Randomized controlled trial of 8 weeks' vs 12 weeks' interval between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer.

AIM: The aim was to compare the pathological complete response (pCR) rate at 8 compared to 12 weeks' interval between completion of neoadjuvant chemoradiotherapy (CRT) and surgery in patients with locally advanced rectal cancer. METHOD: This was a randomized trial which included a total of 330 patients from two institutions. Patients with locally advanced (T3-4N0M0, TxN+M0) rectal cancer were randomized into 8- and 12-week interval groups. All the patients received long-course CRT (45 Gy in 1.8 Gy fractions and concomitant oral capecitabine or 5-fluorouracil infusion). Surgery was performed at either 8 or 12 weeks after CRT. The primary end-point was pCR. Secondary end-points were sphincter preservation, postoperative morbidity and mortality. RESULTS: Two-hundred and fifty-two patients (n = 125 in the 8-week group, n = 127 in the 12-week group) were included. Demographic and clinical characteristics were similar between groups. The overall pCR rate was 17.9% (n = 45): 12% (n = 15) in the 8-week group and 23.6% (n = 30) in the 12-week group (P = 0.021). Sphincter-preserving surgery was performed in 107 (85.6%) patients which was significantly higher than the 94 (74%) patients in the 12-week group (P = 0.016). Postoperative mortality was seen in three (1.2%) patients overall and was not different between groups (1.6% in 8 weeks vs 0.8% in 12 weeks, P = 0.494). Groups were similar in anastomotic leak (10.8% in 8 weeks vs 4.5% in 12 weeks, P = 0.088) and morbidity (30.4% in 8 weeks and 20.1% in 12 weeks, P = 0.083). CONCLUSION: Extending the interval between CRT and surgery from 8 to 12 weeks resulted in a 2-fold increase in pCR rate without any difference in mortality and morbidity.

Prognostic factors affecting recurrence and survival in patients with locally advanced rectal cancer.

PURPOSE: This study aimed at investigating the factors that are likely to affect recurrence and survival in patients with locally advanced rectal cancer. METHODS: The study included patients treated and followed- up between January 1999 and August 2009. Patient and disease data were retrieved from the patients' hospital charts. RESULTS: A total of 221 patients were evaluated. Their median age was 58 years (range 18-83); 69 (31.2%) patients had clinical stage II and 152 (68.8%) clinical stage III. Median follow-up was 40 months (range 8-136). Median disease free survival (DFS) was 77 months and median overall survival (OS) 95 months. The factors affecting local recurrence were pathological lymph node involvement (pN+), pathological T4 (pT4) tumors, and postoperative high serum level of carcinoembryonic antigen (CEA). pN (+) tumors, postoperative high serum CEA level, and perineural invasion increased the risk of both local and distant metastasis. The factors affecting mortality were pN+ tumors, pT4 tumors, poor tumor differentiation, high postoperative CEA level, age > 60 years, and no postoperative adjuvant chemotherapy (CT). The factors affecting DFS were pN+ tumors, pT4 tumors, poor tumor differentiation, postoperative high serum CEA level, perineural invasion, and surgical margin positivity. The factors affecting OS were pN+ tumors, postoperative high serum CEA level, poor tumor differentiation, perineural invasion and no adjuvant CT. CONCLUSION: Some prognostic factors are important in the assessment of prognosis of locally advanced rectal cancer.

Gemcitabine plus infusional 5-fluorouracil and high dose leucovorin in advanced stage pancreatic cancer.

PURPOSE: Advanced pancreatic cancer (APC) has a poor prognosis and chemotherapy remains the primary treatment modality. Gemcitabine (GEM) and 5-fluorouracil (5-FU) are the most active drugs in the treatment of pancreatic cancer. This study evaluated the efficacy and tolerability of the combination of these agents in APC. METHODS: Forty-four patients with APC were treated with GEM and infusional 5-FU with high dose leucovorin (LV5FU2) (GEMFUFOL regimen). RESULTS: A total of 240 chemotherapy cycles were administered. The overall response rate was 27.2%, and all responses were partial. Furthermore, disease stabilization was observed in 12 patients (27.2%). Median survival time and one-year survival rate were 9 months and 36.4%, respectively. The overall grade 3 or 4 adverse events were very low and mostly hematological. CONCLUSION: GEMFUFOL is still an active regimen for the treatment of APC and has an acceptable toxicity.

