Biomedical subjects

B Rau

Publications and source records attributed to B Rau.

At least 19 recordsLinked to original sources

PubMed2000

[Necrosectomy or anatomically guided resection in acute pancreatitis].

Necrotizing pancreatitis is still associated with considerable morbidity and mortality. Formerly, surgical treatment with early and extensive pancreatic resection has been the standard. Improvements in our understanding of the pathogenesis of the disease and progress in the field of intensive care therapy have made conservative therapy the initial standard in the treatment of necrotizing pancreatitis. A considerable percentage of patients with sterile necrosis can be managed with low morbidity and mortality by conservative treatment without operation. Nevertheless, surgical treatment is indicated in patients with infected necrosis and in sterile necrosis if multiorgan failure persists over a limited period of time despite maximum intensive care therapy. Pancreatic resection should be abandoned for surgical treatment of pancreatic necrosis, as results with regard to morbidity, mortality and long-term outcome are unsatisfactory. Today the surgical standard is careful digital necrosectomy, which must be followed by either postoperatve drainage, repeated open lavage or continuous closed lavage. In experienced hands, all three procedures provide similar results with regard to morbidity and mortality.

Debridement↗

PubMed2000

Pathophysiologic role of oxygen free radicals in acute pancreatitis: initiating event or mediator of tissue damage?

BACKGROUND AND OBJECTIVE: Oxidative stress is an important factor in the pathogenesis of acute pancreatitis, as shown in vivo by the beneficial effects of scavenger treatment and in vitro by the potential of free radicals to induce acinar cell damage. However, it is still unclear whether oxygen free radicals (OFR) act only as mediators of tissue damage or represent the initiating event in acute pancreatitis in vivo as well. In the present study the authors aimed to address this issue in an experimental set-up. MATERIALS AND METHODS: Two hundred male Wistar rats were randomly assigned to one of the following experimental groups. In two groups, acute necrotizing pancreatitis was induced by retrograde intraductal infusion of 3% sodium taurocholate. Through the abdominal aorta, a catheter was advanced to the origin of the celiac artery for continuous regional arterial (CRA) pretreatment with isotonic saline (NP-S group) or superoxide dismutase/catalase (NP-SOD/CAT group). In another group, oxidative stress was generated by CRA administration of xanthine oxidase and intravenous administration of hypoxanthine (HX/XOD group). Sham-operated rats received isotonic saline both arterially and intraductally. After observation periods of 5 and 30 minutes and 3 and 6 hours, the pancreas was removed for light microscopy and determination of reduced glutathione (GSH), oxidized glutathione (GSSG), conjugated dienes (CD), and malondialdehyde as a marker for OFR-induced lipid peroxidation as well as myeloperoxidase as a parameter for polymorphonuclear leukocyte accumulation. RESULTS: A significant decrease of GSH was paralleled by an increased ratio of GSSG per total glutathione and elevated CD levels after 5 minutes in the NP-S group versus the sham-operated group. Thereafter, the percentage of GSSG and GSH returned to normal levels until the 6-hour time point. After a temporary decrease after 30 minutes, CD levels increased again at 3 hours and were significantly higher at 6 hours in contrast to sham-operated rats. Myeloperoxidase levels were significantly elevated at 3 and 6 hours after pancreatitis induction. In contrast to NP-S rats, treatment with SOD/CAT significantly attenuated the changes in glutathione metabolism within the first 30 minutes and the increase of CDs after 6 hours. HX/XOD administration lead to changes in levels of GSH, GSSG, and CDs at 5 minutes as well as to increased myeloperoxidase levels at 3 hours; these changes were similar to those observed in NP-S rats. Acinar cell damage including necrosis was present after 5 minutes in both NP groups, but did not develop in HX/XOD rats. In addition, serum amylase and lipase levels did not increase in the latter group. SOD/CAT treatment significantly attenuated acinar cell damage and inflammatory infiltrate compared with NP-S animals during the later time intervals. CONCLUSION: OFRs are important mediators of tissue damage. However, extracellular OFR generation alone does not induce the typical enzymatic and morphologic changes of acute pancreatitis. Factors other than OFRs must be involved for triggering acute pancreatitis in vivo.

Animals↗

PubMed2000

Serum amyloid A versus C-reactive protein in acute pancreatitis: clinical value of an alternative acute-phase reactant.

