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Selected AbstractsResection surgery with neoadjuvant chemoradiotherapy improves outcomes of patients with T4 esophageal carcinomaDISEASES OF THE ESOPHAGUS, Issue 2 2003T. Noguchi SUMMARY The prognosis of patients with T4 esophageal carcinoma is poor, and thus an effective treatment needs to be established. The present study assessed the effect of chemoradiotherapy (CRT), postoperative morbidity and mortality, and survival time in 41 patients with T4 esophageal carcinoma. Of these, 24 received CRT followed by surgery (group A) and the remaining 17 were treated with CRT alone (group B). Postoperative complications in group A were compared with 251 patients (group C) who underwent surgery without CRT during the same period. Postoperative complications were more frequent in group A than group C (29.2%vs 8.4%, P < 0.05). The overall median survival of group A was statistically longer than that of group B (13.8 months and 3.3 months respectively, P < 0.001). Complete histologic response (grade 3) was documented in 4 group A patients (16.7%). The overall median survival of grade 3 patients was statistically longer than the rest of group A (38.9 months vs 8.8 months, P < 0.05). The data confirm that chemoradiotherapy creates tumor regression in some patients and allows resection surgery in T4 esophageal carcinoma. Moreover, surgery with CRT confers a survival advantage in T4 esophageal carcinoma. [source] Final report of RTOG 9610, a multi-institutional trial of reirradiation and chemotherapy for unresectable recurrent squamous cell carcinoma of the head and neck,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2008Sharon A. Spencer MD Abstract Background. Our objectives were to determine the incidence of acute and late toxicities and to estimate the 2-year overall survival for patients treated with reirradiation and chemotherapy for unresectable squamous cell carcinoma of the head and neck (SCCHN). Methods. Patients with recurrent squamous cell carcinoma or a second primary arising in a previously irradiated field were eligible. Four weekly cycles of 5-fluorouracil 300 mg/m2 IV bolus and hydroxyurea 1.5 g by mouth were used with 60 Gy at 1.5 Gy twice-daily fractions. Toxicity was scored according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer (RTOG/EORTC) criteria. Results. Seventy-nine of the 86 patients enrolled were analyzable. The worst acute toxicity was grade 4 in 17.7% and grade 5 in 7.6%. Grade 3 and 4 late toxicities were found in 19.4% and 3.0%, respectively. The estimated cumulative incidence of grade 3 to 4 late effects occurring at >1 year was 9.4% (95% confidence interval [CI]: 0, 19.7) at 2 and 5 years. The 2- and 5-year cumulative incidence for grade 4 toxicity was 3.1% (95% CI: 0, 9.3). The estimated 2- and 5-year survival rates were 15.2% (95% CI: 7.3, 23.1) and 3.8% (95% CI: 0.8, 8.0), respectively. Patients who entered the study at >1 year from initial radiotherapy (RT) had better survival than did those who were <1 year from prior RT (median survival, 9.8 months vs 5.8 months; p = .036). No correlation was detected between dose received and overall survival. Three patients were alive at 5 years. Conclusion. This is the first prospective multi-institutional trial testing reirradiation plus chemotherapy for recurrent or second SCCHN. The approach is feasible with acceptable acute and late effects. The results serve as a benchmark for ongoing RTOG trials. © 2007 Wiley Periodicals, Inc. Head Neck 2008 [source] Could immunosuppressive drugs reduce recurrence rate after second resection for crohn disease?INFLAMMATORY BOWEL DISEASES, Issue 5 2004Arnaud Alves MD Abstract Background: The aim of this study was to assess the possible benefit of postoperative immunosuppressive drugs administration (ie, azathioprine, 6-mercaptopurine, or methotrexate) on long-term surgical recurrence rate after second anastomotic ileocolonic resection. Methods: From 1984 to 2000, 26 patients with CD underwent second resection for ileocolonic anastomotic recurrence. There were 14 women and 12 men (mean age ± SD: 34 ± 9 years). Two groups of patients were compared according to the postoperative treatment: immunosuppressive (IS) drugs group was composed of 14 patients, and control group was composed of 12 patients receiving either salicylates (n = 5) or no treatment (n = 7). Results: Clinical recurrence rate at 3 years was significantly lower in the IS group than in the control group (3/12, 25% vs 6/10, 60%; P < 0.05). Although not significant, after a mean follow-up of 80 ± 46 months (extr. 17,178 months) after the second resection, clinical recurrence rate at follow-up was also lower in IS group (6/14, 43%) than in control group (9/12, 75%). The mean delay of recurrence was similar in both groups (27 ± 13 months vs 28 ± 21; NS). A third intestinal resection was performed less frequently in the IS group than in control group (2/14, 17% vs 7/12, 58%; P < 0.02). Conclusions: In patients treated with IS drugs, the rate of postoperative recurrence after second ileocolonic CD resection is lower than in untreated patients. Our results suggest that IS drugs should be evaluated prospectively for prevention of second postoperative CD recurrence. [source] Seroprevalence of hepatitis C in patients with type 2 diabetes mellitus and non-diabetic on haemodialysisINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2006S. Ocak Summary Type 2 diabetes mellitus (DM) has emerged as the commonest cause of end-stage renal disease. Haemodialysis (HD) treatment constitutes a high-risk environment for the transmission of hepatitis C virus (HCV). The aim of this study was to establish a potential relationship between type 2 DM and HCV infection in HD patients. Of the 267 HD patients, 67 (25.1%) had type 2 DM and 200 (74.9%) were with diverse aetiology for end-stage renal disease. The serum markers of HCV infection were tested by a second-generation enzyme-linked immunosorbent assay test for antibodies and by qualitative reverse-transcription polymerase chain reaction technique for viral RNA. The overall prevalence of anti-HCV antibodies and HCV RNA was found to be 12.7% (34/267) and 10.1% (27/267), respectively. Patients with type 2 DM were found to have a higher HCV prevalence compared with non-diabetic patients [20.8% (14/67) vs. 10% (20/200)] (p < 0.05). The mean period on dialysis of anti-HCV-positive patients with type 2 DM was shorter than that observed for anti-HCV-positive non-diabetic patients (43.9 ± 9.8 months vs. 59.7 ± 28.4 months) (p < 0.05). This study has shown that although the period on dialysis of diabetic patients are shorter than non-diabetic patients, the prevalence of HCV in HD patients with type 2 DM is higher than that detected in non-diabetic HD patients. [source] Lifetime performances in Carora and Holstein cows in VenezuelaJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 2 2002RITA RIZZI A study was conducted in the Central-western region of Venezuela to investigate the lifetime performances of 7918 Carora and 3501 Holstein cows under two different levels of management (low and high) and covering a period from 1961 to 1995. Traits analysed were: herd life, productive life, number of calvings, lifetime milk yield, days in lactation over all lactations and daily milk yield. In Carora cows born from 1961 to 1986 a decrease in herd life, productive life and number of calvings was observed, whereas cows born between 1971 and 1972 showed the lowest lifetime productive traits. Performances of Holstein cows born in the 1981,1986 period were analysed