Patient attitudes towards chemotherapy and survival: a prospective observational study in advanced non-small cell lung cancer.

This multicenter, non-interventional, prospective, observational study aimed to determine whether patients' attitude to chemotherapy is an independent prognostic factor for survival in patients with advanced non-small cell lung cancer (NSCLC) who are treated with gemcitabine-platinum. Chemonaive patients (n=1895) with stage IIIB or IV NSCLC not amenable to curative surgery or radiotherapy were treated with a combination of gemcitabine plus cisplatin/carboplatin and followed for a maximum of 18 months. Patients' attitude to treatment was measured on a 5-point scale and responses were used to assign patients to one of the three need categories: A, maximum extension of survival with the acceptance of high toxicity (60.0% of patients); B, maximum extension of survival only if coupled with normal lifestyle (26.1%); C, relief of symptoms (13.8%). Median survival varied significantly among the need categories (A=13.00 months, B=15.70 months, C=15.33 months; log-rank test P=0.0415). Patient attitude to treatment (need categories) was not a significant prognostic factor for survival after adjusting for known prognostic factors (P=0.0503). After adjusting for baseline differences, patients in this study had a significantly lower risk of death than patients in three randomized trials (hazard ratio 0.879; 95% confidence interval: 0.775, 0.998; P=0.0458). In conclusion, in this observational study, patient attitude to chemotherapy was not an independent prognostic factor of survival.

Gemcitabine and cisplatin treatment over a 3-week versus a 4-week dosing schedule: a randomized trial conducted in Chinese patients with nonsmall cell lung cancer.

BACKGROUND: Gemcitabine plus cisplatin is a standard treatment for stages IIIB and IV nonsmall cell lung cancer (NSCLC). This randomized phase II study evaluated a 3-week versus a 4-week schedule of gemcitabine-cisplatin as first line treatment for Chinese patients with advanced NSCLC. METHODS: Patients were randomized to receive cisplatin 75 mg/m(2) on day 1 plus either gemcitabine 1250 mg/m(2) on days 1 and 8 of a 21-day cycle (3-week group) or gemcitabine 1000 mg/m(2) on days 1, 8 and 15 of a 28-day cycle (4-week group). RESULTS: One hundred patients were enrolled in this study. The response rate was 24% (12/51 patients) in the 3-week group and 27% (13/49 patients) in the 4-week group. There were no statistically significant differences between the two treatment groups in survival (hazard ratio: 1.19; 95% CI: 0.68 - 2.09) with a median survival of 12.1 months and 13.8 months in the 3-week group and the 4-week group respectively. The rate of grade 3/4 toxicity in the 3-week group was 55% compared with 86% in the 4-week group (P = 0.001). The difference in the incidence of grade 3/4 haematological toxicities did not reach statistical significance (3-week: 37%, 4-week: 57%), however grade 3/4 drug related neutropenia (3-week: 27%, 4-week: 51%) and thrombocytopenia (3-week: 8%, 4-week: 31%) were significantly lower in the 3-week group. Grade 3/4 nonhaematological toxicities were less in the 3-week group (33% cf 63%; P = 0.005). CONCLUSIONS: The differences in the efficacy endpoints were all in favour of the 4-week schedule of gemcitabine plus cisplatin, however these differences did not reach statistical significance. Fewer grade 3/4 toxicities were observed in the 3-week group compared with the 4-week group.

Cardiac outcome up to 15 years after the arterial switch operation.

AIMS: To assess the cardiac outcome and risk factors for mortality of infants following the arterial switch operation (ASO). METHODS: A single-centre retrospective review was conducted. Preoperative assessment, operative management and outcome was detailed for 244 patients undergoing the ASO at Green Lane Hospital for transposition of the great arteries (TGA) or double outlet right ventricle. RESULTS: The postoperative survival at 1, 5 and 15 years was 85%, 84% and 83%, respectively. The calendar year of ASO and the presence of a ventricular septal defect (VSD) were the primary predictors of early mortality. Late mortality was associated with a side-by-side configuration of the great arteries. Re-intervention following ASO was more common in patients with prolonged cardiopulmonary bypass time. CONCLUSIONS: Low early and late morbidity and mortality can be obtained in infants with TGA or double outlet right ventricle by definitive repair utilising the ASO.

Gemcitabine administered as a short infusion versus a fixed dose rate in combination with cisplatin for the treatment of patients with advanced non-small cell lung cancer.

