Leszek Gottwald

Long-term survival of endometrioid endometrial cancer patients

Introduction To establish risk factors for onset and progression of endometrioid endometrial cancer still remains the aim of scientists. The aim of the study was to determine disease-free survival (DFS) and overall survival (OS) in women with endometrioid endometrial cancer. Material and methods A retrospective review of 142 patients with endometrioid endometrial cancer after surgery treated with adjuvant radiotherapy and/or chemotherapy in the Regional Cancer Centre in Lodz between 2002 and 2004 was performed. Clinical and pathological data were correlated with clinical outcome and survival. Results In 3 patients (2.1%) clinical progression was diagnosed during the treatment. In 23 patients (16.7%) after primary remission, relapse was diagnosed 2-56 months after treatment. DFS and OS were 81.7% and 83.1% respectively. Better DFS significantly correlated with larger number of pregnancies (> 1), stage I of the disease and optimal surgery. Lower stage of disease, pelvic lymph node dissection, optimal surgery and depth of myometrial infiltration ≤ 50% were independent prognostic factors for better OS. Conclusions The results of our study provided significant evidence that early detection of endometrioid endometrial cancer enables optimal surgery. It reduces the indications for adjuvant therapy in stage I of the disease, and makes the prognosis significantly better. Other clinical and pathological factors such as numerous pregnancies, pelvic lymphadenectomy, and depth of myometrial infiltration, although important, are of less significance. Further prospective, randomized studies are necessary to prove the role of these factors.

The AgNORs count in predicting long-term survival in serous ovarian cancer.

Introduction The value of argyrophilic nucleolar organizer regions (AgNORs) to predict survival in patients with ovarian cancer has not been clearly explained yet. The aim of study was to assess the value of analysis of the mean number of AgNORs per nucleus (mAgNOR) and mean percentage of nuclei with five or more AgNORs per nucleus (pAgNOR) in the prediction of disease-free survival (DFS) and overall survival (OS) in patients with serous ovarian cancer. Material and methods The study examined 52 patients treated for serous ovarian cancer with a follow-up period of 2-143 months. After silver staining paraffin specimens from primary surgery, mAgNOR and pAgNOR in cancer cells were counted and analyzed. Age, grading, radicality of surgery and FIGO staging were analyzed as covariates. Results Mean mAgNOR equaled 4.4 ±0.9 and pAgNOR equaled 42.2 ±20.8%. Both mAgNOR and pAgNOR were the lowest in G1 tumors. The mAgNOR and pAgNOR were lower in stage I than stage IV cancers. The DFS and OS rates were respectively 15.4% and 21.2%. In univariate analysis FIGO staging, grading, and pAgNOR were associated with worse prognosis, while radicality of surgery remained a significant protective factor in terms of DFS. Higher FIGO staging and older age worsened OS. In multivariate analysis FIGO staging remained significantly associated with both DFS (HR 1.98; 95% CI 1.05-3.71) and OS (HR 1.76; 95% CI 1.00-3.10), while age affected OS rates (HR 1.78; 95% CI 1.04-2.95). Conclusions mAgNOR and pAgNOR are useful markers of cellular kinetics. Prospective studies in larger populations are needed to confirm these results in terms of AgNORs’ effects on survival.

The analysis of prognostic factors affecting post-radiation acute reaction after conformal radiotherapy for non-small cell lung cancer.

Introduction The aim was to evaluate the risk of acute side effects in the lung after 3-dimensional conformal radiotherapy (3D-CRT) in patients treated for non-small cell lung cancer (NSCLC). An attempt was made to single out clinical factors and factors related to treatment technique which may induce acute post-radiation pneumonitis. Material and methods The analysis concerned 34 consecutive patients who underwent radical radiation therapy for NSCLC. Intensity of early toxicity was evaluated using modified RTOG/EORTC toxicity score. The endpoint for this analysis was the occurrence of radiation pneumonitis of grade 2 or higher. Factors related to treatment techniques were included in the statistical analysis. Results Fifty-three percent of patients included in the study suffered from acute post-radiation pneumonitis. The results of the study revealed the existence of lung tissue sensitivity to low doses of ionizing radiation. The multivariate analysis showed that total lung volume receiving a low dose of 10 Gy increased the risk of post-radiation pneumonitis (p = 0.01). Conclusions Acute post-radiation pneumonitis was a relevant clinical problem in patients who underwent radical radiotherapy for non-small cell lung cancer. The lung volume receiving a dose of 10 Gy was the most important dosimetric factor which influenced the post-radiation acute pneumonitis.

