Oktay Tarhan

Epidemiology and survival of hepatocellular carcinoma in Turkey: outcome of multicenter study.

OBJECTIVE Hepatocellular cancer (HCC) is one of the important health problems in Turkey. We aimed to determine the clinical and demographic features of HCC in the Turkish population and to evaluate the prognostic and survival features. METHOD Two hundred and twenty-one patients with HCC from five hospitals in Turkey are included in this study. RESULTS In 44.4% of the 221 patients with hepatitis B virus and in 21.3% of the 221 patients with hepatitis C virus were found to be responsible for HCC etiology. It has been shown that HCC developed on cirrhosis basis in 74.2% of the patients. HCC was presented with single solitary nodule in 69.2% of the patients. Non-liver metastasis was present in 12.5% of the patients. In 21.7% of the patients, alpha-fetoprotein (AFP) levels were above the diagnostics level of 400 ng/ml. The median overall survival (OS) of 221 patients was 14 months. The median OS of the patients with Child-Pugh A class was significantly longer than that with Child-Pugh B and C classes. The OS of the individuals with normal AFP levels was also longer than that with high AFP levels. The OS of the patients with Stage I HCC according to tumor node metastasis (TNM) classification, the female patients and the treated patients group was found to be significantly good. CONCLUSIONS In conclusion, the viral etiology (hepatitis B and C infections) in Turkish population is found to be an important factor in HCC development. The Child-Pugh classification, AFP levels, TNM classification, being female and treatment were determined to be important prognostic factors in HCC patients.

Rapid tumor lysis syndrome in a patient with metastatic colon cancer as a complication of treatment with 5-fluorouracil/leucoverin and irinotecan

Tumor lysis syndrome is a potentially fatal complication of anticancer therapy that is usually seen in patients with bulky, rapidly proliferating, treatment-sensitive tumors such as hematological malignancies, but it rarely occurs in a variety of solid tumors such as colorectal carcinoma. Combination chemotherapy with infusional 5-fluorouracil/leucoverin and irinotecan has been recently accepted as the first treatment option for metastatic colorectal cancer. We present a case of tumor lysis syndrome in a patient with metastatic colon carcinoma that occurred 72 hrs after the initial course of a combination chemotherapy with irinotecan and 5-fluorouracil/leucoverin. Despite the immediate treatment with aggressive hydration by a sodium bicarbonate infusion, followed by forced diuresis and uricolytic therapy, he died of a sudden cardiac arrest complicated by acute renal failure. Our case indicates that administration of 5-fluorouracil/leucoverin and irinotecan for bulky tumors of colorectal origin with a rapid doubling time may induce an acute tumor lysis syndrome, which necessitates frequent laboratory monitoring and a close follow-up of the patient as well as prompt initiation of appropriate therapeutic measures.

The development of pulmonary adenocarcinoma in a patient with Job's syndrome, a rare immunodeficiency condition.

The hyperimmunoglobulin E (HIE) (Jobs) syndrome often has it onset in childhood and is characterized by markedly elevated serum IgE levels, chronic dermatitis and recurrent pyogenic infections. Lymphoid malignancies have most commonly been associated with this syndrome while the first case in the literature of carcinoma associated with HIE syndrome was a squamous cell carcinoma of the vulva, described by Clark et al. in 1998. We observed a male patient with Jobs syndrome diagnosed at age three who presented with bone pain and a metastatic epithelial tumor of the bone revealed by biopsy. Diagnostic procedures aimed at detecting the primary site showed multiple mediastinal lymph nodes with lung and liver metastases on computed tomography scans and an extradural spinal metastasis at the upper thoracic level on magnetic resonance imaging. Although the patient refused a bronchoscopic procedure, a diagnosis of pulmonary adenocarcinoma was established on the basis of sputum cytology and the clinical aspects of tumor extent. Intravenous corticosteroids and palliative radiotherapy were given for the spinal metastasis. Palliative chemotherapy could not be started because of the patients poor performance status as well as nosocomial fungal pneumonia and pseudomonal urogenital infection with bacteremia. Despite the antifungal and broad-spectrum antimicrobial treatments, the patient died of pseudomonal sepsis.

