Differential visceral blood flow in the hyperdynamic circulation of patients with liver cirrhosis.

BACKGROUND: With advancing liver disease and the development of portal hypertension, there are major alterations in somatic and visceral blood flow. Using phase-contrast magnetic resonance angiography, we characterised alterations in blood flow within the hepatic, splanchnic and extra-splanchnic circulations of patients with established liver cirrhosis. AIM: To compare blood flow in splanchnic and extra-splanchnic circulations in patients with varying degrees of cirrhosis and healthy controls. METHODS: In a single-centre prospective study, 21 healthy volunteers and 19 patients with established liver disease (Child's stage B and C) underwent electrocardiogram-gated phase-contrast-enhanced 3T magnetic resonance angiography of the aorta, hepatic artery, portal vein, superior mesenteric artery, and the renal and common carotid arteries. RESULTS: In comparison to healthy volunteers, resting blood flow in the descending thoracic aorta was increased by 43% in patients with liver disease (4.31 ± 1.47 vs. 3.31 ± 0.80 L/min, P = 0.011). While portal vein flow was similar (0.83 ± 0.38 vs. 0.77 ± 0.35 L/min, P = 0.649), hepatic artery flow doubled (0.50 ± 0.46 vs. 0.25 ± 0.15 L/min, P = 0.021) and consequently total liver blood flow increased by 30% (1.33 ± 0.84 vs. 1.027 ± 0.5 L/min, P = 0.043). In patients with liver disease, superior mesenteric artery flow was threefold higher (0.65 ± 0.35 vs. 0.22 ± 0.13 L/min, P < 0.001), while total renal blood flow was reduced by 40% (0.37 ± 0.14 vs. 0.62 ± 0.22 L/min, P < 0.001) and total carotid blood flow unchanged (0.62 ± 0.20 vs. 0.65 ± 0.13 L/min, P = 0.315). CONCLUSIONS: Rather than a generalised systemic hyperdynamic circulation, liver disease is associated with dysregulated splanchnic vasodilatation and portosystemic shunting that, while inducing a high cardiac output, causes compensatory extra-splanchnic vasoconstriction - the 'splanchnic steal' phenomenon. These circulatory disturbances may underlie many of the manifestations of advanced liver disease.

A first-in-class, first-in-human, phase I trial of p28, a non-HDM2-mediated peptide inhibitor of p53 ubiquitination in patients with advanced solid tumours.

BACKGROUND: This first-in-human, phase I clinical trial of p28 (NSC745104), a 28-amino-acid fragment of the cupredoxin azurin, investigated the safety, tolerability, pharmacokinetics and preliminary activity of p28 in patients with p53(+) metastatic solid tumours. METHODS: A total of 15 patients were administered p28 i.v. as a short infusion three times per week for 4 weeks followed by a 2-week rest under an accelerated titration 3+3 dose escalation design until either a grade 3-related adverse event occurred or the maximum tolerated dose (MTD) was reached. Single-dose and steady-state serum pharmacokinetics were characterised. Assessments included toxicity, best objective response by RECIST 1.1 Criteria, and overall survival. RESULTS: No patients exhibited any dose-limiting toxicities (DLTs), significant adverse events or exhibited an immune response (IgG) to the peptide. The No Observed Adverse Effect Level (NOAEL) and MTD were not reached. Seven patients demonstrated stable disease for 7-61 weeks, three a partial response for 44-125 weeks, and one a complete response for 139 weeks. Three patients are still alive at 158, 140, and 110 weeks post therapy completion. CONCLUSION: p28 was tolerated with no significant adverse events. An MTD was not reached. Evidence of anti-tumour activity indicates a highly favourable therapeutic index and demonstrates proof of concept for this new class of non-HDM2-mediated peptide inhibitors of p53 ubiquitination.

Natural history of thoraco-abdominal aneurysm in high-risk patients.

