Mozaikinė autologinė kremzlės ir kaulo transplantacija gydant kelio sąnario kremzlės pažeidimus

Rimtautas Gudas1, Romas Jonas Kalesinskas1, Giedrius Bernotavičius1, Eglė Monastyreckienė2, Angelija Valančiūtė3, Darius Pranys41 Kauno medicinos universiteto klinikųOrtopedijos ir traumatologijos klinikaEivenių g. 2, LT-50009 Kaunasel paštas: [email protected] Kauno medicinos universiteto klinikųRadiologijos klinika3 Kauno medicinos universitetoEmbriologijos ir histologijos katedra4 Kauno medicinos universitetoPatologinės anatomijos klinika Tikslas Mūsų prospektyvaus klinikinio tyrimo tikslas – įvertinti mozaikinės autologinės transplantacijos rezultatus gydant kelio sąnario kremzlės pažeidimus. Ligoniai ir metodai 1998–2002 metais KMU Ortopedijos ir traumatologijos klinikoje atliktos 87 autologinės mozaikinės transplantacijos operacijos esant kelio sąnario kremzlės ir kaulo pažeidimams. Pacientų amžiaus vidurkis operacijų metu buvo 24,74 ± 7,20 metų (14–40 metų). Simptomai vidutiniškai truko 21,32 ± 5,57 mėnesio, o pacientai įvertinti praėjus vidutiniškai 24,4 mėnesio (nuo 12 iki 60 mėnesių) po operacijos. Rezultatai apibendrinti naudojant ICRS (International Cartilage Repair Society) anketą, 13 (15%) atvejų – remiantis kartotinių artroskopijų metu atliktu makroskopiniu įvertinimu, 9 (11%) atvejais – histologiniu tyrimu, 57 (67%) atvejais – BMR ir visais atvejais – rentgeno tyrimais. Visus anketinius įvertinimus atliko nepriklausomas gydytojas ortopedas prieš operacijas ir po operacijų praėjus dvylikai, dvidešimt keturiems, trisdešimt šešiems, keturiasdešimt aštuoniems ir šešiasdešimčiai mėnesių. Nepriklausomi nuo tyrimo gydytojai, radiologas ir patologas, atliko visus BMR ir histomorfologinius įvertinimus. Rezultatai Praėjus vidutiniškai 24,4 mėnesio po mozaikinės transplantacijos, ICRS anketos būdu nustatytas klinikinis rezultatų pagerėjimas (p < 0,05). Funkcinis ir objektyvus įvertinimas pagal ICRS anketą buvo toks: 93% atvejų gauti geri ir labai geri operacinio gydymo rezultatai, kitais atvejais (7%) gydymo rezultatai buvo patenkinami. Kartotinių artroskopijų metu (remiantis ICRS protokolu), po operacijų praėjus vidutiniškai 12,4 mėnesio, 11 (84%) iš 13 atvejų buvo nustatytas geras ir labai geras sąnario kremzlės makroskopinis atsitaisymas. Sąnario kremzlės biopsijos ir histologinis tyrimas buvo atliktas 11% pacientų, ir daugumos jų (remiantis ICRS protokolu) sąnario kremzlės ir pokremzlinio kaulo atitaisymo koeficientas buvo geras. BMR tyrimas parodė, kad 94% pacientų sąnario paviršius atkurtas gerai arba labai gerai. Išvados Mūsų tyrimas parodė, kad po mozaikinės autologinės transplantacijos praėjus vidutiniškai 24,4 mėnesio (nuo 12 iki 60 mėn.) fiziškai aktyvių pacientų, kuriems buvo pažeista kelio sąnario kremzlė, klinikinė ir funkcinė būklė labai pagerėjo. Dauguma pacientų po kremzlės mozaikinės autologinės transplantacijos atgauna prieš pažeidimą buvusį fizinio aktyvumo lygį. Histomorfologinis persodintų transplantatų tyrimas parodė, kad visais tirtais atvejais išsilaikė hialininės kremzlės struktūra ir fibroelastinio audinio intarpai tarp transplantatų. Reikšminiai žodžiai: sąnario kremzlės pažeidimai, mozaikinė transplantacija Mosaic-like autologous osteochondral transplantation for the treatment of knee joint articular cartilage injuries Rimtautas Gudas1, Romas Jonas Kalesinskas1, Giedrius Bernotavičius1, Eglė Monastyreckienė2, Angelija Valančiūtė3, Darius Pranys4 Objective The purpose of this prospective clinical study was to evaluate the outcomes of mosaic type autologous osteochondral transplantation procedure for the treatment of the articular cartilage defects of the knee joint. Patients and methods Between 1998 and 2002, a total of 85 patients underwent an osteochondral autologous transplantation (mosaicplasty) procedure for osteochondral or chondral knee joint injury. The patients were evaluated using the ICRS score, arthroscopically, histologically, with MRI and X-ray examinations. The mean duration of symptoms was 21.32 ± 5.57 months and the mean follow-up was 24.4 months (range, 12 to 60 months). The mean age of the patients during the surgery was 24.74 ± 7.20 years (range, 14 to 40 years). An independent observer performed a follow-up examination after six, twelve, twenty-four, thirty-six and forty-eight months. In 13 (15%) of 85 cases 12.4 months postoperatively, arthroscopy with biopsy for histological evaluation was carried out. A radiologist and a pathologist, both blinded to each patient’s treatment, did the radiological and histological evaluations. Results After 24.4 months all the patients showed a significant clinical improvement (p < 0.05). The cartilage Repair Society (ICRS) score, functional and objective assessment revealed 93% to have excellent or good results after mosaicplasty; 7% were fair 24.4 months (range, 12–60 months) after the operations. The ICRS evaluation showed a significant improvement after the mosaicplasty procedure 24.4 months following operations (p = 0.005). No serious complications were reported. The ICRS for macroscopic evaluation during arthroscopy 12.4 months after mosaicplasty demonstrated excellent or good repair in 11 (84%) of 13 cases. Biopsy specimens were obtained from 9 (69%) of 13 patients, and histological evaluation of repair showed good scores (according to ICRS) for most samples after mosaicplasty. A MRI evaluation demonstrated excellent or good repairs in 94% after mosaicplasty. Conclusions On an average after 24.4 months (range, 12 to 60 months) of follow-up, our clinical study has shown a significant improvement of the clinical status of the physically active patients after the mosaic type autologous osteochondral transplantation for the repair of articular cartilage defects in the knee. Histologically, the osteochondral cylinder transplants retained hyaline cartilage. Keywords: articular cartilage injury, osteochondral mosaic-like transplantatio

