Low conversion rates toward total hip arthroplasty after hemiarthroplasty in patients under 75 years of age.

INTRODUCTION: An intracapsular fracture of the femoral neck is frequent in the elderly. Patients can be treated with either total hip arthroplasty or hemiarthroplasty. There is a continuous discussion about the treatment in elderly patients who are still healthy, active and mentally untroubled. A potential consequence of hemiarthroplasty, especially in the relatively young elderly, could be conversion to total hip arthroplasty. The conversion rate must be acceptable, and clinical outcome must be sufficient to justify the treatment with hemiarthroplasty in this group of patients. This study evaluates the conversion rate of hemiarthroplasty to total hip arthroplasty and clinical outcome in patients under 75 years of age. METHODS: This study identified 248 patients, younger than 75 years at time of operation, with a fracture of the femoral neck treated with hemiarthroplasty. Patient-reported outcome measurements (VAS pain during rest and activity and WOMAC) were assessed by telephone interviews. Furthermore, radiographic evaluation for the presence of acetabular wear was performed. RESULTS: At a follow-up of 5.1 (0.9-9.6) years, the conversion rate was 7.3%. Mean VAS pain in rest was 0.89 (0-10), the mean VAS pain during activity was 2.2 (0-10), and the WOMAC showed a mean of 16.51 (0-64). At time of follow-up, 38.7% of patients had died. Radiographic evaluation of the unrevised group showed in one patient signs of acetabulum wear. CONCLUSION: Hemiarthroplasty in the relatively young elderly after a fracture of the femoral neck demonstrates an acceptable conversion rate. Furthermore, unrevised patients show low complaints of pain. To prevent one conversion to total hip arthroplasty, 13.7 patients should be treated with total hip arthroplasty that will not undergo a conversion at a later stage. Therefore, hemiarthroplasty remains a viable treatment of femoral neck fractures in relatively young patients. There seems to be no space for standardized decision making concerning the choice of treatment. An individual approach is required.

No decline in high patient satisfaction after total hip arthroplasty at long-term follow-up.

INTRODUCTION: Patient satisfaction is gaining popularity as an important outcome parameter in today's healthcare system and in particular in evaluating the outcome of joint arthroplasty. Total hip arthroplasty (THA) is a very successful procedure with reports on high patient satisfaction at short-term follow-up. Commonly used clinical outcome parameters remain good at long-term follow-up; however, whether this also accounts for patient satisfaction remains unclear. This study presents a prospective follow-up of patient satisfaction after THA, and a possible correlation with common outcome parameters was established. METHODS: This study entails a concise follow-up of an earlier study on patient satisfaction 2.5 years after THA. Patient satisfaction was repeatedly measured with a visual analogue scale (VAS) after a mean follow-up of 13.5 (12.6-14.2) years in a prospective cohort of 147 patients (153 THAs). In addition, VAS pain and common clinical outcome parameters (WOMAC, OHS and SF-36) were also reassessed and were compared with short-term results after a mean follow-up of 2.5 (1.3-3.0) years. RESULTS: At a follow-up of 13.5 (12.6-14.2) years, the median VAS for satisfaction was 95 (26-100) compared to a median VAS satisfaction of 98 (0-100) at earlier follow-up (p = 0.781). Overall, the clinical outcome parameters also remained good at long-term follow-up without significant changes. However, a rather low correlation with VAS satisfaction was encountered. Pain during activity showed the highest correlation (- 0.686) with VAS satisfaction. CONCLUSION: Patient satisfaction after THA remains high after prolonged follow-up. Apparently patients do not get used to the successful results of their THA. A rather low correlation with common clinical outcome parameters suggests that patient satisfaction is a separate entity. Since patient satisfaction correlated best with pain during activity, this is probably the most important aspect in patient satisfaction. Measurement of patient satisfaction has additional value and may even replace some of the more commonly used questionnaires.

Comparison of tenocytes and mesenchymal stem cells seeded on biodegradable scaffolds in a full-size tendon defect model.

