Bromodeoxyuridine Labeling Index as an Indicator of Early Tumor Response to Preoperative Radiotherapy in Patients with Rectal Cancer

Purpose Assessment of tumor proliferation rate using Bromodeoxyuridine labeling index (BrdUrdLI) as a possible predictor of rectal cancer response to preoperative radiotherapy (RT). Methods and material Ninety-two patients were qualified either to short RT (5 Gy/fraction/5 days) and surgery about 1 week after RT (schedule I), or to short RT and 4–5 weeks interval before surgery (schedule II). Tumor samples were taken twice from each patient: before RT and at the time of surgery. The samples were incubated with BrdUrd for 1 h at 37°C, and the BrdUrdLI was calculated as a percentage of BrdUrd-labeled cells. Results Thirty-eight patients were treated according to schedule I and 54 patients according to schedule II. Mean BrdUrdLI before RT was 8.5% and its value did not differ between the patients in the two compared groups. After RT tumors showed statistically significant growth inhibition (reduction of BrdUrdLI). As the pretreatment BrdUrd LI was not predictive for early clinical and pathologic tumor response, prognostic role of the ratio of BrdUrdLI after to BrdUrdLI before RT was considered. The ratios were calculated separately for fast (BrdUrd LI > 8.5%) and slowly (BrdUrd LI ≤ 8.5%) proliferating tumors and correlated with overall treatment time (OTT, i.e., time from the first day of RT to surgery). One month after RT, accelerated proliferation was observed only in slowly proliferating tumors. Conclusions Pretreatment BrdUrdLI was not predictive for early clinical and pathologic tumor response. The ratio after/before RT BrdUrdLI was correlated to inhibition of proliferation in responsive tumors. The paper was presented at ECCO 13, October 30 to November 03, 2005 in Paris, France     

Skeletonization of internal thoracic artery affects its innervation and reactivity.

OBJECTIVE: The studies showing the superior characteristics of ITA graft and its impact on the clinical results of coronary artery surgery were performed with ITA harvested almost exclusively as a pedicle. This study assesses the impact of ITA skeletonization on its innervation and reactivity. METHODS: Segments of skeletonized and non-skeletonized ITA were stained with antibodies against protein S-100 to look for the presence of sympathetic nerve fibers. The functional studies were performed on segments of discarded human pedicled ITA that were divided into two 3mm rings, one skeletonized and another non-skeletonized. We compared concentration-effect relationships for the contraction to norepinephrine and endothelium-dependent relaxation to acetylcholine and bradykinin, as well as endothelium-independent relaxation to sodium nitroprusside in skeletonized and non-skeletonized segments of the same ITA. RESULTS: Skeletonized ITA was devoid of protein S-100 positive nerve fibers. It contracted stronger (maximal response 37.0+/-2.04 vs. 25.4+/-1.83mN (P<0.001)) and was twice as sensitive to norepinephrine: pD(2) 6.03+/-0.10 vs. 5.70+/-0.12 (P=0.035). The endothelium-dependent relaxation responses did not differ between skeletonized and non-skeletonized ITA rings. The skeletonized ITA rings appeared over 10 times more sensitive to sodium nitroprusside: pD(2) 6.66+/-0.20 vs. 5.59+/-0.37 (P=0.012)-potency ratio 11.61. The maximal responses did not differ significantly: 112.0+/-6.71 vs. 129.4+/-16.4% (P=0.33). CONCLUSIONS: Skeletonization results in sympathectomy of ITA. It has no effect on endothelium-dependent relaxation but increases reactivity of ITA to norepinephrine. This augmented response to alpha-agonist is small, in comparison with over a ten-fold increase in sensitivity to sodium nitroprusside. Pedicled and skeletonized ITA are functionally significantly different vessels when studied in vitro.     

Solvent effects on free-radical polymerization, 5. Analysis of homopolymerization rate on the basis of the reactant-solvent complex model

The rate of polymerization was described as a function of the monomer concentration of 36 monomer/solvent systems in terms of the reactant-solvent complex (RSC) model. One-, two-and three-parameter optimization procedures were used to fit the rate function to experimental data. Fitting increments were the complex equilibrium constant K and the relative monomer reactivity parameter r₁₁. Irrespective of the optimization procedure, K and r₁₁, were found to correlate with the monomer exponent n and to be K = 0 and r₁₁, = 1 at n = 1. In these cases the RSC model reduces to the classical rate model. Despite the weak character of the monomer (radical)/solvent complexation, this interaction should not be neglected in rate modelling. The RSC model is a convenient tool to describe the chain propagation separately.     

Application of the Minnesota Code in evaluating electrocardiographic features of ischemic heart disease in patients exposed to carbon disulphide

Summary We examined 81 men exposed for a long time to carbon disulphide (CS₂) and tested the possible electrocardiographic (ECG) changes of ischemic heart disease (I.H.D.). The subjects were examined twice in two years. In order to make the ECG evaluation more objective, the Minnesota Code was applied. Two obligatory ECG examinations and only one submaximal effort test were carried out. For comparative evaluation, the control group was examined once. We proved that, in spite of the accepted opinion concerning the atheromatous action of CS₂, this compound does not cause ECG symptoms of I.H.D. in a higher percentage of exposed persons. It also does not cause any significant increase in I.H.D. symptoms in dynamic ECG observations.     

