Expression of IAP family proteins and its clinical importance in breast cancer patients.

Inhibitor of apoptosis (IAP) family proteins is involved in mechanisms of resistance to apoptosis in various cancer cells. The aim of this study was to assess the expression of selected IAP proteins such as XIAP, cIAP-1, cIAP-2 and survivin in breast cancer patients and evaluates their relationship with the prognostic and predictive factors and their impact to overall survival (OS) and progression free survival (PFS). The study was conducted with the use of tissue samples prospectively collected from 92 previously untreated female breast cancer patients. The control encompassed 10 fibroadenoma patients. The expression of XIAP, cIAP-1, cIAP-2 and survivin was assessed using flow multicolor cytometry. XIAP expression was present in 99 % of the breast cancer patients (91/92) with the median expression 13.65% (range 1-66.8%). Expression of XIAP in breast cancer was significantly higher compared to the control group (p=0.006). Median expression of cIAP-1, cIAP-2 and survivin in the study group was 25.95% (range 0.8-83.7%), 16.7% (range 1-53.2%) and 4.6% (range 0-43%) respectively. In the rank Spearman test, strong correlations (p<0.001) were seen among the expressions of XIAP, cIAP-2 and survivin, in all combination. Additionally, week correlation between XIAP and cIAP-1 was observed (p=0.02). The median expression of XIAP and survivin was significantly higher in more advanced tumors (stages pT2/pT3 vs. pT1). The median PFS and OS in breast cancer group were 46.15 and 47.1 months respectively. No significant correlations were observed among expressions of IAP family proteins and survival. However, low expression of XIAP in breast cancer showed trend to longer PFS (p=0.08). XIAP, cIAP-1 cIAP-2 and survivin participate in antiapoptotic mechanisms in breast cancer and XIAP and survivin seem to have the most significant prognostic importance. Further studies are needed to establish more complete prognostic and predictive values of IAP family proteins in breast cancer patients.

Membrane expression of trail receptors DcR1 and DcR2 in the normal endometrium, endometrial atypical hyperplasia and endometrioid endometrial cancer.

We aimed to evaluate the membrane expression of DcR1 and DcR2 in the normal endometrium (NE), endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC). The study comprised 101 patients: 20 NE, 14 EAH and 67 EEC. Membrane expression of DcR1 and DcR2 was examined and presented as total score (TS). The membrane expression of both DcR1 and DcR2 was more common in EEC than in NE (p < 0.001; p < 0.001). A strong correlation was found between type of endometrial tissue (NE/EAH/EEC) and the TS of DcR1 (p = 0.001) and DcR2 (p < 0.001). In EEC, the TS of DcR1 and DcR2 was not related to grading and survival. The TS of DcR1 negatively correlated with staging (p = 0.018), but DcR2 did not. The membrane expression of decoy receptors for TRAIL DcR1 and DcR2 is greater in NE than EEC. In EEC patients, membrane expression of DcR1 and DcR2 are not independent predictors of survival.

Membrane expression of the death ligand trail receptors DR4 and DR5 in the normal endometrium, endometrial atypical hyperplasia and endometrioid endometrial cancer.

To assess membrane expression of DR4 and DR5 in the normal endometrium (NE), endometrial atypical hyperplasia (EAH) and endometrioid endometrial cancer (EEC), the study examined 101 patients: 20 NE, 14 EAH and 67 EEC. The expression of DR4 and DR5 was examined and presented as the total score (TS). DR4 expression was seen in 18 NE, 11 EAH and 10 EEC. DR5 expression was seen in 20 NE, 13 EAH and 21 EEC. A strong correlation between type of endometrial tissue and TS of both receptors was identified. In EEC TS of DR4 and DR5 was not related to grading, staging or survival. Malignant transformation in the endometrium is related to reduction of membrane DR4 and DR5 expression. The level of membrane staining of the receptors in EEC is not dependent on grading and staging, and is not sufficient to predict survival in EEC patients.

Nomogram-Based Prognostic Evaluation of Gastric Cancer Patients with Low Counts of Examined Lymph Nodes Outperforms the Predictive Ability of the 7th and 8th Editions of the American Joint Committee on Cancer Staging System.

