Prognostic importance of microvessel density, VEGF expression and perineural invasion in laryngeal cancer treated with adjuvant radiotherapy.

Background and Aims: We aimed to investigate the prognostic importance of the microvessel density (MVD) value, the vascular endothelial growth factor (VEGF) expression, and the presence of perineural invasion (PNI) in laryngeal cancer (LSCC) patients. Methods: Pathological specimens of 62 LSCC patients were assessed for the evaluation of the MVD value, the VEGF expression level, and the presence of PNI of the tumors. The tumor characteristics and prognostic effects of these parameters on local control (LC) and overall survival (OS) were analyzed. Statistical Analysis: Descriptive analyses were done using frequencies for the demographic variables. The survival estimates were calculated by the Kaplan-Meier survival curves. The effects of the parameters on LC and OS were investigated by using the log-rank test comparing the survival rates. Cox regression analysis was used for multivariable analysis. Results: The 5-year LC and OS rates of the 62 LSCC patients were 64.5 and 53.9%, respectively. Twenty-two patients (35.5%) had PNI and the frequency of PNI was higher in the patients with a high-grade disease (P = 0.01). The MVD value was higher in the tumors of older patients (P = 0.035) and was correlated with the VEGF expression (P = 0.009). A higher tumor grade was related to a higher VEGF expression (P = 0.01) and the increase in the VEGF expression was associated with a significant decrease in the OS (P = 0.03). Conclusion: The VEGF expression, the MVD value, and the presence of PNI had no prognostic significance on the LC in the LSCC patients while only the VEGF expression was associated with the OS.

Histopathological and scintigraphic comparisons of the protective effects of L-carnitine and amifostine against radiation-induced late renal toxicity in rats.

1. The aim of the present study was to compare the protective effects of L-carnitine and amifostine against radiation-induced late nephrotoxicity using technetium-99m diethylenetriaminepentaacetic acid scintigraphy and histopathological examination. 2. Seventy-one Albino rats were randomly divided into six groups as follows: (i) AMI + RAD (n = 15), 200 mg/kg, i.p., amifostine 30 min prior to irradiation (a single dose of 9 Gy); (ii) LC + RAD (n = 15), 300 mg/kg, i.p., L-carnitine 30 min prior to irradiation; (iii) LC (n = 10), 300 mg/kg, i.p., L-carnitine 30 min prior to sham irradiation; (iv) AMI (n = 10), 200 mg/kg, i.p., amifostine 30 min prior to sham irradiation; RAD (n = 11), 1 mL/kg, i.p., normal saline 30 min prior to irradiation; and (vi) control (n = 10), 1 mL/kg, i.p., normal saline 30 min prior to sham irradiation. Scintigraphy was performed before treatment and again 6 months after treatment. Kidneys were examined by light microscopy and a histopathological scoring system was used to assess the degree of renal damage. 3. The main histopathological findings were proximal tubular damage and interstitial fibrosis. Glomerular injury was similar in all groups. Tubular degeneration and atrophy were less common in the AMI + RAD group than in the RAD group (P = 0.011 and P = 0.015, respectively), as well as in the LC + RAD group compared with the RAD group (P = 0.028 and P = 0.036, respectively). Interstitial fibrosis in the AMI + RAD and LC + RAD groups was significantly less than that in the RAD group (P = 0.015 and P = 0.015, respectively). The highest total renal injury score (9) was seen in the RAD group. On scintigraphy, there were significant differences in post-treatment time to peak count (T(max)) and time from peak count to half count (T((1/2))) values (P = 0.01 and 0.02, respectively) between groups in the right kidney. In the control and RAD groups, the T((1/2)) of the right kidney was 8 +/- 2 and 21 +/- 2 min, respectively. The T(max) values for the AMI + RAD and LC + RAD groups (2.8 +/- 0.2 and 3.2 +/- 0.2 min, respectively) were similar to those in the control group (2.5 +/- 0.3 min). 4. Based on the results of the present study, L-carnitine and amifostine have comparable and significant protective effects against radiation-induced late nephrotoxicity.

An unusual metastatic site of tongue carcinoma: shoulder muscles.

The incidence of skeletal muscle metastases is reported to be less than 1% of metastases of haematogenous origin. Distant skeletal muscle metastases from head and neck squamous cell carcinomas are exceedingly rare. Only a case with tongue carcinoma metastasized to paravertebral muscles, has been reported so far. The reasons for the rarity of metastatic involvement of skeletal muscle are still unclear. The presence of skeletal muscle metastases in the setting of disseminated disease offers no hope for curative treatment. We report an unusual case of a 63-year-old patient with tongue carcinoma metastasizing to the left shoulder muscles. To our knowledge, this is the first such case to be reported in the English medical literature.

