A new prognostic strategy for gastric carcinoma: albumin level and metastatic lymph node ratio.

AIM: We evaluated the prognostic significance of preoperative serum albumin value and metastatic lymph node ratio for gastric cancer patients. METHODS: We studied patients diagnosed with gastric carcinoma in the first Department of Surgery, Bezmialem Vakif Gureba Training and Research Hospital between January 2004 and December 2010; the patients were studied retrospectively. RESULTS: A total of 67 patients with a mean age of 58.7 ± 11.4 years were included in the study. The majority of patients were male (N.=53 male; N.=14 female). Most patients were in an advanced stage of the disease (stage III-IV) on admission (67.2%). We classified patients according to albumin value as "normal" Group 1 (83%) and "hypoalbuminemic" Group 2 (17%). With albumin, age, resection type, perineural invasion, and ratio of metastatic lymph nodes, T and TNM stages were significant predictors of cancer-specific survival. CONCLUSION: As a result, irrespective of mechanism, pre-operative evaluations of albumin and metastatic lymph node ratio should be performed to stratify the patients for risk analysis and prognosis. A level less than 3.5 g/dL is a negative prognostic factor for resectable gastric cancers.

nm23 Protein expression in larynx cancer and the relationship with metastasis.

The nm23 gene, which encodes nucleoside diphosphate (NDP) kinase, is proposed as a metastatic suppressor gene and has been demonstrated to correlate inversely with metastatic potential in several tumours. To elucidate the role of nm23 in larynx carcinomas, we examined using immunohistochemistry the expression of the nm23 protein in matched sets of primary tumours and metastatic lymph nodes. nm23 Protein was expressed in all the carcinomas as well as in non-neoplastic larynx mucosa. Overexpression of nm23 protein was found in the majority of primary tumours compared with corresponding normal mucosa, while decreased expression was associated with poor differentiation and distant metastasis and/or recurrence. No significant difference in age, sex and stage was found between primary tumours with high and low nm23 protein expression. These results suggest that decreased nm23 protein expression may play a role in metastasis and/or recurrence in larynx cancer and therefore could be used as a prognostic factor.

Acute tumor lysis syndrome following intrathecal methotrexate.

We report a 17-year-old boy with meningeal involvement of lymphoblastic lymphoma who experienced acute tumor lysis syndrome following intrathecal administration of methotrexate. Intrathecally injected methotrexate provides a slow- release reservoir of methotrexate into the bloodstream with prolonged cytotoxic levels. To the best of our knowledge, this is the second case of tumor lysis syndrome to be described after intrathecal methotrexate injection. The pathogenesis of this unusual complication of intrathecal chemotherapy is discussed.

Solitary phalanx plasmacytoma relapse with disseminated extramedullary plasmacytomas and myeloma after short duration of remission.

Solitary bone plasmacytomas account for 5-7% of multiple myeloma cases and are assumed to have a fairly good prognosis, with a long duration of relapse-free survival after primary local treatment. Isolated phalanx plasmacytoma is a very rare entity, because involvement of extremities is seen in less than 1% of all solitary bone plasmacytomas, where they are usually localized centripedally, often in the axial skeleton. A 68 year old patient with a lytic lesion involving 5th phalanx was diagnosed as having a biopsy-proven solitary plasmacytoma, with a negative work-up for coexisting plasma cell dyscrasia. Three and a half months after completion of radiotherapy of the involved phalanx, the patient was readmitted with hypercalcemia, renal insufficiency and subsequently diagnosed as having atypical plasma cell infiltration of marrow, and plasmacytomas involving the right vocal cord and the premaxillary region, as well as pathological ulna fracture. Plasmacytoma of the phalanx, with extreme short duration of remission and an aggressive type of clinical relapse, is in sharp contrast with the natural stable course of a solitary plasmacytoma where the use of systemic treatment is subject to intense debate.

A comparison of two nonsteroidal antiinflammatory drugs (diflunisal versus dipyrone) in the treatment of moderate to severe cancer pain: a randomized crossover study.