Previous studies have indicated that, in combination with cisplatin, fixed dose rate gemcitabine may be more efficacious than standard infusion gemcitabine. This open-label, randomised phase II study was aimed to compare the efficacy and safety of these regimens as treatment for advanced non-small cell lung cancer (NSCLC) in Latin American patients. Sixty-four patients were randomised to receive up to six cycles of treatment with cisplatin 75 mg/m(2) on Day 1 plus either gemcitabine 1000 mg/m(2) over 30 min on Days 1 and 8 of a 21-day cycle (standard arm, N=33) or gemcitabine 1000 mg/m(2) at a fixed dose rate of 10 mg/m(2)/min on Days 1 and 8 of a 21-day cycle (FDR arm, N=31). In the standard arm, 9 of 33 (27%) patients responded compared with 6 of 30 (20%) patients in the FDR arm (odds ratio: 0.67, 95% CI, 0.21-2.2; p=0.56). Median overall survival was 7.5 months in the standard arm and 9.9 months in the FDR arm. One-year survival rates were 35% and 37% in the standard arm and the FDR arm, respectively. Patients in the FDR arm experienced more grade 3/4 haematological toxicity than those in the standard arm (48% versus 21%). The results of this trial do not support FDR administration of gemcitabine in preference to the standard administration in Latin American patients with NSCLC.

A prospective randomised single blinded study comparing harmonic scalpel tonsillectomy with bipolar tonsillectomy.

OBJECTIVE: To compare the differences in pain, analgesic use and bleeding in children after tonsillectomy using either a harmonic scalpel or a bipolar diathermy surgical technique. METHODS: Children 6-15 years presenting for tonsillectomy were randomised to either a harmonic scalpel or bipolar diathermy surgical technique. Post-operative pain scores (VAS, 0-10) were recorded within 30 min of surgery and again at the 4h hospital discharge. A subsequent telephone interview daily for 7 days and then every second day until day 13 was used to monitor pain scores, analgesic use and tonsil bed bleeding. RESULTS: There were 204 children studied. The response rate over the first 7 days was 93% for the children in the harmonic scalpel group and 87% for the bipolar group. Children experienced moderate post-operative pain for the first 6 days, after which pain declined from 4-7 to reach a score of 1-2 by day 11. Children undergoing harmonic scalpel tonsillectomy (n=103) reported higher mean pain scores than those who underwent bipolar diathermy (n=101) for current pain (4.7 versus 4.2, p=0.002), worst pain of the day (6.9 versus 6.2, p<0.001) and pain on swallowing (5.9 versus 5.2, p<0.001) over the first 6 post-operative days. Analgesic use (acetaminophen, ibuprofen) was similar in both groups. Hospital readmission for bleeding in children who underwent harmonic scalpel was similar to those who underwent bipolar diathermy tonsillectomy (9% versus 11%) as was bleeding requiring surgical re-exploration (4% versus 2%). CONCLUSIONS: Tonsillectomy was associated with considerable pain for the first 6 post-operative days. Children undergoing harmonic scalpel tonsillectomy had a slight increase in pain compared to the bipolar diathermy group during this time. Both methods of tonsillectomy are effective and safe.

Surgery for acute type a aortic dissection a 37-year experience in Green Lane Hospital.

PURPOSE: To review the management of patients with acute type A aortic dissection. METHODS: Between June 1967 and December 2003, 246 patients (151 males and 95 females, 20-82 years; median 59 years) underwent operation for type A dissection. Early mortality and aortic dissection-related late events (reoperation and death related to aortic dissection) were assessed and correlated with the surgical approach. RESULTS: Over 37 years, early mortality has markedly improved, 50% in 1970s, 22% in 1980s, 17% in 1990s, and 11% after 2000. However, late deaths occurred at a constant rate, overall late survival at 10 and 20 years were 59% and 9%, respectively, and this did not improve after the 1990s. Preoperative hemodynamic instability, myocardial and kidney malperfusion, smoking history, prolonged bypass and cross-clamp time, and year of surgery were found to be risk factors for early death. The main cause (21%) of late deaths was aortic dissection-related events, especially in the distal aorta. However, no intraoperative risk factors were found to be predictive of late dissection-related events. Surgical techniques including complete resection of the intimal tear or distal extent of the surgery had no impact on late distal event-free survival. CONCLUSION: Despite improvement of short-term outcome over 37 years, patients who had aortic dissection are still living with elevated risk of death. Although late events in the distal aorta were a major risk, aggressive surgical approaches did not improve these outcomes. Vigilant follow-up is necessary for these patients.

Extra-aortic balloon counterpulsation: an intraoperative feasibility study.

