[Pulmonary metastases - 12-year experience with surgical therapy]. / Plicní metastázy - dvanáctileté zkusenosti s chirurgickou lécbou.

INTRODUCTION: Nowadays, radical surgical therapy of selected secondary pulmonary tumours is a generally accepted therapeutic procedure that has been proven to extend long-term survival of the patients with acceptable perioperative morbidity and mortality. The authors present a retrospective analysis of a set of patients who underwent surgery for pulmonary metastases of various tumours in a 12-year period. MATERIAL AND METHODS: In 2001-2012, 159 patients with secondary pulmonary tumours were operated on at the authors department, of whom 80 were men; the median age was 65 years. Solitary metastases were present in 112 patients (70.4%); the other patients had multiple metastases; 24 patients (15.1 %) suffered from bilateral involvement, and 6 patients (3.8%) suffered from relapsed metastatic disease after previous radical surgery. Colorectal carcinoma metastases were diagnosed in most cases (75 people - 47.2%). The median disease-free period from the surgery of the primary tumour was 27 months in the patient set. RESULTS: In total, 166 unilateral (87.4%) and 24 bilateral surgeries were performed using one- or two-stage procedure (12.6%). Precise laser excisions represented the most common type of surgery (59 procedures - 31.1%). In total, 296 metastases were radically resected, and 13 were treated using radiofrequency ablation. Perioperative morbidity was 13.2% with a zero lethality rate. 90 operated patients (56.6%) still survive after the metastasectomy, with median survival of 44 months. The overall 3-year survival in the set was 59%, and 5-year survival was 39%. The number of metastases is a statistically significant factor affecting survival in the patient cohort with colorectal carcinoma metastases, the risk of death being 2.7 times higher in patients with 2 and more colorectal carcinoma metastases. 68 patients (42.8%) live without progression of the disease after the metastasectomy, with the median disease-free interval of 29 months. In total, 43% of the patients were free of any signs of relapse or disease progression for 3 years, and 27% for 5 years. The risk of disease progression is 2.1 times higher in patients with 2 and more metastases of any tumour, and for colorectal carcinoma this risk is 2.3 times higher. CONCLUSION: The achieved results confirm the positive role of pulmonary metastasectomy in disseminated tumour therapy. The number of metastases is the decisive prognostic factor affecting both long-term survival of operated patients and their DFI.

Surgical therapy of pulmonary metastases - 10-year results.

INTRODUCTION: The surgical therapy of selected secondary pulmonary tumors, including both solitary and multiple or bilateral tumours, is currently a generally accepted therapeutic procedure demonstrably extending the long term survival of these patients. PURPOSE: The purpose of the present study is a ten-year retrospective analysis of a group of patients who underwent surgery due to pulmonary metastases of various primary tumors. METHODS: In 2000-2009, 87 patients (of which 44 were male with a median age of 64 years) with secondary pulmonary tumors underwent surgery at the departments of the authors of this study. Solitary metastases were found in 60 patients, multiple metastases in the remaining patients, while 13 patients had bilateral metastases. The median disease-free period from surgery of the primary tumor was 31 months. RESULTS: In total, 74 unilateral and 13 bilateral surgeries were performed in one or two periods. The most common type of surgery included anatomical pulmonary resections (32 procedures), wedge resections (29 procedures) and laser excisions (24 procedures). In total, the radical resection was performed in 156 metastases. Post-operative morbidity was 17.2 % with zero mortality. A proportion of 50.6 % of operated patients survived after resection of metastases with median survival of 39 months. The overall three-year and five-year survivals in the group were 57 % and 38 %, respectively. A proportion of 35.6 % of patients live after resection of metastases without disease progression, and the median is 15 months. CONCLUSION: The achieved results confirm the positive role of pulmonary metastasectomy in the therapy of disseminated cancer disease (Tab. 1, Fig. 5, Ref. 34).