INTRODUCTION: There is considerable interest in the role of novel endovascular techniques for the treatment of patients with complex aneurysms who are unsuitable for standard interventions. Knowledge of the natural history of these lesions, as well as other co-morbidities, is required in order that these techniques may be applied correctly in this high-risk group. METHOD: This study reviews the outcome of patients deemed to be unfit for surgery following assessment under the Scottish National Thoraco-abdominal aneurysm service (TAAA) service (2002-2008). RESULTS: Of 216 patients assessed, 89 (41%) patients were considered to be unfit for intervention. The median (interquartile range, IQR) age of patients was 75 (70-80) years and there were 39 men (44%). Median (IQR) aneurysm size was 6 (5.6-7.0) cm. The median (IQR) follow-up time was 12 (7-26) months. There were 49 (55%) deaths during the follow-up period of which 23 (47%) cases were due to ruptured TAAA and 26 (53%) were not aneurysm-related. Comparing patients with aneurysms <6 cm (33 patients) with those aneurysms > or =6 cm (56 patients) there was no difference in aneurysm-related death (p = 0.32) or all-cause mortality (p = 0.147). CONCLUSION: Aneurysm-related mortality amongst patients unsuitable for open TAAA surgery is considerable and evolving endovascular techniques may permit intervention in selected patients. However any intervention can only be justified if the patient's life expectancy is sufficient to allow benefit to accrue.

Contemporary results for open repair of suprarenal and type IV thoracoabdominal aortic aneurysms.

BACKGROUND: Endovascular and hybrid procedures are not yet widely established in the management of type IV thoracoabdominal aortic aneurysm (TAAA). Open surgery remains the treatment of choice until the long-term outcomes of these novel techniques are known. METHODS: This study reviewed a 10-year experience of open repair of non-ruptured type IV and suprarenal TAAA. All procedures were performed using a totally abdominal approach with supracoeliac clamping of the aorta. RESULTS: There were 53 patients (31 men; 58 per cent) of median age 69 (range 54-82) years. Forty-four patients had a type IV TAAA and nine a suprarenal aneurysm. Three patients (6 per cent) died within 30 days and the 12-month mortality rate for patients followed for at least 1 year was 6 per cent (three of 49). Ten patients (19 per cent) had a cardiac complication, 20 (38 percent) a respiratory complication, three (6 percent) required early reoperation, and one patient (2 percent) developed permanent paraplegia. There was one late death resulting from an aneurysm-related complication. CONCLUSION: Open repair of suprarenal aneurysms and type IV TAAA may be undertaken using a totally abdominal approach with acceptable levels of morbidity and mortality.

What proportion of basic surgical trainees continue in a surgical career? A survey of the factors which are important in influencing career decisions.

INTRODUCTION: Since the launch of Modernising Medical Careers, trainees are selected for a run-through training programme in a single surgical specialty. The surgical training bodies are currently considering the recommendations of the Tooke report as they review the policy for selection into surgical training in the UK. There is little information available on the factors involved in career choices amongst surgical trainees and this study aimed to address this issue. METHOD: Trainees appointed to the Basic Surgical Training Programmes in the west and south-east of Scotland (1996-2006) were contacted by email and invited to participate in an online survey. RESULTS: Of 467 trainees identified, valid email addresses were available for 299 of which 191 (64%) responded to the survey. One hundred and forty-nine (78%) trainees were still working in surgery but 38 (20%) had moved to a non-surgical specialty and 4 (2%) had left the medical profession. Of those who had obtained a NTN at the time of the survey (n = 138), 62 (45%) had a NTN in the specialty they chose at the start of the BST but 34 (25%) had changed to a different surgical specialty and 42 (30%) had left surgery altogether. For those still working in surgery, enjoyment of the specialty was the most important factor affecting career choice. Achieving an acceptable work/life balance was the most significant factor influencing trainees who left surgery. CONCLUSION: The majority of trainees recruited to surgery at an early stage change specialty or leave surgery altogether. Both social and professional factors are important in career choices. The findings of this study support a period of core surgical training to provide flexibility prior to further training in a surgical specialty.