In order to investigate cell-based tendon regeneration, a tendon rupture was simulated by utilizing a critical full-size model in female rat achilles tendons. For bridging the defect, polyglycol acid (PGA) and collagen type I scaffolds were used and fixed with a frame suture to ensure postoperatively a functional continuity. Scaffolds were seeded with mesenchymal stem cells (MSC) or tenocytes derived from male animals, while control groups were left without cells. After a healing period of 16 weeks, biomechanical, PCR, histologic, and electron microscopic analyses of the regenerates were performed. Genomic PCR for male-specific gene was used to detect transplanted cells in the regenerates. After 16 weeks, central ossification and tendon-like tissue in the superficial tendon layers were observed in all study groups. Biomechanical test showed that samples loaded with tenocytes had significantly better failure strength/cross-section ratio (P < 0.01) compared to MSC and the control groups whereas maximum failure strength was similar in all groups. Thus, we concluded that the application of tenocytes improves the outcome in this model concerning the grade of ossification and the mechanical properties in comparison to the use of MSC or just scaffold materials.

Complications and survival of conversion to total hip arthroplasty after failed primary osteosynthesis compared to primary total hip arthroplasty in femoral neck fractures.

INTRODUCTION: Surgical treatment options for patients with an intracapsular fracture of the femoral neck (FFN) are primary osteosynthesis as a femoral head-spearing technique or primary (hemi)arthroplasty. The most common complications after primary osteosynthesis, such as avascular necrosis (AVN) or non-union, can result in conversion to Total Hip Arthroplasty (cTHA). Data concerning complications and survival rates of cTHA in comparison to primary Total Hip Arthroplasty (pTHA) after FFN are limited due to the absence of well-designed studies. METHODS: A multicentre retrospective cohort study was conducted in three Dutch hospitals comparing the rate of postoperative dislocations, periprosthetic fractures, prosthetic joint infections, blood loss during surgery (>1000 mL), postoperative cardiac- and pulmonary complications after pTHA and cTHA in the first year after surgery. As a secondary outcome implant survival of pTHA and cTHA in terms of revision rates was evaluated. RESULTS: In total 548 patients were included (pTHA n = 264 and cTHA n = 284) with a mean follow-up of 5 years (±3.5 SD). No significant differences were found in postoperative complications rates. The revision rate in the pTHA group was 7.2% in comparison to 7.7% in the cTHA group (p = 0.81). No difference in the short-term implant survival was found between both groups (p = 0.81). CONCLUSION: This study showed no significant differences in terms of postoperative complication rates in the first year after pTHA and cTHA in patients with FFN. Also, no significant difference in short-term implant survival of primary and conversion total hip arthroplasty was found.

Therapeutic surgical management of palpable melanoma groin metastases: superficial or combined superficial and deep groin lymph node dissection.

BACKGROUND: Management of patients with clinically detectable lymph node metastasis to the groin is by ilioinguinal or combined superficial and deep groin dissection (CGD) according to most literature, but in practice superficial groin dissection (SGD) only is still performed in some centers. The aim of this study is to evaluate the experience in CGD versus SGD patients in our center. METHODS: Between 1991 and 2009, 121 therapeutic CGD and 48 SGD were performed in 169 melanoma patients with palpable groin metastases at our institute. Median follow-up was 20 and, for survivors, 45 months. RESULTS: In this heterogeneous group of patients, overall (OS) and disease-free survival, local control rates, and morbidity rates were not significantly different between CGD and SGD patients. However, CGD patients had a trend towards more chronic lymphedema. Superficial lymph node ratio, the number of positive superficial lymph nodes, and the presence of deep nodes were prognostic factors for survival. CGD patients with involved deep lymph nodes (24.8%) had estimated 5-year OS of 12% compared with 40% with no involved deep lymph nodes (p=0.001). Preoperative computed tomography (CT) scan had high negative predictive value of 91% for detection of pelvic nodal involvement. CONCLUSIONS: This study demonstrated that survival and local control do not differ for patients with palpable groin metastases treated by CGD or SGD. Patients without pathological iliac nodes on CT might safely undergo SGD, while CGD might be reserved for patients with multiple positive nodes on SGD and/or positive deep nodes on CT scan.

