[Adaptation to intermittent hypoxia-hyperoxia improves cognitive performance and exercise tolerance in elderly].

For improvements in exercise tolerance and cognitive function in geriatric patients Multimodal training programs (MTP) are used as combination of physiotherapy, occupational therapy and cardiovascular training. Intermittent Hypoxic-Hyperoxic Training (IHHT), a modified type of intermittent hypoxic training (IHT) is proposed to be included in MTP to elicit more pronounced beneficial effects in exercise tolerance and cognitive functions of geriatric patients likely by an additional pathway than a single MTP. Thirty four patients of the Geriatric Day Clinic aged between 64 and 92 years participated in the placebo controlled clinical trial. They were randomly assigned to receive MTP plus IHHT (experimental group - EG) or MTP plus placebo-breathing through a machine face mask (control group - CG) in a double blind fashion. Before and after the interventions course cognitive performance was assessed by the Dementia-Detection-Test (DemTect) and the Clock-Drawing-Test (CDT), and functional exercise capacity - by the total distance of 6-Minute-Walk-Test (6MWT). After IHHT combined with MTP cognitive performance (DemTect) increased significantly when compared to NG (+16,7 % vs. +0,39 %, p<0,001). The CDT indicated similar results with a significant increase in the EG while the score of the CG even decreased (+10,7 % vs. -8%, p=0,031). Concerning the functional exercise capacity, both groups improved the total distance in the 6MWT but with a significantly larger increase in the EG compared to the CG (+24,1 % vs. +10,8 %, p=0,021). In addition, there was a significant relationship between the changes of the 6MWT and the DemTect Scores and the CDT. IHHT contributed significantly to improvements in cognitive performance and exercise capacity in elderly performing MTP. IHHT sessions are considered to be easily applicable to and well tolerated by geriatric patients up to 92 years.

[Tonsillotomy and adenotonsillectomy in childhood. Study on postoperative pain therapy]. / Tonsillotomien und Adenotomien im Kindesalter. Studie zu postoperativen Schmerztherapie.

BACKGROUND: The primary aim of this study was to determine whether the combination of i.v. ketoprofen and i.v. paracetamol provides superior postoperative analgesia in children undergoing adenoidectomy or tonsillotomy compared to either drug alone. The secondary goal was to assess the time until rescue analgesia was needed, propofol requirements and the incidence of vomiting and time of discharge from the postanaesthesia recovery unit (PARU). METHODS: This double-blinded study included 120 children (aged 3-13 years) scheduled for elective tonsillectomy, adenoidectomy or adenotonsillectomy. The children were randomly assigned to one of 3 groups of 40 children each, using the sealed envelope method. The children received i.v. ketoprofen 2 mg/kgBW (group 1) or paracetamol 15 mg/kgBW (group 2) or the combination of these 2 drugs (group 3) after induction of anaesthesia. Standardized general anaesthesia consisted of sevoflurane and fentanyl at a dose of 2-3 µg/kgBW. Pain was assessed using a 5-point scoring system based on the Smiley scale. The Smiley scale shows various faces from a laughing face which corresponds to the state of no pain to a very unhappy face which corresponds to the situation of worst pain (1: no pain, 2: mild pain, 3: moderate pain, 4: severe pain, 5: worst pain). Pain was assessed at 30 min, 1 h, 2 h, 3 h and 4 h after arriving in the PACU. If the pain score exceeded 2 an i.v. dose of 0.1 mg/kgBW morphine was administered as rescue analgesia. RESULTS: During the stay in the PACU the children in the combination group required significantly less supplementary rescue analgesia than children in the ketoprofen and paracetamol groups (17.5% versus 30.8% versus 45%, respectively, χ(2) analysis <0.05). Pain scoring was highest after paracetamol, however, this difference was only significant when compared to the group receiving the combination of paracetamol and ketoprofen (U-test p<0.05). Rescue analgesia was administered earliest in group 2 (paracetamol) reaching statistical significance, however, only when compared to group 3 (logrank test p<0.05). Propofol requirements and time to discharge from the PACU did not differ significantly between the 3 groups (χ(2) analysis; U-test; p>0.05). The overall incidence of vomiting was very low in this study with 6.4% (9/139). Significantly more children in the paracetamol group compared to ketoprofen group and combination group suffered from vomiting (17.5% versus 2.6% versus 2.5%; χ(2) analysis; p<0.05). The time to discharge from PACU did not differ significantly between the 3 groups (U-test: p>0.05). CONCLUSION: The combination of i.v. paracetamol and i.v. ketoprofen provides superior postoperative analgesia compared to the single use of paracetamol.