The efficacy of diflunisal in cancer pain was evaluated and compared with dipyrone. Diflunisal was given at the dosage of 500 mg perorally twice a day, and dipyrone was given at the dosage of 500 mg perorally three times a day. Duration of each treatment was 7 days; after a 12-hour wash-out period, patients were given the other drug for another 7 days. A total of 50 patients were enrolled in the study. Pain intensity was assessed by 10-point visual analog scale (VAS). Patients who had a VAS score higher than 5 were included. A total of 47 patients were evaluable. Initial VAS score was a mean of 8.57+/-1.33. Diflunisal reduced the pain score by a mean of 4.65+/-3.10, whereas dipyrone reduced the pain score by a mean of 3.25 < or = 2.85 (p < 0.001). Patients were also analyzed in three subgroups according to the presence of nonmetastatic, metastatic, and bone metastatic diseases. In each of these subgroups, diflunisal reduced the pain score more than dipyrone; however, the difference was statistically significant only in patients who had bone metastasis. Adverse reactions were rare and acceptable with both drugs. Diflusinal is superior to dipyrone at this dosage and schedule in the treatment of moderate to severe cancer pain.

Factors influencing the distribution of metastases and survival in metastatic breast carcinoma.

A total of 370 patients with metastatic breast, carcinoma who had been followed at Hacettepe Oncology Department between 1980 and 1991 were retrospectively analyzed for the factors influencing the distribution of metastases and survival. Median age was 47 years. Radical or modified radical mastectomies were performed in 199 (53.8%). Infiltrative ductal carcinoma was the most common pathologic subtype (69.4%). In 191 patients who were evaluated for estrogen receptor (ER) status, 101 (52.9%) were positive and 90 (47.1%) were negative. The distribution of first metastases did not differ between the soft tissue, bone, and visceral sites. The second, third, and fourth metastases were more common in visceral sites (p < 0.05). ER and menopausal status did not affect distribution. Mortality rate was significantly lower in the group having the first metastasis to the bone (p < 0.05). Of interest, first metastases were predominantly found in visceral sites in patients having radical or modified radical mastectomies (p < 0.05). Response to therapy, presence of initial metastases, axillary status, and age were the important factors influencing the overall survival in univariate analysis, whereas response to therapy, ER status, age, and presence of initial metastases were the important factors according to the multivariate analysis.

Tobacco and cancer in Turkey.

Although the smoking epidemic is decreasing steadily in other parts of the world, it continues to spread at an accelerated rate in underdeveloped and developing countries. Turkey, among other developing countries, faces the increasing threat of tobacco-related cancers, particularly lung cancer, which is the leading cause of cancer death in both sexes. We investigated the relationship between cigarette consumption and the relative mortality rates due to lung cancer in men and women between 1965 and 1992. We found a parallelism between the increasing total and per capita cigarette consumption and the rising relative mortality from lung cancer in both sexes. Total per capita cigarette consumption rose from 1230 cigarettes per year in 1985 to 1495 in 1991, and the per capita yearly cigarette consumption over the age of 15 increased from 1850 in 1965 to 2600 in 1992. During the same period, the relative mortality from lung cancer increased from 25 to 40% in men and from 11 to 16% in women. The tar, nicotine, and carbon monoxide determinations of locally produced and imported cigarettes suggested that the high tar and carbon monoxide content of most locally produced cigarettes smoked over many years could also be a contributory factor to the increased mortality rates due to lung cancer. Only two brands of locally produced cigarettes contained lower than 12 mg of tar per cigarette as allowed in European community states, whereas half of the imported brands of cigarettes met this standard. Four of the six imported brands of cigarettes contained higher tar and carbon monoxide compared with the same brands sold in England. These findings indicate that urgent measures are necessary not only to ban all activities promoting the sale of cigarettes but also to establish standards for both national and foreign brands of cigarettes while making a greater effort to reduce active and passive smoking in the Turkish population.

The impact of diagnosis and treatment on the quality of life in breast cancer patients.

Over the past years, quality of life (QOL) in patients with breast cancer has continued to be a noteworthy area of research. The diagnosis and management of cancer can have a major impact on every aspect of a patient's QOL. Sixteen women with breast cancer (during chemotherapy and 4 months after adjuvant chemotherapy) and 15 healthy women controls underwent 42-item QOL questionnaire in eight dimensions which assessed general well-being, physical symptoms and activity, sleep disturbance, appetite, sexual dysfunction, cognitive functions, medical interaction, social participation, and work performance. The subjects were asked to choose only one of five predefined constant options, which were scored from one to five in a Likert scale with multiple options, and total QOL scores were obtained. Although the total QOL score was not statistically different between the groups (p > 0.05), general well-being, physical symptoms and activity, and sleep disturbance showed significant regression in breast cancer patients compared to the controls (p < 0.05). Appetite (p < 0.02) and physical symptoms and activity (p < 0.05) significantly improved in the group after chemotherapy compared to the group during chemotherapy.

Ifosfamide, mesna and epirubicin as second-line chemotherapy in advanced breast cancer.