Efficacy and toxicity of lower dose UFT without leucovorin in metastatic gastric cancer patients.

PURPOSE: Gastric cancer is the 4th most commonly diagnosed cancer and the 2nd leading cause of cancer death worldwide. In this study assessed were the efficacy and toxicity of the combination of epirubicin, cisplatin and UFT in patients with metastatic gastric cancer (MGC). PATIENTS AND METHODS: In this retrospective study 27 patients with MGC were treated with epirubicin 50 mg/m(2) and cisplatin 60 mg/m(2) i.v. on day 1 and subsequently UFT 250 mg/m(2)/day orally in divided doses for 21 days, followed by a 7/day rest (EP/UFT). RESULTS: Response and toxicity evaluation was possible for 25 patients. Three complete (12%) and 2 partial (8%) responses were observed. With a median follow-up 37 weeks (range 15-117), the median progression-free survival (PFS) and overall survival (OS) were 24 and 31 weeks, respectively. WHO grade 3 or 4 toxicity included neutropenia in 3 (12%) patients and nausea/vomiting in 1 (4%) patient. Neutropenic fever developed in only 1 (4%) patient. CONCLUSION: EP-UFT with lower UFT doses and without leucovorin support is a safe and effective regimen as first -line treatment of MGC.

Complementary-alternative medicine among cancer patients in the western region of Turkey.

PURPOSE: To investigate the complementary/alternative medicine (CAM) applications and factors affecting its use among cancer patients in the western region of Turkey. PATIENTS AND METHODS: Face-to-face interview technique was used. Patients were asked to answer a questionnaire about their socio-demographic features, their level of knowledge about the disease and CAM application features. RESULTS: 220 adult cancer patients (79 male) were evaluated. Ninety-three (42.3%) were using at least one CAM method, the most common being herbal products which were preferred by 81 (36.3%) patients. Stinging nettle (Urtica dioica) was the most commonly used herbal product. Next was nutritional support, preferred by 45 (20.3%) patients. Eighty- nine (44.5%) of 200 patients who knew the diagnosis and 4 of 20 (20%) who did not were using CAM. In the patient group with awareness of the diagnosis, CAM application was significantly higher (p=0.034). CAM applications were detected in 34 of 70 (48.5%) patients with recurrent disease while 54 of 150 (36%) patients without recurrent disease were using CAM. The CAM applications were significantly higher in the group with recurrent disease (p=0.006). Fifty-three of 103 (51.4%) patients who had advanced disease were using CAM, while only 40 of 117 (34.1%) patients with local or locally advanced disease were using it. CAM applications were significantly higher in the group with advanced disease (p=0.030). Besides, knowing the diagnosis and disease recurrence were also independent risk factors for CAM usage [odds ratio (OR(: 3.1; 95% confidence interval (CI): 1.0-9.8 and OR: 2.2; 95% CI: 1.2-4.0 respectively]. As a result, nearly half of the patients (42.3%) in this region were using at least one of the CAM methods. CONCLUSION: The severity of the disease (recurrence and dissemination) and patients' awareness of the diagnosis were the most important factors affecting the CAM applications.

Hypoglycemia induced by long-acting somatostatin analogues in a patient with nonfunctional neuroendocrine tumor.

Somatostatin and its long-acting analogues are effective in symptom control in patients with functional neuroendocrine tumors; they are also able to control tumor growth. Somatostatin analogues are safe and generally well tolerated. In some cases they may cause serious complications. Somatostatin analogues are potent inhibitors of growth hormone (GH) and glucagon secretion. They cause impairment of hepatic glucose output and delay in intestinal absorption of carbohydrates. Patients with huge tumor mass and multiple liver metastases have increased risk of tumor-induced hypoglycemia. In these patients, long-acting octreotide may trigger serious hypoglycemia. The patients whose glucose control is dependent on counter-regulatory hormones should be monitored for the possibility of hypoglycemia. Herein, we present a patient with severe and prolonged hypoglycemia after long-acting octreotide treatment.

Awareness of breast and cervical cancer risk factors and screening behaviours among nurses in rural region of Turkey.