Carotid endarterectomy: are we meeting the two week target?

OBJECTIVE: It has been recommended that carotid endarterectomy should be carried out within fourteen days of the index event if maximum stroke prevention benefit is to be achieved. The aim of this study was to see whether this target was being met in our region and where in the pathway delays occurred. METHODS: This was a retrospective review of all patients (n=75) undergoing carotid endarterectomy in 2006 in a regional vascular unit. Eleven patients were excluded as the timing of onset of symptoms was unclear, leaving 64 patients for further analysis. RESULTS: The median time-interval from onset of symptoms to surgery was 47 days (interquartile range 32-65 days). Five of 64 patients (4.5%) had a carotid endarterectomy within 14 days. Median time from onset of symptoms to presentation to health services was one day (IQR 0-7 days), from presentation to health services to neurovascular clinic was 16 days (IQR 10-23 days), from neurovascular clinic to vascular surgery clinic was 13 days (IQR 9-24 days), and from vascular surgery clinic to operation was 13 days (IQR 8-22 days). Fifteen of the 51 patients (29%) attending a neurovascular clinic and five of the 57 patients (9%) attending a vascular surgery clinic were seen within 14 days. CONCLUSION: The fourteen-day target is difficult to achieve due to the number of steps in the referral pathway. This delay may be jeopardising outcome. Reduction in the delay to surgery would require a multi-disciplinary approach and should involve education of the general public.

Successful management of both early and delayed-onset neurological deficit following extent II thoracoabdominal aneurysm repair.

INTRODUCTION: Delayed-onset paraplegia is an uncommon but devastating complication of thoracoabdominal aneurysm repair. REPORT: We report the successful use of repeat cerebrospinal fluid drainage in the management of both immediate- and delayed-onset (21 days) paraplegia in the same patient undergoing open Type II thoracoabdominal aneurysm repair. DISCUSSION: Few studies have looked specifically at preventing delayed onset of symptoms. We advocate continued attention to blood pressure management and hydration for the duration of hospital stay and recommend repeat CSF drainage if symptoms occur.

Refining the application of direct embryogenesis in sugarcane: Effect of the developmental phase of leaf disc explants and the timing of DNA transfer on transformation efficiency.

A rapid in vitro protocol using direct somatic embryogenesis and microprojectile bombardment was investigated to establish the developmental phases most suitable for efficient sugarcane transformation. Immature leaf roll disc explants with and without pre-emergent inflorescence tissue were compared. It was shown that for effective transformation to occur, explants should be cultured for several days to allow initiation of embryo development prior to bombardment. Leaf roll discs with pre-emergent inflorescences showed a higher degree of embryogenic competence than non-flowering explants, and transformation efficiency was higher when explants containing floral initials were bombarded. Despite the occurrence of high numbers of phenotypically negative plants, combining the use of inflorescent leaf roll discs with direct embryogenic regeneration has the potential to improve the speed and efficiency of transgenesis in sugarcane.

(2,2':6',2"-Terpyridine)platinum(II) complexes are irreversible inhibitors of Trypanosoma cruzi trypanothione reductase but not of human glutathione reductase.

(2,2':6',2"-terpyridine)platinum(II) complexes possess pronounced cytostatic activities against trypanosomes and leishmania. As shown here, the complexes are irreversible inhibitors of trypanothione reductase (TR) from Trypanosoma cruzi, the causative agent of Chagas' disease. The most effective derivatives are the (4'-chloro-2, 2':6',2"-terpyridine)platinum(II) ammine and the (4-picoline)(4'-p-bromophenyl-2,2':6',2" -terpyridine)platinum(II) complexes which in the presence of NADPH inhibit TR with second-order rate constants of about 1.3 x 10(4) M(-1) s(-1). The modified enzyme species possess increased oxidase activities. The inhibition is not reversed upon dialysis or treatment with low-molecular-mass thiols. Kinetic and spectroscopic data suggest that Cys52 in the active site has been specifically altered. Inhibition of this key enzyme of parasite thiol metabolism probably contributes to the antitrypanosomal activity of the compounds. In contrast to the parasite enzyme, most (terpyridine)platinum complexes interact only reversibly with human glutathione reductase and an initial inhibition is completely abolished during the course of the assay.

