Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64.

[Biomechanical evaluation of the gliding nail in trochanteric fractures]. / Biomechanische Evaluation des Gleitnagels in der Versorgung pertrochantärer Frakturen.

AIM: The purpose of the present study is to evaluate wether the gliding nail with it's double-t-shaped geometry is appropriate in the stabilization of unstable trochanteric fractures or not and if this evaluation can be performed with a static finite element simulation. METHODS: Surface-Reconstruction with CT database of a proximal femur and reconstruction with CT based density data was done. After modelling of geometry, isotropic material behaviour and load application during one leg standing in slow walking was done with a limited dataset of relevant muscles. Two relevant fractures are modelled. RESULTS: FE-simulation shows a movement of the femoral head distally, medially and posteriorly. Maximum bending strain is in the femoral diaphysis medial compression and lateral tension strain. In the proximal part we find a nearly homogeneous strain distribution. The clinical effect of lateralization of the proximal main fragment is also result of the simulation. In the area of the modelled fractures there is much more compressive stress than shear stress. CONCLUSION: Elastomechanical behaviour of the gliding nail is demonstrated with correlation of clinical observed effects. In both simulated fracture areas there is a bone union supporting compressive stress. This means in the FE-simulation the gliding nail is appropriate in the stabilization in unstable trochanteric fractures.

Finite element analysis of a bone-implant system with the proximal femur nail.

Static analysis with finite element of a realistic femur nail bone-implant system in a typical proximal femoral fracture under physiological load bearing situations provides results for stress, displacement and strain. The question to be answered is, if simulation with the finite element analysis is able to explain biomechanically clinical observed patterns of failure. Surface-Reconstruction with CT database of a proximal femur and reconstruction with CT based density data was done. Next steps were to unite the bone structure with the Proximal Femoral Nail and to model two relevant fractures (31-A2.2 and A2.3 according AO). After modelling of geometry, isotropic material behaviour and load application numeric calculation of the femur-nail system with FE-software was performed. FE simulation mainly shows an axial dislocation of the femoral head screw with nearly no dislocation of the antirotation screw. This so-called z-effect therefore means: (1) Tilting of the proximal main fragment around the sagittal axis between the screws and (2) relative movement of both screws in the frontal plane. Relative movement of the two screws against each other could be the reason for implant failure, the so called cut out. Furthermore simulation shows different gliding of the screws explaining the so called z-telescoping. The analyzed stress patterns have to be relativized, because isotropic material behaviour of cancellous bone was assumed. Further examinations for this issue are necessary.

Minimal incision abdominal aortic aneurysm repair.

PURPOSE: The use of a limited incision for abdominal aortic aneurysm (AAA) repair was evaluated, and its outcome was analyzed in comparison to laparoscopic-assisted and standard open repair. METHODS: Eleven patients who had an AAA that required a tube graft underwent minimal incision (MINI) repair. The procedure consisted of a standard endoaneurysmorrhaphy performed through an 8- to 10-cm minilaparotomy. Clinical characteristics, in-hospital outcomes, and total in-hospital charges for this procedure were then compared with those of comparative groups of patients who had undergone repair of AAA by means of a laparoscopic-assisted (LAP) approach or a standard open (OPEN) technique. RESULTS: MINI repair was successfully completed in all 11 patients. Patients in the three groups were comparable for age, sex, risk factors, and aortic dimensions. The mean values for operative time, blood loss, length of hospital stay, and total hospital charges for the three comparison groups were: 129. 7 minutes (MINI) vs. 244.8 minutes (LAP)*, 209.9 minutes (OPEN)*; 522.7 mL (MINI) vs. 1214.7 mL (LAP), 1795.8 mL (OPEN)*; 5.18 days (MINI) vs. 18.7 days (LAP), 17.4 days (OPEN); $22,692 (MINI) vs. $59, 922 (LAP)*, $62,324 (OPEN)* (*P <.05). Local complications occurred in 18.2% of patients who underwent MINI repair, 23.5% of patients who underwent LAP repair, and 29.7% of patients who underwent OPEN repair (P = not significant). Patients undergoing minilaparotomy demonstrated decreased compromise of gastrointestinal function, with a decreased need for postoperative fluid resuscitation (6799.7 mL [MINI], 7781.8 mL [LAP] vs. 11061.1 mL [OPEN]*) and shortened nasogastric tube decompression (1.6 days [MINI], 1.5 days [LAP] vs. 4.1 days [OPEN]*; *P <.05). CONCLUSION: MINI repair is a technically feasible technique that combines the benefits of minimally invasive surgery with those of conventional open repair with few, if any disadvantages. Facility of the procedure, combined with the potential cost benefits, encourages further study for consideration of this technique as a viable alternative for the management of AAAs.