A randomized phase II study comparing two schedules of the 21-day regimen of gemcitabine and carboplatin in advanced non-small cell lung cancer.

PURPOSE: Carboplatin area under the curve (AUC) 5 ml/min on day 1 with gemcitabine 1,250 mg/m(2) on day 1 and day 8 is a widely used regimen in advanced non-small cell lung cancer. Grade 3-4 thrombocytopenia and neutropenia are frequent. The aim of this study is to investigate whether toxicity of gemcitabine/carboplatin could be reduced by administering carboplatin on day 8 instead of day 1 without a decrease in response rate (RR). METHODS: Patients received gemcitabine 1,250 mg/m(2) on days 1 and 8, carboplatin AUC 5 on day 1 (arm A) or day 8 (arm B). Drugs were administered over a 21-day cycle. Toxicity and RR were evaluated weekly and every second cycle, respectively. RESULTS: 71 patients were enrolled into the study. We found 79% (95% CI 61-91%) grade 3-4 toxicity (neutropenia and thrombocytopenia) in arm A and 50% (95% CI 32-68%) in arm B; 66% grade 3-4 thrombocytopenia in arm A and 26% in arm B. We observed 30% grade 4 hematological toxicity in arm A and 3% in arm B. In arm A an overall RR of 20% (95% CI 7.7-38.6%) was seen, and 18.2% (95% CI 7-35.5%) in arm B. CONCLUSIONS: Although the study was prematurely closed, the current data are of interest. The schedule with carboplatin on day 8 is associated with substantially lower grade 3-4 neutropenia and thrombocytopenia with comparable dose intensity and RR.

Crop plants versus energy plants--on the international food crisis.

The recent price explosion of important agricultural commodities has lead to an international food crisis. The price rise is attributed to fundamental factors, such as the rising demand for dairy and meat products in China and the development of the bioenergy branch as well as on short-term factors such as the behaviour of speculators. Mobilising the worldwide supply can held to overcome the demand driven shortage of food this can be achieved through a proper design of the agricultural policy both in developed and developing countries.

Outcomes of first-line chemotherapy in patients with advanced or metastatic leiomyosarcoma of uterine and non-uterine origin.

Although leiomyosarcomas (LMSs) form the largest subgroup of soft tissue sarcomas (STSs), the efficacy of chemotherapy in this group is largely unclear, partly because older studies are contaminated with gastrointestinal stromal tumors (GISTs). In this retrospective study we investigated the outcome of first line chemotherapy in 65 patients with unresectable or metastatic LMS. The overall response rate (ORR) was 18%; and the median progression-free (PFS) and overall survival (OS) were 3.8 and 9.7 months respectively. No statistically significant differences in outcomes for uterine and non-uterine LMS were found. In non-uterine LMS, however, the PFS and OS seemed to be longer for females than for males, potentially negatively affecting outcomes in this group. If our observations are confirmed in other series, they would suggest that studies performed in STS patients should not only stratify for histological subtype but also for uterine versus non-uterine LMS and for gender.

The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: a review on 5232 patients.