Emotion regulation and memory: the cognitive costs of keeping one's cool.

An emerging literature has begun to document the affective consequences of emotion regulation. Little is known, however, about whether emotion regulation also has cognitive consequences. A process model of emotion suggests that expressive suppression should reduce memory for emotional events but that reappraisal should not. Three studies tested this hypothesis. Study 1 experimentally manipulated expressive suppression during film viewing, showing that suppression led to poorer memory for the details of the film. Study 2 manipulated expressive suppression and reappraisal during slide viewing. Only suppression led to poorer slide memory. Study 3 examined individual differences in typical expressive suppression and reappraisal and found that suppression was associated with poorer self-reported and objective memory but that reappraisal was not. Together, these studies suggest that the cognitive costs of keeping one's cool may vary according to how this is done.

CI-980 in advanced melanoma and hormone refractory prostate cancer.

INTRODUCTION: CI-980 is a novel chemotherapeutic agent that inhibits polymerization of tubulin. Preclinical studies have indicated a high level activity of this agent against various tumor cell lines. METHODS: 13 malignant melanoma patients who had failed prior chemotherapy and/or immunotherapy and 13 hormone refractory prostate cancer patients, including 4 who had received prior chemotherapy, were treated in 2 separate NCI-supported clinical trials. Subjects received a recommended phase II dose of CI-980 of 4.5 mg/m2/day by continuous infusion for 72 hours every 3 weeks. RESULTS: No activity was seen in either study. Toxicity was tolerable with neutropenia being the most common, significant toxicity. Among the melanoma patients, 15% and 31% developed grade 3 and grade 4 neutropenia, while 7% and 38% of the prostate patients developed grade 3 and grade 4 neutropenia, respectively. CONCLUSIONS: CI-980 at this dose and schedule is ineffective against malignant melanoma and hormone refractory prostate cancer.

Effects of disclosure of traumatic events on illness behavior among psychiatric prison inmates.

To assess the health effects of writing about traumatic events in a clinical population, 98 psychiatric prison inmates were randomly assigned to 1 of 3 conditions in which they were asked to write about their deepest thoughts and feelings surrounding upsetting experiences (trauma writing condition), write about trivial topics (trivial writing control), or go about their daily routine without writing (no-writing control). Both writing groups wrote for 20 min per day for 3 consecutive days. Participants in the trauma condition reported experiencing more physical symptoms subsequent to the intervention relative to those in the other conditions. Despite this, controlling for prewriting infirmary visits, sex offenders in the trauma writing condition decreased their postwriting infirmary visits. These results are congruent with predictions based on stigmatization and inhibition.

Development of the fertility adjustment scale.

OBJECTIVE: To develop a standardized measure of psychological adjustment to infertility. DESIGN: A cross-sectional two-group comparison study. SETTING: Two specialized fertility clinics in large teaching hospitals. PATIENT(S): Fifty men and 50 women undergoing evaluation and/or treatment of fertility problems. INTERVENTION(S): The Fertility Adjustment Scale was administered with the Hospital Anxiety and Depression Scale as a measure of concurrent validity. MAIN OUTCOME MEASURE(S): Scores on the Fertility Adjustment Scale and the Hospital Anxiety and Depression Scale. RESULT(S): Scores on the Fertility Adjustment Scale were distributed normally. Split-half and internal consistency were high. A significant correlation with measures of mood, anxiety, and distress provided evidence of concurrent validity. CONCLUSION(S): Preliminary results suggest that this measure will be a useful tool in assessing psychological reactions to fertility problems and outcomes of treatment.

