FEL performance achieved at PAL-XFEL using a three-chicane bunch compression scheme.

PAL-XFEL utilizes a three-chicane bunch compression (3-BC) scheme (the very first of its kind in operation) for free-electron laser (FEL) operation. The addition of a third bunch compressor allows for more effective mitigation of coherent synchrotron radiation during bunch compression and an increased flexibility of system configuration. Start-to-end simulations of the effects of radiofrequency jitter on the electron beam performance show that using the 3-BC scheme leads to better performance compared with the two-chicane bunch compression scheme. Together with the high performance of the linac radiofrequency system, it enables reliable operation of PAL-XFEL with unprecedented stability in terms of arrival timing, pointing and intensity; an arrival timing jitter of better than 15 fs, a transverse position jitter of smaller than 10% of the photon beam size, and an FEL intensity jitter of smaller than 5% are consistently achieved.

BCR/ABL level at 6 months identifies good risk CML subgroup after failing early molecular response at 3 months following imatinib therapy for CML in chronic phase.

It is unclear if patients with CML treated with imatinib who fail to achieve BCR/ABL transcript levels <10%(IS) at 3 months i.e. an early molecular response (EMR) have a better prognosis if they achieve a response by 6 months. We reviewed 320 patients with chronic myeloid leukemia (CML) in chronic phase receiving Imatinib therapy with 3 and 6 month BCR/ABL transcript levels available, and divided them into four groups. Group I (achieved an EMR at 3 months), Group II (did not achieve an EMR at 3 months, but achieved a transcript level of <1% at 6 months), Group III (did not achieve an EMR at 3 months, then at 6 months achieved a level between 1% and 10%) and Group IV (failed to achieve a response at 3 and 6 months). Compared to Group I, Group IV showed significantly worse freedom from treatment failure (FTF; 93.1% vs 69.0%, P < 0.001), progression free survival (97.7% vs 77.3%, P < 0.001) and overall survival (98.3% vs 78.9%, P < 0.001). While, group III showed inferior PFS (98.3% vs 90.4%, P = 0.013) and OS (97.7% vs 90.4%, P = 0.037), but no difference in FTF (93.1% vs 92.0%, P = 0.520). There were no significant differences between Groups I and II. A BCR/ABL transcript level at 6 months can identify a "good-risk" subgroup among patients who fail to achieve an EMR on Imatinib therapy for CML.

Ten-year comparison of all-cause mortality after endovascular or open repair of abdominal aortic aneurysms: a propensity score analysis.

BACKGROUND: This study aimed to compare the long-term survival after open (OS) or endovascular (EVAR) repair of abdominal aortic aneurysms (AAAs), exploring baseline factors that could affect long-term outcome. METHODS: We identified 774 patients (501 EVAR, 273 OS, during 1996-2004) with data on perioperative risk factors including 37 variables assessed with a standardized patient response instrument. Propensity score was used to adjust for baseline differences between the two cohorts. Matched cohorts survival analysis and Cox multivariate regression were performed. RESULTS: Median follow-up was 6.95 (interquartile range 4.46-9.27) years. EVAR patients were older [75.0 ± 7.7 (SD) vs. 71.3 ± 8.5 years, p < 0.001] and had a higher rate of previous myocardial infarction (39.3 vs. 25.3%, p < 0.001), pulmonary disease (25.9 vs. 18.3%, p = 0.020), and history of malignancy (5.0 vs. 1.8%, p = 0.039). The 30-day mortality was comparable (1.4% EVAR, 1.5% OS). Although the unadjusted survival rate was lower (median survival: 7.4 years EVAR, 8.8 OS, p = 0.011) and early (within 4 years) hazard was higher after EVAR (p = 0.003), no difference in survival was observed after propensity score-matching (p = 0.688) or propensity score-adjusted Cox regression (hazard ratio 1.01, 95 % confidence interval 0.82-1.25, p = 0.911, EVAR vs. OS). There was a trend toward higher hazard later in both groups. A multivariate Cox regression identified age, pulmonary disease, stroke, dialysis, oral anticoagulation, cardiac enlargement, and smoking history as variables associated with poor survival. Lipid-lowering medication was found to be protective. CONCLUSIONS: Over long-term follow-up, survivals after endovascular and open repair of AAA are similar. Baseline patient characteristics are correlated with survival, but whether attention to the modifiable risk factor can alter outcome remains to be defined.

