Treatment Patterns and Prognosis of Palliative Chemotherapy Combined With Targeting Agents in Patients With Unresectable Metastatic Colorectal Cancer: CHOICE, A Multicenter Longitudinal Observational Study.

BACKGROUND/AIM: This study investigated the treatment patterns and prognosis of patients with metastatic or unresectable colorectal cancer (mCRC) treated with chemotherapy with targeting agents. PATIENTS AND METHODS: This longitudinal multicenter study included 963 patients with mCRC who were treated in Korea between 2016 and 2020. Treatment patterns and efficacy were compared according to the mutation status and clinical factors. RESULTS: As first-line therapy, most of the patients (83.5%) received FOLFOX plus bevacizumab (35.4%), followed by FOLFIRI plus bevacizumab (18.8%), FOLFIRI plus cetuximab (17.0%), and FOLFOX plus cetuximab (12.3%). Bevacizumab was the most frequent agent (78.8%) combined with chemotherapy in RAS-mutated CRC, while cetuximab (57.2%) in RAS wild-type CRC. Cetuximab was frequently combined with a doublet regimen in patients with left-sided CRC than in those with right-sided CRC (34.4% vs. 16%). As second-line therapy, most patients (63.4%) also received doublet regimens with bevacizumab, and FOLFIRI plus aflibercept was administered in 15.1%. The objective response rate with FOLFIRI plus cetuximab was significantly higher in patients with left-sided CRC than in those with right-sided CRC (59.2% vs. 30.8%, p=0.008) and marginally higher in patients with RAS wild-type CRC than in those with RAS-mutated CRC (55.6% vs. 0.0%, p=0.092). Progression-free survival (PFS) with FOLFOX plus bevacizumab was significantly shorter than that with FOLFIRI plus bevacizumab (p=0.030) in RAS-mutated CRC, whereas there were no significant differences between regimens in RAS wild-type CRC. CONCLUSION: In patients with unresectable metastatic colorectal cancer, doublet chemotherapy with targeting agents is the most common therapy and efficacy depends on the mutation status as well as clinical factors.

Case mistaken for leukemia after mRNA COVID-19 vaccine administration: A case report.

BACKGROUND: Following the global outbreak of coronavirus disease 2019 (COVID-19), unlike other vaccines, COVID-19 vaccines were developed and commercialized in a relatively short period of time. The large-scale administration of this vaccine in a short time-period led to various unexpected side effects, including severe cytopenia and thrombosis with thrombocytopenia syndrome. Despite many reports on adverse reactions, vaccination was necessary to prevent the spread of COVID-19; thus, it is essential to understand and discuss various cases of adverse reactions after vaccination. CASE SUMMARY: A 77-year-old woman was administered the second dose of Pfizer mRNA COVID-19 vaccine. After vaccination she experienced fever, myalgia, and weakness. Antibiotics were subsequently administered for several days, but there was no improvement in the symptoms. The patient showed severe thrombocytopenia and leukocytosis. Thoracic and abdominopelvic computed tomography showed no infection related findings, but splenomegaly and cirrhotic liver features were observed. A large number of immature cells were observed in the peripheral blood smear; thus, bone marrow examination was performed for acute leukemia. However, there were no abnormalities. The patient recovered after administration of hepatotoxins and transfusion treatment for cytopenia and was diagnosed with an adverse reaction to COVID-19 vaccination. CONCLUSION: Adverse reactions of vaccination could be mistaken for hematologic malignancies including leukemia. We report a patient with leukocytosis following COVID-19 vaccination.

Non-secretory multiple myeloma expressed as multiple extramedullary plasmacytoma with an endobronchial lesion mimicking metastatic cancer: A case report.