and all traits decreased during this time period. In low level herds, Holsteins remained longer (98.5 months vs. 83.3 in herd life; 69.5 vs. 54.3 months in productive life) and had higher lifetime yield (20 925 vs. 18 589 kg) than those in high level herds, but daily milk yield was lower (8.4 vs. 11.0 kg/day). All lifetime performances were higher for Carora cows under the high level management: 116.8 vs. 112.1 months of herd life, 81.8 vs. 77.1 months of productive life, 5.8 vs. 5.2 calvings, 1616 vs. 1299 days of lactation, 16 194 vs. 11 912 kg of milk over all lactations and 6.5 vs. 4.6 kg milk/day. Survival estimates for year of birth were more variable in Holsteins than in Carora cows. Management influenced survival in Holsteins only, the low level showing higher values. Lebensleistung von Carora und von Holstein Kühen in Venezuela In der Zeitspanne zwischen 1961 und 1995 wurde in der zentral-westlichen Region Venezuelas Untersuchungen durchgeführt, um die Lebensleistung von 7918 Carora- und von 3501 Holstein-Kühen in zwei unterschiedlichen Managementstufen (niedrige und hohe) zu untersuchen. Die analysierten Aspekte bezogen sich auf: Alter beim Ausscheiden, Nutzungsdauer, Anzahl an Abkalbungen, Lebensleistung-Milch, Gesamtlaktationstage über alle Laktationen, tägliche Milchmenge. Bei den Carora Kühen, die zwischen 1961 und 1986 geboren wurden, beobachtete man eine Abnahme der Alters, der Nutzungsdauer und Anzahl an Abkalbungen, während man die niedrigsten Milchleistungen in Carora Kühen feststellte, die zwischen 1971 und 1972 geboren wurden. Die Holstein-Kühe, die im Zeitraum 1981,1986 geboren wurden zeigten in allen Bereichen eine Abnahme. Bei Herden in der niedrigen Managementstufe lebten die Holstein Kühe länger (98,5 Monate im Vergleich zu 83,3 Monate Alter beim Ausscheiden; 69,5 Monate im Vergleich zu 54,3 Monate Nutzungsdauer) und brachten eine höhere Lebensleistung-Milch (20 925 kg gegenüber 18 589 kg) im Vergleich zu den Kühen in Herden mit hohem Management, obwohl die Milchproduktion pro Tag geringer war (8,4 kg/Tag im Vergleich zu 11,0 kg/Tag). Alle Lebenszeitleistungen der Carora Kühe bei hoher Managementstufe waren dagegen höher: Alter beim Abgang 116,8 Monate im Vergleich zu 112,1 Monate, 81,8 Monate im Vergleich zu 77,1 Monate Nutzungsdauer, 5,8 Kalbungen im Vergleich zu 5,2 Kalbungen, 1616 Gesamtlaktationstage im Vergleich zu 1299 Gesamtlaktationstage, 16 194 kg Lebensleistung-Milch im Vergleich zu 11 912 kg und 6,5 kg Milch pro Tag im Vergleich zu 4,6 kg. Die Werte des Überlebens in Bezug auf das Geburtsjahr waren bei den Holstein Kühen variabler als bei den Carora Kühen. Die Anwendung von unterschiedlichen Managementstufen beeinflusste das Weiterleben nur bei den Holstein Kühen, da diese bei niedrigerer Managementstufe eine höhere Leistung zeigten. [source] Intra-arterial 5-fluorouracil/interferon combination therapy for hepatocellular carcinoma with portal vein tumor thrombosis and extrahepatic metastasesJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 6 2010Yoshio Katamura Abstract Background and Aims:, We investigated the efficacy of intra-arterial 5-fluorouracil (5-FU) and systemic interferon (IFN)-, (5-FU-IFN) in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis in the first branch or trunk (Vp3/4) and extrahepatic metastases. Methods:, We examined 17 HCC patients with Vp3/4 and extrahepatic metastases (meta group) and 31 HCC patients with Vp3/4 (non-meta group). Baseline intrahepatic tumor factors and the hepatic reserve were similar between groups. The extrahepatic metastases of the meta group were not considered prognostic factors. Following the administration of 5-FU/IFN to all patients, we compared the survival rates, response, time to progression (TTP), and safety between groups. Results:, For intrahepatic HCC, complete response, partial response, stable disease, progressive disease, and drop out were observed in no (0%), one (6%), seven (41%), nine (53%), and no (0%) patients of the meta group, and in five (16%), seven (23%), 13 (42%), five (16%) and one (3%) patient of the non-meta group, respectively. The response rate was significantly lower in the meta group (6% vs 39%, P = 0.018). The median TTP of intrahepatic HCC and the median survival time were significantly shorter in the meta group than in the non-meta group (1.6 vs 6.3 months, P = 0.0001, and 3.9 months vs 10.5 months, P < 0.0001, respectively). The multivariate analysis showed that the absence of extrahepatic metastases was a significant and independent determinant of both TTP of intrahepatic HCC (P < 0.001) and overall survival (P < 0.001). No patient died of extrahepatic HCC-related disease. Conclusions:, The efficacy of 5-FU/IFN for advanced HCC with Vp3/4 and extrahepatic metastases was markedly limited. [source] Clinical manifestations and survival of hepatocellular carcinoma patients with peritoneal metastasisJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 5 2009Chien-Chu Lin Abstract Background and Aim:, Peritoneal metastasis is an uncommon manifestation of hepatocellular carcinoma (HCC). The aim of the present paper was to investigate the characteristics and survival of HCC patients with peritoneal metastases. Methods:, From January 1985 to December 2004, we retrospectively reviewed the records of 53 Taiwanese HCC patients with peritoneal metastases. Results:, Peritoneal metastases were detected at the time of HCC diagnosis (synchronously) in 10 patients and after the initial therapy for the primary tumors (metachronously) in 43 patients. The mean time for development of the metachronous peritoneal metastases was similar whether the primary cancer was treated with surgery (24 months) or transarterial chemoembolization (22.2 months). The single patient whose primary cancer was treated with supportive care alone developed peritoneal metastasis only 7.5 months after detection of the primary cancer. Surgical resection of the peritoneal metastases was possible in two-thirds of the 43 metachronous patients. The median survival for those who received surgery for these metastases was 12.5 months vs. 2.1 months for those without surgery (P = 0.0013). However, there was no difference in survival if patients were stratified to Child-Pugh grade. Conclusions:, Peritoneal metastases of HCC are rare and can occur synchronously or metachronously. Though increased long-term survival was found in patients who had surgical removal of peritoneal metastases, the main determinant of better survival is Child-Pugh grade. [source] Motivation for Alcohol Becomes Resistant to Quinine Adulteration After 3 to 4 Months of Intermittent Alcohol Self-AdministrationALCOHOLISM, Issue 9 2010Frederic W. Hopf Background:, Continued consumption of alcohol despite deleterious consequences is a hallmark of alcoholism and represents a critical challenge to therapeutic intervention. Previous rat studies showed that enduring alcohol self-administration despite pairing alcohol with normally aversive stimuli was only observed after very long-term intake (>8 months). Aversion-resistant alcohol intake has been previously interpreted to indicate pathological or compulsive motivation to consume alcohol. However, given the time required to model compulsive alcohol seeking in previous studies, there is considerable interest in developing more efficient and quantitative rodent models of aversion-resistant alcohol self-administration. Methods:, Outbred Wistar rats underwent 3 to 4 months or approximately 1.5 months of intermittent, home-cage, two-bottle access (IAA) to 20% alcohol (v/v) or water. Then, after brief operant training, the