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.

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.

Large central osteoma of the maxillary antrum.

The aim of this report is to describe a case presenting with complaints of orbital pain, altered facial sensation, nasal obstruction and unilateral spontaneous nose bleeding. Panoramic radiography and computerized tomography disclosed a large pedunculated heterogeneous mineral opacity with two impacted molar teeth invading the maxillary sinus. The patient was operated on under general anaesthesia. Microscopic examination of the surgical specimen revealed relatively dense, compact bone with sparse marrow tissue that was diagnosed as osteoma. Clinical characteristics and biological behaviour of this lesion were evaluated with special regard to the reliability of imaging modalities and surgical procedures.

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.

Primary breast lymphomas--a retrospective analysis of twelve cases.

This study was undertaken to define the natural history and treatment results of patients with primary breast non-Hodgkin's lymphoma (NHL). Twelve female patients who had been followed at Hacettepe University Hospital between 1973 and 1997 were retrospectively evaluated. All patients presented with breast masses (6 in the right breast and 6 in the left) that had recently enlarged. The most common histologic subtype was diffuse, small cleaved-cell lymphoma. Chemotherapy regimens were employed in 9 patients. Radiotherapy was delivered to the breast and its lymphatics in 8 patients. Lumpectomy, simple or modified radical mastectomy was performed in 5 cases. An objective response was attained with surgery, chemotherapy, or radiotherapy alone in 2, 1, and 1 cases, respectively. Combined modality treatment including either two or three modalities was successful in 7 cases. The median progression-free and overall survival times were 49 and 56 months, respectively. Although primary NHL of the breast is a rare disease compared to carcinoma, it should be considered in the differential diagnosis of breast masses.

Treatment of advanced soft tissue sarcomas with ifosfamide and doxorubicin combination chemotherapy.

Our objective was to assess the efficacy of a standard dose ifosfamide and doxorubicin containing regimen in the treatment of advanced soft tissue sarcomas. Forty consecutive patients with a median age of 35.5 years were treated. Ifosfamide was administered at a dose of 2.5 g/m(2)/day as 72-hour continuous infusion with mesna at the same dosage and schedule. Doxorubicin was given at the dose of 60 mg/m(2)/day as 2-hour infusion on day 1. Six patients had a complete response (15%), and 9 (22.5%) had a partial response, fourteen patients (35%) stable disease, and 11 (27.5%) did not respond to chemotherapy. The median duration of response was 13 and 5 months for the complete and partial responders, respectively. The median survival was 37 months. Febrile neutropenia was encountered in 9 cases (22.5%). The present ifosfamide and doxorubicin combination is a moderately effective and well-tolerable regimen in the treatment of advanced soft tissue sarcomas.

The significance of the bone marrow biopsy pattern in chronic lymphocytic leukemia: a prognostic dilemma.

Although bone marrow biopsy pattern (BMBP) has long been suggested to be an independent prognostic factor in chronic lymphocytic leukemia (CLL), conflicting reports continue to appear in the literature. To investigate this issue we retrospectively reviewed 70 CLL patients who had undergone bone marrow biopsy at the time of diagnosis in a multivariate Cox regression analysis together with other prognostic factors. There were 51 (72.8%) males and 19 (27.2%) females with a median age of 60 years (range, 38-77). The median follow-up time was 24 months (range, 1-76), and median survival was 44 months. Thirtyfour patients (48.6%) had diffuse and 36 patients (51.4%) had nondiffuse BMBP (14 nodular, 11 interstitial, and 11 mixed). The median survival for diffuse and nondiffuse BMBP groups were 17 and 53 months, respectively (P= 0.05). Sixteen patients (22. 9%) had stage A, 28 (40.0%) stage B, and 26 (37.1%) stage C disease according to the Binet system, and four patients (5.7%) had low-risk, 39 (55.7%) intermediate-risk, and 27 (38.6%) high-risk disease according to the modified Rai staging system. The difference between the median survivals of patients in different stages was statistically significant (P < 0.0001). The BMBP and staging systems that are thought to be significant predictors of prognosis were used to build a multivariate Cox proportional hazard model. BMBP was not found to add additional information to the prognostic value of the staging systems. Our results underline two points: first, the significance of BMBP must be investigated in multivariate analysis including the stage, and second, BMBP is not a dynamic prognostic parameter, it is an index of tumor burden and does not add any prognostic information beyond that provided by clinical stage.