BACKGROUND: Current methods of counterpulsation or ventricular assistance have significant vascular and limb complications. The aim of this study was to determine the safety and performance of a new method of non-blood-contacting counterpulsation using an inflatable cuff around the ascending aorta (extra-aortic balloon [EAB]). METHODS AND RESULTS: In 6 patients undergoing first time off-pump coronary bypass surgery via sternotomy, the EAB was secured around the ascending aorta and attached to a standard counterpulsation console. At baseline and with 1:2 and 1:1 augmentation, hemodynamic and echocardiographic parameters of ventricular function and coronary flow were measured. High-intensity transient signals were measured using transcutaneous Doppler over the right common carotid artery. No complications occurred. With EAB there was no significant change in heart rate or blood pressure and no increase in high-intensity transient signals. There was a 67% increase in diastolic coronary blood flow (mean left-main diastolic velocity time integral 15.3 cm unassisted versus 25.1 cm assisted, P<0.05). Measurements with transesophageal echocardiography at baseline and with 1:1 counterpulsation demonstrated a 6% reduction in end-diastolic area (P=NS), a 16% reduction in end-systolic area (P<0.01), a 31% reduction in left ventricular wall stress (P<0.05), and a 13% improvement in fractional area change (P<0.005). CONCLUSIONS: EAB counterpulsation augments coronary flow and reduces left ventricular afterload. Further testing is warranted to assess the use of the EAB for chronic non-blood-contacting support of the failing heart.

Bacteriological outcome after valve surgery for active infective endocarditis: implications for duration of treatment after surgery.

BACKGROUND: There has been no systematic evaluation of outcome after surgery for infective endocarditis with respect to duration of antibiotic treatment. METHODS: We performed a retrospective chart review of episodes of valve surgery for active infective endocarditis at Green Lane Hospital (Auckland, New Zealand) for 1963-1999. We recorded the duration of antibiotic treatment before and after valve surgery; the extent of infection at operation; Gram stain, culture, and histopathological testing results for valve samples; and the bacteriological outcome after surgery. The primary outcome measure was relapse, defined as endocarditis due to the same species within 1 year after surgery. RESULTS: For the 358 patients in our study, the median duration of follow-up was 4.8 years. Thirty-two patients (9%) had 36 subsequent episodes of endocarditis. Relapse occurred after 3 (0.8%) of the operations (95% CI, 0.2%-2.0%). Relapse of infection was unrelated to the duration of antibiotic treatment before or after surgery, positive valve culture results, positive Gram stain results, or perivalvular infection. Since 1994, we have reduced the duration of antibiotic treatment by approximately 7 days for those with positive valve culture results and by approximately 14 days for those with negative valve culture results, without any increase in the number of relapses. CONCLUSIONS: Relapse is an uncommon event following surgery for endocarditis. Commonly suggested indications for prolonging postoperative treatment are not associated with higher relapse rates, and their relevance is debatable. We conclude that it is unnecessary to continue treatment for patients with negative valve culture results for an arbitrary 4-6-week period after surgery. Two weeks of treatment appears to be sufficient, and, for those operated on near the end of the standard period of treatment, simply completing the planned course should suffice.

Culture results of heart valves resected because of streptococcal endocarditis: insights into duration of treatment to achieve valve sterilization.

OBJECTIVES: To analyse the culture results of heart valves removed following streptococcal endocarditis in order to gain insight into the duration of treatment required for valve sterilization. PATIENTS AND METHODS: Retrospective review of 131 episodes of streptococcal endocarditis: 94 due to alpha-haemolytic streptococci; 15 due to beta-haemolytic streptococci; 10 due to nutritionally deficient streptococci; eight due to the Streptococcus anginosus group and four due to Streptococcus pneumoniae. Patients had their valves removed during antimicrobial treatment. Culture results were analysed with respect to duration of treatment before surgery. RESULTS: For alpha-haemolytic streptococci, 17 (18%) valves were culture-positive and 77 (82%) culture-negative after a median (range) of 4 (1-20) and 16 (4-58) days of treatment, respectively, P < 0.001. For beta-haemolytic streptococci, two valves (13%) were culture-positive; both patients had received < or = 4 days of treatment. Four patients (40%) with nutritionally deficient streptococci were culture-positive, and had received < or = 8 days of treatment. For the S. anginosus group, two valves (25%) were culture-positive; both patients had received < or = 4 days of treatment before operation. Overall, only one of 131 (0.8%) valves was culture-positive after 14 days of treatment. All valves infected with beta-haemolytic streptococci, nutritionally deficient streptococci and the S. anginosus group, who were treated for more than 8 days before surgery, were culture-negative. CONCLUSIONS: Our findings support current treatment guidelines for endocarditis caused by alpha-haemolytic streptococci. We suggest that the recommended duration of treatment for endocarditis resulting from other streptococci may be excessive and treatment trials evaluating 2 and 4 week regimens are justified.

Changing donor and recipient demographics in a heart transplantation program: influence on early outcome.