Microvessel density as new prognostic marker after radiotherapy in rectal cancer

<p>Abstract</p> <p>Background</p> <p>The extent of angiogenesis is an important prognostic factor for colorectal carcinoma, however, there are few studies concerning changes in angiogenesis with radiotherapy (RTX). Our aim was to investigate changes in tumor angiogenesis influenced by radiotherapy to assess the prognostic value of angiogenesis the microvessel density (MVD) in overall survival after radiotherapy.</p> <p>Methods</p> <p>Tumor specimens were taken from 101 patients resected for rectal cancer. The patients were divided into three groups according to the treatment they received before surgery (not treated, a short course, or long course of RTX). Tumor specimens were paraffin-embedded and immunohistochemistry was performed with primary antibody against CD-34 to count MVD.</p> <p>Results</p> <p>MVD was significantly lower in the group of patients treated with a long course of RTX (p <0.025). The mean MVD for the long RTX group was 134.8; for the short RTX group – 192.5; and for those not treated with RTX – 193.0. There were no significant statistical correlations between MVD and age, sex, grade of tumor differentiation (G) and tumor size (T) in those untreated with RTX. In long RTX group we found a significant prognostic rate for MVD when the density cut off was near 130 with 92.3% sensitivity and 64.7% specificity. When the MVD was lower than a cut off of 130, the survival period significantly increased (p = 0.001), the mortality rate is significantly higher if the MVD is higher than 130 (microvessel/mm²) (1953.047; p = 0.002), if the histological grade is moderate/poor (127.407; p = 0.013), if the tumor is T3/T4 (111.618; p = 0.014), and if the patient is male (17.92; p = 0.034) adjusted by other variable in model.</p> <p>Conclusion</p> <p>Our results show that a long course of radiotherapy significantly decreased angiogenesis in rectal cancer tissue. MVD was found to be a favourable marker for tumor behaviour during RTX and a predictor of overall survival after long course of RTX. Further investigations are now needed to determine the changes in angiogenesis during a shorter course of RTX.</p

The Impact of morphophysiologic peculiarities of the pancreas on pancreas-related morbidity following pancreatoduodenectomy