effect of the bitter-tasting quinine (0.1 g/l) on the motivation to seek alcohol was quantified via progressive ratio (PR). Motivation for quinine-adulterated 2% sucrose under PR was assayed in a separate cohort of 3 to 4 months IAA rats. The effects of quinine on home-cage alcohol consumption in IAA rats and rats with continuous access to alcohol were also examined. Finally, a dose,response for quinine taste preference in IAA and continuous-access animals was determined. Results:, Motivation for alcohol after 3 to 4 months IAA, measured using an operant PR procedure, was not altered by adulteration of alcohol with 0.1 g/l quinine. In contrast, after 3 to 4 months of IAA, motivation for sucrose under PR was significantly reduced by adulteration of sucrose with 0.1 g/l quinine. In addition, motivation for alcohol after only approximately 1.5 months IAA was significantly reduced by adulteration of alcohol with 0.1 g/l quinine. Furthermore, home-cage alcohol intake by IAA rats was insensitive to quinine at concentrations (0.01, 0.03 g/l) that significantly reduced alcohol drinking in animals with continuous access to alcohol. Finally, no changes in quinine taste preference after 3 to 4 months IAA or continuous access to alcohol were observed. Conclusions:, We have developed a novel and technically simple hybrid operant/IAA model in which quinine-resistant motivation for alcohol is evident after an experimentally tractable period of time (3 to 4 months vs. 8 months). Quinine dramatically reduced sucrose and water intake by IAA rats, indicating that continued responding for alcohol in IAA rats despite adulteration with the normally aversive quinine might reflect maladaptive or compulsive motivation for alcohol. This model could facilitate identification of novel therapeutic interventions for pathological alcohol seeking in humans. [source] Safety and efficacy of curative intent surgery for peri-ampullary liver metastasisJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2010Mechteld C. de Jong MD Abstract Introduction The management of patients with peri-ampullary liver metastasis remains controversial. We sought to assess the safety and efficacy of curative intent surgery for peri-ampullary liver metastasis. Methods Between 1993 and 2009, 40 patients underwent curative intent surgery (resection and/or radiofrequency ablation (RFA)) for peri-ampullary liver metastasis. Clinicopathologic and outcome data were collected and analyzed. Results Location of the primary tumor was pancreas head (n,=,20), ampulla of Vater (n,=,10), distal bile duct (n,=,5), or duodenum (n,=,5). Most patients (n,=,27) presented with synchronous disease, while 13 patients presented with metachronous disease following a median disease-free interval of 22 months. Most patients (n,=,25) presented with hepatic metastasis from pancreaticobiliary origin (pancreatic or distal common bile duct) compared with 15 patients who had metastasis from an intestinal-type primary (ampullary or duodenal). There were no differences in metastatic tumor number or size between these groups (P,>,0.05). Post-operative morbidity and mortality was 30% and 5% respectively. Overall 1- and 3-year survival was 55% and 18%. Patients who underwent resection of liver metastasis from intestinal-type tumors experienced a longer survival compared with patients who had pancreaticobiliary lesions (median: 13 months vs. 23 months; P,=,0.05). Conclusion Curative intent surgery for peri-ampullary liver metastasis was associated with post-operative morbidity and a 5% mortality rate. Although the overall survival benefit was modest, patients with liver metastasis from intestinal-type tumors experienced improved survival following resection of liver metastasis compared with pancreaticobiliary lesions. J. Surg. Oncol. 2010;102:256,263. © 2010 Wiley-Liss, Inc. [source] Intra-abdominal metastases from soft tissue sarcomaJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2004FRCS (Ed.), FRCS (Glas.), Kasim A. Behranwala MS Abstract Objective To define the clinical features and prognosis of patients with abdominal metastasis from primary soft tissue sarcoma (STS) at other sites. Methods All patients with abdominal metastasis from STS were identified from the Royal Marsden Hospital Sarcoma Unit prospective database from January 1990 to July 2001. Results Nineteen patients developed abdominal metastasis out of a cohort of 2127 patients (0.9%) evaluated during the study interval. The median age was 49 (19,71) years. The median time to abdominal metastasis from diagnosis of the primary was 27 (8,91) months. The presenting complaints were incomplete intestinal obstruction (n,=,5), abdominal pain (n,=,4), mass (n,=,2), gastrointestinal bleed (n,=,2), urinary obstruction (n,=,2), anorexia (n,=,1), and abdominal distension (n,=,1). Emergency laparotomy was done for perforative peritonitis (n,=,2), intussusception (n,=,2), and bleed in spleen (n,=,1). Two patients were asymptomatic. The common histologies were myxoid liposarcoma (n,=,6) and leiomyosarcoma (n,=,4). The median follow-up of survivors post metastasis was 12 months. Abdominal metastatectomy was performed in 16 patients, 3 of these patients had abdominal recurrences. The 1- and 2-year overall disease specific survival for the 19 patients was 66% (SE,=,11%) and 43% (SE,=,13%) with a median survival of 13 months (95% CI,=,11.8,14.7). Metastasectomy was associated with slight improved median post-metastasis survival (33 months vs. 8 months for unresected patients). Conclusions Although abdominal metastasis is rare, vigilance is warranted. Symptomatic patients should be examined and investigated thoroughly for metastases. Surgery is the treatment of choice for patients with an acute presentation; however, survival is dismal. J. Surg. Oncol. 2004;87:116,120. © 2004 Wiley-Liss, Inc. [source] Disease progression in amyotrophic lateral sclerosis: Predictors of survivalMUSCLE AND NERVE, Issue 5 2002T. Magnus MD Abstract Predicting the rate of disease progression has become important as trials of new medical treatments for amyotrophic lateral sclerosis (ALS) are planned. Bulbar onset, early impairment of forced vital capacity, and older age have all been associated with shorter survival. We performed a retrospective study to compare survival factors with disease progression in a German ALS population. We analyzed disease progression in 155 patients at intervals of 4 months over a period of 3 years. To evaluate disease progression, the ALS functional rating scale (ALS-FRS), forced vital capacity (FVC%), and a Medical Research Council (MRC) compound score based on a nine-step modified MRC scale were used. We compared age (<55 years vs. ,55 years), different sites of disease onset (bulbar vs. limb), and gender to the rate of disease progression and performed survival analyses. No overall significant difference could be detected when analyzing these subgroups with regard to disease progression. By contrast, significantly longer survival was observed in the younger age group (56 months vs. 38 months, P < 0.0001) and in patients with limb-onset disease (51 months vs. 37 months, P = 0.0002). Using Cox analyses values we found that the declines of ALS-FRS, FVC%, and MRC compound score were predictive of survival (P < 0.0001, P = 0.002, and P = 0.003, respectively). Future studies are needed to clarify whether nonspecific factors including muscle atrophy, dysphagia, and coexisting diseases influence prediction of survival in ALS patients. A more precise set of predictors may help to better stratify patient subgroups for future treatment trials. