Bioelectrical Impedance Analysis to Increase the Sensitivity of Screening Methods for Diagnosing Cancer Cachexia in Patients with Colorectal Cancer.

BACKGROUND: Currently used methods for detecting and monitoring cancer cachexia (CC) are not sensitive enough. In this field, there is a need to implement new instruments into clinical practice. OBJECTIVE: Determining the usefulness of bioelectrical impedance analysis (BIA) for detecting and monitoring CC in patients with colorectal cancer (CRC). METHODS: 158 people were invited to the study (70 from CRC and 88 controls). Their body composition was determined using BIA, and their nutritional status was determined according to NRS 2002, SGA, and BMI criteria. For statistical data analysis, Student's t-test, Mann-Whitney U test, and AUC ROC were used. RESULTS: Men with CRC stage I had higher values of FMI, SMMI, and ECW/TBW (p < 0.05) than in stages II-IV, and women with CRC stage I had higher values of FMI, FFMI, and FM/FFM than in the group of stages II-IV (p < 0.05). The ability of FFMI to detect malnutrition relative to SGA was low (sensitivity: women 40%, men 40% and specificity: women 74%, men 70%). CONCLUSIONS: SGA and NRS 2002 scales are dynamic and consider changes in nutritional status over time, while BIA is static and does not consider these changes. Therefore, BIA is not a good tool for screening nutritional status. BIA successfully identifies differences in body composition depending on cancer stage and advancement of CC. Therefore, after the diagnosis CRC, just to monitor the disease advancement and state of CC, it is worth comparing the results of periodically repeated BIA.

Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumours (GIST): Polish Clinical GIST Registry experience.

BACKGROUND: Majority of gastrointestinal stromal tumours (GISTs) are characterised by KIT-immunopositivity and the presence of KIT/platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. PATIENTS AND METHODS: Spectrum and frequency of KIT and PDGFRA mutations were investigated in 427 GISTs. Univariate and multivariate analysis of relapse-free survival (RFS) was conducted in relation to tumours' clinicopathologic features and genotype. RESULTS: Mutations were found in 351 (82.2%) cases, including 296 (69.3%) KIT and 55 (12.9%) PDGFRA isoforms. Univariate analysis revealed higher 5-year RFS rate in women (37.9%; P = 0.028) and in patients with gastric tumours (46.3%; P < 0.001). In addition a better 5-year RFS correlated with smaller tumour size ≤ 5 cm (62.7%; P < 0.001), tumours with mitotic index ≤ 5/50 high-power fields (60%; P < 0.001), and characterised by (very) low/moderate risk (70.2%; P = 0.006). Patients with GISTs bearing deletions encompassing KIT codons 557/558 had worse 5-year RFS rate (23.8%) than those with any other KIT exon 11 mutations (41.8%; P < 0.001) or deletions not involving codons 557/558 (33.3%; P = 0.007). Better 5-year RFS characterised patients with KIT exon 11 point mutations (50.7%) or duplications (40%). By multivariate analysis, tumours with PDGFRA mutations and KIT exon 11 point mutations/other than 557/558 deletions had lower risk of progression than with KIT exon 11 557/558 deletions (both Ps = 0.001). CONCLUSIONS: KIT/PDGFRA mutational status has prognostic significance for patients' outcome and may help in management of patients with GISTs.

Rare oesophageal tumours: experience of one centre.