BACKGROUND: The American Joint Committee on Cancer (AJCC) staging system has limited accuracy in predicting survival of gastric cancer patients with inadequate counts of evaluated lymph nodes (LNs). We therefore aimed to develop a prognostic nomogram suitable for clinical applications in such cases. METHODS: A total of 1511 noncardia gastric cancer patients treated between 1990 and 2010 in the academic surgical center were reviewed to compare the 7th and 8th editions of the AJCC staging system. A nomogram was developed for the prediction of 5-year survival in patients with less than 16 LNs evaluated (n = 546). External validation was performed using datasets derived from the Polish Gastric Cancer Study Group (n = 668) and the SEER database (n = 11,225). RESULTS: The 8th edition of AJCC staging showed better overall discriminatory power compared to the previous version, but no improvement was found for patients with < 16 evaluated LNs. The developed nomogram had better concordance index (0.695) than the former (0.682) or latest (0.680) staging editions, including patients subject to neoadjuvant treatment, and calibration curves showed excellent agreement between the nomogram-predicted and actual survival. High discriminatory power was also demonstrated for both validation cohorts. Subsequently, the nomogram showed the best accuracy for the prediction of 5-year survival through the time-dependent ROC curve analysis in the training and validation cohorts. CONCLUSIONS: A clinically relevant nomogram was built for the prediction of 5-year survival in patients with inadequate numbers of LNs evaluated in surgical specimens. The predictive accuracy of the nomogram was validated in two Western populations.

Correlation of Smac/DIABLO protein expression with the clinico-pathological features of breast cancer patients.

Smac/DIABLO protein promotes caspase-dependent apoptosis by inhibition of inhibitor of apoptosis protein (IAP) family members. The role of Smac/DIABLO in breast cancer has not been yet established. Therefore, the aim of the study was to assess the expression of this protein in tumor cells from breast cancer patients. The expression of Smac/DIABLO was analyzed in 62 breast cancer patients by flow cytometry. The obtained results were compared with expression of this protein in benign breast tumor tissue, which served as the control (11 patients with fibroadenoma). Expression of caspase-3 proteins in breast cancer was also evaluated. Smac/DIABLO expression in breast cancer was correlated with clinical and pathological data. Although the expression of Smac/DIABLO protein was found in all examined samples of both the breast cancer and fibroadenoma patients, the median expression of Smac/Diablo in breast cancer was significantly lower than in the control (39.1% vs. 48.1%; p=0.0047). Smac/DIABLO expression correlated with expression of caspase-3 (p=0.000008). In pT1 breast cancer patients, expression of Smac/DIABLO protein was higher than in those with pT2-3 (p=0.02). Diffuse cancer infiltration significantly correlated with lower expression of Smac/DIABLO protein (p=0.02). Moreover, there was a loose correlation between low expression of Smac/DIABLO protein and cancer embolus in minor blood and lymphatic vessels (p=0.08). Our results indicate that expression of Smac/DIABLO inversely correlates with the tumor stage, which may suggest that this protein may play an important role in the breast cancer development.

Adjuvant chemotherapy with etoposide, adriamycin and cisplatin compared with surgery alone in the treatment of gastric cancer: a phase III randomized, multicenter, clinical trial.

OBJECTIVE: The aim of this study was to evaluate the efficacy of adjuvant chemotherapy with etoposide, Adriamycin and cisplatin (EAP) after potentially curative resections for gastric cancer. METHODS: After surgery, patients were randomly assigned to the EAP or control arm. Chemotherapy included 3 courses, administered every 28 days. Each cycle consisted of doxorubicin (20 mg/m(2)) on days 1 and 7, cisplatin (40 mg/m(2)) on days 2 and 8, and etoposide (120 mg/m(2)) on days 4, 5, and 6. RESULTS: Of 309 eligible patients, 141 were allocated to chemotherapy and 154 to the supportive care group. Four (2.8%) treatment-related deaths were recorded, including 3 due to septic complications of myelosuppression and 1 due to cardiocirculatory failure. Grade 3 or 4 toxicities were found in 17 (22%) patients. According to the intention-to-treat analysis, the median survival was 41.3 months (95% confidence interval, 24.5-58.2) and 35.9 months (95% confidence interval, 25.5-46.3) in the chemotherapy and control group, respectively (p = 0.398). Subgroup analysis revealed survival benefit from chemotherapy in patients with tumors infiltrating the serosa and in those with 7-15 metastatic lymph nodes. CONCLUSION: Three cycles of EAP regimen postoperatively offer no survival advantage in gastric cancer patients.