The ifosfamide, mesna and epirubicin (IMEpi) combination is administered to 16 patients having advanced metastatic breast carcinoma as second-line chemotherapy. We observed complete response in 6%, partial response in 44% (total overall response rate of 50%), stable disease in 12% and progressive disease in the remaining 38% of the patients. The median remission duration in responders was calculated to be 9.6 months. IMEpi regimen had a tolerable toxicity profile including alopecia, nausea and vomiting, microscopic hematuria, leukopenia and neurotoxicity in which serious complications necessitating discontinuation of the chemotherapy were not encountered. It might be concluded that IMEpi chemotherapy combination is an effective alternative among schedules in the management of patients with stage IV breast carcinoma without serious side effects.

A comparison of chemoembolization with conventional chemotherapy and symptomatic treatment in cirrhotic patients with hepatocellular carcinoma.

BACKGROUND/AIMS: The results of transcatheter arterial chemoembolization (TACE) in 28 cirrhotic patients with advanced hepatocellular carcinoma (HCC) were compared to those obtained in 15 cirrhotic patients with HCC treated with systemic chemotherapy, and 14 patients with HCC receiving no specific anti-cancer treatment. MATERIALS AND METHODS: From November, 1986 through May 1994, 235 patients with HCC were seen by the investigators. Twenty eight of these patients actually received TACE. The chemotherapeutic agent used was mitomycin C mixed with Lipiodol and arterial embolization was achieved using Gelfoam. In 19 of 28 cases treated with TACE, the embolization was limited to an artery feeding the tumor, thereby avoiding liver cell injury in non-tumor tissue. In 9 others, the main left or right hepatic artery was embolized. The results obtained in these 28 cases were compared to those obtained in 15 patients with HCC larger than 5 cm. who received systemic mitomycin C and doxorubicin chemotherapy and with those obtained in 14 patients who received no specific anti-tumor therapy. RESULTS: One patient died of liver failure related to the TACE and three patients died of bleeding from esophageal varices within weeks of the TACE procedure. Two of the remaining 24 patients are alive with a follow-up of 6 and 22 months. Twenty-six of the 28 patients treated with TACE died within 1 and 28 months of the initiation of the TACE therapy. The mean survival of those receiving TACE was 13.0 months. Chemotherapy without embolization yielded a mean survival of 7.2 months. The mean survival of the patients receiving no specific anti-cancer treatment was only 6.9 months. There was no statistical differences between the survival of those receiving systemic chemotherapy and those receiving no specific treatment. In contrast, the mean survival of the group receiving TACE was significantly greater than that of either of the other two groups (p < 0.005). CONCLUSIONS: These data suggest that TACE provides the best survival for individuals with larger hepatocellular carcinomas (> 5 cm) not eligible for surgery or percutaneous ethanol injection (PEI).

Combination of docetaxel and doxorubicin as first-line chemotherapy in metastatic breast cancer.

Docetaxel (Taxotere) and doxorubicin have previously demonstrated a significant antitumor activity in patients with metastatic breast cancer. Furthermore, a lack of cross resistance and overlapping toxicities between the two agents have been reported. In a prospective study, docetaxel (80 mg/m2, 1-hr iv infusion) and doxorubicin (60 mg/m2, 1-hr iv infusion) were administered as first-line chemotherapy in metastatic breast cancer patients to evaluate the clinical efficacy and toxicity of the combination. Forty-three patients were enrolled in the study. The median age was 47 years (range, 30-69). The docetaxel-doxorubicin combination was applied with 3-week intervals until progression. Complete response was achieved in 9 (21.4%) of 42 assessable patients and partial response in 24 (57.2%) patients, for an overall response rate of 78.6%. Median response duration was 8 months (3-18 months). Nausea and vomiting (76%), alopecia (64%), neutropenia (35.7%) and mucositis (33%) were the major side effects of the combination. There was one case of cardiac toxicity. In conclusion, the docetaxel-doxorubicin protocol can be considered as an active regimen for the treatment of patients with metastatic breast cancer with acceptable toxicity and a fairly high response rate.

Haemostatic changes; plasma levels of alpha2-antiplasmin-plasmin complex and thrombin-antithrombin III complex in female breast cancer.