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25:000,000, 2002 [source] Non-myeloablative conditioning and allogeneic transplantation for multiple myeloma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010Keren Osman In multiple myeloma (MM), allogeneic stem cell transplantation (alloHCT) carries a lower relapse risk than autologous transplantation but a greater transplant-related mortality. Nonmyeloablative conditioning for allogeneic transplantation (NST) reduces transplant-related toxicity. Results are encouraging when used during first remission in low-risk patients, but less-so in relapsed or refractory disease. This is a single-center retrospective analysis of 20 previously treated MM patients who underwent NST from matched-related or matched-unrelated donors from 2000,2006. Median age was 52.7 years (37.2,68.0). Twenty-five percent had advanced or high-risk disease. Eleven still had active disease prior to NST. Conditioning was total body irradiation 200 cGy on a single fraction on day ,5, followed by antithymocyte globulin (ATG) 1.5 mg/kg/day and fludarabine 30 mg/m2/day on days ,4 to ,2. All received immunosuppression, most commonly with oral mycofenylate mofetil and cyclosporine beginning on day ,5. At day 100, 50% had achieved complete remission. Transplant-related mortality was 25%. Median overall survival (OS) was 21.2 months (0.6,90+) and progression-free survival (PFS) 6.6 months (0.6,90+). Both OS and PFS were 24% at 3 years. OS was significantly greater for patients with age <52 years (median 27 months vs. 7.9 months, P = 0.031), and there was a trend toward greater OS for those with ,2 microglobulin <2.5 mg/l (median 27 months vs. 7.7 months, P = 0.08). Donor characteristics and Ig type had no significant effect on survival. These data suggest a benefit of NST in relapsed/refractory MM. Randomized trials must be performed to confirm and further qualify this benefit. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Recurrent Idiopathic Membranous Nephropathy: Early Diagnosis by Protocol Biopsies and Treatment with Anti-CD20 Monoclonal AntibodiesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2009Ziad M. El-Zoghby Membranous nephropathy (MN) recurs posttransplant in 42% of patients. We compared MN recurrence rates in a historical cohort transplanted between 1990 and 1999 and in a current cohort diagnosed by protocol biopsies, we analyzed the progression of the disease and we assessed the effects of anti-CD20 antibodies (Rituximab) on recurrent MN. The incidence of recurrent MN was similar in the historical (53%) and the current cohorts (41%), although in the later the diagnosis was made earlier (median, 4[2,21] months vs. 83[6,149], p = 0.002) and the disease was clinically milder. Twelve out of 14 patients (86%) with recurrent MN in the current cohort had progressive increases in proteinuria. Eight recipients were treated with Rituximab after their proteinuria increased from median, 211 mg/day (64,4898) at diagnosis to 4489 (898,13 855) (p = 0.038). Twelve months post-Rituximab, 75% of patients had either partial (PR) or complete remission (CR). After 24 months 6/7 (86%) had PR/CR and one patient relapsed. Posttreatment biopsies showed resorption of electron dense immune deposits in 6/7 cases and were negative for C3 (4/7) and IgG (3/7). Protocol biopsies allow early diagnosis of subclinical recurrent MN, which is often progressive. Treatment of recurrent MN with Rituximab is promising and should be evaluated in a prospective randomized controlled trial. [source] Reduced Mortality with Right-Lobe Living Donor Compared to Deceased-Donor Liver Transplantation When Analyzed from the Time of ListingAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2007S. A. Shah Right lobe living donor liver transplantation (RLDLT) is not yet a fully accepted therapy for patients with end-stage liver failure in the Western hemisphere because of concerns about donor safety and inferior recipient outcomes. An outcome analysis from the time of listing for all adult patients who were listed for liver transplantation (LT) at our center was performed. From 2000 to 2006, 1091 patients were listed for LT. One hundred fifty-four patients (LRD; 14%) had suitable live donors and 153 (99%) underwent RLDLT. Of the remaining patients (DD/Waiting List; n = 937), 350 underwent deceased donor liver transplant (DDLT); 312 died or dropped off the waiting list; and 275 were still waiting at the time of this analysis. The LRD group had shorter mean waiting times (6.0 months vs. 9.8 months; p < 0.001). Although medical model for end-stage liver disease (MELD) scores were similar at the time of listing, MELD scores at LT were significantly higher in the DD/Waiting List group (15.4 vs. 19.5; p = 0.002). Patients in Group 1 had a survival advantage with RLDLT from the time of listing (1-year survival 90% vs. 80%; p < 0.001). To our knowledge, this is the first report to document a survival advantage at time of listing for RLDLT over DDLT. [source] Effects of an environmental enrichment using a drum can on behavioral, physiological and productive characteristics in fattening beef cattleANIMAL SCIENCE JOURNAL, Issue 3 2006Toshie ISHIWATA ABSTRACT To evaluate the effects of environmental enrichment on behavioral, physiological and productive characteristics, 71 Japanese Black × Holstein steers (8 months of age; 299.5 ± 22.6 kg) were allocated to three pens in two repetitive experiments. Pen C (n = 11 and 12) consisted of a feeding alley for grain feed, a trough for dry hay, a water bowl and a resting space as a control pen. Pen D (n = 12 and 12) included a drum can (58 cm diameter ×,90 cm height) containing hay. Pen GD (n = 12 and 12) included a drum can that was placed around artificial plastic turf (30 × 120 cm) for grooming. The drum cans were removed after 5 months of installation. Behavioral observations were made for 2 h at 10 min intervals after feeding on three successive days each month for 10 months. Agonistic interactions were also continuously observed for 1 h after feeding to assess the dominance order (DO). Sampling blood and measuring bodyweight were performed bimonthly. The steers used the drum can frequently for 3 months after installation (1st, 2nd, 3rd months vs 4 months, all P < 0.05). The frequency of total eating of grain feed and hay was higher in pen D and pen GD than in pen C (both P < 0.01), while it was lowest in pen GD after removal of the drum can (P < 0.05). Grooming at the drum can was observed more frequently in pen GD than in pen D (P < 0.05). After they finished eating the grain feed, they ate hay at the drum can that contained additional hay rather than at the trough for hay (P < 0.01). Plasma dopamine concentrations were higher in pen D than in pen C (P < 0.05), and serum triglyceride concentrations were higher in pen C than in pen GD (P < 0.05) during the installation of the drum can. After removal of the drum can, serum total cholesterol concentrations became higher in pen D and GD than in pen C (both P < 0.05). Average daily gain correlated positively with the frequency of eating hay at the drum can in pen D (rs = 0.52, P < 0.01). In pen GD, the frequency of using the drum can correlated negatively with DO (rs = ,0.59, P < 0.01). Carcass belly fat was thicker in pens D and GD than in pen C (both P < 0.01). In pen GD, the frequency of eating hay (rs = 0.79, P < 0.01) and grooming at the drum can (rs = 0.63, P < 0.05) correlated positively with the marbling score. Although social factor affected the steers using the drum can, installing it in the early fattening stage