Combination of chemotherapy with interleukin-2 and interferon alfa for the treatment of metastatic melanoma.

PURPOSE: The primary objective of this clinical study was to assess the feasibility of administering recombinant interleukin-2 and recombinant interferon alfa-2a before and after combination cytotoxic chemotherapy. After encouraging initial responses, the study was expanded to further evaluate the therapeutic potential, clarify the toxicities of this regimen, and explore any associated immunologic changes. PATIENTS AND METHODS: Eighty-four patients with metastatic melanoma, including patients with brain metastases, were treated on this 6-week protocol. Patients received combination cisplatin (25 mg/m2/d) and dacarbazine (220 mg/m2/d) on days 1 through 3 and 22 through 24 plus carmustine (150 mg/m2) on day 1. Interleukin 2 (13.5 million IU/m2/d) and interferon alfa (6 MU/m2/d) were administered on days 4 through 8 and 17 through 21. RESULTS: Among 83 patients assessable for response, 12 complete and 34 partial responses were documented (55% response rate). The median time to disease progression was 7 months, the median survival from study entry was 12.2 months, and the median survival from diagnosis of metastatic disease was 15.5 months. Although patients were hospitalized to receive treatment, intensive care unit support generally was not needed. Dose-limiting toxicities were related to elevations in serum bilirubin and serum creatinine levels. No patient developed a grade 4 clinical toxicity. Treatment produced a skin depigmentation, which was associated with prolonged survival. CONCLUSION: A plateau in both the survival and time to progression curves beyond 2 years (15% of the patients) and a greater than 10% disease-free survival beyond 4 years indicate that there may be a long-term benefit for some patients. The limited toxicity of this regimen should permit its use in most oncology settings. A randomized trial of chemoimmunotherapy versus chemotherapy should be performed to establish the value of chemoimmunotherapy for melanoma.

Asthma self-management: do patient education programs always have an impact?

BACKGROUND: During the past 15 years, programs to improve self-management practices in adults with asthma have reported improvement in functional status and reduction of inappropriate use of health care services. However, these programs usually represent an ideal approach, applying multiple patient education methods. Consequently, when these programs are found to be efficacious, it is important to replicate the programs as well as to evaluate less complex methods that may be more appropriate for nonacademic health care settings. METHODS: We compared the following 3 standardized self-management treatments in a randomized, controlled trial: (1) a replication of the self-management program developed at a university medical center that was previously shown to be efficacious; (2) a modified version of this program including only the core elements; and (3) a usual-care program. Outcome measures included medication and inhaler regimen adherence, asthma symptoms, respiratory illness, functional status, and use of health care resources. RESULTS: All 3 groups improved on measures of respiratory illnesses, use of health care services, and functional status. Patients in both education groups did no better than the usual-care group. CONCLUSIONS: The results are inconsistent with the results of the first asthma self-management study at this institution and with those of efficacy studies of similar programs. Two factors, selection of the patient population and historical changes in asthma treatment, most likely contributed to the lack of impact of the self-management programs. As a result of the improved standards for usual care due to both factors, the opportunity to effect patient outcomes was substantially reduced.

Surgical adjuvant active specific immunotherapy for patients with stage III melanoma: the final analysis of data from a phase III, randomized, double-blind, multicenter vaccinia melanoma oncolysate trial.