Background. The factors influencing failure of pancreaticojejunostomy following pancreatoduodenectomy are still ill-defined. Our previous study showed that age of patient, bilirubinemia or malignant nature of peripancreatic tumor had no impact on pancreas-related morbidity following pancreatoduodenectomy. The hypothesis is that it could be influenced by the level of pancreatic fibrosis, diameter of the main pancreatic duct, and exocrine pancreatic function. Aim of the study was to analyze the impact of morphologic and physiologic peculiarities of pancreatic remnant on development of pancreas-related morbidity after Whipple procedure. Material and methods. We have analyzed retrospectively clinical data of 122 patients who have undergone pancreatoduodenectomy in the Department of Surgery of Kaunas University of Medicine Hospital during 1995\u96 2001. Fibrosis of pancreatic parenchyma, diameter of main pancreatic duct, and preoperative exocrine function were evaluated. Pancreas-related morbidity was determined as either peripancreatic sepsis or pancreatic fistula. Fibrosis of pancreatic remnant was determined by computer-aided morphometric analysis. The exocrine pancreatic function was tested the day before surgery by Pancreatic Elastase-1 Stool test

HER2 receptorių ir p53 baltymo padidėjusios raiškos įtaka II stadijos krūties vėžiu sergančių moterų gyvenimo trukmei

Tyrimo tikslas. Ištirti p53 baltymo ir HER2 (c-erbB-2) receptorių padidėjusios raiškos įtaką II stadijos krūties vėžiu sirgusių jaunų moterų penkerių metų išgyvenamumui, atsižvelgiant į hormonų receptorių bei gydymo savitumų reikšmę. Tyrimo medžiaga ir metodai. Retrospektyviai analizuojama 34 Kauno apskrities moterų, gydytų 2001–2003 m. Kauno onkologijos ligoninėje, medicininė dokumentacija ir archyvinė histologinė medžiaga. Tiriamųjų kontingentas – jaunos, iki 50 metų moterys, kurioms diagnozuotas ir morfologiškai patvirtintas II stadijos krūties vėžys. 22 moterys išgyveno penkerius metus, 12 mirė penkerių metų laikotarpiu. Panaudojant archyvinę histologinę medžiagą de novo, tuometinėje KMUK Patologinės anatomijos klinikoje buvo atliktas p53 baltymo ir HER2 receptorių raiškos tyrimas imunohistocheminiu metodu. Panaudojant medicininę dokumentaciją, analizuota pacientėms skirta adjuvantinė chemoterapija, antraciklinų suminė dozė ir hormoninis gydymas. Rezultatai. Tarp visų 34 tiriamųjų 20,6 proc. atvejų rasta padidėjusi p53 baltymo raiška, 26,4 proc. atvejų – HER2 baltymo raiška. Analizuojant išgyvenamumą Kaplan-Meier metodu, nustatyta, kad mirties tikimybė penkerių metų laikotarpiu didesnė, kai naviko histologinėje medžiagoje rastas padidėjęs p53 baltymo kaupimasis, neigiami estrogenų receptoriai ir kai pacientės gydytos nepakankama antraciklino doze (log rank p=0,013, log rank p=0,02, log rank p=0,027, atitinkamai). Nerasta sąsajų tarp padidėjusios HER2 baltymo raiškos ir pacienčių penkerių metų išgyvenimo (log rank p=0,51). Daugiamatės analizės metodu nustatyta, kad vienintelis nepriklausomas veiksnys yra nepakankama antraciklinų dozė (p=0,028). Išvada. Jaunų moterų, susirgusių II stadijos krūties vėžiu, trumpesnei gyvenimo trukmei įtakos turi padidėjusi p53 baltymo raiška, sumažinta antraciklinų dozė ir neigiami estrogenų receptoriai, o HER2 baltymo padidėjusios raiškos įtakos penkerių metų gyvenimo trukmei nepavyko įrodyti. Nepriklausomas prognozinis veiksnys yra nepakankamas adjuvantinis gydymas antraciklinais

Impact of p53 protein and HER2 overexpression on survival of patients with stage II breast cancer

