by a macrolactonization based strategy.