encouraged the steers to eat and groom there and resulted in better carcass characteristics through the prolonged physiological positive effects. [source] SERUM INSULIN-LIKE GROWTH FACTOR-I AND INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-3 FOLLOWING CHEMOTHERAPY FOR ADVANCED BREAST CANCERANZ JOURNAL OF SURGERY, Issue 11 2003Ian M. Holdaway Background: Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) appear to influence the growth of breast cancer cells in vitro, and epidemiological studies suggest higher serum IGF-I levels increase the risk of breast cancer. IGF-I and IGFBP-3 have therefore been measured in women with advanced breast cancer to determine if changes in serum levels predict the response to treatment by chemotherapy. Methods: Serum IGF-I and IGFBP-3 levels were measured in 14 patients before and after 1 week of chemotherapy. Changes in serum levels were compared with duration of survival. Results: Mean basal serum levels of IGF-I and IGFBP-3 were not significantly different between patients with advanced breast cancer and controls or women with early breast cancer. Serum IGFBP-3 fell significantly 1 week after initiation of chemotherapy. Patient survival was not significantly related to baseline IGF-I or IGFBP-3 levels, but when the fall in serum levels 1 week after starting treatment was expressed either as absolute change or as a percentage of baseline, those individuals with a decrease in IGFBP-3 greater than the median had significantly poorer survival (median survival 5.5 months vs 18 months). These results were independent of other prognostic variables such as previous disease-free survival, and were also unaffected by the change in serum albumin with treatment. The fall in IGF-I and IGFBP-3 with chemotherapy mainly occurred in those with hepatic metastases, but prediction of survival was explained solely by the extent of the fall in IGFBP-3. Conclusions: This preliminary study has shown that serum IGFBP-3 falls significantly following initiation of chemotherapy and the extent of reduction significantly predicts the response to treatment. [source] Recurrent ovarian cancer: Treatment with pegylated liposomal doxorubicin; a Westmead Cancer Care Centre experienceASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2010Rachel F DEAR Abstract Aim: To describe the overall survival, progression-free survival, response rate and toxicity of pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer. Methods: A retrospective study of 45 patients with recurrent or progressive ovarian cancer was conducted at the Westmead Cancer Care Centre. Patients received PLD at a starting dose of 30,50 mg/m2 every 4 weeks. Results: A total of 43 patients were included for analysis. The starting dose was 40 mg/m2 in 67% of cases, and 21 % had a dose increase. A median of 2 cycles (mean 3, range 1,7) was given. All patients were assessable for response and 77% stopped treatment due to progressive disease. The overall response rate to PLD assessed by CA-125 criteria was 14 percent (six of 43 patients). Five patients (12 percent) were from the potentially platinum-sensitive group and one (2 percent) was from the platinum-resistant group. The overall median progression-free survival was 52 days (2 months), which was greater in the platinum-sensitive than in the platinum-resistant group (4.4 months vs 1.7 months, respectively, P = 0.030). The median overall survival was 296 days (10.6 months) with a trend for this to be longer in the platinum-sensitive than in the platinum-resistant group (13 vs 9 months, P = 0.393). Overall 25 percent of patients had grade 2 or 3 toxicity. Conclusion: The benefit of PLD in platinum-resistant recurrent ovarian cancer is small and the treatment has considerable toxicity. These data support the need to establish whether chemotherapy in this setting has any favorable effect on quality of life. The Australian New Zealand Gynaecological Oncology Group is currently addressing this question in a large prospective study measuring both the subjective and objective benefit (response and survival) of palliative chemotherapy in platinum-resistant or refractory ovarian cancer in Australia. Clinicians are urged to enter their patients in this study to address this important question. [source] Outcome after autologous stem cell transplantation for multiple myeloma in patients with preceding plasma cell disordersBRITISH JOURNAL OF HAEMATOLOGY, Issue 2 2008Shaji K. Kumar Summary A third of patients with multiple myeloma (MM) have a preceding diagnosis of plasma cell proliferative disorder (PCPD), mostly monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM) or plasmacytoma. While autologous stem cell transplantation (SCT) improves survival in MM, it is not clear if patients with preceding PCPD have a different outcome. We identified 151 patients with preceding PCPD from among 804 patients undergoing SCT, and their outcomes were compared. The response rates, including complete responses, were similar between the groups. Patients with a preceding diagnosis of MGUS had longer time to progression (TTP; 27·5 months vs. 17·2 months, P = 0·01), and longer overall survival (OS) from transplant (80·2 months vs. 48·3 months, P = 0·03) compared to those with de novo myeloma. However no differences were seen among those with a preceding diagnosis of SMM or plasmacytoma in terms of TTP or OS from transplant when compared to those with de novo myeloma. Multivariate analysis indicated that the presence of MGUS prior to myeloma was prognostic for post-transplant relapse independent of other known risk factors. Patients with pre-existing MGUS prior to myeloma diagnosis have a better outcome following HDT, reflecting more indolent disease and a favourable biology than those presenting with de novo myeloma. [source] Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiformeACTA NEUROLOGICA SCANDINAVICA, Issue 3 2010R. Helseth Helseth R, Helseth E, Johannesen TB, Langberg CW, Lote K, Rønning P, Scheie D, Vik A, Meling TR. Overall survival, prognostic factors, and repeated surgery in a consecutive series of 516 patients with glioblastoma multiforme. Acta Neurol Scand: 122: 159,167. © 2010 The Authors Journal compilation © 2010 Blackwell Munksgaard. Objectives,,, To study overall survival (OS), prognostic factors, and repeated surgery in glioblastoma multiforme (GBM). Material and methods, Retrospective study of 516 consecutive adult patients who underwent primary surgery for a GBM in year 2003,2008. Results,,, Median age at primary surgery was 63.7 years (range 18.0,88.0). Median OS was 9.9 months. Age >60 years, poor preoperative ECOG score, bilateral tumor, biopsy rather than resection, and no temozolomide chemoradiotherapy were negative risk factors. Repeat surgery was performed in 65 patients (13%). Median time between first and second surgery was 7 months. Indications for second surgery were increasing neurological deficits (35.4%), raised ICP (33.8%), asymptomatic but reoperated because of tumor progression verified on MRI (20.0%), and epileptic seizures (11%). Patients who underwent repeated surgery had longer OS; 18.4 months vs 8.6 months (P < 0.001). Conclusions,,, OS for adult GBM patients was 9.9 months. Negative prognostic factors were increasing age, poor neurological function, bilateral tumor involvement, biopsy instead of resection, and RT alone compared to temozolomide chemoradiotherapy. Our rate of repeated surgery for GBM was 13% and the main indications for second surgery were raised ICP and increasing neurological deficits. In a carefully selected group of patients, repeat