EGF-R positivity was shown to be present in 2500 (48%) of 5232 breast tumors in 40 different series of patients. The mean of the percentages of EGF-R positivity in the individual series reported by these 40 different groups of investigators is 45% (range 14-91%). Overall there are generally no clear differences between results obtained by radioligand binding assays, immunological methods, autoradiography, and measurement of EGF-R transcripts although the mean percentage of EGF-R-positive tumors determined by immunological methods tends to be somewhat lower. Nearly all studies indicate a negative relationship between EGF-R and steroid receptor status (28 of 31 studies for ER, 12/19 for PR) showing that EGF-R positivity is twice as high in ER or PR- negative tumors compared to ER or PR- positive tumors (approximately 50-60% vs. 30%). With regard to other prognostic factors the majority of investigators (10/18) also reported a significant (positive) correlation with tumor grade, but only a minority found a significant relationship between EGF-R status and patient age (2/9), menopausal status (1/7), histological type (3/7), tumor size (2/17), nodal status (5-9/20), ploidy (1/7), or proliferation indices (3/9). No relationship was observed with tumor insulin-like growth factor I receptor, PRL receptor (PRL-R), and LHRH receptor (LHRH-R) status, but an inverse relationship between EGF-R and somatostatin receptor may be present. However, it has to be stressed that the series in which the relationship between EGF-R status and other prognostic factors were investigated, contained relatively few patients (mostly less than 100). Therefore, when larger groups of patients are investigated, more significant relationships may be observed, especially with respect to nodal status, tumor ploidy, and proliferation indices. In fact, we calculated the presence of EGF-R positivity overall in 35% of 253 aneuploid tumors vs. in only 15% of 114 diploid tumors (P less than 0.0001). In addition most studies observed a trend, if no significant correlation, between higher EGF-R levels in tumors with the highest percentages of S-phase or Ki-67 expression. With regard to relapse-free and overall survival, five of nine different groups of investigators showed significant prognostic value of EGF-R after short-term (1- to 4-yr) follow-up, indicating that patients with EGF-R-positive tumors have a poor prognosis. However, three of five groups with a maximal follow-up of at least 6 yr found only a tendency for any relationship between EGF-R status and long-term outcome.

Multivariable analysis comparing outcome after sentinel node biopsy or therapeutic lymph node dissection in patients with melanoma.

BACKGROUND: Sentinel node (SN) status is the most important prognostic factor for overall survival in stage I or II melanoma. Yet SN-positive tumours with submicroscopic involvement of the SN (clusters of cells smaller than 0.1 mm) have shown a distant recurrence rate of only 9 per cent at 5 years, as good as that in SN-negative patients. This study compared the outcome after completion lymph node dissection (CLND) in SN-positive tumours with elective total lymph node dissection (TLND) in patients with palpable nodes. METHODS: A total of 188 patients were identified; 124 had TLND and 64 had CLND. Median follow-up was 56 and 37 months respectively. There were no significant differences between the groups regarding tumour Breslow thickness, ulceration and site of the primary tumour. Survival rates were calculated from date of primary excision. All patients with primary melanomas on extremities or trunk were included. RESULTS: On univariable analysis, the site of the primary tumour (extremity versus trunk) (P < 0.001), Breslow thickness (P = 0.005) and ulceration (P < 0.001) were prognostic for overall survival. There was a non-significant 13 per cent difference in overall survival at 5 years between CLND and TLND (P = 0.115). Excluding 15 patients who had SN disease with submicrometastases reduced the difference to 6 per cent (P = 0.415). CONCLUSION: This study showed no significant survival benefit for SN-positive CLND compared with TLND, especially when patients with nodes containing submicrometastases were excluded.

Morbidity and prognosis after therapeutic lymph node dissections for malignant melanoma.

Melanoma patients with clinically evident regional lymph node metastases are treated with therapeutic lymph node dissections (TLNDs). The aim of this study was to evaluate morbidity and mortality following TLND in our institution. Moreover, disease-free (DFS) and overall (OS) survival were evaluated and factors that influence prognosis after TLND were assessed. Between 1982 and 2005, 236 patients underwent a TLND. Patients, who received a palliative LND or a sentinel node procedure, were not included. The median Breslow thickness was 2.4mm. Ulceration was present in 23% of patients and unknown in 66%. 37 patients had unknown primary tumors. There were 129 ilio-inguinal, 50 axillary and 61 cervical dissections performed. 37% of the patients experienced at least one operation related complication. The most frequently seen complications were wound infections/necrosis and chronic lymph edema. Ilio-inguinal dissection patients experienced significantly more complications and a longer duration of hospitalization compared to axillary or cervical patients. The duration of hospitalization has been reduced in recent years from 12 to 5days. The mean follow-up was 29months. Kaplan-Meier estimated 5-year regional control was 79%, 5-year DFS was 19% and 5-year OS was 26%. The number of positive lymph nodes, the site of the primary tumor and extra capsular extension (ECE) were independent prognostic factors for DFS and only site and ECE for OS. In conclusion, TLND for stage III melanoma is accompanied with considerable short-term complications, and can achieve regional control and potential curation in approximately one in every four patients.