BACKGROUND: Non-secretory multiple myeloma (MM) is a rare condition that accounts for only 3% of MM cases and is defined by normal serum and urine immunofixation and a normal serum free light chain ratio. Non-secretory MM with multiple extramedullary plasmacytomas derived from endobronchial lesions is extremely rare and can be misdiagnosed as metastasis of solid cancer. CASE SUMMARY: A 36-year-old man presented with progressive facial swelling and nasal congestion with cough. Various imaging studies revealed an endobronchial mass in the left bronchus and a large left maxillary mass with multiple destructive bone metastatic lesions. He initially presented with lung cancer and multiple metastases. However, pathologic reports showed multiple extramedullary plasmacytomas in the left maxilla and the left bronchus. There was no change in the serum and urine monoclonal protein levels, and no abnormalities were observed in laboratory examinations, including hemoglobin, calcium, and creatinine levels. The bone marrow was hypercellular, with 13.49% plasma cells. The patient was diagnosed with non-secretory MM expressed as multiple extramedullary plasmacytomas with endobronchial lesions in a rare location. Radiation therapy for symptomatic lesions with high-dose dexamethasone was started, and the size of the left maxillary sinus lesion dramatically decreased. In the future, chemotherapy will be administered to control lesions in other areas. CONCLUSION: We present a rare case of non-secretory MM with multiple extramedullary plasmacytoma with an endobronchial lesion.

What is the better surgical treatment option for recurrent common bile duct stones?

PURPOSE: Repeating endoscopic retrograde cholangiopancreatography (ERCP) in patients with recurrent common bile duct (CBD) stones is problematic in many ways. Choledochoduodenostomy (CDS) and choledochojejunostomy (CJS) are 2 surgical treatment options for recurrent CBD stones, and each has different advantages and disadvantages. The aim of this study was to compare the 2 surgical options in terms of the recurrence rate of CBD stones after surgical treatment. METHODS: This retrospective multicenter study included all patients who underwent surgical treatment due to recurrent CBD stones that were not effectively controlled by medical treatment and repeated ERCP between January 2006 and March 2015. We collected data from chart reviews and medical records. A recurrent CBD stone was defined as a stone found 6 months after the complete removal of a CBD stone by ERCP. Patients who underwent surgery for other reasons were excluded. RESULTS: A total of 27 patients were enrolled in this study. Six patients underwent CDS, and 21 patients underwent CJS for the rescue treatment of recurrent CBD stones. The median follow-up duration was 290 (180-1,975) days in the CDS group and 1,474 (180-6,560) days in the CJS group (P = 0.065). The postoperative complications were similar and tolerable in both groups (intestinal obstruction; 2 of 27, 7.4%; 1 in each group). CBD stones recurred in 4 patients after CDS (4 of 6, 66.7%), and 3 patients after CJS (3 of 21, 14.3%) (P = 0.010). CONCLUSION: CJS may be a better surgical option than CDS for preventing further stone recurrence in patients with recurrent CBD stones.

Clinical validity of two different grading systems for lumbar central canal stenosis: Schizas and Lee classification systems.

OBJECTIVE: To assess the learnability of two magnetic resonance imaging (MRI) grading systems for lumbar central canal stenosis based on inter-observer agreement and test-retest reliability of doctors with no prior knowledge of the two systems. MATERIALS AND METHODS: Two clinical fellows, one novice radiology resident, one neurosurgeon, and one orthopedic surgeon, who were unaware of the two qualitative MRI grading systems prior to this study, acquainted themselves with the teaching files. All five observers independently assessed the LCCS grade of 70 patients using T2-weighted axial magnetic resonance images at the L2-3, L3-4, L3-4, and L5-S1 disc levels. Analysis was performed twice at an interval of two months. RESULTS: The inter-observer agreement among all five readers was excellent and test-retest reliability was moderate to excellent for both the Schizas and Lee systems. Positive percentage agreements were found to be over 0.8 in almost all observers with relatively narrow 95% confidence limits. CONCLUSION: Both Schizas and Lee MRI grading systems for LCCS are reliable grading systems, and can be used as a learnable method for both clinicians and radiologists.

