Effect of epidermal growth factor receptor status on the outcomes of patients with metastatic gastric cancer: A pilot study.

The expression of epidermal growth factor receptor (EGFR) has been linked to clinical outcome in several solid tumors. However, the clinical significance of EGFR (c-erbB1) in gastric cancer remains unclear. The present study was designed to detect the clinical implications of EGFR in the Turkish population. Paraffin-embedded tissue microarrays containing gastric cancer tissue were obtained from 30 patients. EGFR expression was detected using immunohistochemistry. The correlation of this biomarker to the clinicopathological features and survival of patients with gastric cancer was studied. The overall positivity rate of EGFR was 63.3%. EGFR expression was significantly correlated with an improved progression-free survival (PFS) and overall survival (OS) rate (P=0.039 and 0.01, respectively). EGFR expression is a good prognostic marker for patients with gastric cancer.

Drug interaction between capecitabine and warfarin: a case report and review of the literature.

OBJECTIVE: To report on possible adverse interaction between capecitabine and warfarin in a patient with cancer, who developed subconjunctival and nose bleeding during treatment with these drugs and review of the previously reported five cases in the literature. CASE SUMMARY: In the second week of capecitabine treatment the patient was hospitalized owing to subconjunctival hemorrhage and nose bleeding. Her international normalized ratio (INR) level was found to have increased, and both drugs were discontinued. Fresh frozen plasma replacement was administered. Warfarin and capecitabine treatment were restarted again but the warfarin dose was decreased. The patients INR was kept between 2.5-3 with the reduced dose of warfarin. DISCUSSION: Capecitabine is an orally active prodrug of fluorouracil (FU) and is extensively used as an antineoplastic agent. It is converted to 5-FU in the liver and tumor tissues. Warfarin is an antithrombolytic agent and is metabolized by liver cytochorom P450 (CYP) isoenzymes in liver. Preclinical in vitro studies using human liver microsomes report no inhibitory effects between capecitabine and substrates of CYP. However, the concomitant administration of capecitabine and warfarin resulted in gastrointestinal, retroperitoneal bleeding and hemorrhagic blisters in the five cases previously reported. The exact mechanism of this interaction is unknown; however, a significant pharmacokinetic interaction between capecitabine and S-warfarin resulting in exaggerated anticoagulant activity has recently been demonstrated. Here, we describe another case and use of the Naranjo adverse drug reaction (ADR) probability scale, which indicated a probable relationship between subconjunctival bleeding and epistaxis in this patient after concomitant warfarin and capecitabine use. CONCLUSION: Capecitabine is extensively used in outpatient clinics, and physicians should be aware of ADRs arising from combined used of capecitabine and warfarin. In the light of the current data, INR levels should be closely monitored in patients using this medication regimen.

Gallbladder adenosquamous cell carcinoma: report of two cases.

Adenocarcinoma is the usual histological presentation of the very rare gallbladder carcinoma. Adenosquamous cell carcinoma accounts for less than 3.5% of gallbladder carcinomas, and is characterised by invasive growth, a reduced tendency for lymph node metastasis, an increased tendency for hepatic infiltration or liver metastasis, and a poorer prognosis than adenocarcinoma. We present two cases. The first patient presented to our institution with increased bilirubin levels and dilated intra- and extrahepatic bile ducts. Adenosquamous carcinoma of the gallbladder was diagnosed on the post-operative pathological specimen. After surgery, bilirubin levels decreased, but hepatic metastases occurred that did not respond to conventional chemotherapy. The second patient was admitted to our hospital with jaundice and abdominal pain. Abdominal computed tomography (CT) imaging showed marked thickening of the gallbladder with direct extension of a mass into the left liver lobe. Cytology specimens obtained with an endoscopic retrograde cholangiopancreatography (ERCP) procedure revealed a malignant epithelial tumour. The patient underwent surgery but the tumour was incompletely resected. A regimen of oral UFT (Tegafur + uracil) chemotherapy was begun. Serum bilirubin levels increased due to occlusion in the surgical area 15 weeks after the start of chemotherapy.

Primary thyroid lymphoma: report of two cases.