Breast and cervical cancer are the most common causes of cancer mortality among women worldwide, but actually they are largely preventable diseases. There is limited data on breast and cervical cancer knowledge, screening practices and attitudes of nurses in Turkey. A self-administered questionnaire was used to investigate the knowledge and attitude of nurses on risk factors of the breast and cervical cancer as well as screening programmes such as breast self-examination (BSE), clinical breast examination, mammography (MMG) and papanicolaou (pap) smear test. In total, 125 out of 160 nurses participated in the study (overall response rate was 80.6%). The risk factors and symptoms of breast cancer was generally well known, except for early menarche (23.2%) and late menopause (28.8%). For cervical cancer, the correct risk factors mostly indicated by the nurses were early age at first sexual intercourse (56%), smoking (76%), multiple sexual partners (71.2%). As for screening methods, it was believed that BSE was a beneficial method to identify the early breast changes (84.8%) and MMG was able to detect the cancer without a palpable mass (57.6%). Little was known about the fact that women should begin cervical cancer screening approximately 3 years after the onset of sexual intercourse (23.2%) and if repeated pap smear test were normal, it could be done every 2-3 years. Most of the nurses considered that MMG decreases the mortality in breast cancer (65.6%) and also believed that pap smear test decreases the mortality in cervical cancer (75.2%). Despite high level of knowledge of breast cancer risk factors, symptoms and screening methods, inadequate knowledge of cervical cancer screening method were found among nurses.

The development of metachronous prostate cancer and chronic myeloid leukemia in a patient with metastatic rectal cancer.

We report herein an unusual case of metachronous triple cancers (rectum, prostate and Philadelphia(+) [Ph(+)] chronic myeloid leukemia [CML]). A metastatic rectal cancer was diagnosed in a 76-year-old male patient, who was treated with transanal tumor resection and chemotherapy. Thirty months from the initial rectal cancer diagnosis, prostate cancer was diagnosed and the patient was administered maximal androgen blockade and received palliative radiotherapy to the lumbar spine because of painful bone metastases. Thirty months after the diagnosis of rectal cancer and 12 months after the diagnosis of prostate cancer the patient developed Ph(+) CML and imatinib treatment was started. After one-year period in remission, CML evolved into accelerated phase and the patient died of intracranial hemorrhage.

Synchronous appearance of male breast cancer and pancreatic cancer 15 years after the diagnosis of testicular cancer--report of a case.

The frequency of new neoplastic diseases among patients cured of testicular cancer is higher than in normal population. For these patients, synchronous occurrence of multiple neoplasms is not common. Also, less than 1% of all cases of breast cancer occur in males. We present herein a case having both breast and concurrent pancreatic cancer after being effectively treated for testicular cancer. To the best of our knowledge, this is the first case of synchronous breast and pancreatic cancer in a male patient following testicular cancer. Second cancer is the most severe long-term complication of chemotherapy or radiotherapy for patients with testicular cancer and the possibility of multiple cancers has to be taken into consideration when multiple lesions are present.

Prognostic factors in limited-stage small cell lung cancer of patients treated with combined modality approach.

PURPOSE: To evaluate the combined modality treatment results of patients with limited-stage small cell lung cancer (SCLC), who were treated and followed by the DELCSG. PATIENTS AND METHODS: Sixty-three patients with limited-stage SCLC diagnosed between April 1991 and December 2002 were included. All patients were treated with combined chemotherapy and thoracic radiotherapy. Median age was 59 years (range 36-84), and all patients were male except 4. Surgery was performed for diagnosis in 3 patients. Four cycles of chemotherapy (median) were administered, composed of cisplatin-etoposide (CE) (26 patients), cyclophosphamide-vincristine-adriamycin (CAV) (10 patients) or alternated CE and CAV (18 patients). Nine patients received various chemotherapy regimes other than CE and/or CAV. A total dose of 5000 cGy with 180-200 cGy daily fractions was given to the primary tumor and mediastinum, excluding the spinal cord after 4500 cGy. Prophylactic cranial irradiation (PCI) was performed in 13 (20%) patients. Overall survival (OS) and progression-free survival (PFS) were calculated, beginning from the date of diagnosis and the end of radiotherapy, respectively. Kaplan-Meier method was used for obtaining survival rates. Log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. RESULTS: Median follow-up time was 17 months (range 3-131). Median PFS and OS were 12 (range 1-131) and 17 (range 3-131) months, respectively. Two-years PFS and OS rates were 27 % and 38 %, respectively. During follow-up, 27 (43%) patients developed brain metastasis; among them only 3 had received PCI. Univariate analysis showed that addition of PCI significantly improved PFS (p=0.025) and advanced age was a favorable prognostic factor for OS (p=0.039). In the multivariate analysis, advanced age (p=0.034) and addition of PCI (p=0.004) were independent factors increasing PFS, however no significant prognostic factor influencing OS was found. CONCLUSION: Our treatment results are in accordance with the relevant literature. It is also concluded that PCI should be given to all patients with complete response to chemotherapy. However, analysis of prognostic factors should be cautiously evaluated because of small number and heterogeneous distribution of patients in subgroups. Prospective studies are necessary for better determination of prognostic factors.