The applicability of laparoscopic gastrectomy in the surgical treatment of giant duodenal ulcer perforation.

PURPOSE: The present study aims to provide an applicability of laparoscopic gastrectomy used in the treatment of giant duodenal ulcer perforation. METHODS: Between July 2010 and April 2011, laparoscopic distal gastrectomy with ROUX-EN-Y gastrojejunostomy and truncal vagotomy was performed in consecutive 5 patients with giant duodenal ulcer perforation. RESULTS: There was no conversion to open surgery. There was no severe postoperative complication. The days of normalization of leukocytosis were 3, 1, 2, 2, and 5, respectively. The times to first flatus were postoperative days 2, 3, 5, 2, and 3. The days of commencement of a soft diet were postoperative days 5, 5, 6, 5, and 5. They were discharged on postoperative days 9, 11, 20, 10, and 11. CONCLUSIONS: We suggest that laparoscopic surgery may be a good surgical method to improve surgical outcomes and is worth a try in experts.

A case of gastric adenocarcinoma presenting as meningeal carcinomatosis.

Leptomeningeal carcinomatosis occurs in approximately 5% of patients with cancer. The most common cancers involving the leptomeninges are breast, lung cancer and melanoma. However, gastric adenocarcinoma has been rarely reported with leptomeningeal carcinomatosis. The presenting manifestations are usually headache, visual disturbances and seizures. We report a case of leptomeningeal metastasis that presented as a gastric cancer. A 49-year-old woman was admitted to our hospital with the symptoms of headache and melena for 10 days. The endoscopy showed a thickening of the folds of the stomach compatible with the diagnosis of a Borrman type IV gastric cancer. The biopsy revealed a signet ring cell carcinoma. The MRI of brain showed no abnormal findings; however, the patient complained of an intractable persistent headache, nausea and vomiting on admission day 6. The cytology examination of the cerebrospinal fluid supported the diagnosis of metastatic signet ring cell carcinoma.

A phase II trial of docetaxel plus capecitabine in patients with previously treated non-small cell lung cancer.

BACKGROUND: A combination of docetaxel (T) and capecitabine (X) showed synergistic effects in preclinical studies and phase III randomized trials of metastatic breast cancer. We conducted this phase II study to examine its efficacy in previously treated non-small cell lung cancer (NSCLC) patients. METHODS: Patient eligibility required advanced NSCLC with measurable lesion(s), at least one prior regimen failure and Eastern Cooperative Oncology Group (ECOG) performance status 0-2. Treatment consisted of T 36 mg/m(2) i.v. on days 1 and 8 plus X 1000 mg/m(2) p.o. b.i.d. on days 1-14 of a 21-day cycle (level I) or T 30 mg/m(2) i.v. on days 1 and 8 plus X 625 mg/m(2) p.o. b.i.d. on days 1-14 of a 21-day cycle (level II). RESULTS: A total of 35 patients (M/F=24/11) were enrolled; 29 had received one prior regimen and 19 had received platinum-based regimens. Significant non-hematologic toxicities were observed after the treatment given at level I, including one treatment-related death. Subsequently 29 patients were treated at level II. The treatment at level II was well tolerated with grade 3 or 4 neutropenia only in 10%, grade 3 asthenia in 21% and stomatitis in 14% of patients. Four (15%) of 27 evaluable patients had partial response (PR) at level II and eight (30%) had stable disease (SD). CONCLUSIONS: The TX regimen showed modest antitumor effects in patients with previously treated NSCLC. For further studies, we recommend T 30 mg/m(2) i.v. on days 1 and 8 plus X 625 mg/m(2) p.o. b.i.d. on days 1-14 of a 21-day cycle.

A pilot trial of gemcitabine and vinorelbine plus capecitabine in locally advanced or metastatic nonsmall cell lung cancer.

