Byung Geun Kim

Second-Line Treatment With a Combination of Continuous 5-Fluorouracil, Doxorubicin, and Mitomycin-C (Conti-Fam) in Gemcitabine-Pretreated Pancreatic and Biliary Tract Cancer

Background:Gemcitabine-based chemotherapy is a commonly used first-line treatment for patients with pancreatic and biliary tract cancer. However, a standard second-line chemotherapy regimen has yet to be developed after gemcitabine treatment. We attempted to evaluate the efficacy and safety of a combination of continuous 5-fluorouracil, doxorubicin, and mitomycin-C (conti-FAM) as a second-line treatment in pancreatic and biliary tract cancer. Methods:Patients with advanced pancreatic or biliary tract cancer who were previously treated with gemcitabine-based chemotherapy were enrolled in the study. Chemotherapy was administered as follows: 5-fluorouracil, 800 mg/m2 on days 1 to 5 over 10 hours; mitomycin-C, 8 mg/m2 on day 1; and doxorubicin, 30 mg/m2 on day 1 every 4 weeks. Results:A total of 31 patients received 95 cycles of chemotherapy. Fifteen of the patients had pancreatic cancer. Eleven of the patients had cholangiocarcinoma. Gallbladder cancer was observed in 5 patients. Four (12.9%) patients evidenced partial responses. Eight patients (25.8%) had stable disease. The median time to progression and overall survival time were 2.3 (95% CI: 1.0–3.6) months and 6.7 (95% CI: 4.4–9.0) months, respectively. Major hematologic toxicities included grade 1 to 2 anemia (64.2%), neutropenia (32.6%), thrombocytopenia (20%), and grade 3 to 4 neutropenia (10.5%). The most frequently detected nonhematological toxicities were grade 2 and 3 nausea/vomiting (35.5%). One patient was diagnosed with hemolytic uremic syndrome after 8 cycles of treatment. Conclusion:The conti-FAM regimen seems to constitute a safe and feasible salvage therapy in patients with advanced bilio-pancreatic cancer who had been treated previously via gemcitabine-based chemotherapy.

Clinicopathological significance of altered Notch signaling in extrahepatic cholangiocarcinoma and gallbladder carcinoma

AIM To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma. METHODS One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks. Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies. We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining. Coexistent nuclear localization was evaluated. Clinicopathological parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4. RESULTS Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells, as well as showing weak cytoplasmic expression in non-neoplastic cells. By semiquantitative evaluation, positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%), Notch receptor 2 in 97 (88.2%), Notch receptor 3 in 97 (88.2%), Notch receptor 4 in 103 (93.6), and DLL4 in 84 (76.4%). In addition, coexistent nuclear localization was noted [Notch receptor 1; 18 cases (18.8%), Notch receptor 2; 40 (41.2%), Notch receptor 3; 32 (33.0%), Notch receptor 4; 99 (96.1%), DLL4; 48 (57.1%)]. Notch receptor 1 expression was correlated with advanced tumor, node, metastasis (TNM) stage (P = 0.043), Notch receptor 3 with advanced T stage (P = 0.017), tendency to express in cases with nodal metastasis (P = 0.065) and advanced TNM stage (P = 0.052). DLL4 expression tended to be related to less histological differentiation (P = 0.095). Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P = 0.027) and Notch receptor 4 with less histological differentiation (P = 0.036), while DLL4 tended to be related inversely with T stage (P = 0.053). Coexistent nuclear localization of DLL4 was related to poor survival (P = 0.002). CONCLUSION Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression, and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma.

A comparison of the BISAP score and serum procalcitonin for predicting the severity of acute pancreatitis

Background/Aims The bedside index of severity in acute pancreatitis (BISAP) is a new, convenient, prognostic multifactorial scoring system. As more data are needed before clinical application, we compared BISAP, the serum procalcitonin (PCT), and other multifactorial scoring systems simultaneously. Methods Fifty consecutive acute pancreatitis patients were enrolled prospectively. Blood samples were obtained at admission and after 48 hours and imaging studies were performed within 48 hours of admission. The BISAP score was compared with the serum PCT, Ransons score, and the acute physiology and chronic health examination (APACHE)-II, Glasgow, and Balthazar computed tomography severity index (BCTSI) scores. Acute pancreatitis was graded using the Atlanta criteria. The predictive accuracy of the scoring systems was measured using the area under the receiver-operating curve (AUC). Results The accuracy of BISAP (≥ 2) at predicting severe acute pancreatitis was 84% and was superior to the serum PCT (≥ 3.29 ng/mL, 76%) which was similar to the APACHE-II score. The best cutoff value of BISAP was 2 (AUC, 0.873; 95% confidence interval, 0.770 to 0.976; p < 0.001). In logistic regression analysis, BISAP had greater statistical significance than serum PCT. Conclusions BISAP is more accurate for predicting the severity of acute pancreatitis than the serum PCT, APACHE-II, Glasgow, and BCTSI scores.

A phase II study of irinotecan with biweekly, low dose leucovorin and bolus and continuous infusion 5-fluorouracil (modified FOLFIRI) as first line therapy for patients with recurrent or metastatic gastric cancer.