The Role of Interleukin-1 Inhibitors on Acute Myeloblastic Leukemia Blast Proliferation; Future Potential for Biotherapy.

UNLABELLED: The effect of interleukin-1 (IL-1) as an autocrine growth factor on the proliferation of the acute myeloblastic leukemia (AML) blasts was studied. Bone marrow specimens were obtained from nine patients with different subgroups of AML. IL-1 receptor antagonist (IL-1RA) and IL-1 ß neutralizing antibody (IL-1ß NA) alone or in combination were added to the culture mediums of the AML blast cultures for the detection of their inhibitory effect on AML blast cell proliferation and colony formation. Average colony numbers in the IL-RA, IL-ßNA, and IL-IRA plus IL-IßNA included culture flasks, were 63.7 ± 21.5 %, 69.5 ± 19 %, 53.4 ± 23.7 %, respectively, as compared to those of the control (p < 0.01). Inhibition of colony formation by IL-IRA plus IL-IßNA was more prominent than by IL-IßNA alone (p < 0.01). No correlation between the inhibition of AML blast colony ormation and FAB AML subgroups was seen. RESULT: Both IL-1RA or IL-IßNA or in combination induced varying degrees of inhibition on blast colony formation. IL-I inhibitory molecules could be considered as an alternative therapy for AML in patients whose blast cells are sensitive to IL-1 inhibition.

Evaluation of changes in the attitudes and behaviors of relatives of lung cancer patients toward cancer prevention and screening.

BACKGROUND: Cancer diagnosis affects all the relatives living with the patient; however, whether the behavior of family members changes or not is unknown. To end this we evaluated the relatives of lung cancer patients. MATERIALS AND METHODS: Forty-one questions were used to collect data from the relatives of lung cancer patients who had been living with them for at least one year, to evaluate changes in their attitudes and behaviors related to cancer prevention. RESULTS: The study included 246 lung cancer patients' relatives, of them 172 (69.9%) were women and 74 (30.1%) were men. The median age was 46 years (range: 20-83 years). Patients and their relatives had been living together for an average of 28 years (range: 1-68 years), and 88 (35.7%) of the patients' relatives were their children. We found changes in the attitudes and behaviors toward prevention and screening for cancer in 92 (37.4%) of the relatives. Fifty-two (21.1%) of them changed their smoking habits, 34 (13.8%) altered their eating habits, 25 (10.2%) changed their exercise habits, 13 (5.3%) visited a doctor due to a suspicion of having cancer, 12 (4.9%) changed their lifestyles, seven (2.8%) underwent cancer screening tests, three (1.2%) started using alternative medicines, and three (1.2%) started using vitamins for cancer prevention. CONCLUSIONS: Important changes occur in the attitudes and behaviors of patients' relatives toward cancer prevention and screening after the patients are diagnosed with lung cancer. Being aware of how patients' relatives react to a family member's cancer diagnosis may provide healthcare professionals with more incentive to address the relatives' special needs.

Clinical importance of diastolic sonoelastographic scoring in the management of thyroid nodules.

We determined that the application of a 5-point scoring method by using an external manual compression method synchronized with the diastolic period of the carotid artery by sonoelastography was helpful in the management of thyroid nodules. The mean scores on sonoelastography were 2.74 ± 0.97 for 62 benign nodules and 3.90 ± 0.88 for 10 malignant nodules (P < .01). Eighty-seven percent of benign nodules were determined when a cutoff point between scores 3 and 4 was used.

