PROPROTEIN CONVERTASE 1/3 DEFICIENCY WITH PELVIC EWING SARCOMA.

Proprotein convertase 1/3 (PC 1/3) deficiency is a rare, autosomal recessive disorder caused by mutations in the PCSK1 gene. The disease is characterized by early-onset chronic diarrhea/malabsorption, followed by severe obesity and hormonal deficiencies such as hypocortisolism, hypothyroidism, diabetes insipidus, hypogonadism, growth deficiency, and diabetes mellitus. Ewing's sarcoma is a rare tumor, usually of small dimensions of neuroectodermal origin that is difficult to distinguish pathologically from a primitive neuroectodermal tumor. A 22-year-old female patient with PC 1/3 deficiency was admitted to our clinic with recurrent urinary tract infections. Magnetic resonance imaging (MRI) revealed an 11x12 cm pelvic mass displacing the uterus. A core-needle biopsy was performed on the pelvic mass. As a result of the pathological evaluation, it was diagnosed with pelvic Ewing's sarcoma. The patient was started on the VAC-IE chemotherapy protocol. We report a case of pelvic Ewing's sarcoma in a patient with PC 1/3 deficiency. Further research is needed to assess malignancy risk in metabolic disorders including very rare disorders like PC 1/3 deficiency.

Impact of the obesity on lymph node status in operable breast cancer patients.

PURPOSE: Although many studies have shown association of obesity and tumor size, the association with the lymph node status is not clear. We examined the relationship of the lymph node status and obesity and other possible factors in early breast cancer patients. METHODS: In this retrospective cohort study, 1295 breast cancer patients who had axillary dissection were included. Patients were grouped according to their body mass index (BMI) values at the time of diagnosis. We analyzed the relationship between BMI and patient and tumor characteristics, especially lymph node status. RESULTS: The median patient age was 48 years (range 20- 84). Of the patients 69.6% had modified radical mastectomy and the remaining 30.4% had breast-conserving surgery and axillary dissection. Median BMI of the patients was 27.2 kg/m(2) and 33.1% (N-429) of them had normal BMI, 36% (N-471) were overweight and 30.5% (N=395) were obese at the time of the diagnosis. Of the patients, 44.2% had N0 disease, and 55.8% had lymph node metastasis. N1 disease had 28.3% (N=367), 13.8% (N=179) had N2 and 13.7% (N=177) had N3 disease. When patients were classified as normal (≤24.9 kg/m(2)) and obese (>24.9 kg/m(2)) group, the total number of lymph nodes removed was higher in the obese group and this difference was statistically significant (18.12±10.48 and 20.36±11.37, respectively, p= 0.001). There was strong correlation between the number of the dissected lymph nodes and BMI (r=0.11; p<0.001). However, there was no statistically significant correlation between the number of metastatic lymph nodes and BMI. The mean number of the dissected and involved lymph nodes was higher in the HER2 positive group compared to the negative ones (21 vs 19, p=0.008; 6 vs 3, p<0.001; respectively) CONCLUSION: The number of the dissected lymph nodes was slightly higher in obese patients but there was no correlation between metastatic lymph node number and BMI. The number of the dissected and involved lymph nodes was higher in the HER2 positive group.

Variations in tumor marker levels in metastatic breast cancer patients according to tumor subtypes.

PURPOSE: To investigate whether serum CA 15-3 and CEA levels show differences among subgroups of breast cancer patients at the time of diagnosis of early-stage disease and at disease relapse. METHODS: Patients with metastatic breast cancer diagnosed from 2000 to 2010 were retrospectively analyzed. Data were obtained from medical charts. CA 15-3 and CEA levels of patients with metastatic disease at the time of diagnosis or who relapsed during follow-up were evaluated. Four different breast cancer subtypes were defined: estrogen receptor (ER) and/or progesterone receptor (PR) positive and HER-2 negative (luminal A), ER and/or PR positive and HER-2 positive (luminal B), ER and PR negative and HER-2 positive (HER-2 overexpressing) and triple negative (ER, PR and HER-2 negative). Fifty-eight (13.7%) of the patients were metastatic at the time of diagnosis. RESULTS: 423 metastatic breast cancer patients were included. Of the patients, 232 (54.8%) had luminal A disease, 70 (16.5%) luminal B, 53 (12.5%) HER-2 overexpressing, and 68 (16.1%) triple negative disease. Preoperative CA 15-3 levels were raised in 48.1% of the luminal A group, in 42.8% of the luminal B group, in 26.0% of the HER-2 overexpressing group, and in 33.3% of the triple negative group. CA 15-3 levels after relapse were raised in 44.5% of the luminal A group, in 33.3% of the luminal B, in 28.9% of the HER-2 overexpressing, and in 38.8% of the triple negative group. Preoperative CEA levels were elevated in 44.3% of the luminal A group, in 28.5% of the luminal B, in 43.4% of the HER-2 overexpressing, and in 14.3% of the triple negative group. CEA levels after relapse were raised in 60.8%, 54.7%, 51.1%, and 36.0% of the patients in the 4 subgroups, respectively. CONCLUSION: This study showed that there are differences between the breast cancer subgroups in terms of tumor marker levels in metastatic breast cancer patients. Tumor marker elevation was lower in the triple negative group as compared to the luminal groups. Monitoring CEA levels in luminal A group may be beneficial in determining early relapses. However, this retrospective study requires further prospective confirmative cohort studies.