Consecutive, prospective case series of a new method for ultrasound-guided supraclavicular approach to the brachiocephalic vein in children.

BACKGROUND: During ultrasound (US)-guided cannulation of the subclavian vein (SCV) via an infraclavicular route, the view of the needle behind the clavicle may be obscured. This study describes the US-guided supraclavicular cannulation of the brachiocephalic vein (BCV). METHODS: The 25 mm broadband linear array US probe was placed in the supraclavicular region to obtain a longitudinal view of the BCV beginning at the junction of the internal jugular vein and SCV. Using the in-plane technique, the needle was directed under US guidance into the BCV. RESULTS: Forty-two cannulations in 35 patients (aged 26 months-8 yr, weight range 0.96-21 kg) were included. Central venous catheter placement was successful in all children. In 31 patients (73.8%), the BCV was successfully punctured on the first attempt, in six patients (14.2%) after two attempts, and in five patients (11.9%) after three attempts. Significantly more puncture attempts were needed in the smaller weight and younger children, whereas the time course of the study had no significant impact on the success rate. CONCLUSIONS: This US-guided method offers a new possibility for central venous line placement in small children. It provides good needle guidance without any disturbing US shadow caused by bony structures.

Size of internal jugular vs subclavian vein in small infants: an observational, anatomical evaluation with ultrasound.

BACKGROUND: The primary goal of this study was to compare the size and depth of the internal jugular vein (IJV) and the subclavian vein (SCV) in infants under general anaesthesia. A secondary goal was to determine the correlation of weight, height, head circumference, and age to the size and depth of these veins. METHODS: Sixty small infants weighing from 1.4 to 4.5 kg were included. Using ultrasound, the diameters via short-axis (SAX) and long-axis (LAX) views, cross-sectional area (CSA), and depth of the left and right IJV and SCV were measured. RESULTS: The diameter of the IJV was 7.9% larger on average than that of the SCV as measured via the SAX and LAX views (mean: 3.1 vs 2.9 mm; Wilcoxon's signed-rank test: P<0.01). The CSA of the IJV was 27% larger on average than that of the SCV (mean: 10.2 vs 8.0 mm(2); Wilcoxon's signed-rank test: P<0.01). Seventy-five per cent of the neonates showed a larger CSA of the IJV. The SCV was 8.4% deeper on average from the skin surface than the IJV (mean: 6.4 vs 5.9 mm; Wilcoxon's signed-rank test: P<0.01). There was a significant positive correlation between weight, height, head circumference, and age to the size and depth of the veins (Spearman's rank correlation: P<0.01). CONCLUSIONS: Because of its most likely larger size, the IJV can be recommended as the better choice for cannulation in comparison with the SCV. However, other factors should also be considered.

[Gender specific differences in the frequency of admission to intensive care units, duration of stay and the application of intensive medical care measures in men and women aged 75 years and above in an Austrian region]. / Geschlechtsspezifische Unterschiede bezüglich Aufnahmeraten auf Intensivstationen, Aufenthaltsdauer und durchgeführten intensivmedizinischen Massnahmen bei Personen im Alter ab 75 Jahren in einer Osterreichischen Region.

OBJECTIVE: It was the aim of this study to evaluate the frequency of admission to intensive care units, duration of stay and application of intensive care treatments in patients aged 75 years and above and to analyse possible gender specific differences. METHODS: Analysis of hospital in-patient data of all hospitals of a southern Austrian region (federal state of Carinthia). RESULTS: In the year 2003, 4.7% of the men and 3.2% of the women aged 75 years and above were treated in intensive care units (p<0.001). This gender specific difference was independent of the reason for the intensive care admission. The mean duration of stay in intensive care units was longer for 75-79 year old men compared to women (6.38 vs. 4.91 days, p<0.01). Typical intensive care treatments like mechanical ventilation, artificial airways and vasoactive medication were applied more often to men than to women. CONCLUSION: In the aged there are marked gender specific differences in the application of intensive care treatments, especially in the end-of-life state in Austria. The reasons for these differences should be subject of future research.