OBJECTIVES: We conducted a pilot study of gemcitabine, vinorelbine and capecitabine combination to evaluate its toxicity and efficacy in chemo-naive patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) after a short phase IB trial. METHODS: Eligible chemo-naive patients with stage IIIB or IV NSCLC received outpatient administration of gemcitabine 900 mg/m2 and vinorelbine 25 mg/m2 intravenously on days 1 and 8, every 3 weeks, concurrently with capecitabine 1000 mg/m2 given orally twice a day on days 1 to 5 and 8 to 12 (dose level I), or days 1 to 6 and 8 to 13 (dose level II). RESULTS: Between November 2002 and December 2003, 19 patients participated in the study at either dose level I (7 patients) or dose level II (12 patients). The maximum tolerated dose, defined as the dose at which no more than 1 of 6 patients in a cohort experienced a dose-limiting toxicity (DLT) in the first cycle, was not established. However, 1 of 7 patients at dose level I, and 2 of 12 at dose level II experienced DLTs (ie, grade 3 hepatotoxicity in 2 patients, and grade 3 febrile neutropenia in 1 patient). In addition, 2 patients experienced treatment-related pneumonitis requiring mechanical ventilator support after the second course of therapy. Objective tumor response was observed in 5 (26.3%) of 19 patients. Further patient accrual was stopped according to the study design. CONCLUSIONS: This 3-drug combination showed disappointing antitumor activity against NSCLC with unexpected life-threatening pulmonary toxicity. No further investigation of this regimen is recommended for patients with NSCLC.

Phase II study of weekly irinotecan plus capecitabine for chemotherapy-naive patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: A Phase II study was conducted to evaluate the efficacy and toxicity of an irinotecan plus capecitabine combination, a new nonplatinum regimen, in chemonaive patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS: Between July 2003 and April 2004, 53 patients with a histologically confirmed diagnosis of NSCLC were enrolled. All but 5 patients were male, 52 (98%) had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1, 39 (74%) had AJCC Stage IV disease, and the median age was 61 years. Treatment consisted of intravenous irinotecan at a dose of 90 mg/m(2) on Days 1 and 8 and oral capecitabine at a dose of 1000 mg/m(2) twice daily on Days 1-14 of each 21-day cycle, given up to 12 cycles. RESULTS: Of 53 patients enrolled, 22 achieved objective tumor responses (all partial responses) for an overall response rate of 41.5% (95% confidence interval [95% CI], 28.2-54.8%). After a median follow-up of 17.4 months, the median survival was 14.6 months with a 1-year survival rate of 60.1% (95% CI, 46.9-73.4%) and a median progression-free survival of 5.1 months. Treatment was very well tolerated, with only 10% of patients experiencing NCI-CTC Grade 3 or 4 toxicities. The most common toxicities were hand-foot syndrome and diarrhea. In multiple logistic regression analysis for overall response, only the stage predicted for significantly better response (P = 0.04). Squamous cell carcinoma was marginally predictive for better response (P = 0.08). CONCLUSIONS: The irinotecan plus capecitabine regimen demonstrated an antitumor activity that is favorably comparable with other commonly used cisplatin-based regimens. Given the mild toxicity profile and favorable survival outcome, this nonplatinum regimen warrants further evaluation in a randomized trial.

A phase II study of dose-intensified weekly concomitant administration of cisplatin and irinotecan in chemonaive patients with extensive-disease small-cell lung cancer.

Irinotecan/cisplatin (IP) is an active regimen for extensive-disease small-cell lung cancer (ED-SCLC). However, the optimal dose/schedule is unsettled. To evaluate the efficacy and safety of a dose-intensified, weekly concomitant administration of IP, we conducted a phase II study in chemo-naive patients with ED-SCLC. Between October 2001 and February 2004, 37 patients were enrolled. Twenty-nine (78%) were male, 21 (57%) had ECOG PS 0 or 1, and the median age was 62 yr. The initial six patients received cisplatin 50 mg/m2 followed by irinotecan 90 mg/m2 iv on d 1 and 8 of a 21-d cycle (dose level I), with one treatment-related death, three febrile neutropenias. Thereafter, the doses of cisplatin and irinotecan were reduced to 40 mg/m2 and 80 mg/m2, respectively (dose level II). The treatment was continued for up to six cycles. The overall response rate was 97%, with a complete response (CR) rate of 26%. The median duration of response was 6.4 mo (range, 1.6-13.1 mo). At a median follow-up of 27.3 mo, the median survival time was 11.1 mo and 1- and 2-yr survival rates were 44.1% and 11.8%, respectively. The median progression-free survival (PFS) was 6.0 mo (range, 1.5-13.1 mo) and 1-year PFS rate was 7%. Major grade 3 or 4 toxicities included neutropenia (89%), anemia (59%), and diarrhea (27%). Despite of significant myelosuppresion, this dose-intensified weekly concomitant administration of cisplatin and irinotecan was feasible. This dose-schedule showed promising activity with high rate of complete remission in patients with ED-SCLC.