BACKGROUND: A phase III, randomized, double-blind, multicenter trial of active specific immunotherapy (ASI) using vaccinia melanoma oncolysate (VMO) was performed in patients with stage III (American Joint Commission on Cancer) melanoma to determine the efficacy of VMO to increase the disease-free interval (DFI) or overall survival (OS) in these patients. Two interim analyses of data from this trial were performed in May 1994 and June 1995. Although the results from these analyses showed no statistically significant improvement in DFI or OS in all patients using VMO, two subsets-men aged 44-57 years with one to five positive nodes and all patients with clinical stage I and pathologic stage II disease-showed an overall survival advantage with VMO therapy. A final analysis of data from this trial was performed in May 1996 and is reported here. The design of future melanoma vaccine trials is discussed based on information learned from this first randomized, multicenter trial of ASI therapy. STUDY DESIGN: A polyvalent VMO was prepared using melanoma cells derived from four melanoma cell lines and vaccinia vaccine virus (V). Patients were accrued from 11 United States institutions and were randomized by the Statistical Center at the University of Alabama, Birmingham. Two hundred fifty patients were randomized to treatment with either VMO (1 U containing 2 mg of total protein derived from 5 x 10(6) melanoma cells and 10(5.6) 50% tissue culture infectious dose of vaccinia virus) or control V (1 U containing 10(5.4) 50% tissue culture infectious dose of vaccinia virus) once a week for 13 weeks and then once every 2 weeks for a total of 12 months, or until recurrence. Patient data were collected by the Statistical Center and analyzed as of May 1996 for DFI and OS using Wilcoxon test and log-rank analysis. RESULTS: Two hundred seventeen patients were found to be eligible according to the inclusion criteria. Data from these patients were analyzed for DFI and OS after a median followup of 46.3 months (50.2 months for VMO and 41.3 months for V). This final analysis showed no statistically significant increase in either DFI (p = 0.61) or OS (p = 0.79) of patients treated with VMO (n = 104) compared with V (n = 113). At 2-, 3-, and 5-year intervals, 47.8%, 43.8%, and 41.7% of patients treated with VMO were disease-free, respectively, compared with 51.2%, 44.8%, and 40.4% of patients treated with V. At the same intervals, 70.0%, 60.0%, and 48.6% of patients treated with VMO survived, compared with 65.4%, 55.6%, and 48.2% of patients treated with V. In a retrospective subset analysis, male patients aged 44-57 years (n = 20) with one to five positive nodes showed 18.9%, 26.82%, and 21.3% improvement in survival at 2-, 3-, and 5-year intervals, respectively, after treatment with VMO when compared with V (n = 18) (p = 0.046). CONCLUSIONS: This study was a randomized, multicenter, placebo-controlled evaluation of an active specific immunotherapeutic agent to increase the DFI or OS of patients with stage III melanoma in a surgical adjuvant setting. In this trial, ASI with VMO when compared with V showed no difference in either DFI or OS. In a retrospective subset analysis, however, a subset of men with one to five positive nodes, between the ages of 44 and 57 years, showed a survival advantage with VMO. This result suggests that one must include a detailed subset analysis in the design of future trials of ASI for patients with American Joint Commission on Cancer stage III melanoma. An appropriate control arm also must be included in ASI trials.

Black-white differences on the Strong Interest Inventory General Occupational Themes and Basic Interest Scales at ages 16 to 65.

Black-white differences on the Strong Interest Inventory were examined for a heterogeneous sample of 756 Whites and 85 Blacks aged 16 to 65 years. Multivariate and univariate analyses of variance and covariance were conducted. Race, gender, and IQ were independent variables; the six Holland General Occupational Themes and the 23 Basic Interest Scales were dependent variables; and educational attainment was the covariate. All interactions were nonsignificant, but race was consistently a significant main effect. In general, Whites scored higher than Blacks on Realistic and Investigative themes and scales, and Blacks scored higher in the Social, Enterprising, and Conventional areas. These findings were viewed in the context of counselors' and psychologists' roles in interpreting interest pattern of Black individuals.

Phase I evaluation of interleukin-2-transfected irradiated allogeneic melanoma for the treatment of metastatic melanoma: appendix 1: protocol.