surgery significantly prolongs OS. [source] Randomized trial of paclitaxel versus pegylated liposomal doxorubicin for advanced human immunodeficiency virus-associated Kaposi sarcomaCANCER, Issue 16 2010Evidence of symptom palliation from chemotherapy Abstract BACKGROUND: Paclitaxel and pegylated liposomal doxorubicin (PLD) are active cytotoxic agents for the treatment of human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). A randomized trial comparing the efficacy and toxicity of paclitaxel and PLD was performed, and the effects of therapy on symptom palliation and quality of life were determined. METHODS: Patients with advanced HIV-associated KS were randomly assigned to receive paclitaxel at a dose of 100 mg/m2 intravenously (iv) every 2 weeks or PLD at a dose of 20 mg/m2 iv every 3 weeks. The KS Functional Assessment of HIV (FAHI) quality of life instrument was used before and after every other treatment cycle. RESULTS: The study included 73 analyzable patients enrolled between 1998 and 2002, including 36 in the paclitaxel arm and 37 in the PLD arm; 73% of patients received highly active antiretroviral therapy (HAART) and 32% had an undetectable viral load (<400 copies/mL). Treatment was associated with significant improvements in pain (P = .024) and swelling (P < .001). Of the 36 patients who reported that pain interfered with their normal work or activities at baseline, 25 (69%) improved. Of the 41 patients who reported swelling at baseline, 38 (93%) improved. Comparing the paclitaxel and PLD arms revealed comparable response rates (56% vs 46%; P = .49), median progression-free survival (17.5 months vs 12.2 months; P = .66), and 2-year survival rates (79% vs 78%; P = .75), but somewhat more grade 3 to 5 toxicity for paclitaxel (84% vs 66%; P = .077). CONCLUSIONS: Treatment with either paclitaxel or PLD appears to produce significant improvements in pain and swelling in patients with advanced, symptomatic, HIV-associated KS treated in the HAART era. Cancer 2010. © 2010 American Cancer Society. [source] Clinical characteristics and outcomes for a modern series of primary gliosarcoma patientsCANCER, Issue 5 2010Seunggu J. Han BS Abstract BACKGROUND: Primary gliosarcoma (PGS) is a rare central nervous system tumor with limited experience reported in the literature. In the current study, the authors present a modern series of confirmed PGS cases treated in the era of magnetic resonance imaging (MRI), after the accepted glioblastoma management of resection, radiation, and temozolomide. METHODS: Using a retrospective review, patients with confirmed PGS were identified (1996-2008). Cases were determined to be PGS by central pathology review using the 2007 World Health Organization criteria. Extensive chart review was performed to gather clinical and pathologic data on these cases. RESULTS: All but 1 patient had undergone a preoperative MRI, with 1 patient receiving a computed tomography scan due to a cardiac pacemaker. A total of 10 patients received radiotherapy with concurrent and adjuvant temozolomide chemotherapy, and 8 patients received radiotherapy alone or in combination with other chemotherapeutic agents. In 2 patients, the history of adjuvant treatment could not be confirmed. The overall median survival was 13.9 months (range, 2.2-22.9 months). Patients with gliosarcomas resembling meningioma were found to have a significantly prolonged median survival compared with patients harboring gliosarcoma resembling glioblastoma multiforme (16 months vs 9.6 months; P = .011). However, no difference in survival was noted between patients who received concurrent radiotherapy and temozolomide compared with those who did not (10.4 months vs 13.9 months; P = .946). CONCLUSIONS: The results of the current study support previous hypotheses that there are 2 distinct types of PGS. The type mimicking the appearance of a meningioma appears to carry a significantly more favorable prognosis, most likely due to an increased chance at achieving macroscopic total resection. Cancer 2010. © 2010 American Cancer Society. [source] A randomized phase 2 trial comparing 3-hour versus 96-hour infusion schedules of paclitaxel for the treatment of metastatic breast cancerCANCER, Issue 4 2010MSCI, Stacy L. Moulder MD Abstract BACKGROUND: This study was performed to compare efficacy and toxicity profiles of paclitaxel using 3-hour versus 96-hour infusion schedules. METHODS: Patients with metastatic breast cancer (MBC) were randomly assigned to receive paclitaxel starting at a dose of 250 mg/m2 intravenously (iv) over 3 hours every 21 days or paclitaxel starting at a dose of 140 mg/m2 iv over 96 hours every 21 days. Stratification variables included number of prior chemotherapy regimens and previous response to anthracyclines. Response was assessed every 2 cycles using bidimensional measurements. Patients were allowed to cross over at disease progression or therapy intolerance. RESULTS: A total of 214 patients received therapy (107 patients per arm). Response rates were similar: 23.4% in the 3-hour arm and 29.9% in the 96-hour arm (P = .28). The median duration of response (8.9 months vs 5.7 months; P = .75) and progression-free survival (5.0 months vs 3.8 months; P = .17) slightly favored the 96-hour arm. Overall survival was slightly longer in the 3-hour arm (14.2 months vs 12.7 months; P = .57). One patient who crossed over to the 96-hour arm (N = 18) developed a partial response; no response was noted with crossover to the 3-hour arm (N = 10). Myalgia/arthralgia and neuropathy were more frequent in the 3-hour arm, whereas mucositis, neutropenic fever/infection, and diarrhea were more common in the 96-hour arm. CONCLUSIONS: Paclitaxel given by 3-hour or 96-hour infusion was active in MBC. The 96-hour paclitaxel regimen did not significantly improve response or time to disease progression, was more cumbersome to administer, and was associated with greater myelosuppression (but less neuropathy and myalgia) compared with the 3-hour schedule. Cancer 2010. © 2010 American Cancer Society. [source] The outcomes of elderly patients with hepatocellular carcinoma treated with transarterial chemoembolizationCANCER, Issue 23 2009Thomas Yau MD Abstract BACKGROUND: The authors evaluated and compared the treatment outcomes of transarterial chemoembolization (TACE) between young (,70 years) and elderly (>70 years) patients at their institute over an 18-year period. METHODS: Advanced hepatocellular carcinoma (HCC) patients who received TACE at the authors' center were analyzed retrospectively. The demographic data, TACE-related morbidities, and survival outcome were compared between these 2 age groups. RESULTS: Between 1989 and 2006, 843 patients who were ,70 years old and 197 patients who were >70 years old received TACE treatment for advanced HCC. There were significantly more comorbid illnesses associated with the elderly patients than the young patients (64 % vs 33%, P < .01). Moreover, elderly patients who received TACE treatment for HCC were at earlier stages of disease (P < .01). Both the overall median survival (14.0 months vs 8.1 months, P < .003) and disease-specific survival (15.2 months vs 8.7 months, P < .001) were significantly higher in elderly than young patients. The most commonly encountered TACE-related morbidity in both age groups was liver function derangement. Young patients had a significantly higher rate of developing liver derangement after TACE than elderly patients (21% vs 11%, P < .01). Conversely, the elderly patients had a significantly higher rate of developing peptic ulcer disease with TACE treatment than