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Volum 12 Numarul 3, 2006

176 Editorial

We are glad to welcome you, upon your return from your holiday, with a new issue of our journal. The variety of the contents, we hope, will stimulate your scientific interest to develop new projects, whose final results, in a published form, will be found in our journal.

The analysis by Angelica Chiorean and her colleagues at the Radiological Clinic, which characterizes the in situ breast carcinoma from the imaging point of vue, comes in a timely manner at a moment when, due to the widened access of women to a qualitative mammographic examination, the incidence of non-invasive

breast lesions in our institution is increasing.

The original study of the medical team of the Surgical Clinic IV, lead by prof. M. Cazacu, builds upon previous work by the same team and fits well in the recent tendency to rigorously analyze and generate evidence-based data to characterize unproven methods of treatment such as mistletoe extract.

Alina Herzal reports a mild toxicity profile for the metronomic use of low-dose chemotherapy with cyclophosphamide and methotrexate, in a series of breast cancer patients treated in the Breast Tumors-Radiotherapy I Department. The vast experience of our institute in the field of cervix carcinoma is captured in the presentation by A.

Trăiă and Viorica Nagy on the prognostic factors in locally advanced cervix tumors treated with the association of radiotherapy and surgery. Another presentation in the field of gynecologic tumors, by Liliana Resiga, characterizes the pathogenetic entities and the prognostic factors for endometrial carcinomas, identifying

the necessity for standardized, quantitative methods in the diagnosis of this pathology. The case presentation section is richer in this issue, discussing three particular nosologic entities. The clinical case reported by Claudia Burz brings to the clinicians’ attention the malignant thymoma, a rare tumor localized in the upper mediastinum, and its frequent association with paraneoplastic syndromes. Liliana Resiga and Rodica Cosnarovici present clinical and histological characteristics of a rare pseudo-papillary tumor of the pancreas, in a young female. Anda Cri}an and Liliana Sicoe discuss the particular clinical evolution due to a seldom post-surgical complication in a patient with adenocarcinoma of the ascendant colon, and its resolution by means of multidisciplinary cooperation.

The Oncological Life in Romania contains the presentation made by C. Căinap of the development of the ontological continuous education process in Cluj, putting in perspective the two postgraduate courses with international participation, organized by UMF „Iuliu Ha]ieganu” through the Oncology and Radiotherapy Discipline, in collaboration with the Romanian Society of Radiation Therapy and Medical Oncology: „Delineation of target volumes and modern radiotherapy techniques”, and „ Progress of the year 2005 in the management of the cancer patient- a meeting post ASCO, ESMO, ESTRO”.

Al. Eniu

177 Breast Carcinoma In Situ: Imagistic Aspects and Correlation

Angelica Chiorean1, Maria Duma2, Raluca Roman2, Ildiko Agoston2, Maria Retegan-Turdean3, Larisa Ciule3, S. Dudea1, S. Sfrângeu1

1„Iuliu Haţieganu” U.M.Ph. Cluj Napoca, Dept. of Radiology;

2Cluj Clinical and Emergency County Hospital, Discipline of Radiology;

3Cluj Clinical and Emergency County Hospital, Dept. of Oncology

Although 90% of all breast carcinoma in situ are clinically occult at diagnosis, recent studies show a significant increase in the incidence of Ductal Carcinoma In Situ (DCIS), mostly due to the continous improvements of the imagistic methods used for detections and evaluation of breast cancer. Mammography remains the gold-standard exploration of the breast, especially when it comes to DCIS. Microcalcifications are, in most of the DCIS cases, the only anomaly detectable on mammogram. Ultrasound examination of the breast performed by an experienced operator, using an adequate technique, can depict subtle changes in a majority of DCIS cases and also has an important conribution in detecting mammographically occult lesions. MRI (Magnetic Resonance Imaging) has a wide range of sensibility in detections of DCIS and the imagistic aspects obtained are usually non-specific. Still, the method proves its efficiency in selected cases such as those with multifocal/ multicentric lesions or with remaining postoperative tumoral foci.

Key words: DCIS, Early detection, Mammography, Ultrasound, MRI.