Are two retrograde 3.5 mm screws superior to one 7.3 mm screw for anterior pelvic ring fixation in bones with low bone mineral density?

OBJECTIVES: Osteosynthesis of anterior pubic ramus fractures using one large-diameter screw can be challenging in terms of both surgical procedure and fixation stability. Small-fragment screws have the advantage of following the pelvic cortex and being more flexible.The aim of the present study was to biomechanically compare retrograde intramedullary fixation of the superior pubic ramus using either one large- or two small-diameter screws. MATERIALS AND METHODS: A total of 12 human cadaveric hemipelvises were analysed in a matched pair study design. Bone mineral density of the specimens was 68 mgHA/cm3 (standard deviation (sd) 52). The anterior pelvic ring fracture was fixed with either one 7.3 mm cannulated screw (Group 1) or two 3.5 mm pelvic cortex screws (Group 2). Progressively increasing cyclic axial loading was applied through the acetabulum. Relative movements in terms of interfragmentary displacement and gap angle at the fracture site were evaluated by means of optical movement tracking. The Wilcoxon signed-rank test was applied to identify significant differences between the groups RESULTS: Initial axial construct stiffness was not significantly different between the groups (p = 0.463). Interfragmentary displacement and gap angle at the fracture site were also not statistically significantly different between the groups throughout the evaluated cycles (p ⩾ 0.249). Similarly, cycles to failure were not statistically different between Group 1 (8438, sd 6968) and Group 2 (10 213, sd 10 334), p = 0.379. Failure mode in both groups was characterised by screw cutting through the cancellous bone. CONCLUSION: From a biomechanical point of view, pubic ramus stabilisation with either one large or two small fragment screw osteosynthesis is comparable in osteoporotic bone. However, the two-screw fixation technique is less demanding as the smaller screws deflect at the cortical margins.Cite this article: Y. P. Acklin, I. Zderic, S. Grechenig, R. G. Richards, P. Schmitz, B. Gueorguiev. Are two retrograde 3.5 mm screws superior to one 7.3 mm screw for anterior pelvic ring fixation in bones with low bone mineral density? Bone Joint Res 2017;6:8-13. DOI: 10.1302/2046-3758.61.BJR-2016-0261.

Getting closer to patients: the INCAT Overall Disability Sum Score relates better to patients' own clinical judgement in immune-mediated polyneuropathies.

OBJECTIVE: To determine which widely used disability measure in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) shows the strongest association with patients' rating scores. METHODS: Five disability scales and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) were assessed serially in 20 patients with newly diagnosed GBS (n = 7) or CIDP (n = 13). Also at each visit, the patient's condition was self-assessed as being worse, unchanged or better. Longitudinal regressions were carried out to determine the association between disability scales (independent variables) and SF-36 and patients' rating scores (dependent variables). RESULTS: Higher associations with the SF-36 were found in the Overall Disability Sum Score (ODSS) than other disability measures. A higher correlation with ODSS changes was also found in the rating scores of the patients. CONCLUSION: In addition to literature findings, higher associations were found between Inflammatory Neuropathy Cause and Treatment Group ODSS and outcome assessed from patients' perceptions in immune-related polyneuropathies than in other commonly used disability scales.

Adverse effect on bone marrow protection of prechemotherapy granulocyte colony-stimulating factor support.