Paraneoplastic syndrome of non-small cell lung carcinoma: a case with pancytopenia, leukocytoclastic vasculitis, and hypertrophic osteoarthropathy.

Various remote effects of cancer or paraneoplastic syndromes (PNS) are common in lung cancer, and may be the manifestation of the disease or its recurrence. The symptoms may be endocrine, neuromuscular or musculoskeletal, cardiovascular, cutaneous, hematologic, gastrointestinal, renal, or miscellaneous in nature. Since the symptoms of paraneoplastic syndromes may occur before the local symptoms of the primary tumor, it might be helpful in the early diagnosis of malignancy. We present a 65-year-old man with multiple paraneoplastic syndrome forms consisting of pancytopenia leukocytoclastic vasculitis and hypertrophic pulmonary osteoarthropathy, associated with non-small cell lung carcinoma.

Lung, bone, skeletal muscles and cutaneous metastases from adenoid cystic carcinoma of the parotid gland: a case report and review of the literature.

Adenoid cystic carcinoma is the second most common malignancy of the major and minor salivary glands after mucoepidemoid carcinoma. The risk of distant metastases is approximately 20-50%. Although bone, the central nervous system and the other organs may become involved, the lungs are favored sites for metastases. Skeletal muscle and cutaneous metastases from adenoid cystic carcinoma of the parotid gland are extremely rare. In this case, a 40-year-old man with lung and bone metastases followed by skeletal muscle and cutaneous metastases from adenoid cystic carcinoma of the right parotid gland is presented.

Colonic metastasis from carcinoma of the breast that mimics a primary intestinal cancer.

Although the lung, liver, or bones are the most common location for distant metastases in breast cancer patients, metastases to the intestinal tract are very rarely recognized in the clinic. We will present an unusual case of colonic metastasis from a carcinoma of the breast that mimics a primary intestinal cancer, along with a through review of English language medical literature. Despite the fact that isolated gastrointestinal (GI) metastases are very rare and much less common than benign disease processes or second primaries of the intestinal tract in patients with a history of breast cancer, metastatic disease should be given consideration whenever a patient experiences GI symptoms.

Nasopharyngeal carcinoma with extensive nodular skin metastases: a case report.

Skin metastasis from nasopharyngeal carcinoma is a rare clinical finding. The most common form of appearance is a few solitary skin nodules. However, massive and extensive nodular dissemination or diffuse dermal lymphatic infiltration is extremely rare. We here present a case of a 40-year-old man with widespread nodular skin metastases from undifferentiated nasopharyngeal carcinoma.

Bilateral choroidal metastases as an initial manifestation of small-cell carcinoma of the lung.

The occurrence of clinically symptomatic intraocular metastases as an initial manifestation of primary neoplasm is rare event. The recognition of metastatic ocular tumors is important since they indicate a poor prognosis. Prompt diagnosis and treatment can significantly improve the quality of life for these patients. We report the case of a 48-year-old man presenting with a two-week history of left sided intraocular pain with blurring of vision and headache, which are the first signs of small-cell lung carcinoma.

[An analysis of genetic transmission in a father and son with osteosarcoma]. / Osteosarkomlu baba ve ogulda genetik geçisin irdelenmesi.

Familial osteosarcoma is a rare hereditary disease. We present a 37-year-old father and a 17-year-old son who developed osteosarcoma in the left and right distal femurs, respectively, at a three-year interval. They were treated with chemotherapy followed by surgery. Both had positive immunostaining for p53 tumor suppressor gene and HER-2/neu oncogene. The son also exhibited deletion of the retinoblastoma 1 gene. Pulmonary metastasis was detected in the father at the time of diagnosis and 13 months after primary treatment, whereas no distant metastasis was present in the child. The father died 39 months after the diagnosis from primary symptoms, but the son led a disease-free survival a year after completion of treatment. Genetic abnormalities documented in the father and son corroborate the presence of specific genetic alterations in the pathogenesis of osteosarcoma.

Protective effects of Nigella sativa on gamma radiation-induced jejunal mucosal damage in rats.