[Comparison of the peripheral and central effects of opiates after iliac crest transplants. Reconstruction of severely atrophied maxilla]. / Vergleich der peripheren und zentralen Opiatwirkung bei Beckenkammtransplantaten. Rekonstruktion eines hoch atrophen Oberkiefers.

PURPOSE: Severe pain is one of the main problems after harvesting iliac crest transplants. In this randomized double-blind study differences in the peripheral and central effects of opiates for pain treatment in the iliac crest region after augmentation of the severely resorbed maxilla were examined. MATERIALS AND METHODS: In 20 consecutive patients with severe atrophy of the edentulous maxilla, augmentation was performed with the use of iliac crest transplants. In 10 patients a gelatine sponge soaked with a 10 mg morphine hydrochloride solution was placed in the iliac region after harvesting the transplant ipsilaterally for local opiate therapy. In the control group the same opiate was injected into the contralateral glutaeus maximus muscle for systemic therapy. Both groups were followed up for pain intensity every 2 h during the first 48 h and 3 times a day from postoperative days 3-10. Thereafter the patients were followed up 1, 3, 6 and 12 months postoperatively. At each time of control the VAS score, as well as the quality of pain with and without movement and the consumption of NSAIDs were registered. RESULTS: Lower pain values were registered in the control group within the early postoperative period, whereas the mean VAS score was less from postoperative days 3-10 in the study group (2.3 compared to 1.3 VAS). The consumption of NSAIDs corresponded to the pain scores in both groups during the control periods. There were no statistically significant differences for long term results at 1, 3, 6 and 12 months postoperatively. CONCLUSIONS: The effect of centrally given opiates is more effective in the early postoperative period. In the early rehabilitation period the effect of intraoperatively local peripherally placed opiates is superior to intraoperatively centrally administered opiates.

Patients with Gaucher disease living in England show a high prevalence of vitamin D insufficiency with correlation to osteodensitometry.

AIM: Gaucher disease type 1 (GD-1) is the most prevalent lysosomal storage disorder and frequently causes osteopenia and osteoporosis. Adequate vitamin D levels are essential for bone health. The present study retrospectively analyzed 25-hydroxyvitamin D (25[OH]D) in outpatients with GD-1. PATIENTS AND METHODS: Sixty GD-1 patients living at home and with residence in southern or central England (34 men, 26 women), aged 17-85 years (mean 45.0 years) were seen at routine follow-up visits (range: 1-9, mean: 4.4) between January 2003 and July 2007. Overall, 264 blood samples, collected at different seasons of the year, were present for laboratory testing. The retrospective interpretation of vitamin D deficiency was based on different cut-off levels of 25(OH)D (<25 nmol/L, <50 nmol/L, <80 nmol/L) and the seasons of the year. Vitamin D sufficiency was defined as 25(OH)D >80 nmol/L. RESULTS: The mean+/-SD of 25(OH)D was 58.2+/-30.3. Degrees of vitamin D deficiency (<25 nmol/L, <50 nmol/L, <80 nmol/L) were present in 9.1%, 44.3%, 83.0%, vitamin D sufficiency (>80 nmol/L) in only 17.0%, respectively. A significant seasonal variation of 25(OH)D was present. Results of vitamin D deficiency for December-May were 15.7%, 63.8%, 92.9%, and for June-November 2.9%, 26.3%, 73.7%. The 25(OH)D values representing the seasonal nadir observed during the season December-May showed a significant correlation with T-scores and Z-scores of the lumbar spine and hip. Parathyroid hormone and 25(OH)D were inversely correlated. CONCLUSIONS: Vitamin D deficiency is frequent among GD-1 patients. To optimize treatment of GD-1 vitamin D supplementation should be recommended.

Receptor activator of nuclear factor kappaB ligand and osteoprotegerin in men with thyroid cancer.