[Dying through the hand of man or taken by the hand of man? Results of an opinion poll concerning active euthanasia and the Hospice Movement]. / An der Hand oder durch die Hand eines Menschen sterben? Ergebnisse einer Befragung zu Sterbehilfe und Hospizbewegung.

BACKGROUND: Opinion polls show a growing support of active euthanasia in Germany. The hospice movement rejects active euthanasia and pleads for a qualified care for the dying. The aim of our study was to evaluate how far the work and the ideas of the hospice movement are known in Germany and to which extend this knowledge influences the attitude towards active euthanasia. METHODS: An interview of 200 people in the pedestrian area of Mainz was undertaken. RESULTS: 73% of all interviewees supported active euthanasia. Significant predictors for opposition to active euthanasia were increasing age and belonging to the roman catholic confession. However, 72% of active euthanasia supporters did not know what a hospice is, and 80% were not aware of the existence of such an establishment in Mainz. Opponents of euthanasia had significantly more knowledge of these items. CONCLUSION: The results of our study indicate that physicians should wherever possible explain the aims and the work of the hospice movement who should be their ally in a qualified commitment for the dying. It can be expected that the hospice movement will find a lot of sympathy in the population as 2 of its major aims--openness in communication and dying at home wherever possible--were shared by the vast majority of all interviewees: in case of incurable disease 92% wanted to be informed on their diagnosis, and 84% wanted to die at home or in their families home.

Warfarin anticoagulation in the perioperative period: is it safe?

This study was undertaken to determine if warfarin anticoagulation could be safely continued during surgery and in the perioperative period. An animal model was followed by a prospective human study of all patients on heparin or warfarin at the time of surgery. Twenty-four rabbits underwent laparotomy, during which a controlled liver injury was created and repaired. Group 1 (Warf) was anticoagulated with warfarin to raise the mean international normalization ratio (INR) to 2.5-3.0. Group 2 (Hep) was anticoagulated with heparin to raise the activated partial thromboplastin time to 1.5-2.0 times control. The heparin was then stopped 6 hr prior to surgery and resumed 6 hr postoperatively without a bolus. Group 3 (control) was not anticoagulated and received saline infusion. For the human study, data were collected on 40 patients undergoing 50 operations from October 1996 to January 1998. The results of this study reveal that (1) bleeding was less in the group anticoagulated with warfarin throughout surgery in the animal model, (2) bleeding complications were less in the patients continued on warfarin through surgery than those on heparin (3) older patients may have an increased risk of bleeding, and (4) an INR of >3 at the time of surgery may increase the risk of bleeding.

Relationship of protamine dosing with postoperative complications of carotid endarterectomy.

Protamine sulfate (PS) neutralization of heparin (HEP) given during carotid endarterectomy (CEA) has been previously associated with an increased postoperative stroke rate. Dosing regimens of PS have varied in previous studies. The accuracy of PS dosing and its effect on postoperative complications was analyzed. The medical records of all patients undergoing elective CEAs from January 1993 to June 1996 in our institution were reviewed. A hematoma was defined as either an event requiring return to the operating room or when repeatedly identified in the medical record. The accuracy of dosing PS was determined utilizing a formula calculating the logarithmic exponential decay of HEP, which determined the residual HEP at the time of PS dosing. An ideal PS dose was then calculated and compared to the dose given. Statistical analyses was performed using a Fisher's exact test as well as the Student's t-test. Four hundred-seven CEAs were performed in 365 patients. There were 10/407 (2.5%) postoperative strokes (STROKE) and 11/407 (2.7%) hematomas, 3 of which required reoperation. Results indicate that (1) the administration of PS significantly reduced the incidence of postoperative hematoma; (2) there appears to be an association between the administration of PS and STROKE; (3) the inaccuracy in dosing PS appears to be based on a decision to dose PS to the total HEP given rather than the residual HEP on board at the time of neutralization. The effect of PS overdosing is unclear, but it may play a role in STROKE.