INTRODUCTION: The aim of this study was to compare the efficacy of Nigella sativa in protection of jejunal mucosa against harmful effects of gamma radiation. METHODS: Radiotherapy group received abdominal gamma radiation of 15Gy in addition to physiological saline. Radiotherapy+Nigella sativa treatment group received abdominal gamma radiation of 15Gy in addition to Nigella sativa treatment in the amount of 400mg/kg. Radiotherapy and treatment groups were sacrificed 3 days after the exposure to irradiation. Then, jejunum samples were harvested for biochemical and histological assessment of mucosal injury. RESULTS: Nigella sativa treatment was found to significantly lower elevated tissue malondialdehyde (MDA) levels and, to raise reduced glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activity in intestinal tissues samples. Single dose 15Gy gamma-irradiation was noted to result in a marked jejunal mucosal injury. Three days after exposure to irradiation, the villi and Lieberkühn crypts were observed as denuded, and villous height diminished. Concomitantly with inflammatory cell invasion, capillary congestion and ulceration were observed in the atrophic mucosa. Nigella sativa treatment significantly attenuated the radiation induced morphological changes in the irradiated rat jejunal mucosa. CONCLUSION: Nigella sativa has protective effects against radiation-induced damage, suggesting that clinical transfer is feasible.

Assessment of quality of life of nasopharyngeal carcinoma patients with EORTC QLQ-C30 and H&N-35 modules.

PURPOSE: The current study reports on long-term quality of life (QoL) status after conventional radiotherapy in 187 nasopharyngeal carcinoma patients from 14 centers in Turkey. PATIENTS AND METHODS: Patients with the diagnosis of nasopharyngeal carcinoma, who were treated in 14 centers in Turkey with minimum 6 months of follow-up and were in complete remission, were asked to complete Turkish versions of EORTC QLQ-C30 questionnaire and the HN-35 module. Each center participated with the required clinical data that included age at diagnosis, gender, symptoms on admission, follow-up period, treatment modalities, radiotherapy dose, and AJCC 1997 tumor stage. Each patient's 33 QoL scores, which included function, global health status, and symptoms, were calculated as instructed in EORTC QLQ-C30 scoring manual. All of the scales and single-item measures range from 0 to 100. A high score represents a higher response level. Kruskal-Wallis and Mann-Whitney U nonparametric tests were used for comparisons. RESULTS: One hundred eighty-seven patients with median age of 46 years (range, 16-79 years) participated and completed the questionnaires. Median follow-up time was 3.4 years (range, 6 months-24 years). All patients have received external-beam radiotherapy. Beside external-beam radiotherapy, 59 patients underwent brachytherapy boost, 70 patients received concomitant chemotherapy, and 95 patients received adjuvant/neoadjuvant chemotherapy. Most of the patients in the analysis (75%) were in advanced stage (Stage III, n = 85 [45.4%]; Stage IV, n = 55 [29%]). Mean global health status was calculated as 73. Parameters that increased global health status were male gender, early-stage disease, and less than 4-year follow-up (p < 0.05). Functional parameters were better in males and in early-stage disease. Factors that yielded better symptom scores were short interval after treatment (10 scores), male gender (7 scores), and lower radiation dose (6 scores). Neoadjuvant or adjuvant chemotherapy did not have any effect on QoL, whereas concomitant chemotherapy adversely affected 5 symptom scores. CONCLUSION: Quality of life is adversely affected in our nasopharyngeal carcinoma patients treated with combined therapies. The factors that adversely affect quality of life are advanced tumor stage, female gender, and long-term follow-up. Further controlled studies to evaluate both preradiotherapy and postradiotherapy status are necessary to clarify the contribution of each treatment modality to QoL.

Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods.