Activation of the coagulation cascade in patients with scrub typhus.

This retrospective study aimed to evaluate the levels of coagulation factors and presence of disseminated intravascular coagulation (DIC) in patients with scrub typhus. We included patients confirmed to have scrub typhus at the Chosun University Hospital between September 2004 and December 2009. The DIC scores were evaluated in 365 patients and 36 healthy controls. The median concentrations of fibrinogen, d-dimer, and fibrin/fibrinogen degradation products (FDP) were compared between patients and healthy controls (p<0.001 for all tests). Patients with scrub typhus had longer prothrombin time and lower platelet counts than the controls. Major bleeding was observed in 18/365 patients with scrub typhus. Fifty-one (14.0%) patients presented with severe complications of scrub typhus. Overt DIC and thrombocytopenia (<100,000 platelets/mm3) were observed more frequently in patients with bleeding and severe illness. Furthermore, median platelet counts were low in both groups. Approximately 2.7% (n=10) and 16.4% (n=60) patients with scrub typhus had overt DIC, as defined by the International Society on Thrombosis and Hemostasis DIC score (DIC1) and the DIC-scoring template with a fibrinogen/C-reactive protein-ratio (DIC2), respectively. Three (16.7%) and 10 (55.6%) patients with bleeding had overt DIC, as defined by the DIC1 and DIC2, respectively. Seven (13.7%) and 26 (51%) patients with severe illness had overt DIC, as defined by DIC1 and DIC2, respectively. In conclusion, activation of the coagulation system is an important feature of scrub typhus and is correlated with severe disease, including bleeding. This is the first study to report a relationship between DIC and scrub typhus.

IgG4-related systemic disease presenting with pleural effusion, ascites and dilated cardiomyopathy.

PURPOSE: We report the case of a patient with IgG4-related disease with multiple organ involvement, especially myocardium, that was successfully treated with prednisone. METHODS: We performed several serological tests, electrocardiogram, echocardiography, computed tomography and inguinal lymph node biopsy. RESULTS: We diagnosed the patient with IgG4-related disease by the elevated serum IgG4 level and histological lymph node findings. CONCLUSIONS: This is the first reported case of IgG4-related disease with dilated cardiomyopathy.

Optimal Methods for the Management of Iatrogenic Colonoscopic Perforation.

BACKGROUND/AIMS: Colonoscopic perforations have been managed with exploratory laparotomy, and have resulted in some morbidity and mortality. Recently, laparoscopic surgery is commonly performed for this purpose. The aim of this study was to compare the outcomes of several management strategies for iatrogenic colonoscopic perforations. METHODS: We retrospectively reviewed the medical records of patients who had been treated for colonoscopic perforation between January 2004 and April 2013 at CHA Bundang Medical Center in Korea. RESULTS: A total of 41 patients with colonoscopic perforation were enrolled. Twenty patients underwent conservative management with a success rate of 90%. Surgical management was performed in 23 patients including two patients who were converted to surgical management after the failure of the initial conservative management. Among 14 patients who underwent surgery at 8 hours after the perforation, there was no considerable difference in adverse outcomes between the laparotomy group and the laparoscopic surgery group. The medical costs and claim rate were 1.45 and 1.87 times greater in the exploratory laparotomy group, respectively. CONCLUSIONS: Conservative management of colonoscopic perforation could be an option for patients without overt symptoms of peritonitis or with a small defect size. If surgical management is required, laparoscopic surgery may be considered as the initial procedure even with a delayed diagnosis.

Castleman's disease of the spleen.