Primary thyroid lymphoma is a rare disease. Most of the patients have a history of Hashimoto's thyroiditis. Main histopathologic subtypes are either mucosa-associated lymphoid tissue (MALT) or diffuse large cell lymphomas. Treatment options are surgical resection in localised, low-grade MALT lymphomas or systemic chemotherapy in aggressive, diffuse large cell lymphomas. But, sometimes other histopathologic subtypes can be seen and therapeutic approaches must be done. We report two patients who have primary thyroid lymphoma. There was no history of Hashimoto's thyroiditis in either case, and neither of them had MALT histologic subtype. First patient a sixty four year old woman, admitted to hospital because of bilateral thyroid nodules. Histological subtype was B cell follicular lymphoma. Subtotal thyroidectomy was performed and radiotherapy was administered to the entire neck region. Second patient, a 50 year old man, presented with complaints of a left thyroid mass and dyspnoea. Total thyroidectomy was carried out and chemotherapy was given. Histological diagnosis was diffuse large B cell lymphoma. Thyroid lymphomas had heterogenous histological and clinical characteristics. In localised, non-aggressive subtypes, surgical treatment must be considered. Postoperative chemotherapy or radiotherapy may be necessary in some patients.

Serum levels of soluble E-selectin in colorectal cancer.

Adhesion molecules play an important role in tumor metastasis. E-selectin can support adhesion of colon cancer cells through the recognition of specific carbohydrate ligands. High levels of soluble E-selectin (sE-selectin) had been reported in melanoma and some epithelial tumors, especially in colorectal carcinoma. The concentrations of the sE-selectin were investigated in serum samples of 64 patients (32 men and 32 women) with colorectal cancer and 16 healthy subjects. Median age was 57 (range 20-75). Nineteen patients were staged as Dukes D, 9 of whom had liver metastasis. Serum levels of sE-selectin were determined by ELISA. In the study group, sE-selectin concentrations (mean+/-SE, ng/ml) were not significantly elevated, compared with the control group (41.09+/-4.57 in the control group and 43.80+/-1.88 in patients, p>0.05). Mean sE-selectin levels were 42.27+/-1.85 in non-metastatic and 47.42+/-4.57 in metastatic patients (p>0.05). Serum concentrations of sE-selectin were significantly elevated in patients with colorectal cancer metastatic to liver (59.07+/-7.52) in comparison to other patients without liver metastasis (p=0.013). There were no significant correlations between sE-selectin levels and other parameters such as age of patients, stage of disease, histopathological differentiation or localization of primary tumor. Elevated sE-selectin levels were confirmed as correlating with poor overall survival. In conclusion, sE-selectin concentrations may not be used as a predictive marker of metastasis in colorectal carcinoma, but high levels of sE-selectin may support diagnosis of liver metastasis.

Acute myeloid leukemia 4 years after Kaposi's sarcoma in a renal transplant recipient.

BACKGROUND: Leukemia is a well-known complication of cancer therapy, but development of acute myeloid leukemia (AML) after renal transplantation is rare. Immunosuppressive therapy for organ transplant recipients is complicated by high rates of malignant disease, one condition being Kaposi's sarcoma (KS). CASE REPORT: A 22-year-old woman developed KS 1 year after renal transplantation, and then developed AML another 4 years later. When KS was diagnosed it was already in extensive stage, and she received ABV combination chemotherapy with doxorubicin plus bleomycin plus vincristine intravenously (i.v.) once daily every 2 weeks. She entered remission but the KS relapsed and 8 cycles of i.v. etoposide monotherapy were given and she re-entered remission. 19 months later, the patient was admitted to hospital with severe malaise, leukocytosis, thrombocytopenia, and anemia. The diagnosis was AML (FABM4). The patient received induction chemotherapy consisting of cytarabine and idarubicin. After completion of this induction therapy she developed neutropenic infection, dyspnea and confusion. Her condition deteriorated rapidly after that, and she died. CONCLUSION: KS is one of the most common malignancies in renal allograft recipients, whereas AML is a less frequent problem. To our knowledge, this is the first published case of these two different malignancies developing after renal transplantation. The pathogenesis of the AML is discussed.

Joint pain and arthritis in renal transplant recipients and correlation with cyclosporine therapy.

OBJECTIVE: The aim of this study was to determine the prevalence of joint pain and arthritis in renal transplant recipients and to investigate relationships with various laboratory and clinical parameters. METHODS: Eighty-two patients who underwent renal transplantation (RT) had joint examinations and reported by questionnaire on levels of joint pain and arthritis. Each individual was then followed by the rheumatology department for 1 year, with joint examination and laboratory tests every 3 months. RESULTS: Thirty-one of 82 patients (37.8%) complained of joint pain before RT, of whom seven reported pain continuing after the operation. Seventeen of the 82 (20.7%) began to suffer joint pain after RT. Six (7.3%) and three (3.7%) of the 82 patients, respectively, developed arthritis before and after transplantation. CONCLUSION: The study showed that joint pain is common before and after RT. In renal transplant recipients, joint pain significantly correlated with serum cyclosporine levels higher than 200 ng/ml.