Matrix metalloproteinases and their inhibitors in correlation to proliferative and classical tumour markers during surgical therapy of colorectal liver metastases.

OBJECTIVES: Classical and proliferative tumour markers and matrix metalloproteinases and their tissue inhibitors reflect the features of malignancy and are useful in prediction of prognosis in patients with colorectal liver metastases. There is very limited information about their physiological functions during regeneration and healing of liver parenchyma after any type of liver surgery for malignancy. METHODS: The presented study included the patients, who underwent following surgical procedures for CLM, benign liver lesions and inguinal hernias: Group A: 22 patients with inguinal hernias, Group B: 26 patients with benign liver lesions, Group C: 30 patients with colorectal liver metastases (CLM) who were treated by radiofrequency ablation, Group D: 41 patients with CLM who underwent a radical surgical therapy - resection, and Group E: 22 patients with inoperable CLM who underwent an explorative laparotomy without any surgical procedure. RESULTS: The preoperative and postoperative serum levels of CEA, CA 19-9, TK, TPA, TPS, MMP-2, MMP-9, TIMP-1, and TIMP-2 were statistically analyzed and compared within the groups to estimate the influence of a surgical procedure type. These results reflect the influence of surgical procedure on the serum levels of studied tumour markers during operation. CONCLUSIONS: It was the first description using these types of comparison to all metalloproteinases, their inhibitors, and proliferative and classical tumour markers. It could help us to estimate the critical relations of these tumour markers in prognoses of disease free survival or overall survival in patients after a surgical procedure for CLM (Tab. 5, Ref. 26).

[Pulmonary metastases of the clear cell (conventional) renal cell carcinoma--options and results of surgical treatment]. / Moznosti a výsledky chirurgické lécby plicních metastáz svetlobunecného (konvencního) renálního karcinomu.

BACKGROUNDS: At the diagnosis, up to one third of patients with clear cell (conventional) renal cell carcinoma have metastases, and the disease will progress in a half of patients with localized disease; the lungs are the most frequently affected organ. Despite clear advances in targeted biological treatment, radical surgery of organ, mainly pulmonary, metastases is a justified treatment approach with good results. AIM: A nine-year retrospective analysis of patients with clear cell renal cell carcinoma undergoing surgical treatment of pulmonary metastases. MATERIALS AND METHODS: At our centre, 13 patients with the mean age of 65 years, 9 of which were men, underwent surgical treatment between 2001 and 2009. Surgery was only indicated in patients after renal tumour resection without extrapulmonary metastases in whom presurgical assessment suggested that the pulmonary metastases were resectable (with respect to their number and location) and in whom the benefits of performing the surgery outweighed any potential risks. Metastases were solitary in 9 patients and multiple in the rest, 2 patients had bilateral involvement. Median disease-free interval following nephrectomy was 28 months. RESULTS: A total of 11 unilateral and 2 bilateral resections were performed during one or two surgical operations. Most frequently, wedge resection was performed (7 patients). A total of 23 metastases were resected. Perisurgical morbidity was 15.4%, zero mortality. Of those undergoing metastasectomy, 53.8% are still surviving with a median survival of 24.3 months. Three-year survival in the sample was 66%, 5-year survival was 53%. Five patients (38.5%) have had no disease progression for a median of 8.8 months. CONCLUSION: Our results confirm the positive role of metastasectomy in the treatment of pulmonary metastases of clear cell (conventional) renal cell carcinoma. Long-term survival after pulmonary metastasectomy might be expected in patients with solitary metachrone small metastases with DFI after nephrectomy > 1 year, without tumour involvement of the relevant lymph nodes and R0 resection.

Dynamics of serum levels of tumour markers and prognosis of recurrence and survival after liver surgery for colorectal liver metastases.