Castleman's disease (CD) is a rare lymphoproliferative disorder of unknown etiology. Clinically, it occurs as a localized (unicentric) disease or as a systemic (multicentric) disease. Unicentric Castleman's disease (UCD) presents as a solitary mass and primarily affects the mediastinal, retroperitoneal, and cervical lymph nodes. In contrast to multicentric CD, which involves peripheral lymphadenopathy and numerous systemic symptoms, UCD is not typically associated with generalized symptoms. Three main distinct histologic variants are recognized: hyaline-vascular type, plasma cell type, and mixed type. Extranodal CD is rare. Specifically, UCD exclusively in the spleen is extremely rare, with only 2 cases described in the literature to date. Here, we describe an asymptomatic 75-year-old man with a 5.7 cm × 4.5 cm sized heterogenous enhanced mass located in the spleen. He underwent surgical resection for diagnosis and treatment. A pathologic examination indicated the hyaline-vascular type of CD. In this patient, the preoperative diagnosis was difficult to determine, and therefore, invasive procedures were required.

Evaluation of risk factors in patients with vitamin K-dependent coagulopathy presumed to be caused by exposure to brodifacoum.

BACKGROUND/AIMS: Recently, many cases of vitamin K-dependent coagulopathy of unknown origin have been reported. Such patients lack any relevant family history and have no systemic disease, raising suspicion of superwarfarin intoxication. We evaluated individual risk factors causing coagulopathy and hemorrhagic symptoms in patients with suspected superwarfarin intoxication. In addition, we determined how to effectively treat vitamin K-dependent coagulopathy caused by suspected superwarfarin intoxication. METHODS: Seven patients with suspected superwarfarin intoxication who lacked any definitive history of rodenticide ingestion were included. Thirty-one patients initially diagnosed with rodenticide poisoning were also included. We performed a retrospective chart review of all subjects and examined clinical data including patient demographics and medical histories. RESULTS: Patients initially diagnosed with rodenticide poisoning were divided into two groups, one of which had a laboratory abnormality (prothrombin time [PT] > 13 seconds) and another group with PTs in the normal range. There was no significant difference between the two groups in any of age, gender, the extent of chronic alcohol consumption, the causative rodenticide, psychiatric problems, ingestion of drugs interacting with warfarin, the extent of intoxication, or the type of ingestion attempt. The albumin level of the former group was significantly lower than that of the latter group (p = 0.014). Furthermore, a significant difference between the two groups was evident in terms of simultaneous ingestion of rodenticide and alcohol (p = 0.023). CONCLUSIONS: Most patients with superwarfarin poisoning did not exhibit any complication. When such complications were evident, they were associated with serum albumin level and coingestion of rodenticide and alcohol.

Changes in osteoblastic activity in patient who received bortezomib as second line treatment for plasma cell myeloma: a prospective multicenter study.

We conducted a prospective multicenter study identifying the role of bortezomib in patients with relapsed or refractory plasma cell myeloma (PCM) in bone resorption and formation via bone turnover markers. A total of 104 patients received at least 1 cycle of bortezomib. Most of them had advanced disease (n = 89). Among them, 75 patients completed 4 cycles of treatment. Most of the patients (81.7%) were treated in combination with steroid. After the 4th cycle treatment, 47 of 75 patients achieved CR, nCR, VGPR, and PR (64.4%), while 26 patients achieved less than PR (35.6%). The proportion of patients who achieved ≥ PR increased as patients received more treatment cycles, reaching 90% after the 8th cycle. DKK-1 levels decreased significantly posttreatment. Bone formation markers (bALP and OC) and osteoclast regulator such as sRANKL also decreased significantly. These findings were observed primarily in patients who received steroid and who had a longer disease duration. While sRANKL demonstrated significant reduction posttreatment, osteoprotegerin (OPG) level did not significantly change posttreatment, resulting in a decreased sRANKL/OPG ratio (P = 0.037). In conclusion, our clinical data suggest that treatment with bortezomib and steroid may rearrange the metabolic balance between osteoblast and osteoclast activities in PCM.

A case of catamenial hemoptysis treated by bronchial artery embolization.