AIM OF STUDY: The aim of this study is to compare demographic and clinical data as well as applied treatment methods in patients with rare benign and malignant tumours of the oesophagus. METHODS: Eight hundred and thirty patients with oesophageal cancer were treated in the Department of Surgical Oncology in 1960-2005. In 15 cases (1.8 %), rare benign (n = 11) or malignant (n = 4) types of tumours were diagnosed. Patients with rare oesophageal tumours were included in the study, excluding those with squamous cell carcinoma or adenocarcinoma of the oesophagus. Demographic and clinical data were analysed from each patient qualified for the study. Oesophageal X-rays with contrast medium, gastroscopies and, as of 1991, computed tomographies (CTs) were performed as preoperative diagnostic procedures. RESULTS: In the postoperative histopathological examinations, all benign tumours proved to be oesophageal leiomyomas. Four different malignant tumours-a sarcoma, a neuroendocrine carcinoma, a lymphoma, and a squamous cell carcinoma in a patient with Crohn's disease, were diagnosed in the other four patients. In a group of 15 patients with rare oesophageal tumours there were ten (66.7 %) males and five (33.3 %) females. In patients with benign and malignant tumours, the mean age for the benign group reached 44 years (range: 26-75 years old) and 54.7 years (range: 47-59 years old) for the malignant group. In the preoperative period, symptoms such as swallowing disturbances, retrosternal pains, and epigastric pains were observed. Dysphagia was the leading symptom in patients with benign and malignant oesophageal tumours. Out of 15 patients, surgical procedure was carried out in 13 cases with rare oesophageal tumours. In the group of 11 patients, with benign tumours, ten (90.2 %) warranted surgical treatment. Three patients (75 %) with malignant oesophageal tumours underwent an extensive Akiyama procedure of oesophageal resection. Chemo- and radiotherapy alone were performed on one (25 %) patient with oesophageal lymphoma. Postoperative complications were observed in only four (26.6 %) patients; pneumonia in the postoperative period was diagnosed in two patients who underwent surgery; infections of the postoperative wounds were diagnosed in the other two patients. CONCLUSIONS: Benign oesophageal tumours are characterised by similar clinical symptoms to malignant tumours of this organ. It is more complicated to obtain biopsy specimens for a histopathological examination in cases of benign tumours in comparison to malignant tumours. Treatment methods should be adjusted individually for each patient with a rare oesophageal tumour. For rare benign oesophageal tumours, the results of treatment are very good; however, for malignant tumours the prognosis depends on their histopathological type.

Eicosanoids in prevention and management of diseases.

Eicosanoids, which originate from polyunsaturated fatty acids (PUFAs), have a major impact on homeostasis maintenance as secondary signal transducers. Signal cascade, which includes reception, processing and signal transduction coming from the environment into the cell, determines the type of response evoked. Signal distortion may take place on every level of this cascade and this in consequence could lead to the development of many diseases. Any intervention into PUFAs metabolism leads to quantitative and qualitative changes of synthesized eicosanoids. Some of them promote, whereas others inhibit carcinogenesis, some are pro- or anti-inflammatory and the overall result depends on the outcome of these contradictory effects. The type and amount of produced eicosanoids depends on substrates' availability and activity of enzymes catalyzing different stages of their transformation. A particularly negative role was assigned to the over expression of phospholipase A2, cyclooxygenase-2, 5- and 12-lipoxygenases, while the contribution of other oxygenases and their metabolites is considerably less clear. The information about their interplay is extremely sparse and inadequate to understand intricacies of the mechanisms involved. There are indications that utilization of selected eicosanoids (their analogs, agonists or antagonists) could be a better way of disease prevention and treatment, more effective than excessive dietary supplementation of fatty acids. This review presents a more global picture of oxygenases and their PUFA metabolites giving a brief summary of our current understanding of perspectives and pitfalls of their regulation and mediatory action in human diseases.

The influence of radioisotope vehicle on breast sentinel node detection.

AIM: To assess the relationship between carrier molecule size and time elapsing between marker injection and sentinel node(s) biopsy in patients with breast cancer. MATERIAL: The study performed on 122 women, in whom the sentinel node(s) was identified according to the procedure described below. In Group I (n=72 patients), SN identification was done with radioisotope marker of 400-3000 nm molecule size (tin colloid). In Group II (n=50 patients) radioisotope marker of <100 nm molecule size (colloidal albumin) was used. METHODS: All the patients of both groups received the markers with a single-point, intradermal, periareolar injection. Four hours after the injection (Group I - surgery in the next day) or immediately before the surgery (in this same day) (Group II), stationary lymphoscintigraphy was performed. RESULTS: Mean numbers of sentinel nodes identified with the radioisotope method in Groups I and II were 1.22 and 1.48, respectively. The difference was statistically significant (p<0.01). CONCLUSIONS: There is a relationship between the radioisotope marker molecule size and the injection-to-intra-operative evaluation time. Administration of small molecule size radioisotope marker several hours prior to the planned surgery appears to be the optimum procedure in this method of SN identification in patients with breast cancer.

Overexpression of cathepsin B correlates with angiogenesis in colon adenocarcinoma.