Weekly docetaxel in combination with capecitabine in patients with metastatic gastric cancer.

Docetaxel (T) and capecitabine (X) are active agents against gastric cancer with synergistic antitumor effects. We conducted the current phase II study to assess the response rate and toxicity of combination TX regimen in patients with metastatic gastric cancer. Eligible patients were treated with docetaxel (36 mg/m2 intravenously) on days 1 and 8 and capecitabine (1000 mg/m2 orally twice a day) on days 1-14 of a 3-week schedule until progression occurred. From December 2001 to May 2003, 55 patients with median age of 54 years (range, 22-73 years) were enrolled; 47 patients had measurable lesions. A total of 358 courses of treatment were given, with a median of 5 (range, 1-22+) per patient. Objective responses were documented in 19 of 47 patients with measurable lesions (response rate, 40.4%; 95% confidence interval [CI], 25.9-54.9), with the median response duration of 5.6 months (range, 2.1-13.6+). At a median follow up of 15.9 months for all of 55 study patients, the median time to progression and survival were 4.5 months (95% CI, 3.4-5.6) and 12.0 months (95% CI, 7.5-16.6), respectively. Hematologic toxicities were mild to moderate, and the observed grade 3 nonhematologic toxicities, the most frequent of which was stomatitis, were generally manageable. Four patients experienced pneumonitis, but all of them responded to steroid treatment. The TX regimen was relatively well tolerated and effective against metastatic gastric cancer, with the added advantage of being an outpatient regimen.

Gefitinib as a first-line therapy of advanced or metastatic adenocarcinoma of the lung in never-smokers.

PURPOSE: A subset of patients with adenocarcinoma of the lung who had never smoked cigarettes showed excellent tumor responses to gefitinib therapy. To evaluate the efficacy of gefitinib as a first-line therapy in this subgroup of patients, we conducted a phase II study. EXPERIMENTAL DESIGN: Eligible patients had no smoking history, stage IIIB or IV adenocarcinoma, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate organ functions. Treatment consisted of daily oral administration ofF 250 mg gefitinib for 28 days until disease progression. Responses were assessed after every two cycles of therapy. RESULTS: Of 37 patients enrolled, 36 were assessed for response. Twenty-five patients (69%) had partial response, 4 (11%) had stable disease, and 7 (19%) had progressive disease. Of 10 patients with evaluable brain metastases, 7 had objective responses in both intracranial and extracranial lesions, 1 had stable disease in the brain and dramatic response in the extracranial lesions, and 2 had progressive disease in both sites. After a median follow-up of 48 weeks (range, 4-70 weeks), 26 patients had disease progression, with median progression-free survival of 33 weeks, and 9 patients died, all due to disease progression. The median survival time has not been reached yet but the estimated 1-year survival rate was 73%. Common toxicities were skin rash and mild diarrhea but there was no significant hematologic toxicity. CONCLUSIONS: Gefitinib showed very dramatic antitumor activity, even in the brain, with unprecedented survival outcome in never-smoker adenocarcinoma patients. These data support the use of gefitinib as a first-line therapy in this particular subgroup.

Fourier transformation of arterial Doppler waveforms of the lower extremity.

PURPOSE: Although it is well known that the normal, triphasic pulsatile arterial Doppler waveform changes in shape as flow is impaired, interpretation of the waveform has largely been subjective. We aimed to describe the Doppler waveforms of the lower extremity objectively using Fourier transformation. METHODS: Sixty-eight zero-crossing detector arterial recordings from 25 lower extremities were grouped as follows: group 1, no ischemic symptoms with an ankle-brachial index (ABI) > 0.9 (n = 17, 8 limbs); group 2, no ischemic symptoms with ABI < 0.9 (n = 18, 5 limbs); group 3, symptoms of claudication (n = 19, 7 limbs); group 4, rest pain or tissue loss (n = 14, 5 limbs). The waveforms were Fourier transformed and their amplitudes and phases were compared up to the third harmonic (H3). RESULTS: Amplitudes of both the fundamental (H1) and second harmonic (H2) were predominant in group 1. In contrast, amplitudes of the H2 and H3 decreased with altered flow (p < 0.0001 for group 1 versus others). The phases of the H1 and H2 were delayed with altered flow (p < 0.05 for group 1 versus others). Phases of the H1 were different between group 2 and 4 (p < 0.05). The difference of phase between the H3 and H1 was shortened with altered flow (p < 0.05 for group 1 or 2 versus group 4). Multivariate analysis revealed that the relative amplitudes of the H2 and H3, the phases of the H1 and H2, and the relative phase of the H3 were significant discriminators among the groups. CONCLUSION: Abnormal waveforms could be characterized by the predominant amplitude of the H1, phase delay of the H1 and H2, and shortening of the relative phase of the H3. These parameters may be useful in the evaluation of Doppler waveforms in patients with peripheral arterial disease.