Does fecal diversion offer any chance for spontaneous closure of the radiation-induced rectovaginal fistula?

Analysis of the clinical course of patients with postirradiation rectovaginal fistula after fecal diversion. The studied group included 17 women with postirradiation rectovaginal fistula who underwent fecal diversion as a sole mode of treatment, between January 1987 and December 2002, in our department. All patients were subjected to radiotherapy due to cancer of the uterine cervix, administered 5-107 months before the fistula appearance (mean, 22.9 months). In 3 of 17 patients (18%), spontaneous closure of fistula was observed after 5, 6, and 9 months, respectively, from fecal diversion. Closure was confirmed by endoscopy. Length of follow-up after fecal diversion ranged from 0.5 to 122 months. The actuarial probability of spontaneous closure of postradiotherapy rectovaginal fistula was 0.24 at 9 months of follow-up and then remained stable thereafter. In conclusion, colostomy alone gives hardly a chance for closure of the postradiotherapy rectovaginal fistula. Additional surgical measures are necessary.

Astonishingly rapid growth of malignant cystosarcoma phyllodes tumor in a pregnant woman--a case report.

There are very few reports concerning the presence of malignant cystosarcoma phyllodes (CSP) in breasts of pregnant women. In the hereby described case, a 28-year-old woman presented in our department with huge (18 x 11 x 8 cm) tumor of left breast, 2 weeks after labor. The patient discovered a tumor in 34th week of pregnancy, 6 weeks before labor. Histopatholgic examination of excised tumor revealed the presence of malignant CSP tumor. Simple mastectomy was proposed to patient as a best treatment modality. However, the patient refused. She underwent excision of tumor bed (2-cm tumor-free margin was achieved). Despite insufficient treatment, she remains free of disease 20 months after the wide excision of breast malignancy. It is not known how pregnancy influences prognosis of patients with malignant CSP. Lack of such information prompted us to describe the clinical course of our patient.

[Asthma: Adapting the therapeutic follow-up according to the medical and psychosocial profiles]. / Adapter l'accompagnement thérapeutique de l'asthmatique en fonction des profils médico-psycho-sociaux. Enseignements de l'enquête REALISE™ chez des patients asthmatiques adultes et repères éducationnels pour la pratique.

INTRODUCTION: This work is based on the data of REALISE™, a survey conducted among 8000 European patients to identify the profiles of adult asthma patients and how these are linked with treatment adherence behaviors. METHODS: A cluster analysis was performed by combining data in three ways: control of asthma, attitude towards the disease, compliance with treatment. A multidisciplinary group analyzed the results for the 1024 French survey respondents. RESULTS: Four patient profiles were identified: "rather confident" (28% of patients), rather young patients with a low level of concern about their asthma. "Rather committed" (23%) patients considering themselves to be mostly healthy, reporting better therapeutic declared. "Rather questing" (26%), patients poorly controlled, seeking to manage their asthma themselves. "Rather concerned" profile (23%), a bit older, with poor clinical control, considering their asthma to be severe. CONCLUSIONS: Cluster analysis provides a multidimensional approach to understand the therapeutic behavior of the different patient profiles better and so adjust communication by and education of healthcare professionals.

[Patients with asthma: Disease control, patients' perceptions and observance. Results of the French REALISE™ survey]. / Patient asthmatique : contrôle, ressenti et observance. Résultats français de l'enquête REALISE™.

INTRODUCTION: Poor adherence to treatment is a cause of inadequate asthma control and increased exacerbations. Better understanding of the factors associated with adherence could lead to recognition of appropriate solutions. METHOD: An online, quantitative, self-completed questionnaire-based survey was conducted among 1024 French adults with asthma (aged 18-50years). Data were collected on socio-demographic characteristics, asthma control, patient perception of the disease and adherence. RESULTS: Only 11% of asthma patients considered that their asthma is uncontrolled while 48% were uncontrolled according to the GINA criteria. More than half (56%) of respondents admitted not taking their maintenance therapy every day. The perception that asthma was well controlled and lack of impact of the disease on daily activities were the most common reasons cited (46% of respondents) for not taking maintenance therapy. The other main reasons cited were forgetting and use only during symptomatic periods (21% and 14% of respondents, respectively). CONCLUSION: Adult asthma patients tend to overestimate their level of asthma control. Improving the management of asthma requires systematic detection of respiratory symptoms, awareness of the patient that asthma is a chronic disease and improved physician assessment of patients' expectations and perception of their disease.