BACKGROUND: Suppressive thyroid hormone therapy is generally a lifelong treatment for patients with differentiated thyroid cancer (DTC). However, long-standing thyrotropin (TSH) suppression is a risk factor for osteoporosis. Osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB ligand (RANKL) are central regulators of bone turnover. The aim was to analyze the effects of a suppressive thyroid hormone therapy in males with DTC on the OPG/RANKL system and on bone metabolism. PATIENTS AND METHODS: The OPG and soluble RANKL (sRANKL) were determined in 40 men (mean age, 53.2 years) with DTC on suppressive thyroid hormone therapy (TSH; 0.053 +/- 0.037 mU L(-1), duration 5.7 +/- 4.4 years) and 120 healthy controls matched for age. The markers of bone metabolism were C-terminal telopeptide of type I collagen in serum (sCTx) and osteocalcin (OC). RESULTS: The control group had OPG values (mean +/- SD) of 1.9 +/- 1.0 pmol L(-1) and sRANKL values of 0.40 +/- 0.62 pmol L(-1). In patients with DTC, results for OPG were 3.03 +/- 1.04 pmol L(-1) (P < 0.05) and for sRANKL were 0.13 +/- 0.16 pmol L(-1) (P < 0.05). The control group presented values for sCTx of 2669 +/- 1132 pmol L(-1) and for OC of 17.89 +/- 6.5 ng mL(-1). Patients with DTC on suppressive thyroid hormone therapy had increased sCTx values of 3810 +/- 2020 pmol L(-1) (P = 0.03) but comparable OC values of 19.21 +/- 7.67 ng mL(-1) (NS). CONCLUSIONS: Suppressive thyroid hormone therapy in men with DTC increased bone degradation and induced significant changes in the OPG/RANKL system. These changes include, besides the risk of osteoporosis, possible negative effects on the vascular function and an increased risk of cardiovascular disease.

[Long-term outcome of stomach carcinoma achieved in an Austrian standard hospital with an oncologic focus]. / Langzeitergebnisse beim Magencarcinom erzielt in einem österreichischen Standardkrankenhaus mit onkologischem Schwerpunkt.

INTRODUCTION: Although two large prospective and randomized planned European studies failed to show any benefit of radical D2 lymphadenectomy for gastric cancer, the value of radical lymphadenectomy is still a matter of controversy. METHODS: A radical surgical approach principally using D2, D3 lymphadenectomy, as defined by the Japanese Research Society for Gastric Cancer, has been prospectively performed since January 1984. Out of 729 patients with gastric cancer, 521 were surgically treated for potential cure between 1984 and 31 December, 1998. Clinical, histopathological and surgical factors were evaluated for their influence on long-term survival by means of univariate and multivariate analysis. RESULTS: Tumor-specific 5- and 10-year survival rates for all patients were 58.5% and 57.5% for patients who underwent tumor resection 59% and 58%. For operated patients upon with the aim of achieving cures, the tumor-specific 5- and 10-year survival rates were 63.3% and 62.2% and the median survival time was more than 144 months. Postoperative hospital mortality was 7.7%, 4.6% for R0 resected patients, 8.6% for R1,2 resected patients and 21.3% for those undergoing palliative procedures. Multivariate analysis using the Cox model identified an age older than 65, total gastrectomy as well as high pN- and pT category as detrimental factors with an independent influence on survival. CONCLUSION: After updating the long-term results of gastric cancer, as already published earlier, it is impressively obvious that also in a European setting of gastric cancer patients, with a presupposed appropriate surgical technique and experience, very constant cure rates are achievable with comparatively low mortality and morbidity.

Long-term prognosis for colon cancer related to consistent radical surgery: multivariate analysis of clinical, surgical, and pathologic variables.