Radioterapie & Oncologie Medicală, 2006, 3:177-186

187 Survival Analysis of Advanced Colorectal Cancer Patients Treated with Mistletoe Extract

  1. Oniu1, M. Cazacu1, N. Rednic2, Anca Mihailov2, M. Man1

1 „Iuliu Haţieganu” U.M. Ph. Cluj-Napoca, 4th Surgical Clinic;

2 University Hospital, 4th Surgical Clinic

Background: Although mistletoe has been studied in the therapy of colorectal cancer since decades, a modern approach taking in account the association of mistletoe extracts with the modern chemotherapy arsenal is needed in order to take mistletoe therapy to the field of evidence based medicine. Patients & Methods: 109 advanced colorectal cancer patients (stage Dukes C and D), randomized into two groups: the „Immunotherapy group” (– 50 patients receiving immunotherapy with mistletoe extract associated in most of the cases with chemotherapy, after the surgical removal of the primary tumor), and the „Control group” (– 59 patients, most of which received chemotherapy only after surgery) were comparatively analyzed with regard to the long term survival. Results: Immunotherapy group showed a significantly increased survival compared with the control group (median survival and 5-year survival: 36 months and 28,3% vs. 20 months and 5,6%). Conclusions: Mistletoe immunotherapy could be the next step in the multimodal treatment of colorectal cancer, along with the cytotoxic drugs irinotecan and oxaliplatin and the new targeted therapy.

Key words: Advanced colorectal cancer, Immunotherapy, Mistletoe extract, Survival analysis, Chemotherapy.

Radioterapie & Oncologie Medicală, 2006, 3:187-198

199 Favorable Toxicity Profile of Metronomic Chemotherapy with Antiangiogenic Effect in Breast Cancer

Alina Amalia Herzal1, Gabriela Morar-Bolba1, R.Tănăsescu1, Dana Grecea1, Cristina Vitoc1, N.Ghilezan1,2, Al. Eniu1

1„Prof. Ion Kiricuta” Cancer Institute, Dept. of Breast Tumors;

2U.M.Ph. ”Iuliu Haţieganu” Cluj-Napoca.

Background: Anticancer chemotherapy acts with mecanisms of direct cytotoxicity on tumor cells. Metronomic chemotherapy is a type of treatment with low doses in continuous or frecvent administrations. The drug acts through an alternative mechanism, an antiangiogenic mechanism.It has been described in several common anticancer agents, including cyclophosphamide, methotrexate, anthracyclines, taxanes. Patients and Methods: We evaluated the toxicity and the efficacy of metronomic chemotherapy with cyclophosphamide and methotrexate as a paliative treatment in breast cancer and its toxicity as adjuvant treatment. Methotrexate was administered 2,5mg bd on days 1 and 2 each week and cyclophosphamide 50mg-day continuously. We studied two groups of patients. 1st group with 20 pts. With metastatic breast cancer, with paliative treatment: mean age 58,2 years, performace status 0-2, ductal invasive carcinoma (95%), medular carcinoma (5%), negative hormonal receptors (65%), positive hormonal receptors (35%), previously treated with up to 3 regimens. 2nd group with 13 pts. with breast cancer, with adjuvant treatment for 1 year or until progresion of disease: mean age 50,9 years, performace status 0-2, ductal invasive carcinoma (69,2%), medular carcinoma (7,69%), lobular invasive carcinoma (23%), negative hormonal receptors (100%), previously treated with up to 2 regimens. Results: We found only grade 1 toxicities. 1st group: anaemia (21,5%), leucopenia (3,8%), emesis (6,3%), elevated ASAT or ALAT (1,2%), stomatitis (2,5%),thrombocytopenia (1,2%), diarheea (2,5%). 2nd group: anaemia (23%), leucopenia (23%), elevated ASAT or ALAT (30,7%), thrombocytopenia (1,2%). Concerning the efficacy of metronomic chemotherapy we observed: 10% partial response, 80% stable disease, 10% evolutive disease. Conclusions: Continuously low-dose cyclophosphamide and methotrexate is minimally toxic when we use it in paliative or adjuvant treatament in patients with breast cancer.

Key words: Metronomic Chemotherapy, Cyclophosphamide, Methotrexate, Antiangiogenic. Mechanism.