BACKGROUND: Increased proliferation of endogenous bone marrow progenitor cells in response to the administration of hematopoietic growth factors, followed by reduced cell cycling or entrance of the cells into a quiescent state upon withdrawal of the growth factors, may have clinically relevant effects on the tolerance of the hematopoietic system to subsequent myelotoxic treatments. PURPOSE: We investigated the ability of granulocyte colony-stimulating factor (G-CSF) to protect progenitor cells in the bone marrow of cancer patients from the toxic effects of subsequent treatments with chemotherapeutic agents. METHODS: Thirty-six patients with histologically documented, locally advanced or metastatic breast cancer were randomly assigned to receive doxorubicin once every 3 weeks at a dose of 75 mg/m2 and cyclophosphamide at a dose of 1000 mg/m2, with G-CSF administered either before and after chemotherapy (18 patients) or after chemotherapy only (18 patients). For prechemotherapy administration of G-CSF, recombinant human methionyl (r-met Hu) G-CSF was administered subcutaneously to patients twice per day for 5 days at a dose of 5 micrograms/kg, with the last dose given 48 hours before the start of chemotherapy. For postchemotherapy administration of G-CSF, r-met Hu G-CSF was administered subcutaneously to patients once per day for 7 days at a dose of 5 micrograms/kg, with the first dose given 24 hours after chemotherapy. RESULTS: The incidence or the duration of grade 4 neutropenia was not reduced in all patients by the use of prechemotherapy G-CSF; the incidence over all cycles of chemotherapy was 74% for patients treated with prechemotherapy and postchemotherapy G-CSF and 66% for patients treated with postchemotherapy G-CSF only (two-sided P, adjusted for dose = .21) and the median duration in both treatment arms was 3 days (two-sided P = .19). Unexpectedly, the incidence of grades 3 and 4 thrombocytopenia was much greater in patients who received prechemotherapy G-CSF compared with those who did not (54% versus 6%, respectively, over all chemotherapy cycles; two-sided P, adjusted for dose < .001). No difference in the decrease in hemoglobin level (adjusted for red blood cell transfusions) between patients in the two treatment arms was observed. CONCLUSIONS AND IMPLICATIONS: No beneficial effects were associated with the administration of G-CSF to cancer patients prior to chemotherapy. The observation of more severe thrombocytopenia in patients treated with prechemotherapy G-CSF led us to conclude that the proliferation of progenitor cells was still increased 48 hours after the last dose of G-CSF and that the administration of chemotherapy at or within this time period actually worsens the toxic effects on bone marrow. This result has important ramifications for the design of clinical cancer treatment protocols, especially those that involve shortened intervals between cycles of chemotherapeutic agent administration.

[Standardization and modeling of surgical processes]. / Standardisierung und Modellierung von Operationsprozessen.

BACKGROUND: Due to the technological developments around the operating room, surgery in the twenty-first century is undergoing a paradigm shift. OBJECTIVE: Which technologies have already been integrated into the surgical routine? How can a favorable cost-benefit balance be achieved by the implementation of new software-based assistance systems? METHODS: This article presents the state of the art technology as exemplified by a semi-automated operation system for otorhinolaryngology surgery. The main focus is on systems for implementation of digital handbooks and navigational functions in situ. RESULTS: On the basis of continuous development in digital imaging, decisions may by facilitated by individual patient models thus allowing procedures to be optimized. The ongoing digitization and linking of all relevant information enable a high level of standardization in terms of operating procedures. This may be used by assistance systems as a basis for complete documentation and high process reliability. CONCLUSION: Automation of processes in the operating room results in an increase in quality, precision and standardization so that the effectiveness and efficiency of treatment can be improved; however, care must be taken that detrimental consequences, such as loss of skills and placing too much faith in technology must be avoided by adapted training concepts.

Interleukin-2-induced thyroid dysfunction is correlated with treatment duration but not with tumor response.