Despite the improvement in its prognosis in most Western countries, death from colon cancer is still a major problem. In a prospectively planned observation study, a large patient collective from a single institution in Austria was analyzed in terms of the surgical approach and factors influencing survival. A total of 696 patients with colonic carcinomas were admitted to our surgical department between January 1, 1984 and December 31, 1997. Radical surgery for localized tumors was consistently performed, including wide resection margins and complete removal of the regional lymph drainage zones. Clinical, histopathologic, and therapy-related factors were examined for their influence on long-term survival by means of univariate and multivariate analysis. The overall tumor resection rate was 99.3% (691/696); complete tumor removal (R0) was possible for 84.8% (590/696) of all patients. The overall postoperative hospital mortality rate was 3.2% (22/696), and it was 13% (7/556) for potentially curative resections. Five- and ten-year tumor-specific survival rates for stage I to III R0 resections were 83.8% and 78.8%, respectively. Adjuvant chemotherapy reduced tumor recurrence for stage III patients by 52.4%. The depth of tumor infiltration, lymph node status, and adjuvant chemotherapy were found to have an independent influence on survival as identified by the Cox models. In conclusion, a consistent radical surgical approach for potentially curative resected colonic cancer patients had survival rates that surpassed those of most published series without sacrificing low complication rates. In addition, adjuvant chemotherapy for stage III substantially improved survival.

Long-term monitoring of sister chromatid exchanges and micronucleus frequencies in pharmacy personnel occupationally exposed to cytostatic drugs.

OBJECTIVES: Many antineoplastic drugs were found to have carcinogenic, mutagenic and teratogenic potential. The aim of this study was to carry out cytogenetic and internal dose monitoring of hospital pharmacy personnel regularly involved in the preparation of cytostatic agents, in order to test possible cytostatics-induced genotoxic effects due to occupational exposure under routine working conditions, and in cases of accidental contamination. METHODS: Platinum in whole blood and anthracyclines in plasma were measured to assess internal exposure to cytostatics. The level of cytogenetic damage was determined in peripheral blood lymphocytes with the micronucleus test and the sister chromatid exchange assay. Five series of monitoring were performed over a period of 2 years. RESULTS: No significant differences in the mean frequencies of sister chromatid exchanges (SCE) and micronuclei (MN) were found between occupationally exposed probands and controls (9.9 +/- 1.4 vs 10.1 +/- 1.2 SCEs/cell and 21.2 +/- 7.2 vs 23.3 +/- 7.5 MN/2000 binucleated (BN) cells, n = 16). Significant elevations of SCE or MN were detected in seven out of 12 cases of accidental contamination at the workplace, whereas no increase in platinum in blood and anthracyclines in plasma was observed in these probands. Two cases of non-reported contamination were identified by measurement of epirubicin in plasma. Smoking was found to increase the SCE significantly. No correlation between individual SCE scores and MN scores was observed. CONCLUSIONS: Our findings support a transient increase in SCE or MN after relevant exposure to cytostatic drugs in cases of accidental contamination. The lack of significant differences in SCE and MN between hospital pharmacy personnel and unexposed controls, points to high standards of safety at the corresponding workplaces.

[Stomach carcinoma. Optimizing therapy by extended lymph node dissection]. / Magenkarzinom. Optimierung durch Erweiterung der Lymphknotendissektion.

BACKGROUND: The prognosis for surgically treated gastric cancer patients remains poor in most Western countries compared with reports of Japanese investigators over the last three decades. The aim of the study was to prove whether D2, D3 lymphadenectomy is able to improve long-term survival in a Western gastric cancer patients collective as well. METHODS: A radical surgical procedure using D2, D3 lymphadenectomy on principle as defined by the Japanese Research Society for Gastric Cancer was done prospectively since January 1984. Out of 626 patients with gastric cancer, 433 were surgically treated for potential cure between January 1st, 1984 and December 31st, 1996. Postoperative complications and long-term survival were evaluated. RESULTS: For curatively operated patients five- and ten-year tumor specific survival rates were 57.7% and 44.3%, the median survival time was 96 months. Postoperative hospital mortality was 4.8% for R0 resected patients and 10.4% for palliative procedures. CONCLUSION: Radical D2, D3 lymphadenectomy yielded survival rates similar to those in Japanese investigations without negative effect on low postoperative mortality. These results reaffirm the value of radical lymph node dissection with wide resection margins.

Long-term results of radical surgery for rectal cancer: multivariate analysis of prognostic factors influencing survival and local recurrence.