Catamenial hemoptysis is a rare condition, characterized by recurrent hemoptysis associated with the presence of intrapulmonary or endobronchial endometrial tissue. Therapeutic strategies proposed for intrapulmonary endometriosis with catamenial hemoptysis consist of medical treatments and surgery. Bronchial artery embolization is a well-established modality in the management of massive or recurrent hemoptysis, but has seldom been used for the treatment of catamenial hemoptysis. We report a case of catamenial hemoptysis associated with pulmonary parenchymal endometriosis, which was successfully treated by a bronchial artery embolization.

Deferasirox improves hematologic and hepatic function with effective reduction of serum ferritin and liver iron concentration in transfusional iron overload patients with myelodysplastic syndrome or aplastic anemia.

BACKGROUND: Transfusional iron overload and its consequences are challenges in chronically transfused patients with myelodysplastic syndromes (MDSs) or aplastic anemia (AA). STUDY DESIGN AND METHODS: This was a prospective, multicenter, open-label study to investigate the efficacy of deferasirox (DFX) by serial measurement of serum ferritin (S-ferritin) level, liver iron concentration (LIC) level using relaxation rates magnetic resonance imaging, and other laboratory variables in patients with MDS or AA. RESULTS: A total of 96 patients showing S-ferritin level of at least 1000 ng/mL received daily DFX for up to 1 year. At the end of the study, S-ferritin level was significantly decreased in MDS (p=0.02366) and AA (p=0.0009). LIC level was also significantly reduced by more than 6.7 mg Fe/g dry weight from baseline. Hemoglobin level and platelet counts were significantly increased from baseline (p=0.002 and p=0.025, respectively) for patients showing significant anemia or thrombocytopenia. Elevated alanine aminotransferase was also significantly decreased from baseline. CONCLUSIONS: This study shows that DFX is effective in reducing S-ferritin and LIC level in transfusional iron overload patients with MDS or AA and is well tolerated. In addition, positive effects in hematologic and hepatic function can be expected with DFX. Iron chelation treatment should be considered in transfused patients with MDS and AA when transfusion-related iron overload is documented.

Health-related quality of life among cancer survivors in Korea: the Korea National Health and Nutrition Examination Survey.

OBJECTIVE: The purpose of this study was to investigate the quality of life among cancer survivors compared with individuals without a history of cancer (noncancer controls) using the Korea National Health and Nutrition Examination Survey. METHODS: The study subjects were 783 adult cancer survivors and 36 456 noncancer controls who participated in the third, fourth and fifth Korea National Health and Nutrition Examination Survey. Demographic factors, health-related behavior, clinical characteristics and health-related quality of life were assessed with self-reported questionnaires. The EuroQoL-5Dimension was used to evaluate health-related quality of life. Descriptive statistics and multiple regression analysis were used to compare health-related quality of life between cancer survivors and noncancer controls. RESULTS: About 67% were women and the mean age of the cancer survivors was 60.9 ± 12.4 years. About 52% of survivors were diagnosed with cancer between 45 and 64 years, and more than half of cancer survivors were diagnosed 5 years or less before the interview. The pain/discomfort dimension was the highest reported problem: 43.6% for cancer survivors. The proportion of any reported problem was significantly higher among cancer survivors compared with noncancer controls in terms of mobility (adjusted odds ratio (aOR), 1.56, 95% confidence interval, 1.24-1.97), usual activities (aOR, 1.45, 95% confidence interval, 1.11-1.89), pain/discomfort (aOR, 1.26, 95% confidence interval, 1.04-1.52) and anxiety/depression (aOR, 1.61, 95% confidence interval, 1.29-2.01). CONCLUSIONS: Cancer survivors had a significantly lower quality of life compared with noncancer controls. The pain/discomfort dimension was the highest reported problem in cancer survivors.

Health behaviors of cancer survivors: the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV, 2007-09).