Some studies have shown the influence of proteases and vascular density in colorectal primary tumors on spreading and on the course of colorectal cancer. In the present study we have analyzed the relationships between overexpression of cathepsin B protein and angiogenesis intensity in resected colon tumors and their impact on prognosis. It has been investigated in a series of 90 colon cancer patients. Immunohistochemistry was used to evaluate cathepsin B overexpression in cancer cells and to visualize microvessels with antibodies against von Willebrand factor. Overexpression of cathepsin B was observed if more than 50% of cancer cells in searched field showed immunoreactivity with antibody against cathepsin B. Intensity of angiogenesis was evaluated as a mean number of microvessels from three fields with highest vessel number. In 36 cases (40%) overexpression of cathepsin B was detected. Increased angiogenesis (above median 31 vessels per 0.785 mm2) correlated positively with cathepsin B overexpression (p=0.0006). Higher vascular density associated with the presence of metastases in regional lymph nodes (p=0.01). Overexpression of cathepsin B was observed more often in group of older people (age above median 65 years; p=0.005). According to univariate analysis metastases in regional lymph nodes (p=0.0007), increased angiogenesis (p=0.0085), and distant metastases (p=0.02) were the features potentially influencing prognosis. Multivariate analysis revealed independent prognostic value only in case of metastases in regional lymph nodes (p=0.013) and when distant metastases were present (p=0.021), but not when increased angiogenesis in primary colon adenocarcinoma was observed (p=0.078). In conclusion we can say that there is a close relationship between intensity of angiogenesis and overexpression of cathepsin B protein in cancer cells in resected colon adenocarcinoma.

Neural cell adhesion molecule in breast, colon and lung carcinomas.

Neural cell adhesion molecules (NCAM) play an important role in embryogenesis and in some tumors, especially of neuroectodermal origin. In this study, 18 cases of invasive breast carcinoma, 7 cases of sigmoid colon carcinomas and 17 cases of the non-small-cell lung carcinoma were immunostained for NCAM. NCAM expression, usually focal, was observed in some cases only. NCAM was expressed in the membranes, in a fine granular pattern. In 3 cases of breast cancer cytoplasmic localisation of NCAM was also observed, which may suggest its cytoplasmic formation. Furthermore, in 3 cases expression of NCAM in histologically normal ductal lobular units adjacent to invasive breast cancers without the presence of this antigen in cancer tissue was observed. The immunostaining was weak or absent in sigmoid colon carcinomas. In this study we confirm the observation of some authors that NCAM expression occurs in some cases of non-small-cell lung carcinomas.

Malformations of angiogenesis in the low differentiated human carcinomas. immunohistochemical study.

Our previous observations showed that the perivascular mesenchyma of the thin-walled vessels (capillaries) in cancers may be the source of organ-specific stem cells. We suggested that the cells forming vascular channels in altered stroma participate in the tumor development. This study was designed to examine the distribution of the vessels and their appearance in the breast, lung and colon cancers. Using immunohistochemical methods, we have shown that in the low differentiated tumors both CD31 and factor VIII antigens may be expressed in capillaries chiefly on the periphery of neoplastic foci. Many of these vessels were discontinuous, with interruptions or unformed tubules. Sporadically, CD31 protein and factor VIII antigens were not expressed in capillaries inside the very low differentiated cancer cases. It is difficult to assess by immunohistochemical means whether the vascular malformations are the primary or secondary phenomena in the malignancy and why these abnormalities were especially visible in some low differentiated cancers.

[Elevation of serum Ca 15-3 antigen: an early indicator of distant metastasis from breast cancer. Retrospective analysis of 733 cases]. / Wzrost stezenia antygenu CA 15-3 w surowicy--wczesny wskaznik przerzutów odleglych raka piersi: retrospektywna analiza 733 chorych.