Treatment results in renal transplant recipients with non-Hodgkin's lymphoma.

The purpose of this study was to investigate the incidence of non-Hodgkin's lymphoma (NHL), response to treatment, and survival time in renal transplant recipients at our center who developed this form of neoplasia. Between October 1985 and August 2002, 1077 renal transplantations were carried out at our center. The incidence of NHL after transplantation was 1.1% (12/1077). All patients had their immunosuppressive doses reduced after they were diagnosed with NHL. Complete remission was achieved in eight cases, and five of these individuals were still alive at the time of writing. The circumstances for each of the three deaths in this group were as follows: (1) progressive gastric adenocarcinoma 9 years after being diagnosed with NHL, (2) stage III NHL cured with chemotherapy, but died of infection 2 years after NHL diagnosis, and (3) recurrent intestinal lymphoma, with death during second line chemotherapy. Of the five survivors in the remission group, one had to return to hemodialysis. The four patients who did not enter remission all died. The median time from transplantation to diagnosis of NHL was 66 months. At the time of writing, the median survival time for the eight patients who achieved complete remission was 41.5 months. The study showed that treatment of localized disease (skin or intestinal NHL) with surgery and/or radiotherapy/chemotherapy leads to complete remission and long survival times; however, patients in remission are at risk for other causes of death.

The clinicopathologic characteristics of colorectal cancer in patients under 50 years of age: experience of an oncology center.

BACKGROUND/AIM: Colorectal cancer is seen mostly among patients older than 50 years of age. An aggressive behavior is a frequently cited as characteristic of colorectal cancer in young patients. The purpose of the present study was to reveal the clinicopathologic characteristics of colorectal cancer among patients under 50 years of age. METHODS: Two hundred and seventy-one patients with colorectal cancer admitted to our oncology center were evaluated, and clinicopathologic findings of the young and old patients were compared. Patient gender, site distribution, tumor stage classification, lymph node involvement, metastatic site, histologic classification, histologic differentiation, family history of malignant tumors, presenting symptoms and survival rates were compared. RESULTS: One hundred patients were 50 years of age or under. Clinical, histopathologic characteristics and overall survival of the two groups did not differ. A higher rate of familial cancer syndromes was detected among young patients. CONCLUSIONS: The presentation and outcome of the disease in young patients do not differ from those of older patients. A significant family history of colorectal cancer in the young patients showed the need for screening whereas the outcome of metastatic disease was poor. In order to anticipate long survival, early detection and aggressive treatment is necessary.

Cisplatin plus vinorelbine as a salvage regimen in refractory breast cancer.

AIMS AND BACKGROUND: Breast cancer refractory to known effective agents is one of the major clinical problems frequently encountered in practice. Cisplatin and vinorelbine are known to be active drugs in anthracycline-refractory cases. In this phase II study, the effectiveness and tolerability of cisplatin and vinorelbine was investigated when used in combination as a salvage regimen in the treatment of metastatic refractory breast cancer. STUDY DESIGN: Twenty-four patients with advanced refractory breast cancer who had been previously treated with a regimen containing doxorubicin were included in the study. Six of the 24 patients also received taxanes after failure of doxorubicin. Cisplatin at 80 mg/m2 on day 1 and vinorelbine at 25 mg/m2 on days 1 and 8 were given every 3 weeks. RESULTS: A total of 98 cycles of chemotherapy was given, with a median of 4/patient. The response rate was 25% (2 [8.3%] complete and 4 [16.7%] partial responses). The median survival rates were 14 months in responders and 5.5 months in nonresponders (P = 0.0282). One complete and one partial response were observed in patients previously treated with paclitaxel (overall response rate, 33%). The median response duration was 12.5 mo (range, 4-21) in complete and 4.5 mo (range, 1.5-13) in the partial response group. Grade 3 and 4 neutropenia occurred in 9 patients, with no toxic deaths. Grade 2-3 nausea and vomiting in 6 patients and grade 1 neuropathy in 1 patient were noted. CONCLUSIONS: Although the number of cases is insufficient to indicate that the combination will be effective, it is noteworthy in consideration of anthracycline and taxane refractory cases. A combination of cisplatin and vinorelbine seems to be a reasonable and acceptable choice as an alternative salvage regimen in such cases.

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.