OBJECTIVE: This study aimed to describe the health behaviors of cancer survivors in the Republic of Korea and to compare them with the health behaviors of two control groups: (i) individuals with no history of cancer but with other chronic diseases and (ii) individuals with no history of cancer or other chronic diseases. METHODS: This is a cross-sectional study of 17 311 adults at least 19 years of age who participated in the Fourth Korea National Health and Nutrition Examination Survey (2007-09). Smoking, alcohol drinking, physical activity and cancer screening behaviors of cancer survivors were assessed and compared with those of the two control groups. χ(2) tests and multiple logistic regression analyses were performed to determine the likelihood and predictors of health behaviors. RESULTS: The proportion of cancer survivors who were current smokers, heavy drinkers and engaged in physical activity were 9.6, 6.6 and 26.0%, respectively. Cancer screening rates reported among survivors were 44.2, 17.0, 49.8 and 47.7% for stomach, colorectal, breast and cervical cancers, respectively. Cancer survivors showed lower smoking and alcohol drinking rates compared with both control groups after adjusting for sex, age, marital status, education, household income and health insurance. Cancer survivors also showed stomach, breast and cervical cancer screening rates that differed from both control groups. However, in multiple analyses, these differences were not significant. CONCLUSIONS: Cancer survivors are more likely to adopt good health behaviors than individuals without a history of cancer. Further study is needed to determine the factors that lead to continued unhealthy behaviors after cancer diagnosis.

The Ratio of Descending Aortic Enhancement to Main Pulmonary Artery Enhancement Measured on Pulmonary CT Angiography as a Finding to Predict Poor Outcome in Patients with Massive or Submassive Pulmonary Embolism.

BACKGROUND: The purpose of this study was to evaluate whether measuring the ratio of descending aortic enhancement (DAE) to main pulmonary artery enhancement (MPAE) on pulmonary computed tomography angiography (PCTA) can predict poor outcome in patients with acute massive or submassive pulmonary embolism (PE). METHODS: We retrospectively, reviewed computed tomgraphy findings and charts of 37 patients with acute PE and right ventricular dysfunction. We divided the enrolled patients into 3 groups; group Ia (n=8), comprised of patients with major adverse event (MAE); group Ib (n=5), consisted of those with PE-related MAE; and group II (n=29), those without MAE. We analyzed the right ventricular diameter (RVD)/left ventricular diameter (LVD) and DAE/MPAE on PCTA. RESULTS: For observer 1, RVD/LVD in group Ia (1.9±0.36 vs. 1.44±0.38, p=0.009) and group Ib (1.87±0.37 vs. 1.44±0.38, p=0.044) were significantly higher than that of group II. For observer 2, RVD/LVD in group Ia (1.71±0.18 vs. 1.41±0.47, p=0.027) was significantly greater than that of group II, but RVD/LVD of group Ib was not (1.68±0.2 vs. 1.41±0.47, p=0.093). For both observers, there was a significant difference of DAE/MPAE between group Ib and group II (0.32±0.15 vs. 0.64±0.24, p=0.005; 0.34±0.16 vs. 0.64±0.22, p=0.004), but no significant difference of DAE/MPAE between group Ia and group II (0.51±0.3 vs. 0.64±0.24, p=0.268; 0.53±0.29 vs. 0.64±0.22, p=0.302). Intra-class correlation coefficient (ICC) for the measurement of DAE/MPAE (ICC=0.97) was higher than that of RVD/LVD (ICC=0.74). CONCLUSION: DAE/MPAE measured on PCTA may predict PE-related poor outcomes in patients with massive or submassive PE with an excellent inter-observer agreement.

Spontaneous tumor lysis syndrome with resolution of pancytopenia and disappearance of lymphadenopathy in a patient with peripheral T cell lymphoma unspecified.