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.

VB-CHEP chemotherapy regimen for aggressive non-Hodgkin's lymphomas.

Despite intensive search for the optimal combination chemotherapy for aggressive non-Hodgkin's lymphoma (NHL), the CHOP (cyclophosphamide, adriamycin, vincristine and prednisolone) regimen is still the standard therapy. We investigated the clinical efficacy of a new combination regimen consisting of vincristine, bleomycin-cyclophosphamide, adriamycin, etoposide and prednisolone (VB-CHEP) in patients with aggressive NHL. A total of 29 patients with aggressive NHL was enrolled into the protocol. Eight patients were consolidated with cisplatin and cytarabine and 5 patients received radiotherapy for bulky disease. Objective response was achieved in 82.8% of the patients. Complete remission (CR) and partial remission rates were 72.4%, and 10.3%, respectively. CR rate was significantly lower in patients with advanced stage, extranodal disease and bone marrow involvement. Median follow-up time is 34+ months; 17 patients are disease-free while 12 died and only 2 patients with CR have relapsed so far. Median response duration is 29+ months and the median survival is 48+ months. The survival rate is 69% in the first year and 66% in the second year. A total of 152 cycles were evaluated for toxicity. Major hematological toxicity was myelosuppression and neutropenia, detected in 50.65%, was mostly grades 1-2. Neutropenic fever occurred in only 11 cycles. The side effects of the consolidation therapy were also acceptable. We conclude that the VB-CHEP regimen with consolidation therapy for high-risk patients may be an effective treatment for advanced stage aggressive NHL.

Bolus and continuous infusion mitoxantrone in newly diagnosed adult acute lymphoblastic leukemia: results of two consecutive phase II clinical studies.

Two consecutive phase II clinical studies were designed to evaluate the efficacy and safety of bolus and continuous infusion (CI) mitoxantrone (MTZ) in 39 patients with newly diagnosed acute lymphocytic leukemia (ALL). MTZ was used as part of the classical ALL induction regimen. Twenty patients were treated with bolus MTZ (10 mg/m2 for 3 days) combined with vincristine and prednisone. The same regimen was given to a second set of 19 patients, except that MTZ was administered as a 24-hr CI. Both groups received bimonthly intensifications with vincristine and prednisone for 3 years, along with oral maintenance therapy. Patients in the CI-MTZ study arm received additional MTZ on the first day of intensification cycles. Seventeen patients (85%) in the bolus arm and 15 patients (79%) in the CI arm achieved complete remission (CR). Median disease-free survivals (DFS) in the bolus and CI groups were 11 and 15 months after median follow-ups of 16 (3.5-96) and 13 (2.3-32) months, respectively. At 2.5 years, DFS rates were 29.4% and 34.4% in the bolus and CI groups (p > 0.05). There were no significant differences between two groups in rates of early death, degree of organ toxicity, or duration of neutropenia and thrombocytopenia. Significant cardiac toxicity was not observed in either group. Bolus or CI administration of MTZ was equally effective and was well tolerated. Neither the mode of administration nor increasing the dose intensity of MTZ by incorporating intensification cycles reduced relapse rates. Development of new antileukemia agents and novel treatment approaches are still needed to improve the high relapse rates in adult ALL once a complete response is achieved.

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.

Circulating intercellular adhesion molecule-1 and E-selectin levels in gastric cancer.