Comparison of FIGO 1989 and 2009 recommendations on staging of endometrial carcinoma: pathologic analysis and cervical status in 123 consecutive cases.

Incidences of endometrial carcinoma (EC) among women of Western countries is increasing, reaching a level of 18/100,000. In 2009, the International Federation of Gynecology and Obstetrics (FIGO) proposed a new staging system in EC. The purpose of this study included the evaluation of distribution of EC in categories of age, histologic grade, and surgical staging according to the 1989 and the 2009 FIGO guidelines. The original staging assessments have been updated to reflect the current staging system in 123 consecutive patients. Statistical analysis was carried out. The median age of patients was 61 years. A comparison of old and new staging systems shows that a significant number of patients moved to stage I: 78.05%, versus 56.91% based on the 1989 classification (P=0.044). The number of patients in stage II changed as well: 9.76% according to new staging system and 30.89% by definitions of FIGO 1989 (P=0.001). Of patients in stage II, 21.1% had G1 tumors according to the old versus 8.3% by the new classification (P=0.001). We have not identified any associations between the histologic status of a cervix and EC. The most common type of EC is the endometrioid subtype, found in 87.8% of patients. We have noted a significant association between the tumor grade and cervical stromal infiltration. The new classification system for EC seems to be an improved staging instrument. Having up to 80% of patients with endometrial cancer in stage I and following them, might elucidate the impact of current staging on survival and life quality.

Primary uterine rhabdomyosarcoma in a patient with a history of breast cancer and gastrointestinal stromal tumor

We describe a unique case of a 67‐year‐old patient with primary uterine rhabdomyosarcoma with a history of breast cancer and gastrointestinal stromal tumor of the stomach. Uterine rhabdomyosarcoma was diagnosed in our patient during adjuvant treatment of breast cancer with anastrozole. To the best of our knowledge, the development of primary uterine rhabdomyosarcoma has never been described in patients treated with anastrozole. Due to the suggested causative role of tamoxifen in the development of uterine sarcomas, it is interesting to analyze whether the new drug, anastrozole, exerts any pathogenic effect on the development of uterine sarocomas.

Significance of Bax expression in breast cancer patients.

UNLABELLED Bax protein, the proapoptotic member of Bcl-2 protein family, plays the key role in apoptosis pathway. THE AIM OF THE STUDY was to assess the expression of Bax protein in breast cancer cells. MATERIAL AND METHODS Sixty-two breast cancer patients were included in the study. The control group encompassed 11 fibroadenoma patients. Single cells were isolated from defrosted samples and prepared for flow cytometry measurement. RESULTS Median expression of Bax protein in study group was 7.9% (range: 0-49.4%) and was significantly lower than in control (median expression 15.8%; range 4.9-30.9%; p=0.034). Expression of Bax correlated with expression of p53 and caspase-3 proteins (p<0.01, rank Spearman test). In patients under 70 years old and with positive estrogen receptors status the expression of Bax protein was significantly higher (p=0.03 and p=0.01 respectively). CONCLUSIONS Lower expression of Bax protein in breast cancer cells may suggest the potential way of apoptosis avoidance of tumor cells. Correlations among Bax protein, p53 and caspase-3 are likely associated with active apoptotic mechanism in breast cancer cells expressing Bax protein. Further investigation with long time follow-up should be performed to establish the prognostic role of Bax protein expression in breast cancer patients.

The comparison of common cancer types and the coincidence of concomitant chronic diseases between palliative home care patients in Lodz Voivodeship and the general Polish population.