Sentinel node biopsy in patients with breast cancer--evaluation of exposure to radiation of medical staff.

AIM: To measure the absorbed doses of radiation to hands of medical staff performing sentinel node biopsy in breast cancer patients. METHODS: The study was conducted in 2004, during sentinel node biopsies in 13 breast cancer patients (T1/T2N0). Sentinel nodes were identified with the use of combined radiotracer/blue dye technique (lymphoscintigraphy--99mTc on albumin carrier, surgery after 24 h; blue dye; intraoperative detection of gamma radiation). Highly sensitive thermoluminescent dosimeters (TLD) made of LiF were used to assess the absorbed doses of radiation during the procedure. During lymphoscintigraphy and during surgical procedure a total of 57 TLDs was placed on different parts of hands of medical staff. RESULTS: Maximal dose recorded during lymphoscintigraphy by TLDs placed on the hands of the physician injecting the radiotracer was 164 microSv. Mean recorded doses were higher for non-dominant hand, especially for distal parts of the index finger, third finger and thumb. During the surgical procedure, TLDs placed on the hands of medical staff recorded much lower doses of radiation than during lymphoscintigraphy. The highest dose was recorded by TLD placed on the pulp of the dominant hand index finger (22 microSv) of the operating surgeon. Mean doses recorded by TLDs placed on the hands of the operating surgeon ranged from 2 to 8 microSv. The absorbed dose of radiation to hands of the scrub nurse was similar to that absorbed to hands of the operating surgeon. CONCLUSION: The maximum recorded dose during sentinel node biopsy in this study was 2200 times smaller than current 1-year dose limit.

Clinically silent Paget disease of male nipple.

Male breast cancer constitutes less than 1% of all breast cancer cases. Special types, such as Paget disease of the breast, are extremely rare. To our knowledge there are less than 50 cases of Paget disease of male breast described in world medical literature. Authors present pathologically proven but clinically silent case of Paget disease of the nipple in an 86-year old male with breast cancer. Literature data suggest that the prognosis of male Paget cancer is worse than in "ordinary" male breast cancer. Therefore, the histologic diagnosis of Paget disease, even in an asymptomatic male patient, may have negative prognostic value.

The expression of the proliferating antigen Ki67, PCNA and products of suppressor gene p53 in primary invasive ductal breast carcinoma.

The classification of histological malignancy by Bloom and Richardson used in ductal invasive breast cancer seems to be not sufficient. In the same group of patients with the same clinical status as well as pathological malignancy the prognosis can be different and unpredictable. The aim of the study was to examine a consecutive series of primary ductal invasive tumours to find out: a) the expression of some biological cellular parameters as proliferating antigens Ki67 and PCNA and the products of the suppressor gene p53; b) the correlation between the levels of expression of those factors and classical prognostic factors, such as tumour diameter, status of axillary lymph nodes, status of steroids receptors, degree of histological differentiation. It seems that the estimation of proliferating antigens together with products of suppressor gene p53 might have greater prognostic value than the estimation of single factors.

The expression of products of oncogens c-erbB2 and EGFR and proliferating antigens Ki67 and PCNA in primary invasive ductal cancer of female breast.

The aim of the study was to examine the consecutive series of primary ductal invasive tumours and find out: a) the expression of some biological cellular parameters as proliferating antigens Ki67 and PCNA and products of gene EGFR, erbB2; b) correlation between the levels of expression of those factors and classical prognostic factors, such as diameter of tumour, status of axillary lymph nodes, status of steroids receptors, the degree of histological differentiation. We found that: 1. The presence of the expression of oncoproteins c-erbB2 and EGFR, high index IP PCNA, Ki67 and low levels of steroids receptors correlates with high histological malignancy (Bloom III0); 2. The lack of expression of oncoproteins c-erbB2, EGFR and low index IP PCNA, Ki67 correlates with high levels of steroids receptors; 3. The estimation of high levels of index IP PCNA, IP Ki67 can be helpful for separate tumours of high proliferating activity; 4. The expression of oncoprotein c-erbB2 and EGFR does not correlate with the diameter of tumour as well as with the involvement of axillary lymph nodes. It seems that the estimation of proliferating antigens together with the expression of oncoproteins might have greater prognostic value than the estimation of one of these factors.

Patients with Paget disease of nipple and with palpable mass in breast have unfavorable prognosis.