Weekly irinotecan in patients with metastatic gastric cancer failing cisplatin-based chemotherapy.

BACKGROUND: The goal of this study is to determine the efficacy and toxicity of weekly irinotecan as second-line chemotherapy in advanced gastric cancer after failure of cisplatin-based regimen. METHODS: Gastric cancer patients failing cisplatin-based chemotherapy received 125 mg/m(2) of irinotecan weekly for 4 weeks followed by 2-week rest, until disease progression. RESULTS: Thirty-seven patients were enrolled into this study. The objective response was documented in seven of 35 patients with measurable lesion (response rate 20%, 95% CI: 6.1-33.9). Eight patients (22.9%) had stable disease and overall tumor control rate was 42.9%. The disease remained stable in both of two patients without measurable disease. At a median follow-up duration of 15.8 months, median time to progression and overall survival were 2.6 months (95% CI: 2.4-2.8) and 5.2 months (95% CI: 3.6-6.7), respectively. Neutropenia and diarrhea were the main toxicities. Among 37 patients treated, grade 3/4 (G3/4) neutropenia occurred in 43.2/24.3% of patients, respectively, and was accompanied with fever in three patients. Non-hematologic toxicities consisted mainly of delayed diarrhea (G3/4, 18.9/0%) and nausea/vomiting (G3/4, 18.9/0%). These toxicities were manageable and there was no treatment-related death. CONCLUSIONS: This weekly schedule of irinotecan was modestly active against cisplatin-refractory gastric cancer and relatively well-tolerated with appropriate dose modification.

A phase II study of weekly docetaxel plus capecitabine for patients with advanced nonsmall cell lung carcinoma.

BACKGROUND: Docetaxel is an active agent in advanced nonsmall-cell lung carcinoma (NSCLC) and demonstrates preclinical and clinical synergism with capecitabine. We conducted the current Phase II study to evaluate the efficacy and safety of the docetaxel/capecitabine combination in chemotherapy-naive patients with advanced NSCLC. METHODS: Eligibility required Stage IIIB or IV NSCLC, bidimensionally measurable disease, and an Eastern Cooperative Oncology Group performance score of 2 or lower. Treatment consisted of docetaxel 36 mg/m(2) intravenously on Days 1 and 8 plus capecitabine 1000 mg/m(2) orally twice per day on Days 1-14 of a 21-day cycle, for a maximum of 6 cycles. RESULTS: Of 39 patients enrolled, 39 and 36 patients were evaluated for toxicity and response, respectively. The overall response rate was 53% (95% confidence interval [CI], 37-69%) with 19 partial responses (no complete response). The median duration of response was 6.2 months (range, 2.1-15.7 months). At a median follow-up of 14.2 months, 19 patients died. The median overall survival time was 17.8 months, with a 1-year survival rate of 56.4% (95% CI, 40.9-72.0%). There were two treatment-related deaths (one death due to pneumonia and one due to sepsis). Hematologic toxicity was mild to moderate. Thirteen percent of the patients had Grade 3 or 4 neutropenia. However, Grade 2 or 3 nonhematologic toxicities were frequent, which included asthenia (51%), stomatitis (33%), hand-foot syndrome (33%), and diarrhea (29%). CONCLUSIONS: The docetaxel/capecitabine combination showed promising antitumor activity for chemotherapy-naive patients with advanced NSCLC, However, it was frequently associated with moderate-to-severe nonhematologic toxicities, suggesting clinical synergism in both efficacy and toxicity. Further adjustment of the dose schedule is recommended to maximize the therapeutic index.