BACKGROUND: The authors present a statistical analysis of the dynamics of tumour markers and compare these with single serum levels in patients before and after liver surgery for colorectal liver metastases (CLM). PATIENTS AND METHODS: The serum levels of tumor markers conventionally used in clinical practice (CA19-9, CEA, CA72-4) and markers informing of the proliferation activity of malignancy (TKI TPA, TPS) were statistically analysed. The authors studied 144 patients who underwent liver surgery for colorectal liver metastases between September 1999 and June 2005. Serum levels of tumor markers before surgery (maximally two weeks before the operation), after surgery (maximally one month after the operation - usually on the day of dismission), six months (+/- one month) and twelve months after the surgery (+/- one month) were determined. The Log Rank test and the Wilcoxon test were used for statistical evaluation. The survival rate and disease-free intervals (DFI) were computed using the Kaplan-Meier method. RESULTS: The statistical analysis of tumour marker dynamic after liver surgery (speed and power of recurrence) supported the dynamics of CA 19-9 and CEA as excellent prognostic factors of early recurrence of CLM in contrast to proliferative tumor markers. CONCLUSION: The results of the study suggest the importance of tumour markers for the prediction of a short survival rate or DFI. This approach would be very helpful for the planning of palliative oncological treatment for patients with liver malignancies that cannot be treated by surgical therapy. Current patients with a high tendency of recurrence of CLM after liver surgery should be followed up more thoroughly to increase the possibility of successful reoperation.

Prognostic importance of thymidine kinase in colorectal and breast cancer.

BACKGROUND: Thymidine kinase (TK) plays an essential role in the processing of thymidine within the cell and therefore it is an important marker of proliferation, particularly in tumor cells. The aim of our study was to determine the diagnostic, prognostic and predictive importance of TK measurement in cancer. PATIENTS AND METHODS: TK was measured using radioreceptor analysis (RRA) with Immunotech assay kits. The serum level of TK was measured in 1087 patients with malignant disease (355 patients with hematology malignancies and 732 patients with solid tumors). RESULTS: Serum levels of TK were significantly elevated in inflammatory and immunological diseases in comparison with healthy individuals. Malignant diseases were associated with elevated serum levels of TK only in particular cases (e.g. hematological malignancies, cervical cancer). This marker has a high sensitivity for use as a primary diagnostic tool. It also has a high sensitivity during the follow-up period in breast and colorectal cancer for the prediction of relapse at the time of primary diagnosis and 3 months earlier than the diagnosis of relapse by imaging methods. CONCLUSION: TK represents a secondary tumor marker which is particularly useful for cancer disease monitoring. Interpretation of this marker must be performed only in association with evaluation of clinical status since all other possible non-specific causes (inflammatory or immunological diseases) of elevated serum levels must be excluded.

Tumor markers in pleural effusions.

AIM: The aim of this study was to determine the diagnostic capabilities of tumor markers in pleural effusion and their importance for assessment of the etiology of pleural effusions. PATIENTS AND METHODS: In pleural effusions from 166 patients hospitalized during the period 2003-2005 at the Department of Oncology and Radiotherapy, Faculty Hospital in Pilsen, the following tumor markers were determined: thymidine kinase (TK), neuron-specific enolase (NSE), cytokeratins [tissue polypeptide antigen (TPA), tissue polypeptide-specific antigen (TPS) and cytokeratin fragment 19 (CYFRA 21-1)], carcinoembryonic antigen (CEA) and mucinous markers (CA 15-3, CA 19-9, CA 125). The inflammatory marker procalcitonin-PCT was also assessed. RESULTS: Tumor markers CA 125, TPA, TPS were significantly elevated in exudates, irrespective of the etiology, as a non-specific reaction in mesothelial cells. TK had a sensitivity of over 80% for all the types of cancer examined, while CA 15-3 had a sensitivity of over 90%. CONCLUSION: Significant positivity of PCT and CA 15-3 in pleural effusions indicate a suspicion of inflammatory disease. Positivity of TK and CA 15-3 indicate a strong suspicion of malignant exudates.

[Sclerosing epithelioid fibrosarcoma]. / Sklerozující epiteloidní fibrosarkom.