AIMS AND BACKGROUND: Disorders of hemostasis in patients with malignancies are based on several mechanisms, such as ability of the tumor to alter the coagulation system by producing blood clotting factors or decreasing their inhibitors by increasing fibrinolysis, and by inducing an alteration of blood vessels in relation to the state of local invasion. We investigated the fibrinolytic system marker alpha2-antiplasmin-plasmin complex (APP) and clotting system marker thrombin-antithrombin III complex (TAT) in patients with breast cancer and compare them with CA 15-3, the most well-known breast cancer antigen. METHODS: Plasma levels of APP and TAT and serum level of CA 15-3 were determined in 57 patients with breast cancer (28 in remission and 29 with active breast cancer) and 13 healthy women. RESULTS: In patients with active breast cancer, plasma APP levels were significantly elevated compared to those of other groups (P<0.05). In addition, we observed a poor but positive correlation between plasma levels of APP and those of CA 15-3 (r=0.24; P=0.038). Plasma TAT levels, which reflect the activation of thrombin, were also significantly elevated in patients with active breast cancer (P<0.01), and there was a significant correlation between CA 15-3 and TAT (r=0.24; P=0.041). CONCLUSIONS: We demonstrated that increased APP and TAT levels might reflect enhanced activation of coagulation and the fibrinolytic system in patients with active breast cancer.

Neoadjuvant chemotherapy in locally advanced breast cancer: a preliminary report. Turkish Oncology Study Group.

AIMS AND BACKGROUND: A pilot study of neoadjuvant chemotherapy with cyclophosphamide-epirubicin-5-fluorouracil (FEC) was performed on 85 patients with locally advanced breast cancer. METHODS AND STUDY DESIGN: Patients received four cycles of neoadjuvant chemotherapy followed by surgery, radiotherapy and a treatment with cyclophosphamide-methotrexate-5-fluorouracil for three cycles. RESULTS: Major clinical response was obtained in 76 (89%) patients. Complete response was documented in 14 (17%) patients at pathologic examination of surgical specimen. Grade 1-2 nausea and vomiting was the most common (77%) side effect. Grade 2-3 alopecia was 66%. Grade 2-3 neutropenia occurred in 16% of patients. None of the patients developed febrile neutropenia. Sinus tachycardia was observed only in one patient. Three patients had a more than 10% decrease in the left ventricular ejection fraction without any clinical signs. Nine patients had progressive or stable disease and 4 did not undergo surgery or receive radiation therapy; thus 13 were excluded from survival analysis. After a median followup of 31 months (range, 15-41), disease-free survival and overall survival were 20 (range, 13-32) and 23 months (range, 17-32). CONCLUSIONS: The FEC combination is safe and effective for a neoadjuvant setting in locally advanced breast cancer. A longer follow-up is necessary for the end point results.

Non-Hodgkin's lymphomas of the tonsil: a retrospective analysis of twenty-eight patients with primary tonsillary lymphoma.

AIMS: To analyze the clinical and therapeutic aspects of patients with primary tonsillary non-Hodgkin's lymphoma. METHODS: Twenty-eight patients with primary tonsillary non-Hodgkin's lymphoma who had been followed in the Hacettepe Oncology Institute between 1974 and 1992 were retrospectively analyzed. Fifteen patients were male, 13 were female. Median age was 55 years. RESULTS: Constitutional symptoms were present in 10 patients (35.7%). Stages according to the Ann Arbor classification were I and II in 12 and 16 patients, respectively. According to the Rappaport classification, poorly differentiated lymphocytic was the most common pathologic subgroup (42.9%). Grades according to the Working Formulation were low, intermediate and high in 3, 22 and 3 patients, respectively. Twenty-two patients had received chemotherapy. Cyclophosphamide, vincristine and prednisone (CVP), and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were the regimens most commonly employed. Eighteen patients received radiotherapy to Waldeyer's ring and neck. Eight patients achieved remission with chemotherapy plus radio-therapy, 7 patients with chemotherapy alone, and 5 patients with radiotherapy alone. In addition to the 20 patients who achieved complete remission, 3 patients achieved partial remission; the overall response rate was 82.1%. The response rates and survival attained with the combined modality, chemotherapy, or radiotherapy alone were not statistically different (P > 0.05). The median follow-up was 14 months. Overall and disease-free survival at 5 years were 62.6% and 77.6%, respectively. Pathologic grade was the most important prognostic factor influencing overall survival in the Cox multivariate model. CONCLUSIONS: Poorly differentiated lymphocytic lymphomas were the most common pathologic subtype, and pathologic grade was the most important prognostic factor to influence survival in the present study. Although combined modality treatment did not appear to be superior to chemotherapy or radiotherapy alone, a larger number of patients is needed to draw definite conclusions.

Ifosfamide and etoposide in previously treated patients with advanced breast cancer.