Recent data indicate that in breast cancer patients the presence of Paget disease of the nipple may be related to poor prognosis. Therefore, we decided to assess long-term results of the treatment of such patients, and to assess the relationship between the physical and pathological findings and prognosis. The files of 60 patients with Paget disease of the nipple who were treated between 1977 and 2000 were analyzed retrospectively with respect to the results of physical and pathologic examinations, disease recurrence and survival. In 38/60 patients, the cancer was invasive. In 26/60 patients, palpable masses in the breast were diagnosed. The 5-year overall survival probability was 0.68; the probability was 0.82 for patients without palpable masses, 0.51 for those with palpable masses, 0.91 for patients without invasive cancer and 0.58 for patients with associated invasive cancer. In conclusions, patients with Paget disease of the nipple and with palpable mass in the breast had unfavorable diagnosis. The nature of all nipple changes should be explained as early as possible in order to diagnose the disease when no mass is palpable in the breast.

[1000 quadrantectomies--personal experience]. / 1000 kwadrantektomii--doswiadczenia wlasne.

Analysis of 1000 quadrantectomies performed because of malignancy suspicion has been carried out to evaluate the long-term results of this method. Authors underline that only 5% of patients with breast cancer was able to be qualified to quadrantectomy.

[The evaluation of granulocyte function before and after surgical treatment in patients with chronic inflammation of the middle ear and palatine tonsils]. / Ocena funkcji granulocytów (PMNL) przed i po leczeniu operacyjnym u chorych z przewleklym ropnym zapaleniem ucha srodkowego i migdalków podniebiennych.

The aim examinations was the evaluation of granulocytes (PMNL) pre- and postsurgical treatment in patients with chronic inflammation of middle ear and palatine tonsils. The examined 40 persons and divided into three groups: I--18 patients with chronic inflammation of middle ear, II--10 ones with chronic tonsillitis and III--12 healthy persons. There were evaluated: "in vivo" and "in vitro" migration, bactericidal index and absorption of S. aureus labeled 14C isotope (phagocytic index) in the own modification. Preoperative treatment in patients with chronic inflammation of middle ear and palatine tonsils in comparison to the healthy were noticed: characteristic increase of the migration area, the MIF liberation and the phagocytic index, decrease in the bactericidal index (but more in group II). After a year postsurgical treatment the function of granulocytes in patients of group II was more similar to the healthy than in group I.

[The influence of phleum pratense and secale cercale allergens on selected functions of PMNL granulocytes]. / Wplyw alergenów phleum pratense i secale cercale na wybrane funkcje granulocytów obojetnochlonnych (PMNL).

The evaluation of granulocytes function (PMNL) at patients with pollinosis. There were 59 people examined and divided into: 30 patients with pollinosis, 29 healthy people. There were evaluated: absorption of isotope (phagocytic index) in our modification migration in vivo and the bacteriotoxic index. The function of granulocytes (postpreincubation) of allergens Phlenum pratens and Secale cercale in patients with pollinosis were changed more in comparison with the healthy people.

[Evaluation of granulocyte (PMNL) function in patients with chronic inflammation of the middle ear and palatine tonsils]. / Ocena funkcji granulocytów (PMNL) u chorych z przewleklymi zmianami zapalnymi ucha i migdalków podniebiennych.

The evaluation of granulocytes function (PMN) in patients with chronic inflammation of middle ear and palatine tonsils. There were 39 people examined and divided into: 28 patients with chronic inflammation of middle ear and palatine tonsil, 11 healthy persons. The function of granulocytes in patients with chronic inflammation of middle ear and palatine tonsil were changed more in comparison with the healthy people.

[The evaluation of granulocyte (PMNL) function of patients with chronic hypertrophy of larynx and paranasal sinuses]. / Ocena funkcji granulocytów (PMNL) u chorych ze zmianami rzerostowymi krtani i zatok przynosowych.

The evaluation of granulocytes function (PMNL) at patients with chronic hypertrophy of larynx and paranasal sinuses. There were 40 people examined and divided into: 10 patients with hypertrophy of larynx, 13 patients with hypertrophy of paranasal sinuses and 17 healthy people. There were evaluated: emission of chemiluminescence (CL), absorption of isotope (phagocytic index) in our modification migration in vivo and in vitro and the bacteriotoxic index. The function of granulocytes in patients with hypertrophy of larynx and paranasal sinuses were changed more in comparison with the healthy people.