Introduction The continued growth in the number of elderly with cancer and age-related chronic diseases will cause in Poland an increase in demand for palliative care. The aim of the study was to identify chronic comorbidities and cancer types in palliative home care patients and to compare their incidence with the general Polish population. Material and methods The data was obtained from 543 patients who received palliative home care between 2005-2009. The occurrence of the most common chronic conditions such as arterial hypertension, ischemic heart disease, diabetes, chronic pulmonary diseases and central nervous system diseases were analysed together with the cancer types. Results The study group included 259 women (47.7%) and 284 men (52.3%) aged 25-91 years old. The most common primary neoplasm locations for men were lung (28.2% vs. 21.4% in general population) and colorectal cancer (18.7% vs. 11.4% in general population), and in women breast (19.7% vs. 22.8% in general population) and colorectal cancer (17.4% vs. 9.2% in general population). The incidence of ischemic heart disease, diabetes, and chronic pulmonary diseases was significantly different in comparison to the general populations (47.0% vs. 11.3%; 20.3% vs. 6.8%; 16.6% vs. 27.5%, respectively). The mean number of concomitant diseases was 1.6 for women and 1.8 for men vs. 1.7 and 1.2 in the general Polish population respectively. Conclusions The majority of the patients had concomitant disease, with cardiovascular diseases being most common. The most common primary neoplasm diagnoses in palliative home care patients were lung and colorectal cancer, which corresponds to the cancer prevalence in the general population.

Isolated metastasis to the foot as an extremely rare presenting feature of primary endometrial cancer.

Endometrial cancer is the most common invasive cancer of the female genital tract, with an increasing incidence rate. Abnormal uterine bleeding is the presenting symptom in 75-90% of cases [1, 2]. The majority of patients with endometrial cancer are diagnosed with no evidence of extra-uterine spread (70-80% stage I), which gives patients better prognosis [1, 3]. In more advanced disease the sites commonly affected outside the uterus are pelvic and para-aortic lymph nodes and the ovaries [4]. Similarly to uterine sarcomas, distant metastases in advanced or recurrent endometrial cancer most commonly involve the lungs, liver, central nervous system and skin [4–6]. Metastases to bones have been described in 2-15% of patients with metastatic disease, and the most common site of osseous metastases are vertebrae, with pelvic bones, ribs and sternum [3, 7]. Isolated metastases to bone extremities are extremely rare, and thought to result from the haematological spread of cancer cells [5]. The review of the Medline database by searching the items endometrial cancer and metastases to extremities showed twenty such cases, with only nine cases when metastatic tumour of the foot was the first manifestation of endometrial cancer (Table I) [3, 5, 7–13]. Table I Isolated metastasis to the bones of the extremities as the first manifestation of endometrial cancer – review of the literature A 74-year-old female suffered from pain and swelling of the right foot from October 2006. In the X-ray picture and bone scintigraphy, suspected lesion of the right calcaneus, talus and metatarsal bones was detected (Figure 1). Afterwards it was histologically verified in the biopsy as metastatic cancer (Figure 2). The patient had no vaginal bleeding or other gynaecological symptoms, but subsequent computed tomography scans showed an enlarged uterus. Uterine curettage confirmed the diagnosis of endometrial cancer. The patient was treated with total abdominal hysterectomy, bilateral salpingo-oophorectomy without pelvic lymph node dissection in December 2006. The histological diagnosis was a moderate differentiated (G2) endometrioid endometrial cancer invading the outer half of the myometrium (> 1/2) with invasion of cervical stroma. The fallopian tubes and the ovaries showed no signs of metastases. No evidence of macroscopic abdominopelvic metastases was found at surgery. Her disease was classified as clinical stage IVB according to FIGO 2009 staging, but in the TNM classification it was pT2 Nx M2. Figure 1 Radiograph of the right foot demonstrating metastases of the endometrial cancer Figure 2 Metastatic endometrial cancer cells in the fine needle aspiration of the tumour of the foot (H + E, 200× magnification) In January 2007 the patient was admitted to the department of palliative radiotherapy. She received irradiation by Co 60 until a total dose of 20 Gy to the tumour of the right foot, with complete resolution of symptoms. The patient was discharged from hospital in March 2007. During the observation from surgery in December 2006 until June 2010 no other metastases were detected. The patient remains alive and asymptomatic 43 months after the diagnosis of metastatic endometrial cancer to the foot. Our report presented in the previous section has three main peculiar features: 1) it demonstrates endometrial cancer that presented with osseous metastasis, which is a rare occurrence, 2) the metastatic tumour was located in the foot, which is extremely rare, 3) the bone lesion was a single bone metastasis, which is unusual in such cases. Additionally, the case in which isolated metastatic tumour of the extremity was the first manifestation of endometrial cancer is the tenth such case reported in the literature (Table I), and the second one located in the calcaneus and involving talus and metatarsal bones [8]. Despite the rarity of metastases to the upper and lower extremities, there is a need to have a high index of suspicion for metastasis in patients with a history of endometrial cancer who present with swelling or bony tenderness. The initial diagnosis can be challenging, as the symptoms of pain and swelling are often attributed to other more common benign conditions such as soft tissue inflammation, trauma, arthritis, and osteomyelitis [7]. It is important to consider bone metastasis as a possible diagnosis also in patients without history of cancer, but with osseous pain not responding to conservative treatment [5, 9–13]. Appropriate imaging may include plain X-ray picture and radionuclide bone scans [3]. Technetium diphosphonate bone scans can be positive up to 18 months before a lesion is detectable on plain X-ray [14]. Therefore, a biopsy should be performed in patients with suspected lesions, and who demonstrate evidence of bony destruction [4]. The treatment strategy in patients with confirmed isolated metastatic lesion in the bone extremity still remains a topic of controversy, because of the few descriptions available in the literature and the different bone sites involved. For these reasons, a common suitable treatment regimen cannot be established and treatment should be tailor suited to each patient. The treatment of irradiation with or without surgery, hormone therapy and chemotherapy is reported as effective in most cases and may be curative [4, 5, 7, 9, 11, 12]. The main goal of treatment should be to eliminate or palliate pain and prolong survival.

