Cem Uzal

Extrapulmonary Small-Cell Carcinoma Compared With Small-Cell Lung Carcinoma A Retrospective Single-Center Study

The study was conducted with the aim of reviewing the clinical features, therapy, and natural course of patients with extrapulmonary small‐cell carcinoma (EPSCC) and small‐cell lung carcinoma (SCLC) to better define current concepts regarding EPSCCs.

Total-body irradiation and cataract incidence: A randomized comparison of two instantaneous dose rates

PURPOSE To assess the influence of instantaneous total-body irradiation dose rate in hematological malignancies, we randomized 157 patients according to different instantaneous dose rates. METHODS AND MATERIALS Between December 10, 1986 and December 31, 1989 157 patients have undergone a total-body irradiation before bone-marrow transplantation according to two different techniques: either in one fraction (1000 cGy given to the midplane at the level of L4, and 800 cGy to the lungs) or in six fractions (1200 cGy over 3 consecutive days to the midplane at the level of L4, and 900 cGy to the lungs). Patients were randomized according to two instantaneous dose rates, called LOW and HIGH, in single-dose (6 vs. 15 cGy/min) and fractionated (3 vs. 6 cGy/min) TBI groups; there were 77 cases for the LOW and 80 for the HIGH groups, with 57 patients receiving single-dose (28 LOW, 29 HIGH) and 100 patients receiving fractionated total-body irradiation (49 LOW, 51 HIGH). RESULTS As of July 1992, 16 (10%) of 157 patients developed cataracts after 17 to 46 months, with an estimated incidence of 23% at 5 years. Four (5%) of 77 patients in the LOW group, 12 (15%) of 80 patients in the HIGH group developed cataracts, with 5-year estimated incidences of 12% and 34%, respectively (p = 0.03). Ten (18%) of 57 patients in the single-dose group, and 6 (6%) of 100 patients in the fractionated group developed cataracts, with 5-year estimated incidences of 39% and 13%, respectively (p = 0.02). When the subgroups were considered, in the single-dose group, 3 (11%) of 28 LOW patients, and 7 (24%) of 29 HIGH patients developed cataracts, with 5-year estimated incidences of 24% and 53%, respectively; in the fractionated group, 1 (2%) of 49 LOW patients, and 5 (10%) of 51 HIGH patients developed cataracts, with 5-year estimated incidences of 4% and 22%, respectively (single-dose LOW vs. single-dose HIGH vs. fractionated LOW vs. fractionated HIGH, p = 0.006). There was no statistically significant difference in terms of 5-year estimated cataract incidence between the patients receiving steroids and those not (30% vs. 25%, p = 0.22). Multivariate analyses revealed that the instantaneous dose rate was the only independent factor influencing the cataractogenesis (p = 0.04). CONCLUSION We conclude that the total-body irradiation regimen (instantaneous dose rate and/or fractionation) may have an influence on the development of cataracts following bone-marrow transplantation.

An ambiguous phenomenon of radiation and drugs: recall reactions.

The term ‘radiation recall’ describes an acute inflammatory reaction in previously irradiated areas after the administration of certain inciting systemic agents. It was first described in 1959 by D’Angio that dermatitis is related to the application of actinomycin D on the skin. Though this reaction occurs frequently on the skin, it may also be seen in the oral mucosa, the larynx, esophagus, small intestine, lungs, muscle tissue, and brain. Most drugs associated with recall reactions are cytotoxics, however, several other drugs may also elicit the phenomenon. Although this phenomenon is well known, its etiology is not understood. Radiation recall reactions are generally associated with megavoltage radiotherapy. The time interval between the completion of radiotherapy and the recall reaction ranges from days to years. The recall reaction occurs on average 8 days (3 days to 2 months) after the application of the promoting agent. Although no standard treatment exists, some authors suggest discontinuation of the inciting drug and the use of corticosteroids or nonsteroidal anti-inflammatory agents.

Postmastectomy irradiation in breast in breast cancer patients with T1-2 and 1-3 positive axillary lymph nodes: Is there a role for radiation therapy?

BackgroundWe aimed to evaluate retrospectively the correlation of loco-regional relapse (LRR) rate, distant metastasis (DM) rate, disease free survival (DFS) and overall survival (OS) in a group of breast cancer (BC) patients who are at intermediate risk for LRR (T1-2 tumor and 1-3 positive axillary nodes) treated with or without postmastectomy radiotherapy (PMRT) following modified radical mastectomy (MRM).MethodsNinety patients, with T1-T2 tumor, and 1-3 positive nodes who had undergone MRM received adjuvant systemic therapy with (n = 66) or without (n = 24) PMRT. Patient-related characteristics (age, menopausal status, pathological stage/tumor size, tumor location, histology, estrogen/progesterone receptor status, histological grade, nuclear grade, extracapsular extension, lymphatic, vascular and perineural invasion and ratio of involved nodes/dissected nodes) and treatment-related factors (PMRT, chemotherapy and hormonal therapy) were evaluated in terms of LRR and DM rate. The 5-year Kaplan-Meier DFS and OS rates were analysed.ResultsDifferences between RT and no-RT groups were statistically significant for all comparisons in favor of RT group except OS: LRR rate (3%vs 17%, p = 0.038), DM rate (12% vs 42%, p = 0.004), 5 year DFS (82.4% vs 52.4%, p = 0.034), 5 year OS (90,2% vs 61,9%, p = 0.087). In multivariate analysis DM and lymphatic invasion were independent poor prognostic factors for OS.ConclusionPMRT for T1-2, N1-3 positive BC patients has to be reconsidered according to the prognostic factors and the decision has to be made individually with the consideration of long-term morbidity and with the patient approval.