Objective. To assess the prognostic signifi cance and impact of p53 protein and human epidermal growth factor receptor 2 (HER2) overexpression on 5-year survival in young patients with stage II breast cancer (aged less than 50 years). Material and methods. Material from medical records and archived tumor tissues from 34 young women diagnosed with stage II breast cancer and obtained between 2001 and 2003 was analyzed retrospectively. Twelve (35%) patients died from breast cancer. Using archived tumor tissues, p53 protein and HER2 overexpression was determined immunohistochemically. Using medical records, and adjuvant chemotherapy, adequacy of anthracycline dose, and hormonotherapy administered for the patients were analyzed. Results. p53 protein and HER2 overexpression was documented in 20.6% and 26.4% of women, respectively. Kaplan-Meier survival analysis showed that patients with tumors positive for p53 protein and negative estrogen receptors, and treated with an inadequate dose of anthracyclines died within shorter period after diagnosis (log-rank P=0.016, log-rank P=0.027, log-rank P=0.013, respectively). There were no signifi cant associations between HER2 overexpression and 5-year survival in this population (log-rank P=0.51). Multivariate analysis revealed that an inadequate dose of anthracyclines (P=0.028) was the only independent factor for poor outcome. Conclusions. p53 protein overexpression, negative estrogen receptors in tissue samples, and inadequate chemotherapy with anthracyclines were associated with reduced overall survival in young women with stage II breast cancer. Inadequate adjuvant therapy with anthracyclines was the only independent prognostic factor

Diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration cytological smears and cell blocks: A Single-institution experience

Background and Objective: Endobronchial ultrasound (EBUS) is a minimally invasive endobronchial technique, which uses ultrasound along with a bronchoscope to visualize the airway wall and structures that are adjacent to it. Indications for endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) are samplings of mediastinal, hilar lymph nodes, and tumors adjacent to airway walls. EBUS-TBNA has been used in our clinic since 2009. The aim of the study is to evaluate the sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of cytological and histological specimens, and the safety of EBUS-TBNA in an unselected patient population that has been referred to our hospital. Materials and Methods: We have retrospectively analyzed the medical documentation of 215 patients who had EBUS-TBNA performed in our clinic from April 2009 to February 2014. Results: There were 215 patients who underwent EBUS-TBNA. A total of 296 lymph nodes were sampled. EBUS-TBNA was diagnostic in 176 (81.9%) cases of cytological, 147 (68.4%) cases of histological, and 191 (88.9%) cases of the combined evaluation. In the lung cancer patients, EBUS-TBNA cytology had a sensitivity of 72.9% and histology of 72.9%, and in the sarcoidosis group, it had a cytology of 55.8% and histology of 64.5%. As all positive cytology and histology specimens were assumed to be true positive, specificity and positive predictive value (PPV) were 100%. The sensitivity and diagnostic accuracy was significantly higher when cytology and histology specimens were combined, compared with cytology or histology results evaluated separately (p < 0.05) (for lung cancer 84.1% and for sarcoidosis 78.8%). The sensitivity and diagnostic accuracy of EBUS-TBNA procedures increased significantly over time, with increased experience. There were no complications with EBUS-TBNA in our clinical practice. [...]

The Association of Low-To-Moderate Alcohol Consumption with Breast Cancer Subtypes Defined by Hormone Receptor Status.

Alcohol is a well-established risk factor for breast cancer, but pathways involved in alcohol-related breast carcinogenesis are not clearly defined. We examined the association between low-to-moderate alcohol intake and breast cancer subtypes by tumor hormone receptor status.A hospital-based case-control study was performed in 585 cases and 1,170 controls. Information on alcohol intake and other risk factors was collected via a questionnaire. Logistic regression was used for analyses. All statistical tests were two-sided.The odds ratio of breast cancer was 1.75 (95% confidence interval [CI]: 1.21-2.53) in women who consumed ≤5 drinks/week, and 3.13 (95% CI: 1.81-5.43) in women who consumed >5 drinks/week, both compared with non-drinkers for ≥10 years, after adjustment for age and other confounders. The association of alcohol intake with estrogen receptor-positive breast cancer was stronger than with estrogen receptor-negative: the odds ratio per 1 category increase was 2.05 (95% CI: 1.49-2.82) and 1.29 (95% CI: 0.85-1.94) (P-heterogeneity = 0.07). There was no evidence of an interaction between alcohol intake and menopausal status (P = 0.19) in overall group; however, it was significant in estrogen receptor-positive breast cancer (P = 0.04).Low-to-moderate alcohol intake is associated with the risk of estrogen receptor-positive breast cancer with the strongest association in postmenopausal women. Since alcohol intake is a modifiable risk factor of breast cancer, every woman should be informed and advised to control alcohol use