Clear cell adenocarcinoma of the uterine cervix in a 24-year-old woman. Case report and review of the literature.

Carcinoma of the uterine cervix is the most common gynecologic malignant neoplasm all over the world [1, 2], but the second one in Poland after carcinoma of the endometrium [3]. In 2009 in Poland the number of its new cases was 3102, and the age-adjusted incidence rate was 10.2 per 100 000 women. In the age group 20-24 year the age-adjusted incidence rate of the cervical cancer was 0.4 per 100 000, and there were 6 new cases noted in Poland. It constituted 1.86% of the cancer incidence rate of all localizations in this age group in Poland [3]. The most common histological type of malignant cervical neoplasms is squamous cell carcinoma. Adenocarcinomas account only for approximately 15% of malignant cervical tumors [1, 2, 4, 5]. The screening based on exfoliative cytology introduced in the 1950s by Papanicolau, followed by colposcopy in appropriate patients, is an effective method for identifying squamous intraepithelial lesions [1, 2].

Does obesity hinder radiotherapy in endometrial cancer patients? The implementation of new techniques in adjuvant radiotherapy – focus on obese patients

The increasing incidence of obesity in Poland and its relation to endometrioid endometrial cancer (EEC) is resulting in the increasing necessity of treating obese women. Treatment of an overweight patient with EEC may impede not only the surgical procedures but also radiotherapy, especially external beam radiotherapy (EBRT). The problems arise both during treatment planning and when delivering each fraction due to the difficulty of positioning such a patient – it implies the danger of underdosing targets and overdosing organs at risk. Willingness to use dynamic techniques in radiation oncology has increased for patients with EEC, even those who are obese. During EBRT careful daily verification is necessary for both safety and treatment accuracy. The most accurate method of verification is cone beam computed tomography (CBCT) with soft tissue assessment, although it is time consuming and often requires a radiation oncologist. In order to improve the quality of such treatment, the authors present the practical aspects of planning and treatment itself by means of dynamic techniques in EBRT. The authors indicate the advantages and disadvantages of different types of on-board imaging (OBI) verification images. Considering the scanty amount of literature in this field, it is necessary to conduct further research in order to highlight proper planning and treatment of obese endometrial cancer patients. The review of the literature shows that all centres that wish to use EBRT for gynaecological tumours should develop their own protocols on qualification, planning the treatment and methods of verifying the patients’ positioning.