A diversity of adhesive interactions occur between the cancer cell and host extracellular matrix which potentiate neoplastic expansion and metastatic dissemination. In miscellaneous malignant diseases, tumour progression has been observed to be associated with alterations in adhesion molecule expression. Recently, circulating soluble intercellular adhesion molecules have been identified. In this study, serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble E-selectin (sE-selectin) were determined in patients with gastric cancer. The study group consisted of 27 patients with previously untreated gastric adenocarcinoma. Four patients had stage II, two patients stage III and 21 patients stage IV disease according to the TNM classification. Nineteen patients had distant metastasis. The sera obtained from 18 healthy volunteers served as controls. Serum sICAM-1 and sE-selectin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). In addition, we also studied other tumour-associated antigens, i.e. CEA and CA 19-9. Serum sICAM-1 levels were significantly increased in patients with gastric cancer (P < 0.0001). However, sE-selectin levels did not differ from the controls. sICAM-1 concentrations were also significantly higher in patients with distant metastasis and peritoneal spread (P = 0.0045 and P = 0.0157 respectively), whereas sE-Selectin levels were elevated only in patients with peritoneal metastasis (P = 0.033). Serum concentrations of sICAM-1 and sE-selectin correlated with CEA levels (P = 0.0013 and P = 0.003 respectively). Elevated levels of sE-selectin were associated with poorer prognosis (P = 0.0099), whereas sICAM-1 had no significant impact on survival. Our results suggest that increased sICAM-1 serum levels may reflect widespread disease and contribute directly to the progression of gastric cancer. Further investigation of the molecular mechanisms of adhesive tumour-host interactions may lead to a better understanding of the natural history of gastric cancer.

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.

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.

A randomized Phase III trial of etoposide, epirubicin, and cisplatin versus 5-fluorouracil, epirubicin, and cisplatin in the treatment of patients with advanced gastric carcinoma. Turkish Oncology Group.

BACKGROUND: Gastric carcinoma is a substantial health problem in Turkey, and the majority of patients present with inoperable disease. The aim of this randomized trial was to assess the activity of 5-fluorouracil versus etoposide when combined with epirubicin plus cisplatin in patients with advanced gastric carcinoma (AGC). METHODS: In this prospective, randomized, multicenter Phase III study, previously untreated patients with histopathologically proven AGC enrolled after giving informed consent. Patients were allocated to receive either EEP (etoposide 120 mg/m2, epirubicin 30 mg/m2, and cisplatin 40 mg/m2 on Days 1 and 8) or FEP (5-fluorouracil 600 mg/m2, epirubicin 60 mg/m2, and cisplatin 80 mg/m2 on Day 1), and the regimens were to be repeated every fourth week. RESULTS: Of a total of 131 eligible patients, 64 were in the EEP group and 67 were in the FEP group. The objective response (complete + partial) rates for evaluable patients (n = 118) were comparable (P = 0.63) in the EEP (20.3%, 12/59) and FEP (15.3%, 9/59) groups, respectively. Actuarial analyses revealed comparable median progression free survival (6 vs. 7 months, P > 0.05) and overall survival (6 vs. 5 months, P > 0.05) duration in the EEP and FEP groups. Both regimens were well tolerated. The most common toxicity was Grade 1-2 nausea with or without vomiting. No chemotherapy-related death occurred. CONCLUSIONS: The current study resulted in inadequate response rates for EEP and FEP regimens. Neither combination, as used at the doses and schedules in this study, can be recommended as standard treatment for patients with AGC.

Maintenance therapy with alpha-interferon following first-line VAD in multiple myeloma.

The aim of this study was to evaluate the response characteristics of vincristine, adriamycin and dexamethasone (VAD) as a first-line chemotherapy and to determine the efficacy of maintenance alpha-interferon (alpha-IFN) in multiple myeloma (MM). Between January 1985 and December 1994, a prospective trial was performed in stage II and III MM patients. The study population received only VAD with no maintenance therapy before 1990 (n=31), and those recruited after 1990 (n=33) were planned to be maintained with alpha-IFN (5 mU, 3 times per wk) during the plateau to a maximum of 2 yr. Median follow-up duration (44 vs. 39 months), time to response (3.4 vs. 3.5 months) and rate of objective response (61.3%, 19/31 and 63.6%, 21/33) were similar in VAD-only and VAD+IFN groups, respectively. The survival analyses revealed higher median progression-free (39.6 vs. 12 months) and overall survival (65+ vs. 24 months) durations in VAD+IFN group compared to VAD-only group. VAD regimen was well tolerated and IFN-related side effects were reversible. These findings denote that IFN maintenance prolongs the duration of response obtained by VAD.

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.

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.