PURPOSE: To analyze the putative relationship between immunotherapy-associated dysthyroidism and the probability of a tumor response. PATIENTS AND METHODS: A total of 89 consecutive patients with advanced cancer were treated with interleukin-2 (IL2)-based immunotherapy in a prospective study. RESULTS: Twenty patients developed thyroid dysfunction. Repeatedly positive tests for thyroid antibodies developed in 28% of the patients. Twenty-two patients achieved a response. There was no relationship between the formation of antibodies and the probability of response. There appeared to be a trend toward a relationship between thyroid dysfunction and response (P = .23). A strong relationship was found between response on the one hand and cumulative dose of IL2 (P = .01) and treatment duration with IL2 (P = .025) on the other. The frequency of thyroid dysfunction was also significantly correlated with treatment duration (P = .001). After adjustment for cumulative dose of IL2 and treatment duration, no relationship between thyroid dysfunction and response remained (P = .99). CONCLUSION: There is no relationship between thyroid dysfunction and the probability of tumor response. Thyroid dysfunction is merely a function of treatment duration and cumulative dose of IL2.

Patient participation in clinical decision-making for treatment of T3 laryngeal cancer: a comparison of state and process utilities.

PURPOSE: To study the use of two different approaches, and feasibility of four commonly used utility assessment methods to assess preferences for treatment of T3-laryngeal cancer by surgery or radiation therapy (RT). METHODS: Utility assessment methods, namely, time trade-off (TTO), standard reference gamble (SRG), rating scale (RS), and direct comparison (DC), were used to assess utilities in two groups of former cancer patients (n = 10 for both), a group of clinicians (n = 9), and a group from the general population (n = 10). For the treatment modalities, ie, surgery and RT, two types of scenarios were developed and used: the state scenario, which describes a stable health state after treatment, and the process scenario, which describes a dynamic process. First, utilities were assessed based on state scenarios. Next, respondents were thoroughly informed and educated with respect to the relevant aspects of both treatment modalities. Subsequently, utilities were again assessed, but now based on the process scenarios. The outcome of each approach was calculated and expressed in a quality-adjusted life-expectancy (QALE) score for each treatment modality, and the treatment with the highest outcome was said to be the preferred treatment modality. RESULTS: In general, a higher QALE score for each treatment modality was found for clinicians and for the general population as compared with the former-cancer-patient groups. When the outcome of both approaches was compared on an individual level dependent on the utility assessment method, 32% to 43% of respondents showed an inconsistent treatment preference. CONCLUSION: The approach to assess utilities and the extent to which respondents are informed about treatment modalities have a major effect on individual treatment preferences.

Fractionated high-dose-rate brachytherapy in primary carcinoma of the nasopharynx.

PURPOSE: A growing body of data suggests that local control in nasopharyngeal cancer (NPC) is related to the radiation dose administered. We conducted a single-institution study of high-dose radiotherapy (RT), which incorporated high-dose-rate (HDR) brachytherapy (BT). These results were analyzed together with data obtained from controls who did not receive BT. PATIENTS AND METHODS: The BT group comprised 42 consecutive patients of whom 29 patients were staged according to the tumor, node, metastasis system as T1 through 3, 13 patients were T4, and 34 patients were N+ disease. BT was administered on an outpatient basis by means of a specially designed flexible nasopharyngeal applicator, and the dose distributions were optimized. Treatment for T1 through 3 tumors comprised 60 Gy of external-beam radiotherapy (ERT) followed by six fractions of 3 Gy BT (two fractions per day). Patients with parapharyngeal tumor extension and/or T4 tumors received 70 Gy ERT and four fractions of 3 Gy BT. The no-BT group consisted of all patients treated from 1965 to 1991 (n = 109), of whom 82 patients had stages T1 through 3, 27 patients had T4, and 80 patients had N+ disease. Multivariate Cox proportional hazards analyses were performed by using the end points time to local failure (TTLF), time to distant failure (TTDF), disease-free survival (DFS), cause-specific survival (CSS), and the prognostic factors age, tumor stage, node stage, and grade. Because the overall treatment time varied substantially in the no-BT group, the dependence of local failure (LF) on the physical dose as well as the biologic effective dose (BED) corrected for the overall treatment time (OTT) (BEDcor10) was studied. RESULTS: The BT group had a superior 3-year local relapse-free rate (86% v 60%; univariate analysis, P = .004). Multivariate analysis showed hazards ratios for BT versus no-BT of 0.24 for TTLF (P = .003), 0.35 for TTDF (P = .038), 0.31 for DFS (P < .001), and 0.44 for CSS (P = .01). The best prognostic group consisted of patients with T1 through 3, N0 through 2b tumors treated with BT who attained a 5-year TTLF of 94% and CSS of 91%. In contrast, the worst prognostic group, i.e., 5-year TTLF of 47% and CSS of 24%, was composed of patients with T4 and/or N2c through 3 tumors who did not receive BT. CONCLUSION: High doses of radiation (73 to 95 Gy) can be administered to patients with NPC with minimal morbidity by means of optimized HDR-BT. The use of a BT boost proved to be of significant benefit, particularly in patients with T1 through 3, N0 through 2b disease. The steep dose-effect relationship seen for the physical dose and the BEDcor10 indicates that the results are dose related. The analysis has identified a poor prognostic group in whom treatment intensification with chemotherapy (CHT) is indicated.