Radioterapie & Oncologie Medicală, 2006, 3:199-204

205 Prognostic Factors in Locoregionally Advanced Cervical Cancer Treated with Surgery Associated with Radiotherapy

Al. Trăilă1, Viorica Nagy2,4, N. Todor2, A C. Rancea1,4, Claudia Ordeanu3, O. Coza3,4, L. Lazăr1,4

„Prof. I. Kiricuta” Cancer Institute Cluj-Napoca;

1 Dept. of Surgery,

2 2ndRadioterapy Dept.,

3Brachytherapy Dept.;

4„Iuliu Haţieganu” U.M.Ph. Cluj-Napoca

Purpose: To evaluate the main prognostic factors: disease stage, histopathological examination, tumor volume and age, correlated with survival and therapeutic failures in patients treated with surgery associated with radiotherapy. Patients and methods: The study was carried out on 272 patients with epidermoid carcinoma of the cervix treated with radiotherapy or radiochemotherapy followed by surgery (Wertheim’s hysterectomy), performed at the „Prof. I. Kiricuta” Institute of Oncology, Cluj-Napoca, between March 1999 and August 2002. The patients’ age ranged between 24 and 58 years; 189 patients were in stage IIB while 83 were in stage IIIB. The tumor volume was under 4 cm in 157 patients and over 4 cm in 115 patients. Results: Survival at 5 years was of 86% in stage IIB patients and of 87% in stage IIIB patients ( (p=0.62). Therapy failed in 31 stage IIB patients (16%) and in 13 stage IIB patients (15%) (p=0.6). The survival at 5 years was of 92% in 174 patients with histologically negative resected piece after radiotherapy, associated or not with chemotherapy, and of 76% in 98 patients with remaining tumor (p<0.01). Therapy failed in 16 patients (9%) with negative histology as opposed with 28 patients (28%) with positive histology (p<0.01). The survival at 5 years was of 90% in 240 patients with negative lymph nodes and of 61% in 32 patients with positive lymph nodes (p<0.01). Therapy failed in 29 patients (12%) with negative lymph nodes and in 15 patients (46%) with positive lymph nodes (p<0.01). The survival at 5 years was of 88% in stage IIB patients with tumor volume < 4 cm and of 83% in patients with tumor volume > 4 cm (p=0.38). The survival at 5 years was of 97% in stage IIIB patients with tumor volume < 4 cm and of 79% in those with tumor volume > 4 cm (p=0.02). Therapy failed in 18 patients (11%) with tumor volume < 4 cm and in 26 patients (22%) with tumor volume > 4 cm (p<0.01). The survival of patients under 40 years of age was of 82% while that of patients over 40 was of 89% (p=0.19). Conclusions: The study showed that the following are significant prognostic factors for patients with locoregionally advanced cervical cancer who underwent surgery after radiotherapy associated or not with chemotherapy: sterilization of the resected piece, the condition of the lymph nodes, the number of resected lymph nodes (< 10, > 10 lymph nodes) and the tumor volume that influenced survival in stage IIIB. The disease stage and the patients’ age proved not to have prognostic value.

Key words: Cervical carcinoma, Prognostic factors, Survival, Therapeutic failures.

Radioterapie & Oncologie Medicală, 2006, 3:205-211

212 Endometrial Carcinoma – Pathogenesis Pattern and Prognostic Factors

Liliana Resiga1, Viorica Nagy2, Milena Duma1, Iulia Diaconu1, A. ªerban3,4, N. Todor2, C.D. Olinici1,2

„Prof. I. Kiricuta” Cancer Institute Cluj-Napoca:

1Dept. Of Pathology;

22nd Radiotherapy Dept.;

3„Iuliu Haţieganu” U.M.Ph. Cluj-Napoca, Dept. Of Morphopathology;