Sclerosing epithelioid fibrosarcoma (SEF) was first described in 1995 and since then 39 cases have been reported. Here we describe 6 cases of SEF (3 in women and 3 in men). The patients aged from 22 to 79 years. The tumours were located in soft tissues of the extremities (in 3 cases in the lower, in 2 instances in the upper extremity) and of the trunk (in 1 case). The lesions were partially nodular, of gray-white colour, and hard in consistency. Histologically, they were composed of epithelioid round to ovoid small cells with a sparse cytoplasm and a very low mitotic activity. The tumour cells formed cords and alveoli or were scattered individually within a dense hyalinized collagenous stroma. The neoplasms also contained foci of conventional fibrosarcoma, necrosis, calcification, and metaplastic bone. On immunohistochemistry, the neoplastic cells were positive for vimentin. Two cases were immunoreactive for epithelial membrane antigen and one tumour also for cytokeratins. The proliferative activity, assessed by MIB 1 antibody (Ki-67), was detected in 1-6% of neoplastic cells in primary tumours. Follow-up information was available in 5 patients. In two cases, there were local recurrences and distant metastases (in the lungs, upper extremity, and mediastinum). One of these patients died of SEF. The differential diagnosis of this relatively low-grade fibrosarcoma is broad and includes, along with a variety of benign and malignant soft tissue lesions, infiltrating carcinoma, and, to a lesser extent, sclerosing lymphoma.

Glassy hyaline globules in granular cell carcinoma, chromophobe cell carcinoma, and oncocytoma of the kidney.

The presence of glassy hyaline globules (GHG) in renal carcinomas has been rarely emphasized in the literature. We studied the frequency of these globules in numerous renal carcinomas, including granular cell, mixed clear cell/granular cell, papillary renal cell, and chromophobe renal cell carcinoma, as well as oncocytomas. GHG are eosinophilic bodies in the hematoxylin-eosin stained sections with a size ranging from 1 to 30 micrometer and strongly positive with the periodic acid-Schiff (PAS) histochemical stain. Ultrastructurally, they are seen as amorphous secretion inside of the cisternae of the rough endoplasmic reticulum. GHG were found in 49 of 64 cases of granular cell and mixed clear cell/granular cell renal carcinomas and in 5 of 33 papillary renal cell carcinomas. No GHG were found in 22 cases of chromophobe cell carcinomas and 26 renal oncocytomas. Our findings suggests that GHG are a characteristic feature of granular cell carcinomas, mixed clear cell/granular cell renal carcinomas, and in a small minority of papillary renal cell carcinomas. In addition, it suggests that the presence of GHG in a renal cell tumor may be of aid for excluding a diagnosis of chromophobe cell carcinoma or oncocytoma.

Phyllodes tumour of the breast: immunohistochemical study of 37 tumours using MIB1 antibody.

In our study, the expression of Ki-67 antigen in phyllodes tumours of the breast was investigated in order to estimate its significance in assessing the grade of malignancy and in predicting the clinical behaviour of these tumours. Formalin-fixed and paraffin-embedded tissue specimens of 37 cases of phyllodes tumour of the breast (eight graded as malignant and 29 as benign according to histopathological criteria) and 20 breast fibroadenomas were stained by an immunoperoxidase technique, using the monoclonal antibody MIB1 directed against cell proliferation-associated Ki-67 antigen. A MIB1 index was calculated to express the percentage of MIB1 positive proliferating stromal cells. Our data indicate that there are statistically significant differences in MIB1 indices between histologically benign and malignant phyllodes tumours (alpha = 0.001), between benign phyllodes tumour and fibroadenoma (alpha = 0.01), and between malignant phyllodes tumour and fibroadenoma (alpha = 0.001). Our results also indicate a good correlation between the conventional grading of phyllodes tumours based on histological criteria and MIB1 indices. However, little predictive value of the MIB1 index in phyllodes tumours of the breast can be derived from our study.