Perioperative predictors of colonic ischemia after ruptured abdominal aortic aneurysm.

PURPOSE: Colonic ischemia and colonic resection occur frequently after ruptured abdominal aortic aneurysm (rAAA). The purpose of this study was to identify the perioperative risk factors that might help to determine earlier in the postoperative period which patients are at risk for colonic ischemia and colonic resection. METHODS: The medical records of the 43 patients who underwent repair of rAAA from January 1989 to November 1997 were reviewed. The data were reviewed for the following factors: acidosis, pressor agents, lactate levels, guaiac status, cardiac index, coagulopathy, early postoperative bowel movement, the lowest intraoperative pH level, the temperature at the conclusion of the case, the location and duration of aortic cross clamping, the amount of fluid boluses administered after surgery, the amount of packed red blood cells administered during the case, and the average systolic blood pressure at admission and during surgery. Univariate analysis was performed with Fisher exact test, chi2 test, and Student t test. Multivariate analyses also were performed with the variables that were found to be significant on the univariate analysis. RESULTS: Thirteen of the 43 patients (30. 2%) had colonic ischemia, and seven of the 13 underwent colonic resection (53.8%). The overall mortality rate was 51.2% (22/43) five of the deaths were intraoperative and excluded from the study. In a comparison of the patients who had colonic ischemia with those who did not, statistically significant differences were found in the following variables: average systolic blood pressure at admission 90 mm Hg or less, hypotension of more than 30 minutes' duration, temperature less than 35 degreesC, pH less than 7.3, fluid boluses administered after surgery 5 L or more, and packed red blood cells 6 units or more. Multivariate analysis indicated that the number of these variables present correlated significantly with the positive predicted probability of colonic ischemia occurring. No patient with two factors or fewer had an ischemic bowel, and the positive predictive probability of colonic ischemia for those patients with six factors was 80%. CONCLUSION: The results of this study show that: (1) colonic ischemia after rAAA may be predicted with the presence of two or more specific perioperative factors, (2) the lack of a guaiac-positive bowel movement may be misleading for the early diagnosis of colonic ischemia, and (3) more than 50% of the patients with colonic ischemia will require a colonic resection. We recommend that any patient with rAAA with more than two perioperative factors undergo sigmoidoscopy every 12 hours after surgery for 48 hours to rule out colonic ischemia without waiting for early or guaiac-positive bowel movement.

[Quality management in the hospital]. / Qualitätsmanagement im Krankenhaus.

Quality management in hospitals is a much discussed topic. However, mainly theorists take the floor, who have some good advice, but rarely have practical experience. All those theorists have been heard by the responsible person of the Fritz-König-hospital in Bad Harzburg, as well. At the end, however, an own system of quality management was developed with the aid of an external expert. This article describes the step-by-step introduction of quality management and the related experiences.

Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared to hydrochlorothiazide.

OBJECTIVE: To compare the antihypertensive efficacy of a new angiotensin II antagonist, valsartan, with a reference therapy, hydrochlorothiazide (HCTZ). METHODS: In this double-blind study, 167 adult out-patients with mild-to-moderate essential hypertension were randomly allocated in equal number to receive valsartan 80 mg or HCTZ 25 mg for 12 weeks. In patients whose blood pressure (BP) remained uncontrolled after 8 weeks of monotherapy, atenolol 50 mg was added to the initial treatment. Patients were assessed at 4, 8 and 12 weeks. The primary efficacy variable was change from baseline in mean sitting diastolic BP (SDBP) at 8 weeks. Secondary variables included change in sitting systolic BP (SSBP) and responder rates (percentage of patients with SDBP < 90 mmHg or drop > or = 10 mmHg compared to baseline) at 8 weeks. RESULTS: Valsartan and HCTZ were both effective at lowering diastolic and systolic blood pressure at all time points. Similar falls were seen in both groups with no significant differences between treatments. For the primary variable (decrease in SDBP) there was no significant difference between treatments. For SSBP there was also no significant difference observed. Responder rates at 8 weeks were 74% for valsartan and 62% for HCTZ (P = 0.10). Both treatments were well tolerated, both as monotherapy, and when combined with atenolol 50 mg per day. CONCLUSION: The data show valsartan 80 mg to be as effective as HCTZ in the treatment of mild-to-moderate hypertension. The results also show valsartan to be well tolerated when taken alone or in combination with atenolol.