AIMS AND BACKGROUND: Ifosfamide is an active alkylating agent in the treatment of breast cancer, as a first-line therapy and in advanced disease. Since the combination of etoposide with an alkylating agent produces a synergistic and tolerable activity in various malignancies, in the present study, ifosfamide and etoposide were administered to patients with advanced breast cancer to evaluate the response characteristics and the toxicity profile. STUDY DESIGN: The combination of ifosfamide, mesna and etoposide was prospectively administered to 41 previously treated patients with stage IV breast carcinoma. The treatment schedule consisted of ifosfamide, 1500 mg/m2, infused over 24 hrs with 1500 mg/m2 mesna on days 1 to 5 and 120 mg/m2 etoposide, infused over 1 hr on days 1 to 3, to be repeated every 4th week. RESULTS: After a median follow-up of 10 months, an objective response rate of 23% (overall 2.5% complete remission and 20.5% partial remission) and a median response duration of 5.3 months were obtained in 39 assessable patients. The non-responder group consisted of 28.3% stable disease and 48.7% progressive disease. The prior status of chemotherapy was the only significant prognostic factor with an impact on the response rate. The overall toxicity was generally mild, with grade 3 myelotoxicity encountered in 25.7% of patients. CONCLUSIONS: The tolerable side effect profile of the ifosfamide and etoposide combination might be advantageous as regards the quality of life. To improve the rate and/or the duration of response and to clarify the precise role of the ifosfamide-etoposide combination in previously treated advanced breast cancer, further trials are warranted.

Procarbazine, CCNU, vincristine combination in the treatment of brain tumors.

Forty patients with primary malignant brain tumor were treated by combination chemotherapy after prior treatment with surgery and radiotherapy. The chemotherapy schedule consisted of PCV: procarbazine per os, 100 mg/m2, during 14 consecutive days; CCNU, per os, 80 mg/m2 on day 1 and vincristine, intravenously, 1.4 mg/m2 on days 1 and 14. This protocol was planned to be repeated every 45 days for 6 courses. Median 5 courses (range, 2-6) of chemotherapy was administered to patients. The median relapse free (RFS) and overall survival (OS) rates were found to be 28 and 79+ months, respectively. According to univariate analysis, performance status (PS) of patients was an important prognostic factor on RFS and OS where extent of surgery was an additional significant determinant of OS. Multivariate analysis of pretreatment factors revealed the influence of sex, type of histopathology and PS on RFS and that of PS on OS rates (P < 0.05). The toxicity of this regimen was mild to moderate. The major toxicity noted was myelosuppression. Severe (grade III-IV) neutropenia and thrombocytopenia has been observed in 13 (7%) and 6 courses (3.5%), respectively. In general, PCV is well tolerated and the median RFS and OS times elucidated are comparable with particular trials utilizing combination chemotherapy and longer than using radiotherapy alone.

Can bone scintigraphy detect additional metastatic sites unrevealed by CT in patients with recurrent ovarian carcinoma?

A patient who presented with recurrent ovarian carcinoma with elevated levels of CA 125 was evaluated for skeletal metastases by routine whole body bone scintigraphy. Although no bone metastasis was visualized, there was intense accumulation of tracer in the soft tissues corresponding to the liver, pelvis, and intestinal/peritoneal surface, suggestive of metastatic disease. Although liver and pelvic soft tissue metastases were confirmed by CT and USG, intestinal/peritoneal metastases could not be disclosed by either modality.

What is the most fearful intervention in ambulatory oral surgery? Analysis of an outpatient clinic.

The aim of this study was to evaluate the levels of fear and anxiety in patients undergoing different types of minor oral surgery procedures by using conventional rating scales adjusted to the population characteristics. A demographic form and translated versions of the Modified Dental Anxiety Scale (MDAS) and Dental Fear Survey (DFS) were completed by 500 patients having hard or soft tissue pathologies, third molar removal, implant placement, tooth extraction procedures and 200 non-clinical participants. MDAS and DFS were highly correlated (r = 0.79; P < 0.05). The structural properties of the MDAS were similar to the original, but the DFS required substantive changes to achieve comparable measurement properties. Anxiety levels decreased with age and were greater in females, those with higher education and following a previous unpleasant experience (P < 0.05 for all). The third molar group scored higher than most of the surgical categories in both questionnaires (P < 0.05 for each). DFS showed they tended to avoid surgical procedures and were more susceptible to environmental and chair-side effects (P<0.05 for all). Regarding oral surgery, third molar patients should be targeted to increase overall comfort of the treatment. Assessments should be adjusted to cultural differences.