PURPOSE: The aim of this study was to compare the radioprotective efficacies of L-carnitine (LC) and amifostine against radiation-induced acute ovarian damage. MATERIALS AND METHODS: Forty-five, 3-month-old Wistar albino rats were randomly assigned to six groups. Control (CONT, n = 7); irradiation alone RT: radiation therapy (RT, n = 8); amifostine plus irradiation (AMI + RT, n = 8); LC plus irradiation (LC + RT, n = 8); LC and sham irradiation (LC, n = 7); and amifostine and sham irradiation (AMI, n = 7). The rats in the AMI + RT, LC + RT and RT groups were irradiated with a single dose of 20 Gy to the whole abdomen. LC (300 mg/kg) and amifostine (200 mg/kg) was given intraperitoneally 30 min before irradiation. Five days after irradiation, both antral follicles and corpus luteum in the right ovaries were counted, and tissue levels of malondialdehyde (MDA) and advanced oxidation protein product (AOPP) were measured. RESULTS: Irradiation significantly decreased antral follicles and corpus luteum (P: 0.005 and P < 0.0001). LC increased the median number of antral follicles and corpus luteum (P: 0.009 and P < 0.0001, respectively). Amifostine improved median corpus luteum numbers but not antral follicle (P < 0.000, P > 0.05). The level of MDA and AOPP significantly increased after irradiation (P = 0.001 and P < 0.0001, respectively). MDA and AOPP levels were significantly reduced by LC (P: 0.003, P < 0.0001) and amifostine (P < 0.0001, P: 0.018). When comparing CONT group with AMI + RT and LC + RT groups, MDA and AOPP levels were similar (P > 0.005). The levels of both MDA and AOPP were also similar when LC + RT is compared with AMI + RT group (P > 0.005). CONCLUSIONS: L-carnitine and amifostine have a noteworthy and similar radioprotective effect against radiation-induced acute ovarian toxicity.

The protective effect of amifostine on radiation-induced acute pulmonary toxicity: detection by (99m)Tc-DTPA transalveolar clearances.

PURPOSE: The purpose of this study was to determine by using (99m)Tc-diethylenetriaminepentaacetic acid (DTPA) lung scintigraphy whether amifostine given before irradiation protects alveolocapillary integrity in a rabbit model. METHODS AND MATERIALS: Twenty white New Zealand rabbits were randomly divided into 4 groups: (1) control (CONT), (2) amifostine alone (AMF), (3) radiation (RAD), and (4) radiation plus amifostine (RAD+AMF). The AMF and RAD+AMF groups received amifostine. The RAD and RAD+AMF groups were irradiated to the right hemithorax with a single dose of 20 Gy using a (60)Co treatment unit. Amifostine (200 mg/kg) was given i.p. 30 min before irradiation. The (99m)Tc-DTPA radioaerosol study was performed 14 day after irradiation. RESULTS: The mean clearance rate of (99m)Tc-DTPA in control subjects was 140 +/- 21 min. The highest t((1/2)) value was noted in the RAD group (603 +/- 105 min, p = 0.001). There were no significant differences between the (99m)Tc-DTPA lung clearance rates of the CONT, RAD+AMF (238 +/- 24 min), and AMF groups (227 +/- 54 min). The mean penetration index values of CONT, RAD, AMF, and RAD+AMF are 63% +/- 1.6%, 63% +/- 2.5%, 60% +/- 2.9%, and 63% +/- 2%, respectively. CONCLUSIONS: We concluded that amifostine treatment before the lung irradiation protects the lung alveolocapillary integrity. This study confirms the protective effect of amifostine in an acute phase of radiation lung injury.

The potential cardioprotective effects of amifostine in irradiated rats.

PURPOSE: The aim of this study is to determine the cardioprotective efficacy of amifostine. The study consists of researching the relationship between plasma brain natriuretic peptide levels and the electrical and morphologic changes in irradiated rats with or without amifostine. METHODS AND MATERIALS: Sixty Wistar albino rats were divided into 4 groups, and their hearts were given 15 Gy/fraction with (60)Co. In Groups I and II, the rats were killed after 24 hours to detect early effects; in Groups III and IV, the rats were killed 100 days after irradiation to detect late effects. Before irradiation, Groups I and III received 0.9% saline solution, whereas Groups II and IV received amifostine (200 mg/kg). Twenty rats were used as a control group. RESULTS: On the 100th day, mild myocardial degeneration was detected in 5 rats (33%) from Group III (no amifostine). This percentage was statistically different from that of Group IV (treated with amifostine) and the controls (p = 0.042). There was no statistically significant difference between the mean plasma brain natriuretic peptide values of the groups (p > 0.05). There was no significant difference in electrocardiographies between the groups. There was no correlation between continuous variables. CONCLUSION: In the amifostine group (IV) on the 100th day, there was no myocardial degeneration, suggesting that amifostine has a cardioprotective effect.

The effect of low-dose external beam radiation on extraneural scarring after peripheral nerve surgery in rats.