The prognostic impact of obesity on molecular subtypes of breast cancer in premenopausal women.

PURPOSE: The increasing incidence of obesity throughout the world will result in expansion of the number of women at risk for developing breast cancer. Obesity is associated with adverse outcomes in postmenopausal women with breast cancer. In premenopausal women, the association is less clear. We investigated the impact of obesity on tumor features, hormonal status, recurrence and mortality in premenopausal breast cancer patients, classified according to molecular subtypes. METHODS: 818 premenopausal women with nonmetastatic breast cancer were analysed. Patients were classified into 3 groups according to body mass index (BMI): i) normal body weight (BMI: 18.5-24.9 kg/m(2)); ii) overweight (BMI: 25-29.9 kg/ m(2)); and iii) obese (BMI:>30 kg/ m(2)). Clinocopathologic characteristics and survival rates were analyzed for triple negative, HER-2 overexpressing and luminal subtypes. RESULTS: Obese patients compared with normal-weight women were older at diagnosis (p<0.001) and more often had high grade tumor (57.1 vs 42.3%; p=0.04) with lymphovascular invasion (79.5 vs 63.9%; p=0.03). The median follow-up period after diagnosis was 29 months. According to the molecular subtypes, overall survival (OS) and disease free survival (DFS) were significantly shorter in obese patients with triple negative breast cancer (TNBC) (p=0.001 and p=0.006, respectively). Obesity (HR 1.4; 95% CI 1.0-2.1; p=0.04) and lymphovascular invasion (HR 2.1; 95% CI 1.3- 3.3; p=0.02) were found to be independent prognostic factors for TNBC mortality. CONCLUSION: Obesity is associated with estrogen (ER) and progesterone receptor (PR) negative tumors and poor OS in premenopausal women with breast cancer.

Administration of contrast media just before cisplatin-based chemotherapy increases cisplatin-induced nephrotoxicity.

PURPOSE: There is a clinical need to predict the probability of cisplatin-induced nephrotoxicity (CIN) in order to make decisions about patient management and relevant preventive measures. The purpose of this study was to develop a risk prediction methodology of CIN. METHODS: 197 consecutive cancer patients, whose serum creatinine was measured at least 48 h before every cycle of cisplatin-based chemotherapy, were included in the study. Demographic and clinical data were collected from the patient medical records. Renal function was evaluated at least 48 h before treatment (day 0) of each cycle, based on the Modification of Diet in Renal Disease (MDRD) formula. CIN was defined as a decrease of ≥ 25% in glomerular filtration rate (GFR) compared to baseline GFR values. RESULTS: The mean age of the study population was 54.5±9.6 years. Fifty-eight patients (29.4%) whose GFR had decreased by at least 25% compared to baseline values formed the CIN group, and the remaining 139 patients formed the non-CIN group. No significant differences were noted between the CIN and non-CIN groups in terms of age, gender, body mass index and smoking history. Metastatic disease was similar in both groups (p=0.86). History of hypertension (p=0.81), diabetes mellitus (p=0.72), and cardiovascular disease (p=0.58) were similar in the two groups. Chemotherapeutic agents used concurrently with cisplatin were similar in both groups. Significantly more radiologic examinations using contrast media were performed in the CIN group compared with the non-CIN group (p=0.01). In patients exposed to contrast media within a week before cisplatin administration, the risk of CIN was 2.56-fold higher (957 percent; CI 1.28-5.11) than in patients without such exposure (p=0.009). CONCLUSION: In patients with exposure to contrast media within a week before cisplatin administration, the risk of CIN was significantly higher than in patients without such an exposure. No additional risk factors for CIN were found in this retrospective observational study.

Association between family history and clinicopathologic characteristics in 1987 breast cancer patients: single institution experience from Turkey.

PURPOSE: To evaluate the clinicopathologic characteristics and survival of patients with family history of breast/ ovarian cancer (FHBOC). METHODS: In this study with 1987 breast cancer patients, we analyzed their tumor characteristics and outcomes, as well as the total number, degree and age of affected relatives, and their type of cancer. Results were assessed using Pearson chi-square test, Kaplan-Meier method and Cox regression analysis. RESULTS: 24.1% (n=479) of the patients had FHBOC. Patients with FHBOC were younger (47.7 vs. 49.1 years; p=0.03) and tended to have node-negative breast cancer (45.4 vs. 39.8%; p=0.006). The median overall survival (OS) was shorter in patients with FHBOC with a borderline p-value (p=0.063), compared to patients with no family history. The median OS was shorter in patients who had ≥ 2 relatives with breast cancer (p=0.014), in those having first degree relatives with breast cancer, presenting with metastatic disease (p= 0.020). FHBOC patients with triple negative breast cancer had the highest risk of death (p<0.0001) and recurrence (p<0.0001). Patients who had at least one relative with breast cancer aged ≤ 50 years were also at increased risk of recurrence (p7equals;0.006). CONCLUSION: Our results suggest that patients with FH7horbar;BOC are younger, tend to have small tumor size, node-negative disease and their survival is shorter compared to patients without family history. This is the first study evaluating the clinicopathologic differences of patients with and without FHBOC in Turkish population.