Is preoperative cardiac evaluation for abdominal aortic aneurysm repair necessary?

PURPOSE: It is reported that 25% to 50% of patients with abdominal aortic aneurysms (AAA) have severe coronary artery disease (CAD) and should undergo an aggressive cardiac workup before AAA repair. In contrast, it has been our policy that patients referred for AAA repairs undergo no cardiac testing before surgery. METHODS: This report reviews the last 113 consecutive patients who underwent elective AAA repair by the senior author using this policy. Seventy-four patients (group A) had only an electrocardiogram before surgery. The remaining 39 patients (group B) were referred having already had additional testing that included a thallium stress test (n = 20), echocardiogram (n = 18), multiple gated acquisition (MUGA) scan (n = 3), cardiac catheterization (n = 8), or some combination of these. RESULTS: There was no statistical difference between group A and group B with regard to age, sex, tobacco use or history of coronary artery disease, diabetes mellitus, stroke (CVA), hypertension, peripheral vascular disease, or chronic obstructive pulmonary disease. Group B more commonly had a history of myocardial infarction (41% vs 19%, p < 0.03) and congestive heart failure (23% vs 7%, p < 0.03). During surgery there was no significant differences in blood loss, transfusion requirements, or operative times. There were no myocardial infarctions in group A and two (5.1%) in group B, which was not significantly different. Other complications, such as CVA, renal failure, pulmonary failure, pneumonia, wound infection, and hemorrhage, were not significantly different between the two groups. Postoperative hospital stay was not significantly different. There were three deaths in the entire series (2.7%), and only one in group B was cardiac-related in a patient with known end-stage cardiac disease and a symptomatic 8 cm AAA. CONCLUSIONS: These data indicate that most patients with AAA can safely undergo repair with no cardiac workup and that cardiac workup before AAA repair contributes little information that impacts on treatment or final clinical outcome. We conclude that cardiac testing in preparation for AAA repair is not usually necessary and that intraoperative hemodynamic management may be the most important variable in determining outcome.

Laparoscopic-assisted abdominal aortic aneurysm repair.

Since the advent of laparoscopy, the sweeping changes seen in general surgery have not been paralleled in vascular surgery. There have been case reports of laparoscopic-assisted aortobifemoral bypass for occlusive disease. Because aneurysmal disease comprises the majority of aortic surgery, we pursued animal and cadaveric feasibility studies for laparoscopic-assisted abdominal aortic aneurysm (AAA) repair. We present a case report of the first clinical case performed under Institutional Review Board protocol using this technique. The patient was a 62-year-old male with a 6-cm infrarenal AAA. After obtaining a pneumoperitoneum, a modified fish retractor was used to exclude the bowel. Ten 11-mm ports provided access to laparoscopically dissect the neck of the aneurysm and the iliac vessels. Then, a 10-cm minilaparotomy was performed and standard vascular clamps were inserted via the port incisions. Standard aneurysmorraphy was performed with a polytetrafluoroethylene (PTFE) tube graft. Laparoscopy conferred three major benefits: better visualization of the aneurysm neck, less bowel manipulation, and avoidance of hypothermia. This case report illustrates the feasibility of laparoscopic-assisted aneurysm repair. Controlled human studies will define the role of laparoscopy in AAA surgery.

Hemodialysis graft salvage.

Hemodialysis access procedures account for a large percentage of patients undergoing surgical treatment. Salvage procedures are frequently used to extend the life of a thrombosed graft and thereby maximize the limited available access sites. Factors that may influence the success of salvage procedures, as well as the financial risk to benefit comparison, may be of increasing importance in the era of aggressive medical cost containment. The charts of 70 patients who underwent 116 thrombectomies or revisions of polytetrafluoroethylene (PTFE) hemodialysis arteriovenous grafts of the upper extremity for thrombosis were retrospectively analyzed. Patency of salvaged grafts by life-table analysis was 75.0 percent at two days, 45.0 percent at 30 days, 18.0 percent at 120 days and 2.5 percent at one year. Patency was 59 and 25 percent for revised grafts at 30 and 120 days, respectively, versus 30 and 10 percent at the same time intervals for thrombectomized grafts only. Minimum combined operative and hospital costs were $4,350 per salvage attempt. Salvage patency of PTFE dialysis grafts of the upper extremity was dismal, especially when thrombectomy alone was used. No specific patient factors were predictive of patency interval. Based upon these results, we cannot continue to recommend graft thrombectomy alone for thrombosed dialysis grafts. Because the poor results with graft revision as well, placement of a new graft without any attempt at salvage may be the best therapeutic and cost-effective option.