OBJECTIVE: Scar tissue is an inevitable result of peripheral nerve surgery. A variety of substances have been used to prevent epineurial scarring. In this study, the effect of low-dose radiation therapy on epineurial scarring was investigated. METHODS: Seventy-eight male Sprague-Dawley rats were studied. A total of 60 rats were subjected to one of three types of surgical procedure on the sciatic nerve, as follows: Procedure 1, external neurolysis (n = 20); Procedure 2, abrasive injury (n = 20); and Procedure 3, anastomosis (n = 20). On the left sciatic nerves, 700 cGy external beam radiation was administered 24 hours after surgery, and the right sciatic nerves served as a control group (surgery only). Eighteen animals without surgical intervention were used to establish the fibrotic effect of radiotherapy on normal nerves. A neurological examination was performed weekly. Six weeks after surgery, the extent of extraneural scarring was examined by gross microdissection by means of a numerical grading scheme and histological analysis. Cellular density and surface measurements of scar tissue were also evaluated. RESULTS: The dissection around the nerve was easier in rats treated with low-dose radiation compared with the control group. Furthermore, grading scores in both nerve adherence and nerve separability were significantly lower in treated nerves than in the control group (P < or = 0.05). Low-dose radiotherapy decreased the scores of cellular density and surface measurement of scar tissue (P < or = 0.05). In normal nerves, radiotherapy did not produce any fibrotic effects and the density of fibroblasts/fibrocytes was also very low. CONCLUSION: In the case of surgery or local trauma to peripheral nerve, the use of low-dose radiation therapy may be a safe method of limiting postoperative epineurial scar formation.

The histopathological comparison of L-carnitine with amifostine for protective efficacy on radiation-induced acute small intestinal toxicity.

BACKGROUND: The aim of the study was to compare the protective efficacy of l-carnitine (LC) to amifostine on radiation-induced acute small intestine damage. MATERIALS AND METHODS: Thirty, 4-week-old Wistar albino rats were randomly assigned to four groups - Group 1: control (CONT, n = 6), Group 2: irradiation alone (RT, n = 8), Group 3: amifostine plus irradiation (AMI+RT, n = 8), and Group 4: l-Carnitine plus irradiation (LC+RT, n = 8). The rats in all groups were irradiated individually with a single dose of 20 Gy to the total abdomen, except those in CONT. LC (300 mg/kg) or amifostine (200 mg/kg) was used 30 min before irradiation. Histopathological analysis of small intestine was carried out after euthanasia. RESULTS: Pretreatment with amifostine reduced the radiation-induced acute degenerative damage (P = 0.009) compared to the RT group. Pretreatment with LC did not obtain any significant difference compared to the RT group. The vascular damage significantly reduced in both of the AMI+RT (P = 0.003) and LC+RT group (P = 0.029) compared to the RT group. The overall damage score was significantly lower in the AMI+RT group than the RT group (P = 0.009). There was not any significant difference between the LC+RT and RT group. CONCLUSIONS: Amifostine has a marked radioprotective effect against all histopathological changes on small intestinal tissue while LC has limited effects which are mainly on vascular structure.

The Protective Effect of Curcumin on Ionizing Radiation-induced Cataractogenesis in Rats.

OBJECTIVE: The aim of the study was to determine the protective effect of curcumin against ionizing radiation-induced cataract in the lens of rats. MATERIAL AND METHODS: Rats were divided into six groups. Group 1: Control, Group 2: Dimethyl sulfoxide (DMSO), Group 3: DMSO+curcumin, Group 4: Irradiation, Group 5: Irradiation+DMSO, Group 6: Irradiation+DMSO+curcumin. A 15 Gy total dose was given to 4, 5, 6 groups for radiation damage. Curcumin (100 mg/kg) was dissolved in DMSO and given by intragastric intubation for 28 days. At the end of the experiment, lenses were graded and enucleated. The lenticular activity of the antioxidant enzymes, total antioxidant and glutathione peroxidase (GSH-Px), and the malondialdehyde (MDA) were measured. RESULTS: 100% Cataract was seen in the irradiation group. Cataract rate fell to 40% and was limited at grade 1 and 2 in the curcumin group. In the irradiation group, antioxidant enzyme levels were decreased, MDA levels were increased. There was an increase in antioxidant enzyme levels and a significant decrease in MDA in the group which was given curcumin. CONCLUSION: Curcumin has antioxidant and radioprotective properties and is likely to be a valuable agent for protection against ionizing radiation. Hence, it may be used as an antioxidant and radioprotector against radiation-induced cataractogenesis.

Radiation-induced chronic oxidative renal damage can be reduced by amifostine.