Frequency of comorbid illnesses in cancer patients in Turkey.

PURPOSE: Comorbidities in cancer patients can adversely affect the management and outcome of their primary illnesses at all levels from diagnosis to therapy. We sought to examine comorbid conditions of cancer patients, treated at 4 university hospitals, each representing a different geographic location in Turkey. METHODS: A total of 769 consecutive cancer patients presenting to outpatient clinics were recruited between November 2007 and May 2008. The patients filled in a questionnaire on comorbidities. Based on the questionnaire, Charlson Comorbidity Index (CCI( was calculated. RESULTS: The patient median age was 55 years (range 21-87) and 456 (59.3%) were female. Breast (36.5%), colorectal (21.4%) and lung cancers (13.9%) were the 3 most frequent malignancies. Of the patients, 59.3% had at least one comorbid disease and 46.3% were using at least one medication daily. The most frequent comorbidities were hypertension (25.3%), diabetes mellitus (13.1%) and peptic ulcer (7.7%). Increasing age positively correlated with the extent of comorbidities (r=0.30, p<0.001), number of medications (r=0.32, p<0.001) and the CCI (r=0.20, p<0.001). CONCLUSION: It is crucial to remember that comorbid illnesses are not rare and many patients are treated for conditions unrelated to their cancer, which potentially may affect various stages of their clinical management.

The evaluation of mannitol therapy in acute ischemic stroke patients by serial somatosensory evoked potentials.

The effects of mannitol infusion therapy on acute ischemic stroke were investigated by serial median nerve somatosensory evoked potentials (SEP) in 31 patients with abnormal SEP recordings within 72 hours after onset. In 10 patients with missing N20 waves mannitol had no effect. In 12 patients mannitol improved N20 and central conduction time (CCT) latencies. In 9 patients absent N20 waves appeared after mannitol. As regard to the location of infarcts, CT revealed 7 hemispheric infarcts in patients with absent N20 waves in spite of mannitol infusion. The remaining patients' CTs revealed cortical and subcortical infarcts. This study concludes that mannitol treatment improved microcirculatory flow in the ischemic penumbra of acute ischemic stroke patients. We suggest that SEPs can be used in evaluating the effects of drugs to be used in the therapy of acute cerebrovascular accidents.

Evoked potentials and the effect of flumazenil in patients with liver cirrhosis.

The presence of increased amount of ligands for benzodiazepine receptors has been demonstrated in cirrhotic patients. Evoked potentials (EP) recordings are a simple, suitable, and objective method for comprehensive evaluation of hepatic encephalopathy (HE). We evaluated the visual EP, brain stem auditory EP, and somatosensory EP (SSEP) and the effect of benzodiazepine receptor antagonist flumazenil in patients with liver cirrhosis. EP of 38 patients with liver cirrhosis were recorded on the electrodiagnostic system Neuropack 8 (JB-441 B, Nihon Kohden). Eleven patients (nine males and two females; mean age 60 years; six with stage 0,4 with stage one, and one with stage 2 HE) showed impairment in SSEP N13-N19 interval. After baseline period, boluses of 1 mg, 2 mg, and 3 mg flumazenil were injected every thirty minutes and SSEP recordings were repeated after every dosage. We did not find any difference before and after flumazenil in SSEP N13-N19 interval (7.3 +/- 0.4, 7.1 +/- 0.5, 7.1 +/- 0.4, and 7.1 +/- 0.6 minutes, respectively) (p < 0.05). But four patients (36%) showed a clear SSEP improvement with flumazenil. Our results suggest that in a subset of cirrhotic patients, flumazenil may have a role.

Unusual branching and course of the testicular artery.

In a Turkish male, the right testicular artery was found to originate from the aorta at nearly the same level as and anterior to the renal artery. This testicular artery was seen to give off the inferior phrenic and superior suprarenal arteries. During its course the artery was posterior to the inferior vena cava. In addition to the above mentioned characteristics, the artery arose 5 mm below the renal vein and, after ascending to the superior border of the renal vein, arched over and descended in front of it to continue along its downwards course. This case implies that the lateral mesonephric arteries form anastomoses and that different arteries may interfere with each other's development. Another significant fact in this case is that the testicular artery crossed over the renal vein and descended anterior to it; a condition which may cause pathological disturbances.

Case of an abductor pollicis longus muscle: variation or differentiation?

A variation of the abductor pollicis longus muscle in a 65 year old cadaver was encountered during routine dissection in our department. The muscle was found to split into two bellies and give off two tendons, one of which inserted to the abductor pollicis brevis, opponens pollicis and flexor pollicis brevis muscles. The other tendon inserted to the first metacarpal bone which is considered a normal insertion site for the abductor pollicis longus muscle.