Brief depression among patients in general practice. Prevalence and variation by recurrence and severity.

Depression with substantial psychosocial impairment, but not qualifying as depressive disorder according to the standard diagnostic manuals, is frequent among primary care patients. Recurrent brief depression (RBD) is a diagnostic category intended to identify a major proportion of this group of patients. The WHO study on "Psychological Problems in Primary Health Care" was used as a vehicle to estimate the proportion of patients with this diagnosis and to evaluate the validity of this diagnosis as well as of alternative concepts of brief depression with multiple episodes. This study applies a two-stage sampling scheme; 300 patients also underwent an additional interview tailored for variants of brief depression. 7.6% of primary care patients were identified as RBD with the majority not receiving any other psychiatric diagnosis (DSM-III-R). These patients reported substantial psychosocial impairment, and the majority were identified as psychological cases by general practitioners. However, patients experiencing other variants of brief episodes were also found to be substantially psychosocially impaired, although they were not identified as psychiatric cases by DSM-III-R. Thus, a less restrictive definition of RBD is proposed. The diagnostic definition of RBD has a major impact on the sex ratio of cases: the less restrictive the diagnosis, the more balanced are the prevalence rates between males and females.

Hypothermia and bleeding during abdominal aortic aneurysm repair.

Patients undergoing abdominal aortic aneurysm repair routinely have a depressed core body temperature during surgery, and hypothermia is known to cause abnormalities in coagulation. This study was designed to determine whether platelet function is altered as a result of hypothermia or heparin during abdominal aortic aneurysm repair. Ten patients scheduled for abdominal aortic aneurysm surgery were prospectively studied. Bleeding times and temperature were measured every hour beginning preoperatively. Each patient was heparinized intraoperatively, and the effects reversed with protamine sulfate prior to closure. Despite efforts to keep the patients warm, all of them developed hypothermia (mean lowest core temperature 34.8 +/- 0.7 degrees C). A significant linear relationship between the change in core temperature and the change in bleeding time was demonstrated. In 7 of 10 cases the greatest change in bleeding time occurred when patients experienced the lowest mean core temperature and not when they were heparinized. These data suggest that hypothermia has a marked effect on platelet function during abdominal aortic aneurysm repair. Although heparin can cause abnormalities in platelet function, hypothermia may be a more important role in inhibiting normal platelet function. By preventing severe hypothermia (< 35 degree C), excessive bleeding associated with abdominal aortic aneurysm repair may be minimized without the concomitant risk of blood product transfusion.

[A one year study of single administration of nilvadipine. Results of the effectiveness and long-term tolerance in hypertension]. / Einjahresstudie über die Einmalgabe von Nilvadipin. Ergebnisse zur Wirksamkeit und Langzeitverträglichkeit bei Hypertonikern.

AIM: To test the efficacy and long-term tolerability of a single daily dose of nilvadipine. STUDY DESIGN: Open, multicenter follow-up study of 8-months duration following a 4-month randomized double-blind preliminary study (vs. nifedipine). PATIENTS: 307 ambulatory hypertensives with a diastolic blood pressure of < or = 95 mm Hg at the end of the preliminary study. MEDICATION: One capsule of nilvadipine retard 8 or 16 mg taken once a day (in the morning). PARAMETERS: Monthly recording of blood pressure, pulse rate and body weight, and any adverse reactions: global assessment by the physician of tolerability and efficacy in month 12; in addition, ECG and laboratory parameters in months 6, 9 and 12. RESULTS: In more than 95% of the patients, nilvadipine reduced blood pressure to normal levels. Some 95% of the physicians investigated assessed efficacy and tolerability to be "good" to "very good". The direct changeover of medication from nifedipine t.i.d. to a single daily dose of nilvadipine presented no problems.