Tumor lysis syndrome is a well-described, serious complication of chemotherapy administered to treat malignancies. However, a very rare event resulting in the spontaneous necrosis of a tumor prior to therapy can also occur, which is termed spontaneous tumor lysis syndrome (STLS). We present a case of a 27-year-old male who presented to the hospital with epistaxis, dyspnea, and cervical lymphadenopathy. Laboratory findings included progressive pancytopenia, hyperuricemia, and acute renal failure. Bone marrow biopsy showed a T cell lymphoid neoplasm that had entirely infiltrated the marrow stroma. The patient was diagnosed with STLS in the setting of a T cell lymphoma with bone marrow infiltration. The patient was immediately treated with a blood transfusion and hemodialysis. After this urgent treatment, the patient's pancytopenia resolved and the lymphadenopathy disappeared spontaneously. One month post-treatment, the patient's cervical lymphadenopathy recurred and peripheral T cell lymphoma, not otherwise specified, was confirmed. STLS has previously been reported, however, most known cases of STLS did not show a decreased tumor burden resulting from massive tumor cell death. We present a rare case of STLS with resolution of pancytopenia and disappearance of lymphadenopathy in a patient with peripheral T cell lymphoma not otherwise specified.

Colon perforation during sorafenib therapy for advanced hepatocelluar carcinoma. A case report.

There are no effective conventional systemic cytotoxic therapies for patients with unresectable or advanced hepatocellar carcinoma (HCC). Sorafenib, an oral multi-targeted tyrosine kinase inhibitor, was recently approved for the treatment of patients with HCC. Sorafenib is generally well tolerated and has an acceptable toxicity profile.Gastrointestinal perforation is a rare adverse event. We present a case of transverse colon perforation during sorafenib therapy for advanced HCC. A 68-year-old woman with advanced HCC was treated with sorafenib. Eight weeks later the patient presented with the sudden onset of sharp abdominal pain. Emergency surgery was performed for panperitonitis and a perforation involving the transverse colon.

Idiopathic hypereosinophilic syndrome involving thoracic spine.

Hypereosinophilic syndrome is a rare hematologic disorder with sustained eosinophilia. Peripheral blood eosinophilia without an underlying etiology and with organs dysfunction has been designated hypereosinophilic syndrome. We report a rare case of symptomatic spinal infiltration of eosinophils at osteolytic T5 in patient with idiopathic hypereosinophilic syndrome.

Effects of silybinin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen in rats.

The effects of silybinin, an antioxidant, on the pharmacokinetics of tamoxifen and its metabolite, 4-hydroxytamoxifen, were investigated in rats. A single dose of tamoxifen was administered intravenously (2 mg/kg) and orally (10 mg/kg) without or with silybinin (0.5, 2.5 and 10 mg/kg) to rats. Silybinin significantly altered the pharmacokinetics of orally administered tamoxifen. Compared to those in the oral control group (given tamoxifen alone), the area under the plasma concentration-time curve (AUC(0-infinity)) and the peak plasma concentration (C(max)) of tamoxifen were significantly (p<0.05 for 2.5 mg/kg, p<0.01 for 10 mg/kg) increased by 40.2-71.3% and 45.2-78.6%, respectively, with silybinin. Consequently, the absolute bioavailability (AB) of tamoxifen in the presence of silybinin (2.5 and 10 mg/kg) was 31.1-38.1%, which was significantly enhanced (p<0.05) compared to that in the oral control group (22.2%). Moreover, the relative bioavailability (RB) of tamoxifen was 1.40- to 1.72-fold greater than that in the control group. Silybinin (10 mg/kg) significantly increased the AUC(0-infinity) (p<0.05, 40.0%) of 4-hydroxytamoxifen, but the metabolite-parent ratio (MR) of 4-hydroxytamoxifen was significantly altered (p<0.05 for 10 mg/kg), implying that the formation of 4-hydroxytamoxifen was considerably affected by silybinin. The enhanced bioavailability of tamoxifen by silybinin might be due to the promotion of intestinal absorption in the small intestine and the reduction of first-pass metabolism of tamoxifen in the small intestine and in the liver. If these results are confirmed in clinical trials, the tamoxifen dosage should be adjusted when tamoxifen is administered with silybinin or silybinin-containing dietary supplements.