BACKGROUND: The purpose of this study was to investigate whether broadening acceptance criteria for donor hearts and changing recipient demographics resulted in an increased perioperative morbidity and mortality in a heart transplant program. METHODS: Donor and recipient data of 137 consecutive heart transplants performed from 1987 to 2001 were retrospectively analyzed and divided into three equal eras, each of 5 years: 1987 to 1991, 1992 to 1996, and 1997 to 2001. Multivariate analyses of recipient and donor demographics and operative factors were performed to identify the predictors of low cardiac output, intraaortic balloon pump utilization, 30-day mortality, and duration of intensive care and hospital stay. RESULTS: Significant increases in number of female recipients (p = 0.025), cardiopulmonary bypass (p < 0.001), recipient cross-clamp (p < 0.001), donor age (p = 0.009), donor ischemic times (p < 0.001), use of cardioplegia (p < 0.001) and the bicaval technique (p < 0.001), brain death to retrieval time (p = 0.006), and need for postoperative dialysis were observed for the three study periods, whereas length of intensive care and hospital stay decreased. Female donor (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.0 to 5.7) was identified as a risk factor for low cardiac output. Female donor (OR, 3.7; 95% CI, 1.3 to 10.7), donor cardiac arrest (OR, 6.4; 95% CI, 1.6 to 25.9), and cardiopulmonary bypass time more than 2 hours (OR, 7.6; 95% CI, 2.1 to 28.1) were associated with increased intraaortic balloon pump utilization. Intensive care stay was prolonged by the biatrial technique (OR, 3.9; 95% CI, 1.3 to 11.9) and reduced by the use of cardioplegia (OR, 0.3; 95% CI, 0.1 to 0.9), longer cardiopulmonary bypass (OR, 0.2; 95% CI, 0.1 to 0.6) and aortic cross-clamp times (OR, 0.1; 95% CI, 0.03 to 0.6). CONCLUSIONS: Although a number of significant changes were observed during the study period, no donor, recipient, or operative factors influenced 30-day mortality. This study justifies our current donor and recipient selection policies.

Use of Monogen for pediatric postoperative chylothorax.

BACKGROUND: Postoperative chylothorax is a potentially serious complication of pediatric cardiac surgery. The purpose of this study was to report the use of Monogen enteral formula for the management of pediatric postoperative chylothorax. METHODS: A retrospective, single-institution 2-year study of all patients with a diagnosis of postoperative chylothorax was conducted. Chylothorax was diagnosed in 25 patients after a total of 535 cardiac operations in children younger than 10 years, for an incidence of 4.7%. Eighteen patients had been given Monogen, an enteral low long-chain triglyceride formula, as initial treatment. Six had been given total parenteral nutrition. The following variables were related to outcome and response to Monogen: age, sex, weight, underlying condition, type of surgery, interval between surgery and chylothorax diagnosis, duration and daily volume of chyle leak, central venous pressure, residual lesions, and weight loss. RESULTS: Enteral feeding with Monogen was successful for 14 of 18 patients with a response to treatment evident by the end of the third day. No variables predicted which patients would respond to Monogen. Body weight was maintained or increased in 14 of the 17 surviving patients taking Monogen. A return to normal diet at 4 +/- 1 weeks from the day of pleural drain removal did not result in recurrent chylothorax. CONCLUSIONS: A trial of Monogen is recommended as initial treatment for postoperative chylothorax unless enteral feeding is contraindicated.

Extended follow up after isolated aortic valve replacement in the elderly.

The present paper reviews the extended follow up of all patients aged >/=70 who underwent isolated aortic valve replacement at our institution in the 1980s. Patients were identified from the surgical database and clinical information was gathered. Long-term follow up information was obtained from the patient, their family, or doctor. Ninety-three patients aged >/=70 years (median 73, range 70-80) comprised the study population. The indication for surgery was aortic stenosis in 68 patients (73%). Fifty-two patients (56%) received an allograft valve, 17 (18%) a bioprosthetic valve, and 24 (26%) a mechanical prosthesis. The median hospital stay was 12 days (range 0-105 days). Five surgical deaths occurred. Detailed follow up was obtained for the 71 patients who died later, and the 16 living patients (one patient lost). The median length of follow up was 6.8 years (range 0.1-18.9 years). Patients who received an allograft aortic valve had a significantly better long-term survival (median 10.6, 95% confidence intervals (CI) 8.1-13.8 years) compared to those receiving mechanical or bioprosthetic valves (median 6.5, 95% CI 4.7-11.9 years), P = 0.03. For the entire group, survival was similar to the age- and sex-matched population. Of the 16 patients alive at follow up (mean age 87, range 83-92), most were free of angina (12, 75%) and heart failure (10, 63%). The conclusion from the current study is that isolated aortic valve surgery in the elderly, particularly with an allograft valve, is associated with an excellent long-term outcome. A survival benefit was demonstrated comparing allograft aortic valve replacement to other valve types.