A cell line (UISO-H-MEL-2) was established from the neoplastic cells of a patient with malignant melanoma during the natural course of the patient's treatment. The melanoma cells express defined MHC Class I histocompatibility determinants including determinants specified by the HLA-A2 Class I allele, along with a common melanoma-associated T-cell epitope derived from the tyrosinase gene. The gene for human interleukin-2 (IL-2) was transduced into the cells with a provirus (pZipNeoSVIL-2), packaged in GP + envAM12 cells. Integration of the IL-2 gene into genomic DNA of the transduced cells and its expression were established. The IL-2-secreting cell line (UISO-H-MEL-2-IL-2) was found to be free of recombinant retroviruses and other infectious agents. The IL-2-secreting cells will be subjected to 5000 rads X-irradiation and administered to 12 informed patients with metastatic malignant melanoma in a Phase I toxicity study. The dose of X-irradiation was sufficient to inactivate one hundred percent of the cells, but insufficient to completely inhibit IL-2 synthesis during a fourteen-day period of analysis. Patients who have failed all standard forms of treatment will become eligible for inclusion in the study if they develop metastatic melanoma, and if their tumor cells express products of the tyrosinase gene. The patients will differ with the cellular immunogen at no less than three of six MHC Class I alleles, but will share identity at the HLA-A2 Class I allele. The patient's antimelanoma immune response to the injected cells will be determined by both in vivo and in vitro parameters. Background studies performed in inbred mice indicate that X-irradiated IL-2-secreting cells that express both melanoma-associated antigens and allogeneic Class I histocompatibility antigens are more antigenic in terms of their capacity to induce an antimelanoma response than X-irradiated IL-2-secreting melanoma cells. Of significance for the future potential of this form of therapy in melanoma patients, the period of survival of mice was established melanoma treated with the IL-2-secreting allogeneic cells was significantly (P < 0.001) longer than that of untreated animals, or animals treated with X-irradiated melanoma cells. An analogous protocol was reviewed and approved by the Recombinant DNA Advisory Committee of the National Institutes of Health.

Increased survival of patients treated with a vaccinia melanoma oncolysate vaccine: second interim analysis of data from a phase III, multi-institutional trial.

OBJECTIVE: The efficacy of vaccinia melanoma oncolysate (VMO) vaccine to increase overall survival and disease-free survival of patients with surgically resected International Union Against Cancer (UICC) stage II melanoma was studied in a phase III, randomized, multi-institutional trial. SUMMARY BACKGROUND DATA: Phase I and II trials with VMO showed minimal toxicity and clinical efficacy in patients with melanoma. In a recently completed phase III VMO trial, the first interim analysis performed in April 1994 showed an increasing trend in the survival of patients treated with VMO. The second interim analysis was performed in April 1995. METHODS: Patients with surgically resected stage II (UICC) melanoma were treated with VMO (N = 104) or placebo vaccinia vaccine virus (V) (N = 113) once a week for 13 weeks and then once every 2 weeks for a total of 12 months. Patients' clinical data were collected as of May 1995 and analyzed for survival. RESULTS: In this second interim analysis, the mean follow-up time is 42.28 months. No survival difference was observed between VMO and V treatments. However, in a retrospective subset analysis, a subset of males between the ages of 44 and 57 years and having one to five positive nodes (at 2-, 3-, and 5-year intervals, 13.6%, 15.9%, and 20.3% difference insurvival in favor of VMO [N = 20] when compared to V [N = 18] [p = 0.037]) and another subset of patients with clinical stage I (at 3- and 5-year intervals, 30% and 7% difference in survival in favor of VMO [N = 20] when compared to V [N = 23], [p = 0.05]) showed significant survival advantage with VMO. CONCLUSIONS: Although VMO vaccine therapy in surgical adjuvant setting did not produce a significant survival benefit to all patients with melanoma, patients from the above two subsets had significant survival benefit.