4Adults Clinical Hospital of Cluj-Napoca, Dept. of Pathology

Aims: To carry out a retrospective analysis of the endometrial carcinoma casuistics in the „Ion Kiricuta” Institute Cancer Register (ICR), concerning the binary pathogenesis of precursor lesions: (1) atypical hyperplasia, (2) endometrial intraepithelial carcinoma, and to prognostic factors. Material and method: 228 new entries were registered during 1999-2000, 208 of which could be evaluated as for the disease-free interval (74% at 36 months) and treatment responsively (n=190). Intrauterine localization of the tumor (n=185), additional modifications, depth of the myometrial invasion, the FIGO staging and grading, and the WHO grading were specified. A semiquantitative assessment of the estrogenic hormone receptors status (RhE, n=114) and of the p53 protein overexpression (n=37) was performed, by means of immunostaining of routinely paraffin-embedded material. Results: The disease-free interval was inversely correlated with both the depth of the myometrial invasion and with the FIGO staging. The disease-free interval was 95% (n=83) in tumor invasions of less than half of the myometrium thickness, and 65% (n=93) in invasions of over half the myometrium thickness, respectively. Further, it was 81% in FIGO stage I (n=125), 72% in stage II (n=38), and 56% in stage III (n=42). The FIGO staging was directly correlated with the myometrial invasion, while RhE expression showed an inverse correlation with the WHO grading, averaging 37% in grade I, 26% in grade II, 7% in grade III, and 0% in grade IV. Overexpression of the p53 protein was directly correlated with the WHO grade, averaging 2% in grade I, 16% in grade II, 34% in grade III and 83% in grade IV. Positive treatment response appeared inversely correlated with the depth of the tumor invasion, being 100% with no invasion, 96% in invasions of less than half and 71% in invasion of over half of the myometrium thickness. This results are obtained from a study stage. Conclusions: For differentiating borderline lesions, as well as semiquantitative assessment of immunostainings are largely subjective. Proper characterization of endometrial lesions and evaluation of immunostainings require quantitative methods with higher sensitivity and specificity, that is morphometric parameters.

Key words: Endometrial carcinoma, p53, Hormone receptors, Morphometry.

Radioterapie & Oncologie Medicală, 2006, 3:212-222

223 Malignant Thymoma and Auto-immune Disorders Associated

Claudia Burz1, N.Ghilezan2

1„Iuliu Haţieganu“ U.M.Ph. Cluj-Napoca, Discipline of Oncology

2“Prof. I Kiricuta” Cancer Institute Cluj-Napoca, 2nd Radiotherapy Dept.

Thymoma is a rare mediastinal tumor that occurs in the anterosuperior mediastinum. The most common paraneplastic syndroms associated to thymomas is miastenia gravis (10-75%). Pure red cell aplasia, considered an autoimmune disorder, is found in 5% of patients with thymoma.This article presents the clinical data about two patients with malignant thymomas treated in Cancer Institute Cluj-Napoca in 2003: PV 48 years old, atipical malignant thymoma + miastenia gravis and BM 36 years old with malignant thymoma Stage IV + pure red cell aplasia (PRCA).The difficulties of the diagnosis, therapeutical problems and the up to date strategies are discussed..

Key word: Malignant thymoma, Miastenia gravis, Erythroblastopenie, Strategy.

Radioterapie & Oncologie Medicală, 2006, 2:223-230

231 Solid-Pseudopapillary Tumor of the Pancreas. Case Report and Review of the Literature

Liliana Resiga1, Rodica Cosnarovici2, C.D. Olinici1,3

„Prof. I. Kiricuta” Cancer Institute Cluj-Napoca,

1Parthology Department,

2Department of Oncology;

2 „Iuliu Haţieganu” U.M.Ph. Cluj-Napoca, Department of Pathology

The authors present the case of a 15-year-old female, diagnosed with a solid-pseudopapillary tumor of the pancreas. The clinical and histological features, the origin and the molecular biology of the disease are briefly discussed.

Key words: Solid-pseudopapillary tumor; Pancreas.

Radioterapie & Oncologie Medicală, 2006, 2:231-235

236 Adenocarcinoma of Ascending Colon Treated by Surgery. Postoperative Complications and Treatment.

Anda Crişan1, Liliana Sicoe1, N.Ghilezan1, R. Badea2

1 Cancer Institute „Prof. I. Kiricuta“, Cluj-Napoca, 2nd Radiotherapy Dept.;

2 3rd Medical Clinic, Dept. of Radiology & Medical Imagery

The clinical case of a 66 years old patient with an adenocarcinoma of ascending colon,G1, treated by surgery, pT4N1,stage III Dukes MAC C2,is presented evolution and terapheutic guidance for a differential diagnosis between a postoperative fistula and local recurrence and decision concerning the adjuvant treatment.

Key words: Ascending colon, Postoperative fistula.

Radioterapie & Oncologie Medicală, 2006, 2:236-239

240 Continuous Medical Education – Need or a Debt of Medical School

  1. Căinap, V. Cernea