UNLABELLED: Aim of study was to summarize six-year institutional experience with serial evaluation of circulating CA15-3 antigen as a method of early detection of breast cancer relapse. MATERIAL AND METHODS: CA15-3 concentrations were assayed immuno-enzymatically in the sera of 733 women with breast carcinoma: in 707 cases marker was analyzed serially (every 4 months during follow-up after completion of radical treatment and when the relapse of breast cancer was clinically suspected) and in 26 patients--at diagnosis of locoregional relapse and\or breast cancer dissemination; 5493 assays of the CA15-3 antigen were performed in total. The cut-off limit was established at 30 u/ml. Results of CA15-3 tests were analyzed in relation to clinical status of the disease and dominant site of breast cancer relapse. RESULTS: 1) in patients with distant metastases (N = 149), mean serum CA15-3 values and the percentage of positive results were significantly higher as compared to cases with locoregional relapse and carcinoma of the contralateral breast (N = 54; p < 0.0001) and those without clinical evidence of relapse (N = 530; p < 0.0001), in agreement with previous studies; 2) the highest mean values of CA15-3 were observed in patients with liver and multiple metastases, lower in those with bone or lung secondaries, and the lowest when the metastatic involvement of supraclavicular nodes was noticed; 3) the CA15-3 sensitivity rates were higher in patients with liver or bone metastases (91.7% and 91.4%, respectively), as compared to those with multiple (79.5%) and lung (72.4%) secondaries, and the lowest when metastases in supraclavicular nodes (40.0%) or other organs (60.0%) were diagnosed; 4) the comparison of subjects with liver secondaries and those with other sites of breast cancer dissemination indicated statistically significant difference in the mean CA15-3 values (p < 0.0001) and the number of positive results of the test (p < 0.05); 5) the sensitivity rates of CA15-3 antigen for one, two, three and more skeletal metastases detected by bone scintigraphy were 50%, 100% and 100%, respectively (N = 30); 6) in 84 out of 116 (72.4%) patients with distant metastases, the increased CA15-3 concentration preceded the clinical diagnosis of the relapse with the median lead time 9 months (range: 1-40); 7) the highest positivity rates of the lead time were observed in patients with liver or lung metastases (93.8% and 81.0%, respectively) and the lowest one in those with multiple sites of metastases (43.0%). CONCLUSION: The study confirmed the validity of serial CA15-3 assays in the early diagnosis of breast metastatic disease. It is worth to emphasize the high sensitivity of the CA15-3 test in detecting bone metastases (100% in patients with scintigraphically diagnosed two or more metastatic lesions), but the group of patients was too small to make our observation conclusive. In none of the studies published previously, the beneficial impact of serial CA15-3 assays during follow-up on survival and quality of life in breast cancer patients was clearly demonstrated. Thus, modifying treatment based solely on increasing marker levels is not recommended.

[Chylothorax and chyloperitoneum]. / Chylothorax i chyloperitoneum.

We report three cases of chylous leakage. Chylothorax and chyloperitoneum following radical esophagectomy are described in one patient. Chylothorax in the course of lymphoma malignum, and chylothorax due to traffic accident are described in two other patients. All three patients undergone surgical intervention to repair leaking lymphatics. In two patients with chylothorax this kind of treatment was successful, however in patient with lymphoma malignum success was temporary only.

Epithelial-mesenchymal cell interactions and participation of the neuroendocrine markers in tumor development. Immunohistochemical study.

Existence of the organ stem cell population seems to decide on ability of the tissue to regenerate and, likewise, on carcinogenesis. The source of the organ specific stem cells may be perivascular mesenchyma of thin-walled vascular channels. Our previous study on the breast cancer indicates that the perivascular mesenchyma of thin-walled vessels appears to be source of myoid cells (myofibroblasts) from which cancer cells arise. Similar results have been observed in the cancers of lung, salivary gland and colon, investigated in the current study. The perivascular cells of thin-walled channels are the source of myoid cells with expression of synaptophysin (Syn) and/or chromogranin A (Chg A), and from these cells neoplastic cells could originate. Syn and/or Chg A positive neoplastic cells were particularly well visible in connection with the vascular channels on the peripheries of tumors while other parts of tumors were only weak positive or negative for those neuroendocrine markers. Similarly as in breast cancers, the S100-protein positive dendritic cells with various of distribution were seen, expressing intimate connection with neoplastic cells. The epithelial pearls especially abundant in non-small cell lung carcinomas demonstrated immunohistochemical analogy to Hassall's bodies: they had monocytogenic cell inside and they displayed thymosin alpha 1 (TA1), as well as mucin secretion and minute calcification. Some epithelial cells expressed desmin and Syn. All types of investigated cancers demonstrated TA1. Results of our present study suggest that the perivascular cells have a differentiation defect. Such defect may initiate abnormal stromal environment, commonly observed in neogenesis, however, the presence of thymic growth factors may favor tumor growth.

[A case of returning radial nerve function after the excision of a neuro-sarcoma type tumor]. / Przypadek powrotu czynnosci nerwu promieniowego po resekcji guza typu neurosarcoma.

A case of 68 years old patient with neurosarcoma of the radial nerve is presented. After total resection of the tumour and the suture of the sheath of the nerve its function has returned. Eight years later the recurrence took place and 2 years later the limb has been amputated.

[Lymphangiosarcoma of the leg following radiotherapy for cervical carcinoma]. / Naczyniakomiesak limfatyczny konczyny dolnej po napromienieniu z powodu raka szyjki macicy.

A case of lymphangiosarcoma of lower extremity was observed in a female aged 68 years who had had radiotherapy for cervical carcinoma. The late therapeutic result was bad, and this indicates the necessity of radical management, that is amputation in hip joint already in an early stage of the disease, although this decision is extremely difficult for the physician.