MDCT findings in neuroendocrine carcinoma of the gallbladder: case report.

Neuroendocrine tumors are commonly seen in the gastrointestinal tract, but they are extremely rare in the gallbladder. In this study, sonographic and multidetector-row computed tomographic findings of a patient with neuroendocrine tumors of the gallbladder are presented.

5-fluorouracil increases the number and complexity of premature complexes in the heart: a prospective study using ambulatory ECG monitoring.

The cardiac toxicity of LV5FU2 (de Gramont) regimen which is a widely used chemotherapy regimen in gastrointestinal system cancers is not well defined. We aimed to evaluate the impact of this regimen on cardiac rhythm. Two Holter ECG recordings were obtained in all patients with gastrointestinal system cancers treated with LV5FU2 regimen as first-line chemotherapy (one before and the second during the first 24 h of chemotherapy). Records were reviewed for the heart rate, rhythm, atrial premature complexes (APC), ventricular premature complexes (VPC), grades according to Lown-Wolf grading system and ST segment changes. Holter ECG recordings were evaluated in 27 patients. In the baseline evaluation, neither clinical symptom nor ST segment changes were observed. During the treatment period, chest pain was observed in two patients without any cardiac enzyme and ST segment changes. Moreover, a decrease in mean heart rate, and an increase in the number and complexity of premature complexes secondary to treatment were observed. The mean heart rate, APC per hour and VPC per hour (+/-SD) before vs. during treatment were, respectively, 93.1+/-16.4 vs. 81.6+/-12.7 (p=0.001), 18.9+/-54.0 vs. 45.3+/-53.8 vs. (p=0.049) and 12.7+/-29.6 vs. 38.1+/-42.1 (p=0.002). LV5FU2 regimen leads to a decrease in mean heart rate and a significant increase in APC and VPC which may lead to serious arrhythmias. These effects must be better understood for a safer administration of this useful and widely used drug regimen.

Bax, bcl-2 and c-kit expression in non-small-cell lung cancer and their effects on prognosis.

In non-small-cell lung cancer (NSCLC), stage of the disease is still the most important prognostic factor. Other than stage, many biological markers and many other prognostic factors are studied to define their effects on prognosis of lung cancer. In this study, we aimed to evaluate the expressions of Bax and bcl-2 genes which are important in apoptosis and c-kit, which is a tyrosine kinase transmembrane receptor, as well as searched their response to treatment modalities and effects on survival. Sixty-nine NSCLC cases' pathological samples were stained with specific Bax, bcl-2 and c-kit dyes by immunohistochemical (IHC) methods. IHC evaluation was done by the semichantitative method according to the distribution and intensity of the staining. Twelve of 69 cases (17.4%) were stage I, 28 (40.5%) were stage II, 17 were (24.6%) stage IIIA, nine cases were (13.1%) stage IIIB and three cases (4.4%) were stage IV patients. Their histological subtypes were as follows: of 69 cases, 36 (52.2%) were squamous cell carcinoma, 28 (40.6%) were adenocarcinoma, five (7.2%) were adenosquamous cell carcinoma (two patients) and large-cell carcinoma (three patients). The positive immunostaining rates for Bax and bcl-2 in whole group, squamous cell carcinoma and adenocarcinoma groups were 40.6%/36.2%, 55.6/69.4% and 25.0/0.0%, respectively. The positive immune staining rates for c-kit in whole group, squamous cell carcinoma and adenocarcinoma groups were 7.2, 5.6 and 7.1%, respectively. We didn't find any correlation with Bax, bcl-2 and c-kit expressions and clinicopathological parameters such as age, tumour size, lymph node involvement, smoking, stage of the disease, response to radiotherapy and chemotherapy. Results are interpreted according to survival; bax and bcl-2 expressions were not so effective both in whole group and histologically subgrouped patients. C-kit expression was also found not related with survival in whole group whereas found as a bad prognostic factor in patients with squamous cell carcinoma. These findings could indicate that the expression of apoptotic pathway markers and c-kit may have a role in the prognosis of early stage NSCLC, especially with squamous cell carcinoma subtype.