Analysis of cumulative probabilities shows that the efficacy of 5HT3 antagonist prophylaxis is not maintained.

PURPOSE: Several investigators have reported that the efficacy of 5HT3 receptor antagonists is maintained over repeated cycles of chemotherapy. These investigators presented conditional probabilities of protection. Because conditional analyses by definition only include patients with protection in previous cycles, the results are flattered. PATIENTS AND METHODS: We applied a novel statistical approach to investigate whether the efficacy of the 5HT3 receptor antagonist ICS 205-930 (tropisetron) is maintained over repeated cycles of weekly high-dose cisplatin. Overall protection was determined based on cumulative probabilities with the Kaplan-Meier method. Complete protection was calculated with a three state model for transitional probabilities. Eighty-three patients were studied. RESULTS: Over six consecutive cycles, protection against both acute and delayed emesis decreased significantly. The initial complete and overall protection rates against acute emesis of 71% and 95%, respectively, decreased to 43% and 72% in the sixth cycle of chemotherapy. Similarly, the protection rates of 31% and 68% against delayed emesis decreased to 6% and 40%, respectively. CONCLUSION: We conclude that overall and complete long-term protection is more accurately measured by cumulative probabilities than with a method that is based on conditional probabilities. Our statistical approach shows that the efficacy of 5HT3 antagonists is not maintained.

Effect of methylprednisolone when added to standard treatment with intravenous immunoglobulin for Guillain-Barré syndrome: randomised trial.

BACKGROUND: Despite available treatment with intravenous immunoglobulin (IVIg), morbidity and mortality are considerable in patients with Guillain-Barré syndrome (GBS). Our aim was to assess whether methylprednisolone, when taken with IVIg, improves outcome when compared with IVIg alone. METHODS: We did a double-blind, placebo-controlled, multicentre, randomised study, to which we enrolled patients who were unable to walk independently and who had been treated within 14 days after onset of weakness with IVIg (0.4 g/kg bodyweight per day) for 5 days. We assigned 233 individuals to receive either intravenous methylprednisolone (500 mg per day; n=116) or placebo (n=117) for 5 days within 48 h of administration of first dose of IVIg. Because age is an important prognostic factor, we split treatment groups into two age-groups-ie, younger than age 50 years, or 50 years and older. Our primary outcome was an improvement from baseline in GBS disability score of one or more grades 4 weeks after randomisation. Analysis was by intention to treat. FINDINGS: We analysed 225 patients. GBS disability scores increased by one grade or more in 68% (76 of 112) of patients in the methylprednisolone group and in 56% (63 of 113) of controls (odds ratio [OR] 1.68, 95% CI 0.97-2.88; p=0.06). After adjustment for age and degree of disability at entry, treatment OR was 1.89 (95% CI 1.07-3.35; p=0.03). Side-effects did not differ greatly between groups. INTERPRETATION: We noted no significant difference between treatment with methylprednisolone and IVIg and IVIg alone. Because of the relevance of prognostic factors and the limited side-effects of methylprednisolone, the potential importance of combination treatment with the drug and IVIg, however, warrants further investigation.