Colonic Metastasis from Carcinoma of the Breast that Mimicks 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.

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 (Tmax) and time from peak count to half count (T½) values (P = 0.01 and 0.02, respectively) between groups in the right kidney. In the control and RAD groups, the T½ of the right kidney was 8 ± 2 and 21 ± 2 min, respectively. The Tmax 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.

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

OBJECTIVEScar 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. METHODSSeventy-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. RESULTSThe 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 ≤ 0.05). Low-dose radiotherapy decreased the scores of cellular density and surface measurement of scar tissue (P ≤ 0.05). In normal nerves, radiotherapy did not produce any fibrotic effects and the density of fibroblasts/fibrocytes was also very low. CONCLUSIONIn 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.

Oncocytic Carcinoma of the Parotid Gland

Background: Oncocytic carcinoma is a rare tumor of major salivary glands. Despite being described 5 decades ago, not much is known about these rare tumors. Histochemical or electron microscopic confirmation of the oncocytic nature of the tumor cell is needed for differential diagnosis. The main treatment modality is surgery with or without adjuvant radiotherapy. Malignant oncocytomas have the potential risk of developing distant metastases and demand long term follow-up after therapy. Case Report: A 58-year old man presented with a recurrent mass in the left parotid gland with a prior diagnosis of monomorphic adenoma in the same localization which had been treated by tumor excision in July 2002. Left superficial parotidectomy followed by radiotherapy into tumor bed and upper neck were carried out in September 2004. To date, he has had no evidence of recurrence for 14 months. Conclusion: For an accurate approach in the management of patients, oncocytic adenocarcinoma should be considered in the differential diagnosis of lesions of the parotid gland, most of which are benign.

Amifostine use in radiation-induced kidney damage. Preclinical evaluation with scintigraphic and histopathologic parameters.

Purpose:To assess the degree of protective effects of amifostine on kidney functions via semiquantitative static renal scintigraphy and histopathologic analysis.Material and Methods:30 female albino rats were divided into three equal groups as control (CL), radiotherapy alone (RT), and radiotherapy + amifostine (RT+AMI). The animals in the CL and RT groups were given phosphate-buffered saline, whereas the animals in the RT+AMI group received amifostine (200 mg/kg) by intraperitoneal injection 30 min before irradiation. RT and RT+AMI groups were irradiated with a single dose of 6 Gy using a 60Co unit at a source-skin distance of 80 cm to the whole right kidney. They were followed up for 6 months. CL, RT, and RT+AMI groups underwent static kidney scintigraphy at the beginning of the experiment and, again, on the day before sacrificing. Histopathologically, tubular atrophy and fibrosis of the kidney damage were evaluated.Results:After irradiation, the median value of right kidney function was 48% (44–49%) and 50.5% (49%–52%) in RT and RT+AMI groups, respectively (p = 0.0002). Grade 1 kidney fibrosis was observed to be 60% in the RT group, while it was only 30% in the RT+AMI group. Grade 2 kidney fibrosis was 30% and 0% in the RT and RT+AMI group, respectively. Grade 1 tubular atrophy was 70% and 50% in the RT and RT+AMI group, respectively. Grade 2 tubular atrophy effect was the same in both groups (10%).Conclusion:Static kidney scintigraphy represents an objective and reproducible method to noninvasively investigate kidney function following irradiation. Amifostine produced a significant reduction in radiation-induced loss of renal function.Ziel:Beurteilung der protektiven Wirkung von Amifostin auf die Nierenfunktion mittels semiquantitativer statischer szintigraphischer und histopathologischer Analyse.Material und Methodik:30 weibliche Albinoratten wurden in drei Gruppen mit jeweils zehn Tieren aufgeteilt: Kontrolle (CL), alleinige Radiotherapie (RT) und Radiotherapie + Amifostin (RT+AMI). Die Ratten in der CL- und RT-Gruppe erhielten eine Plazebosalzlösung, die Ratten in der RT+AMI-Gruppe 200 mg/kg Amifostin intraperitoneal 30 min vor der Bestrahlung. Die rechten Nieren in der RT- und RT+AMI-Gruppe wurden mit 6 Gy Einzeldosis mit einem 60Co-Gerät bestrahlt. Die Nachbeobachtungszeit betrug 6 Monate. Eine Nierenszintigraphie wurde direkt vor der Bestrahlung und vor Sektion bei den Tieren der RT- und RT+AMI-Gruppe durchgeführt. Der Nierenschaden wurde in der histopathologischen Untersuchung mit Tubulusatrophie und Fibrose qualitativ beurteilt.Ergebnisse:Die mediane Nierenfunktion der rechten Niere betrug in der RT- und RT+AMI-Gruppe 48% (44–49%) und 50,5% (49–52%; p = 0,0002). Grad-1-Fibrose lag in der RT-Gruppe bei 60% und in der RT+AMI-Gruppe bei 30%. Grad-2-Fibrose betrug in der RT-Gruppe 30% und in der RT+AMI-Gruppe 0%. Tubulusatrophie Grad 2 war in beiden Gruppen vergleichbar (10%).Schlussfolgerung:Die statische Nierenszintigraphie ist eine objektive, wiederholbare und nichtinvasive Methode zur Beurteilung der Nierenfunktion nach Bestrahlung. Im Tiermodell konnte Amifostin die strahleninduzierten Nierenschäden verringern.

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.