AIMS: To evaluate consistent radical surgery performed over a 13-year period for rectal cancer in terms of local tumour control and long-term survival. METHODS: Radical surgical procedure principally using total mesorectal excision (TME) for middle and lower rectal tumours, high ligation of the inferior mesenteric artery and sphincter-saving resections (SSR) whenever possible, has been performed prospectively since January 1984. RESULTS: Tumour resection was possible in 98.8% (636/644), potentially curative resections (UICC/AJCC R0 resection) in 85.7% (552/644) and sphincter preservation in 71.7% (462/644). Five- and 10-year observed survival rates, surgical mortality not excluded, for all patients were 49.2% and 37.4%. Tumour-adjusted 5- and 10-year survival rates were 60.5% and 55.3%. For curatively operated patients (UICC/AJCC R0) 5- and 10-year observed survival rates were 56.3% and 42.6% and tumour-adjusted survival rates were 68.6% and 62.7%. The 5- and 10-year local recurrence rates for R0 resected patients were 12.0% and 12.6%. Post-operative hospital mortality was 3.1%. CONCLUSIONS: Multivariate analysis using Cox's model identified increasing pT category and pN category, old age and low tumour location as detrimental factors having independent influence on survival. For local tumour failure only pT and pN category as well as adjuvant radiation therapy were identified in the Cox model as having an independent detrimental influence.

Consolidation radiotherapy after carboplatin-based chemotherapy in radically operated advanced ovarian cancer.

OBJECTIVE: The aim of the study was to evaluate the effect of additional radiotherapy after chemotherapy on the relapse-free and overall survival rates of patients with advanced ovarian cancer. METHODS: Between 1985 and 1992 64 patients with radically operated ovarian cancers (4 stage IC, 2 stage II, 54 stage III, and 4 stage IV) were enrolled in a randomized study. Radical surgery comprised total abdominal hysterectomy and bilateral salpingo-oophorectomy, omentectomy, and pelvic and paraaortic lymphadenectomy. All patients received adjuvant chemotherapy with carboplatin IV 400 mg/m2, epirubicin IV 70 mg/m2 on day 1 and prednimustine orally 100 mg/m2 on days 3 to 7 at 1-month intervals. Thirty-two patients without residual disease were randomized to whole abdominal radiation (30 Gy, administered over 4 weeks). An additional 21.6 Gy were delivered to the pelvis and 12 Gy to the paraaortic region up to the diaphragm for total doses of 51.6 and 42 Gy, respectively. Cancer-related survival was calculated with the Kaplan-Meier and Cox proportional hazards methods. RESULTS: The relapse-free and overall survival rates of patients who received adjuvant chemoradiotherapy were significantly higher than those of patients who received adjuvant chemotherapy only (68% vs 56% at 2 years and 49% vs 26% at 5 years, P = 0.013, and 87% vs 61% at 2 years and 59% vs 33% at 5 years, P = 0.029). The differences were most pronounced in patients with stage III disease (77% vs 54% at 2 years and 45% vs 19% at 5 years, P = 0. 0061, and 88% vs 58% at 2 years and 59% vs 26% at 5 years, P = 0. 012). Toxicities were acceptable. CONCLUSION: Sequential combination of platinum-based chemotherapy with open-field abdominal radiotherapy is a promising adjuvant regimen for patients with advanced ovarian cancer.

Long-term survival analysis of gastric cancer limited to the subserosa.

Long-term survival following surgery for gastric cancer limited to the subserosa was analyzed. Between 01.01.1984 and 30.06.1995. 265 patients were operated for gastric cancer that did not invade beyond the subserosa. Extended lymphadenectomy was performed in all cases and was constant as all patients were operated by only two surgeons. The survival outcome was analyzed with particular regard to the exact depth of tumor infiltration and lymph node involvement. The percentage of patients with positive lymph nodes increased drastically from 1.7% for mucosal invasion to 22.7% for submucosal tumor involvement. A further substantial increase was observed from 34.3% for involvement of the muscularis propria to 66.1% for subserosal involvement. The 10-year tumor specific survival rate for tumors limited to the mucosa was 100%, for submucosa and muscularis propria invasion 79.3% and 72.9% respectively, for subserosal involvement 10-year survival was 54.6%. In multivariate analysis of pathohistological variables only pT- and pN-categories according to the UICC were found to have independent prognostic influence on survival. Long-term survival indicates that gastric cancer limited to the mucosa may well be treated with a less radical approach. Gastric cancer of the submucosa and muscularis propria both have a similar good long-term prognosis with radical surgery alone whereas cancer of the subserosa probably requires some form of adjuvant therapy.