Irinotecan Combined with Infusional 5-Fluorouracil and High-Dose Leucovorin for the Treatment of Advanced Gastric Carcinoma as the First-Line Chemotherapy

Background: Because of insufficient activity and high toxicity of current chemotherapy regimens in advanced gastric cancer (AGC), there is a need for newer regimens. Methods: Twenty-five chemonaive patients with AGC have been treated with FOLFIRI regimen consisting of irinotecan 180 mg/m2 over 30 min on day 1 combined with leucovorin 200 mg/m2 over 2 h followed by 5-fluorouracil 400 mg/m2 as bolus and 600 mg/m2 as a 22-hour infusion on day 1 and 2. The treatment was administered every 14th day until progression or intolerable toxicity. Results: Twenty-five patients (17 male, 8 female; 22 patients with PS 0–1 and 3 patients with PS 2), median age 54 (range 25–77), received a total of 230 courses of chemotherapy (median 9; range 1–18). Objective responses were observed in 9 patients (36%), all being partial. Median progression-free survival, 1- and 2-year progression-free survival rates were 8.6 months, 28.4% and 15.3%, respectively. Median overall survival, 1- and 2-year overall survival rates were 11.6 months, 48.0% and 17.8%, respectively. As serious adverse events, grade 3–4 neutropenia was observed in 5 patients (20.0%), grade 3 diarrhea in 4 patients (16.0%). No treatment-related death occurred. Conclusion: FOLFIRI regimen is an active regimen with acceptable toxicity for the treatment of AGC.

Gemcitabine Combined with Infusional 5-Fluorouracil and High-Dose Leucovorin for the Treatment of Advanced Carcinoma of the Pancreas

Background: 5-Fluorouracil (5-FU) and gemcitabine are the major active drugs in the treatment of pancreatic cancer. Methods: Twenty-two patients with advanced pancreas cancer were treated with a new chemotherapy regimen consisting of infusional 5-FU and high-dose leucovorin with gemcitabine (GEMFUFOL). Results: A total of 200 cycles of chemotherapy were administered. The response rate was 27.3%, all responses being partial. The median survival time and 1-year survival rate were, respectively, 13 months and 60.4%. The toxicity was very low and severe hematological toxicity was exceptional. Conclusion: The GEMFUFOL regimen can be an active regimen for the treatment of advanced pancreatic cancer and has a low toxicity.

Uracil/tegafur as a possible salvage therapy in chemo-refractory colorectal cancer patients: a single institutional retrospective study.

Aim of the study Our aim was to determine the activity and toxicity of uracil/tegafur and leucovorin combination in metastatic colorectal cancer (mCRC) patients who have progressed with all currently active agents. Material and methods This study was a retrospective analysis of 50 mCRC patients who had previously failed to respond to all available chemotherapeutics and who received subsequent treatment with uracil/tegafur 250 mg/m2 d1–5 in combination with leucovorin 90 mg/day, d1–5 followed by two days’ rest. Results The median age of the patients was 60 years. Most of them (60%) were male. Bevacizumab was used in 65% and cetuximab in 55% of the patients. Thirty-nine patients (78%) were treated with uracil/tegafur in the fourth line setting. The median treatment duration was 4.2 months (range, 2–24 months). The objective response rate and the disease control rate were 4% and 34%, respectively. Median progression-free survival was 4.1 months (95% CI, 3.6–4.6 months) and overall survival was 6.6 months (95% CI, 4.5–8.6 months). Grade 3 or 4 toxicity was seen in 20% (n = 10) of the patients while 60% (n = 6) of them required dose reductions. Conclusions This retrospective data show that uracil/tegafur may be considered in heavily pretreated mCRC patients because of its activity, lower toxicity, and feasibility.

A patient with rectum cancer, and subcutaneous and pulmonary metastases

A 27-year-old male patient was admitted to Dokuz Eylul University Hospital (Izmir, Turkey) with complaints of constipation and weight loss for a period of 4 months. His history was not significant, except for the early age at which he started to smoke, resulting in a smoking habit of one pack of cigarettes per day for 12 years. There was no history or evidence of cancer in any of his close relatives.