A retrospective comparative study of surgery followed by chemotherapy vs. non-surgical management in limited-disease small cell lung cancer.

OBJECTIVE: The role of surgery in limited SCLC is still a matter of controversy. Even though the response rates to chemotherapy are very high, prognosis of SCLC patients has remained poor with a median survival of only 12-14 months for limited disease. High incidence of local relapses after chemotherapy in limited-stage SCLC led to reassessment of the role of local treatment in the multimodality management of this tumor. METHODS: We performed retrospective comparative analysis of survival in a series of 134 limited-stage SCLC patients treated between 1984 and 1996 with either complete resection followed by chemotherapy (67 patients), or with conventional non-surgical management (67 patients). In all patients who underwent resection, the diagnosis of SCLC was established only postoperatively. The control (non-surgical) group was selected using 'pair-matched case-control' methodology, out of 176 limited-stage patients potentially suitable for surgery (i.e. with no pleural effusion or other local advancement, no supraclavicular lymph node involvement and good performance status), but treated without resection. The major prognostic factors were well balanced between these two groups. Total series included 109 males and 25 females, 20 patients with T1 and 114 patients with T2 disease, 51 N0, 43 N1 and 40 N2 disease. RESULTS: Median survival in patients treated with and without surgery was 22 months and 11 months, respectively, (P < 0.001). The two-year and five-year survival probabilities were 43 and 27%, respectively, in the surgical group, and 17 and 4%, respectively, in the non-surgical group. Subset analysis confirmed significantly longer survival with surgery in all T and N categories, except for N2 disease. Local relapse occurred in 15 and 55% of patients treated with and without surgery, respectively, (P < 0.001). Distant relapse probabilities were similar in both groups (36 and 40%, respectively). The most common site of metastases in the entire series was brain, followed by liver, lymph nodes, bone, lung and skin. CONCLUSIONS: Our results suggest a possible role of surgery in limited-stage SCLC. Thus, a randomised study addressing this issue seems to be justified.     

Postoperative radiotherapy and radiotherapy combined with CCNU chemotherapy for treatment of brain gliomas

A prospective, randomized trial evaluates the effects of two postoperative treatment regimens on survival in 198 adult patients with supratentorial gliomas. All patients were irradiated with 6 000 rads after possibly radical removal of tumors. CCNU administration in the dosis of 100 mg/sq m of body surface every 6–8 weeks following surgery proved to have no significant effect on the survival of patients. The median survival time in patients receiving radiation therapy alone was 61±7 weeks, while in those receiving additional chemotherapy was 56±4 weeks. Tumor histological malignancy and patients age were found to be the only important prognostic factors, irrespective of the treatment modality. Address for offprints: T Trojanowski, Department of Neurosurgery, Medical School, Jaczewskiego 8, 20-950 Lublin, Poland     

Glucocorticoids modulate TGF-beta production

TGF- is thought to play a central role in pulmonary fibrosis inducing fibroblast differentiation and extracellular matrix synthesis. In human lung fibroblasts, it is still unclear how various TGB- isoforms affect TGF- production and whether glucocorticoids, commonly used agents to treat fibrotic lung disease, modulate these processes. To this end, human fetal lung fibroblasts (HFL-1) were cultured with various concentrations of glucocorticoids (budesonide, dexamethasone or hydrocortisone) with and without TFG-1, -2, and -3. TGF- mRNA was assessed by real time RT-PCR. Smad 2, 3, and 4 and AP-1 complex (c-fos and c-Jun) cellular localization were evaluated by immunostaining. TGF-2 and -3 stimulated TGF-1 production significantly (p < 0.01 relative to control). TGF-1 stimulated TGF-2 production (p < 0.01 relative to control). TGF-3 was undetectable. Glucocorticoids significantly inhibited TGF-1 and -2 production and reduced expression of the upregulated TGF-1 and -2 mRNA induced by exogenous TGF-1, -2 or -3 (p < 0.01 for each) but had no effect on Smads. Although c-jun-related nuclear staining was not intensified in TGF--stimulated cells, it was reduced by glucocorticoids. Thus, TGF- isoforms may stimulate production of various TGF- isoforms in the lung. Glucocorticoids then may block TGF- production by modulating mRNA levels and c-Jun.     

10 years survival of patient with lung cancer and cerebral metastasis

The authors describe the case of survival for the period of 10 years after brain metastasis surgery and removal of the left lung upper lobe due to adeno-squamous cells carcinoma. Surgery did not generate any complications. Within 8 years after the surgery the radiological examination showed infiltrations resembling changes typical for tuberculosis. Microbiological analysis showed a culture of Mycobacterium kansasi leading to diagnosis of mycobacteriosis. Hence the antituberculous treatment was extended to 12 months to be interrupted due to liver damage. Two years later the patient experienced incident of haemoptysis. Detailed examination and assessment of the respiratory tract condition revealed COPD without features of renewal of the neoplastic process or infection by Mycobacterium tuberculosis or mycobacterium other than tuberculosis. This case demonstrates that aggressive surgical approaches to lung cancer with solitary cerebral metastasis significantly improve patient survival and justifies its widespread use.