Randomized comparison of total androgen blockade alone versus combined with weekly epirubicin in advanced prostate cancer.

Hormone deprivation is the gold standard for the treatment of metastatic prostate cancer. However, prostate cancer being primarily a heterogeneous tumor comprising hormone-dependent, hormone-sensitive, and hormone-insensitive cells, at least the latter remain unaffected by hormonal manipulations, thus making disease progression almost inevitable. In quest of a more comprehensive therapy we therefore studied the concept of early combined chemoendocrine therapy in a prospective randomized multicenter trial. The purpose of this study was to evaluate whether patients with previously untreated advanced prostate cancer benefit from combining total androgen blockade (TAB) with weekly epirubicin chemotherapy (E-TAB). From April 1988 to January 1991, 145 previously untreated patients with either metastatic (n = 117) or locally advanced (n = 28) histologically confirmed prostate cancer were randomly allocated to treatment with TAB by bilateral orchiectomy and flutamide 250 mg t.i.d. or TAB plus weekly epirubicin 25 mg/m2 i.v. for 18 weeks (E-TAB). The study endpoints were progression-free survival and overall survival. In addition the effects of treatment on quality of life were assessed by two methods. At regular intervals patients self-assessed ten qualities of physical, functional and emotional health using 5-point scales. In order to evaluate the time without disease progression and treatment-induced adverse effects, a modified Q-TWiST (quality-adjusted time without symptoms and toxicity) model was applied. At a median follow-up of 81 months, progression-free survival and overall survival in the TAB and E-TAB groups were 12 and 18 months (p < 0.02) and 22 and 30 months (p = 0.12), respectively. In patients with > 5 sites of bone metastasis (D2max), the corresponding periods were 9 and 14 months (p = 0.005) and 17 and 27 months (p = 0.06), respectively. Subjective quality of life assessment showed no impairment of quality of life by epirubicin treatment. Stage D and D2max patients treated with E-TAB had an average gain in Q-TWiST of 5 months (p = 0.098) and 8 months (p = 0.03), respectively, compared to the TAB treatment. Objective toxicities were generally mild with either treatment. In conclusion, the combination of TAB and epirubicin was well tolerated by patients with advanced prostate cancer and resulted in a significant extension of progression-free survival. This effect of E-TAB on objective treatment outcome was accompanied by prolonged time without treatment-induced adverse effects and tumor progression, i.e., time with good quality of life. Therefore, further studies with E-TAB appear warranted in patients with advanced prostate cancer.

Effect of extracorporeal shock wave lithotripsy on prostate specific antigen.

PURPOSE: We evaluated the effects of extracorporeal shock wave lithotripsy (ESWL) of distal ureteral calculi on serum prostate specific antigen (PSA). MATERIALS AND METHODS: A total of 29 consecutive men with distal ureteral calculi at a maximum of 25 mm. from the ureteral orifice, and without any history of urinary tract infection, benign prostatio hyperplasia or prostate cancer underwent ESWL with the Dornier MPL 9000 X lithotriptor. The therapeutic focus size was 48 X 7 mm. PSA was measured exactly 5 minutes before ESWL, as well as 120 minutes, 24 hours and 7 days after termination of treatment. RESULTS: Fragmentation rate was 100% and all patients were stone-free within 1 week of therapy. There was no statistically significant difference between PSA values before and after treatment. Only 15 patients had a slight increase in PSA at 120 minutes after treatment (range 0.01 to 0.41 ng./ml., mean 0.07). CONCLUSIONS: ESWL can be performed in men at risk for prostate cancer without impairing the predictive value of PSA.

A 10-year experience with Japanese-type radical lymph node dissection for gastric cancer outside of Japan.