In the current study, amifostine is evaluated for its radioprotective role in serum and kidney tissue by oxidative (malondialdehyde-MDA, advanced oxidation protein product-AOPP) and antioxidative markers (catalase, glutathione-GSH, free-thiols-F-SH). Thirty Wistar albino 3-4 months old, female rats, were randomly divided into Group I (n = 10): Control, Group II (n = 10): Irradiation-alone, Group III (n = 10): Amifostine before irradiation. In Group II and III, right kidneys of the rats were irradiated with a single dose of 6 Gy using a 60Co treatment unit. Rats in Group III received 200 mg/kg amifostine intraperitoneally, 30 min prior to irradiation. Following sacrification at 24th week, blood and kidney tissue samples were collected. Statistical analysis was done by One-way ANOVA, Post hoc Bonferroni, Dunnett T3, and Mann-Whitney U tests. Administration of amifostine significantly decreased the serum AOPP and MDA levels when compared to the irradiation-only group (P = 0.004, P = 0.006; respectively). Also amifostine significantly increased serum catalase activities and GSH levels, when given 30 min prior to irradiation (P = 00.02, P = 0.000; respectively). In the kidney tissue, administration of amifostine significantly decreased AOPP and MDA levels (P = 0.002, P = 0.016; respectively). Tissue GSH activity was increased following amifostine administration (P = 0.001). There was no statistically significant result on histopathological evaluation. Amifostine may reduce radiation-induced nephropathy by inhibiting chronic oxidative stress. Biomarkers of oxidative stress in serum and kidney tissue may be used for evaluation of the radiation-induced nephropathy.

Role of amifostine on acute and late radiation nephrotoxicity: a histopathological study.

BACKGROUND: The present study was performed to determine the effect of amifostine in the prevention of radiation-induced acute and late period morphologic damages in rat kidney via light and electron microscopic examinations. MATERIALS AND METHODS: Control rats (n=6) received saline solution 30 min before sham irradiation; the radiotherapy alone group (n=12) received saline solution 30 min before irradiation (a single dose of 15 Gy, applied unilaterally to the kidney) and a final radiotherapy +amifostine group (n=12) received 200 mg/kg amifostine 30 min prior to irradiation. RESULTS: Microscopic examinations of irradiated kidneys revealed presence of glomerular tuft capsular adhesion, fusion of the foot processes and ballon-like cellular degeneration and loss of luminal brush border in tubules as early as eight weeks after irradiation. By 24 weeks post-irradiation, these changes were advanced and associated with focal mesangiolysis, segmental sclerosis and focal tubular atrophy. In addition, local irradiation caused interstitial fibrotic lesions in the kidney. Pretreatment of amifostine markedly prevented these glomerular and tubular changes, and interstitial fibrotic lesions. CONCLUSION: This study suggests that amifostine pretreatment may contribute to prevention of radiation-induced acute and late nephrotoxicity.

Evaluation of morphine effect on tumour angiogenesis in mouse breast tumour model, EATC.

Breast cancer is the leading cause of death among women, and morphine is used to relieve the pain of patients with cancer. The data on the effects of morphine on tumour growth and angiogenesis are contradictory. We determined in mouse breast cancer model whether analgesic doses of morphine would affect tumour angiogenesis, and then the correlation between microvessel density (MVD), Doppler sonography (DS) and 99mTc-Tetrofosmin (TF) uptake. Ehrlich ascites tumour cell xenografts, Pgp-negative tumour were divided into two groups: (a) Morphine sulphate [0.714 mg/kg/day (equivalent to 50 mg per day for a 70 kg human)], (b) no-morphine. For the determination of angiogenesis in mice tumour tissue, TF scintigraphy, microvessel density and DS were done. MVD was significantly different between groups (49.4±1.8 vs. 41.8±1.9, morphine and no-morphine groups, respectively, P<0.001). A strong correlation was found between late uptakes of mass at scintigraphy and degree of angiogenesis in histopathologic examination (r=0.52, P<0.01). There was statistically significant inverse correlation between degree of angiogenesis in histopathologic examination and washout ratio of TF (r=0.40, P<0.05). The higher values for angiogenesis are related to higher TF reuptake. There was no statistically significant correlation between DS and TF. A strong correlation was found between MVD and grade of DS (r=0.51, P<0.01). Our preclinical mice study indicates that morphine at clinically relevant doses stimulates angiogenesis, and angiogenesis triggered of morphine is demonstrated with MVD and DS, but not TF. However, uptake and washout of TF are compared with immunohistochemically assessed morphine-stimulated angiogenesis in tumour tissue.