young patients (2.5% vs 0.5%, P = .01). Overall, there was no significant difference in TACE-related mortality between the young and elderly patients (3% vs 4%, P = .49). CONCLUSIONS: This study has confirmed the comparable efficacy and tolerability in using TACE for the treatment of advanced HCC in young and elderly patient populations. Cancer 2009. © 2009 American Cancer Society. [source] Radioembolization of colorectal hepatic metastases using yttrium-90 microspheresCANCER, Issue 9 2009Mary F. Mulcahy MD Abstract BACKGROUND: The objective of the current study was to determine the safety and efficacy of Yttrium-90 (Y90) microsphere treatment in patients with liver-dominant colorectal metastases. METHODS: Seventy-two patients with unresectable hepatic colorectal metastases were treated at a targeted absorbed dose of 120 Gray (Gy). Safety and toxicity were assessed using version 3 of the National Cancer Institute Common Terminology Criteria. Response was assessed by anatomic imaging and positron emission tomography (PET). Survival from the diagnosis of hepatic metastases and first treatment were estimated using the Kaplan-Meier method. Substratification analyses were performed. RESULTS: The median dose delivered was 118 Gy. Treatment-related toxicities included fatigue (61%), nausea (21%), and abdominal pain (25%). Grade 3 and 4 bilirubin toxicities were observed in 9 of 72 patients (12.6%). The tumor response rate was 40.3%. The median time to hepatic progression was 15.4 months, and the median response duration was 15 months. The PET response rate was 77%. Overall survival from the first Y90 treatment was 14.5 months. Tumor replacement (,25% vs >25%) was associated with significantly greater median survival (18.7 months vs 5.2 months). The presence of extrahepatic disease was associated negatively with overall survival (7.9 months vs 21 months). Overall survival from the date of initial hepatic metastases was 34.6 months. A subset analysis of patients who had an Eastern Cooperative Oncology Group performance status of 0 demonstrated a median survival of 42.8 months and 23.5 months from the time of hepatic metastases and Y90 treatment, respectively. CONCLUSIONS: Y90 liver therapy appears to provide sustained disease stabilization with acceptable toxicity. Asymptomatic patients with preserved liver function at the time of Y90 appeared to benefit most from treatment. Cancer 2009. © 2009 American Cancer Society. [source] Chemotherapy with 5-fluorouracil and a platinum compound improves outcomes in metastatic small bowel adenocarcinoma,CANCER, Issue 8 2008Michael J. Overman MD Abstract BACKGROUND. Metastatic small bowel adenocarcinoma (SBA) has a poor prognosis. Because of the rarity of SBA, only a few studies have evaluated the role of chemotherapy in the treatment of metastatic SBA; thus, the benefit, if any, of adding a platinum compound to fluorouracil (5-FU) is unknown. The objective of this retrospective study was to determine whether the addition of a platinum compound to 5-FU provided any benefit in the treatment of patients with metastatic SBA. METHODS. The authors identified 80 patients with metastatic SBA who were treated with chemotherapy at the University of Texas M. D. Anderson Cancer Center between 1978 and 2005. Response rates, progression-free survival (PFS), and overall survival (OS) were compared between patients who received 5-FU and a platinum compound and patients who received other chemotherapy combinations. RESULTS. The median patient age was 53 years. The primary tumor site was the jejunum in 35 patients (43%), duodenum in 30 patients (38%), ileum in 6 patients (8%), and nonspecified small bowel in 9 patients (11%). Of all 80 patients, 29 patients (36%) received 5-FU and a platinum compound, 41 patients (51%) received 5-FU without a platinum compound, and 10 patients (13%) received non-5-FU,based treatment. Compared with other chemotherapy regimens, treatment with 5-FU and a platinum agent resulted in a higher response rate (46% vs 16% with other regimens; P = .01) and longer median PFS (8.7 months vs 3.9 months; P , .01) but not better OS (14.8 months vs 12 months; P = .1). In multivariate analysis, treatment with 5-FU and a platinum compound was a significant predictor of response (odds ratio, 4.5; 95% confidence interval [CI], 1.3-15.8; P = .02) and PFS (hazard ratio. 0.49; 95% CI, 0.29-0.84; P = .01) but only reached borderline significance for OS (hazard ratio, 0.63; 95% CI, 0.37-1.07; P = .08). CONCLUSIONS. To the authors' knowledge, the current analysis represents the largest number of patients with metastatic SBA treated with chemotherapy in the literature, and the results suggested that the combination of 5-FU and a platinum compound leads to a higher response rate and PFS compared with other chemotherapy regimes. The authors concluded that prospective investigation of platinum analogues in the treatment of SBA is warranted. Cancer 2008. © 2008 American Cancer Society. [source] Randomized phase 2 study of irinotecan plus cisplatin versus gemcitabine plus vinorelbine as first-line chemotherapy with second-line crossover in patients with advanced nonsmall cell lung cancerCANCER, Issue 2 2008Ji-Youn Han MD Abstract BACKGROUND. The current study was performed to compare the nonplatinum-based combination of gemcitabine and vinorelbine (GV) with the combination of irinotecan and cisplatin (IP) as first-line chemotherapy with second-line crossover in patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. Patients were randomly assigned to received either irinotecan at a dose of 65 mg/m2 plus cisplatin at a dose of 30 mg/m2 (Arm A) or gemcitabine at a dose of 900 mg/m2 plus vinorelbine at a dose of 25 mg/m2 (Arm B), each of which was administered on Days 1 and 8 every 3 weeks as the first-line therapy followed by crossover at the time of disease progression. RESULTS. A total of 146 patients were enrolled (75 patients in Arm A and 71 patients in Arm B); 138 patients were evaluable for tumor response and toxicity. During first-line therapy, IP was found to result in more grade 2+ nausea and vomiting (toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) (41% vs 12%; P = .0001) and alopecia (36% vs 10%; P = .0003). Pneumonitis was noted only with GV therapy (7% vs 0%; P = .058). During second-line therapy, IP was found to result in more grade 3 diarrhea (17% vs 2%; P = .039) and GV featured more cases of grade 3+ neutropenia (78% vs 40%; P = .0003). IP tended to generate more tumor responses (38% vs 26% as first-line therapy, and 30% vs 13% as second-line therapy) compared with GV. IP also demonstrated a favorable trend in median progression-free survival (4.6 months vs 3.8 months as first-line therapy and 4.5 months vs 2.6 months as second-line therapy) and overall survival (15.9 months vs 13.1 months; P = .3), but this difference was not statistically significant. The majority of patients who were refractory to IP also failed to respond to GV in the second-line setting. CONCLUSIONS. The platinum-based IP regimen appeared to be superior to the GV combination in terms of response rate. However, given the similar survival and better tolerability of the nonplatinum GV regimen, either treatment sequence would appear to be acceptable for the treatment of patients with advanced NSCLC. Cancer 2008. © 2008 American Cancer Society. [source] Survival in patients with brain metastases from breast cancerCANCER, Issue 11 2008The importance of HER-2 status Abstract BACKGROUND Brain metastases (BM) are the most common intracranial tumors in adults. To the authors' knowledge, established