BACKGROUND: The prognosis for surgically treated gastric cancer remains poor in most Western countries compared with reports from Japanese investigators during the past 3 decades. METHODS: A radical surgical procedure principally to extended lymphadenectomy as defined by the Japanese Research Society for Gastric Cancer was performed prospectively from January 1984 to June 30, 1994 for 512 patients with gastric cancer, 345 of whom were treated with potentially curative surgery. Clinical, histopathologic, and surgical factors were examined for their influence on long term survival by univariate and multivariate analyses. RESULTS: Five- and 10-year survival rates for all patients were 40.5% and 34.3%, respectively, and for patients who underwent tumor resection were 45.7% and 38.6%, respectively. For patients who underwent curative surgery, 5- and 10-year adjusted survival rates were 57.7% and 44.3%, respectively, with a median survival of 96 months. Postoperative hospital mortality was 6.8%:4.9% for R-0 resected patients, 9% for R-1 and R-2 resected patients, and 13.4% for those with palliative procedures. Multivariate analysis using the Cox model identified age older than 65 years, prior total gastrectomy, an increasing number of positive lymph nodes, a high pathologic N classification, male sex, a high pT classification, and low preoperative hemoglobin level as detrimental factors with an independent influence on survival. CONCLUSION: Radical lymphadenectomy in this 10-year Austrian study yielded survival rates similar to those in Japanese investigations without sacrificing low postoperative mortality. In particular, the relatively high overall survival rates seemed to reaffirm the value of radical lymph node dissection with wide resection margins.

Multivariate comparison of complications after laparoscopic cholecystectomy and open cholecystectomy.

OBJECTIVE: To answer the question whether laparoscopic cholecystectomy (LC) or open cholecystectomy (OC) is safer in terms of complications, the authors evaluated complications relating to 1440 cholecystectomies performed by the same surgeons in a retrospective study. SUMMARY BACKGROUND DATA: A definite pronouncement on whether LC truly is superior to OC is not possible because prospective trials are burdened with problems of recruitment. METHODS: After the introduction of LC at the authors' institution in April 1991 and until October 1993, 94.6% (700/740) of all patients admitted for operation because of symptomatic gallstone disease could be treated laparoscopically. The clinical records of the last 700 patients who underwent OC before the introduction of LC were re-evaluated with regard to both overall complications and the grade of complication (severity grade 1-4). A comparison of the incidence of complications relating to the two surgical methods, age, sex, common bile duct stones, acute cholecystitis, concomitant illness, Apache score, and length of operation was calculated by multivariate analysis using the logistic regression model. RESULTS: The total rate of complications in the OC group was 7.7%, with five postoperative deaths, compared with 1.9% and one postoperative death in the LC group. Multivariate analysis for OC revealed that both old age (p = 0.014) and the existence of common bile duct stones (p = 0.02) had independent prognostic influences in increasing the overall complication rate, whereas only old age (p = 0.019) influenced the overall complication rate after LC. Multivariate analysis of all cholecystectomies (n = 1440) showed that the overall complication rate was influenced independently by OC as a detrimental factor. CONCLUSIONS: As this analysis emphasizes, LC can be performed safely with an overall complication rate that is distinctly lower than that of OC. For selective surgery, LC is undoubtedly superior to OC and can probably be seen as a new "gold standard" for cholecystectomies.

Hepatic resection for metastases from colorectal carcinoma--a survival analysis.

Between 1 January 1984 and 31 December 1992, 66 patients with hepatic metastases from colorectal carcinomas underwent liver resection. 40 of these patients had synchronous hepatic metastases, and liver resection was carried out simultaneously with radical resection of the primary tumour; in 26 cases metachronous metastases in the liver were surgically removed. 25 patients had an anatomical resection and the remainder underwent atypical resections. The postoperative mortality rate was 4.5% and the major complication rate was 19.7%. Univariate and subsequently multivariate analyses were used to predict the influence of various clinical, histopathological and surgical variables. The observed 5-year survival rate was 29.6% and the 5-year disease-free survival rate 13.9%. Furthermore, the observed median survival time was 24.7 months and the mean disease-free survival time was 16.7 months. Multivariate analysis showed that stage of primary (pTN) (P = 0.043), tumour grading (P = 0.013) and site of primary (P = 0.007) were factors which independently influenced 5-year disease-free survival whereas stage of primary (pTN) (P = 0.008), tumour grading (P = 0.004) and type of resection (P = 0.035) were identified as having independent influence on 5-year observed survival. We consider liver resection to be an effective form of treatment for patients with resectable liver metastases from colorectal carcinoma, although the overall chances for cure are generally not very promising. It appears that the biological behaviour of the primary tumour, in terms of tumour stage and grading, has the greatest influence on survival.