Background:To determine the activity and toxicities of a low-dose leucovorin plus 5-fluorouracil (5-FU) regimen, combined with irinotecan and administered every 2 weeks (modified FOLFIRI), as a first-line therapy for patients with advanced gastric cancer. Method:Patients were treated with cycles of 150 mg/m2 irinotecan on day 1 plus 50 mg of LV, followed by a 400 mg/m2 5-FU bolus and a 22-hour continuous infusion of 600 mg/m2 5-FU on days 1 and 2. Results:The median patient age was 55 years (range, 29–75 years), and 77% (34/44) of the patients had a performance status (Eastern Cooperative Oncology Group) of 0 or 1. Of the 44 patients evaluated for their tumor response, 3 patients (6.8%) and 14 patients (31.8%) achieved a complete and partial response, respectively, with an overall response rate of 38.6% (95% confidence interval, 23.7%–53.6%). 13 patients (29.6%) evidenced a stable disease, and 14 patients (31.8%) progressed during the course of the treatment. The median time to progression and overall survival time were 4.9 months (range, 0.9–22.8 months) and 10.3 months (range, 1.2–29.0 months) from the start of the chemotherapy, respectively. A total of 293 cycles were assessed for toxicity. The major hematologic toxicities included grade 1 to 2 anemia (27.6%), neutropenia (48.8%), and grade 3 to 4 neutropenia (12.6%). There were 7 cycles of neutropenic fever. Nonhematological toxicities were observed grade 3 vomiting (6.8%), grade 3 diarrhea (4.5%), and grade 3 mucositis (2.3%). We noted no treatment-related deaths. Conclusions:The modified FOLFIRI regimen—lowering of irinotecan and LV doses—is a safe and feasible regimen as a first-line therapy for patients with recurrent or metastatic gastric cancer.

Efficacy of I-scan endoscopy in the diagnosis of gastroesophageal reflux disease with minimal change.

Background/Aims The aim of the study was to evaluate the efficacy of i-scans for the diagnosis of gastroesophageal reflux disease, especially where only minimal change is involved. Methods The esophageal mucosa was inspected using an i-scan following conventional white light endoscopy. The examination with iscan was performed under tone enhancement (TE) esophagus (e) mode. Patients with subtle distal esophageal mucosal changes without definite mucosal breaks, such as blurring of Z-line (B), mucosal coarseness (C), hyperemic or purplish discoloration (D), erythema (E), ectopic gastric mucosal islet (I) and mixed type were classified as minimal change. Results A total of 156 patients were included. Using i-scan endoscopy, the number of minimal change was found to further increase from 94 (conventional endoscopy; 19B, 9C, 29D, 13E, 5I, 19 mixed type) to 109 (i-scan; 15B, 8C, 29D, 16E, 5I, 36 mixed type). And 14 patients who had single type by conventional endoscopy were converted to mixed type after i-scan. Therefore, 29 of 156 patients were upgraded after i-scan, they were account for 19% (p<0.0001; 95% confidence interval, 0.13 to 0.25). Conclusions The use of i-scan endoscopy significantly improves the identification of minimal change and helps to identify more precisely the type of minimal change.

Splenic infarction associated with sorafenib use in a hepatocellular carcinoma patient

Sorafenib, a multitargeted tyrosine kinase inhibitor, has been shown to improve survival in patients with advanced hepatocellular carcinoma (HCC). As the clinical use of sorafenib increases, many adverse effects have been reported, such as hand-foot skin reaction, diarrhea, anorexia, asthenia, alopecia, weight loss, hypertension and arterial thromboembolism. However, there are no prior reports of splenic infarction as an adverse effect of sorafenib. Here, a case of splenic infarction in a patient with HCC who was treated with sorafenib is reported. The patient had no other predisposing factors to explain the splenic infarction except for the administration of sorafenib. The splenic infarction improved after sorafenib was discontinued; however, the HCC progressed.

Segmental tissue Doppler image-derived tei index in patients with regional wall motion abnormalities.

Background and Objectives Although the Tei index is a useful predictor of global ventricular function, it has not been investigated at the level of regional myocardial function. We therefore investigated the segmental tissue Doppler image derived-Tei index (TDI-Tei index) in patients with regional wall motion abnormalities. Subjects and Methods We prospectively studied 17 patients (mean age 62±9 years, 5 women) with left ventricular (LV) regional wall motion abnormalities. The Tei index, defined as the sum of isovolumetric contraction time (IVCT) and isovolumetric relaxation time (IVRT) divided by ejection time (ET), was measured in the basal and mid segments of the LV walls from standard apical views (4-, 2-, and 5-chamber views). We also obtained TDI velocity data in each segment. LV wall motion was classified as normal, hypokinetic, or akinetic, based on visual analysis. The TDI-Tei index, peak systolic myocardial velocity (Sm), early diastolic myocardial velocity (Em), and late diastolic myocardial velocity (Am) were analyzed in a total of 203 segments. Results Mean LV ejection fraction was 41.8±8.5%. TDI-Tei indices of dysfunctional segments (akinesis or hypokinesis, n=63) were significantly higher than those of normal segments (n=140) (0.714±0.169 vs. 0.669±0.135, p=0.041, respectively). Average values of TDI-Tei index, Sm, Em, and Am were 0.742±0.201, 4.206±1.336, 5.258±1.867, and 5.578±2.354 in akinetic segments; 0.677±0.101, 4.908±1.615, 5.369±2.121, and 5.542±2.492 in hypokinetic segments; and 0.669±0.135, 5.409±1.519, 6.108±2.356, and 6.719±2.466 in normal segments, respectively. A significant negative correlation was apparent between the TDI-Tei index and Sm (r=-0.302, p<0.001). Conclusion These data suggest that the value of the segmental TDI-Tei index differs significantly according to regional function grade.