prognostic factors for survival after the diagnosis of BM in breast cancer patients do not take into account HER,2 status, which may have increasing relevance in the trastuzumab therapy era. METHODS The authors identified 83 patients with breast cancer and new parenchymal BM diagnosed between January 1, 2001 and December 31, 2005 who were treated at Massachusetts General Hospital. Survival was estimated using the Kaplan-Meier method and curves were compared using the log-rank test. A Cox proportional hazards model was used to determine independent predictors of survival. RESULTS The median overall survival from the time of BM was 8.3 months. On univariate analysis, HER-2-positive patients were found to have prolonged survival after BM compared with HER-2-negative patients (17.1 months vs 5.2 months). Patients with triple negative disease had a median survival of 4.0 months, compared with 11.2 months for all other patients. Additional predictors of improved survival on univariate analysis included ,3 BM, controlled or absent systemic disease, and controlled local disease. On multivariate analysis, only HER-2 status, number of BM, and local disease status remained independent predictors of survival. CONCLUSIONS HER-2 status is a strong predictor of survival after the diagnosis of BM. The survival of breast cancer patients with BM appears to be improving, but a better understanding of both the predictors of brain recurrence and the delayed effects of treatment is needed to properly counsel patients regarding the risk-benefit ratio of various treatment modalities. Cancer 2008. © 2008 American Cancer Society. [source] Carboplatin hypersensitivity reaction in pediatric patients with low-grade gliomaCANCER, Issue 4 2008A Canadian Pediatric Brain Tumor Consortium experience Abstract BACKGROUND. Carboplatin-based regimens have demonstrated activity in pediatric patients with low-grade glioma (LGG). However, carboplatin hypersensitivity reaction (Cb HSR) represents a common and limiting factor for the continuation of therapy. METHODS. The objectives of this study were to describe the prevalence, characteristics, and management of Cb HSR and to detail their impact on outcome. The authors conducted a comprehensive, national, retrospective review of children who were diagnosed with LGG between 1985 and 2004 and received treatment with carboplatin. RESULTS. One hundred five patients from 10 Canadian centers were included. The median patient age at diagnosis was 3.5 years (range, 0.3,16.8 years), and 33 patients (31.4%) had neurofibromatosis type 1. Carboplatin was administered monthly in 46 children and weekly in 59 children. Forty-four patients (41.9%) developed Cb HSR after a median of 10.5 infusions (range, 3,39 infusions). Cb HSR occurred significantly earlier among children on the weekly schedule (4.4 months vs 9.1 months; P = .02). The first allergic reaction was grade I or II in 36 patients (82%). The cumulative incidence of Cb HSR increased with the number of infusions, and there was no evidence of a plateau. The only predictive factor was being a girl rather than a boy (P = .02). Thirty-four of 44 patients with Cb HSR were re-exposed to carboplatin, and 24 of 34 patients (70.5%) had recurrent Cb HSR. A desensitization approach did not provide any advantage compared with premedication alone for altering Cb HSR. The median number of additional Cb infusions delivered was 4 (range, 0.5,34 infusions). The effect of Cb HSR on the 5-year progression-free survival rate was not statistically significant (P = .1). CONCLUSIONS. Forty-two percent of children with LGG who received carboplatin regimens experienced Cb HSR. Most rechallenged children had recurrent Cb HSR despite Cb HSR-altering regimens. Cb HSR did not have an impact on progression-free survival. Cancer 2008. © 2007 American Cancer Society. [source] High circulating HER2 extracellular domain levels correlate with reduced efficacy of an aromatase inhibitor in hormone receptor-positive metastatic breast cancer: A confirmatory prospective studyCANCER, Issue 10 2007Ramon Colomer MD Abstract BACKGROUND. In this specifically designed, prospective study, the authors addressed the predictive value of circulating levels of the extracellular domain (ECD) of HER2 in patients with metastatic breast cancer who were treated with letrozole. METHODS. Two hundred twenty-six patients with hormone receptor-positive, metastatic breast cancer received letrozole (2.5 mg daily) until they developed either disease progression or unacceptable toxicity. Efficacy was measured primarily as the time to progression (TTP) and, secondarily, as the objective response rate (ORR) and overall survival. HER2 ECD levels were determined by using a sandwich enzyme HER2/neu immunoassay before letrozole treatment was initiated. Positive HER2 ECD status was correlated with treatment efficacy. RESULTS. Forty-two patients (19%) had elevated HER2 ECD levels, which were associated with primary tumor HER2 expression (P < .001) but not with age, performance status, location, or number of metastatic sites. The median TTP was significantly shorter among patients who had elevated HER2 ECD compared with the median TTP among patients who had normal levels (4 months vs 14 months; P = .0004), and the ORR was lower in the group with elevated HER2 ECD levels (14% vs 30%; P < .036). Overall survival was significantly shorter among patients with elevated serum HER-2 ECD (P < .0005). CONCLUSIONS. Elevated HER2 ECD concentrations predicted poorer outcomes in postmenopausal women with metastatic hormone receptor-positive breast cancer who were treated with aromatase inhibitors like letrozole. © 2007 American Cancer Society. [source] Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL),CANCER, Issue 10 2007Oliver G. Ottmann MD Abstract BACKGROUND Elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) have a poor prognosis, with a low complete remission (CR) rate, high induction mortality, and short remission duration. Imatinib (IM) has a favorable toxicity profile but limited antileukemic activity in advanced Ph+ALL. Imatinib in combination with intensive chemotherapy has yielded promising results as front-line therapy, but its value as monotherapy in newly diagnosed Ph+ALL is not known. METHODS Patients with de novo Ph+ALL were randomly assigned to induction therapy with either imatinib (IndIM) or multiagent, age-adapted chemotherapy (Indchemo). Imatinib was subsequently coadministered with consolidation chemotherapy. RESULTS In all, 55 patients (median age, 68 years) were enrolled. The overall CR rate was 96.3% in patients randomly assigned to IndIM and 50% in patients allocated to Indchemo (P = .0001). Nine patients (34.6%) were refractory and 2 patients died during Indchemo; none failed imatinib induction. Severe adverse events were significantly more frequent during Indchemo (90% vs 39%; P = .005). The estimated overall survival (OS) of all patients was 42% ± 8% at 24 months, with no significant difference between the 2 cohorts. Median disease-free survival was significantly longer in the 43% of patients (21 of 49 evaluable) in whom BCR-ABL transcripts became undetectable (18.3 months vs 7.2 months; P = .002). CONCLUSIONS In elderly patients with de novo Ph+ALL, imatinib induction results in a significantly higher CR rate and lower toxicity than induction chemotherapy. With subsequent combined imatinib and chemotherapy consolidation, this initial benefit does not translate into improved survival compared with chemotherapy induction. Cancer 2007. © 2007 American Cancer Society. [source] | |||||||||||||||||||||||||