OBJECTIVES: The acute-phase reactant C-reactive protein (CRP) is currently the serum variable of choice for an early, accurate, and cost-effective severity assessment of acute pancreatitis in the daily clinical routine. Serum amyloid A (SAA) proteins comprise a family of apolipoproteins that constitute another major acute-phase reactant and thus could be a potential alternative to CRP assessment. In the present study we investigated the clinical usefulness of SAA determinations in acute pancreatitis using an automated immunoassay technique. DESIGN: Cohort study, comparing patients with complicated and mild acute pancreatitis; control groups included individuals with further abdominal disorders and healthy volunteers. SETTING: A collaborative study between the department of general surgery and the routine laboratory of the department of clinical chemistry/pathobiochemistry. PATIENTS: We enrolled 66 patients with acute pancreatitis in the present study. Control groups consisted of healthy subjects (n = 30), patients with chronic pancreatitis (n = 20), patients with pancreatic carcinoma (n = 20), and patients with acute appendicitis (n = 20). INTERVENTIONS: Blood samples were collected during 14 consecutive days in patients with acute pancreatitis. A single blood specimen was taken in all control groups after the diagnosis was established. MEASUREMENTS AND MAIN RESULTS: SAA concentrations were 3 mg/L (median; range, 3-93) in healthy subjects. Although SAA and CRP both reached their maximum within 4 days after onset of symptoms in patients with acute pancreatitis, SAA concentrations rose faster above normal ranges and reached 676 mg/L (median; range, 12-1880), higher than CRP, which reached 313 mg/L (median; range, 29-613). As observed for CRP, SAA was significantly higher in patients who developed complications such as necrosis, infection of necrosis, or multiple organ dysfunction syndrome or in patients who died. SAA achieved best results in discriminating between necrotizing pancreatitis and interstitial edematous pancreatitis. However, CRP provided an earlier differentiation between both entities and a significantly better overall accuracy, as shown by receiver operating characteristics analysis. SAA concentrations in patients with chronic pancreatitis were 6 mg/L (median; range, 3-756). In patients with pancreatic carcinoma, SAA concentrations were 7 mg/L (median; range, 3-492), and in patients with acute appendicitis, they were 50 mg/L (median; range, 3-2140). CONCLUSION: SAA is a nonspecific and rapidly produced variable in inflammatory abdominal disorders with a wider dynamic range than CRP. The current assay technique renders SAA an applicable and readily available variable under clinical routine conditions. In cases of acute pancreatitis, however, CRP is still superior to SAA for early and accurate stratification of patients with a complicated course.

Acute Disease↗

PubMed2000

[Preoperative radiochemotherapy of rectal carcinoma. Current status].

BACKGROUND: In locally advanced rectal cancer RO-resectability is limited and outcome is combined with a relatively high rate of local recurrences. This paper focuses on experiences with preoperative (neo-)adjuvant therapy and the potential improvement of treatment results. PATIENTS AND METHODS: Different therapy regimen were demonstrated under consideration of therapeutic induced side effects, treatment response (downstaging) in relation to resectability, recurrence free and overall survival. RESULTS: The rate of treatment induced toxicity of preoperative radio-(chemo-)therapy in locally advanced rectal cancer is acceptable with regard to the obtained treatment results. Through the pretreatment it was possible to gain a downstaging by nearly 60%. The frequency of local recurrence is significantly reduced by preoperative radiotherapy, and combined radiochemotherapy possibly increases the disease free survival. In what extent the results of treatment could be improved through hyperthermia and/or consecutive postoperative chemotherapy, is proved at present. CONCLUSIONS: Preoperative radio-(chemo-)therapy should be increasingly introduced into the standard treatment regimen of locally advanced rectal cancer and has to be optimised within the scope of further studies.

Disease-Free Survival↗

PubMed1999

The role of polymorphonuclear leukocytes and oxygen-derived free radicals in experimental acute pancreatitis: mediators of local destruction and activators of inflammation.

Using a retrograde infusion sodium taurocholate pancreatitis model in the rat treatment with oxygen radical scavengers or monoclonal anti-ICAM-1 antibody decreased tissue damage and polymorphonuclear leukocytes (PMN) infiltration. Scavengers or anti-ICAM-1 treatment attenuated the activating capacity of blood PMNs following zymosan stimulation. The local production of oxygen free radicals in the pancreas by systemic infusion of hypoxanthine and regional infusion of xanthine oxidase did not induce acute pancreatitis, although an increase of infiltrating PMNs was observed. Our data suggest that oxygen free radicals and infiltrating PMNs aggravate acute pancreatitis and that both are important mediators of local destruction and systemic activation of PMNs.

Acute Disease↗

PubMed1999

Scanning E-field sensor device for online measurements in annular phased-array systems.

PURPOSE: A measurement device for noninvasive and simultaneous control of antennas during regional radiofrequency (rf) hyperthermia and, subsequently, the estimation of the power distribution in the interior of patients are essential preconditions for further technological progress. Aiming at this, the feasibility of an electro-optical electric field sensor was investigated during clinical rf hyperthermia. MATERIAL AND METHODS: The electro-optical electric field (E-field) sensor is based on lithiumniobate crystals and the Mach-Zehnder interferometer structure, and was tested in an earlier phantom study. For this study, a mechanical scanning device was developed allowing the registration of the E-field during clinical application. Data were recorded along a curve in the water bolus of the SIGMA 60 applicator of the annular phased-array system BSD-2000 (BSD Medical Corp., Salt Lake City, UT) close to the base points of the flat biconical dipole antennas. The results were compared with modeling calculations using the finite-difference time-domain (FDTD) method. For the latter, different antenna models were assumed. For systematic registration of the E-field curves in amplitude and phase, we employed an elliptical lamp phantom with fat-equivalent ring (filled with saline solution) and an elliptical polyacrylamide phantom with acrylic glass wall. Further measurements were carried out during the treatment of 5 patients with 20 hyperthermia treatments. RESULTS: Data of both phantom and patient measurements can be satisfactorily described by the FDTD method, if the antenna model is refined by taking into account the conical form of the dipoles and the special dielectric environment of the feeding point. Phase deviations can be entered ex posteriori for correction in the calculation algorithm. A comparison of amplifier power measurement (forward and backward power) and bolus E-field scans near the antenna base points demonstrates that E-field measurements between antennas and patient are a necessity for the appropriate characterization of antenna radiation properties. These measurements are sensitive to variations of the lossy medium in position and shape, and can be correctly predicted with current models. However, the differences between different patients are moderate and unspecific in both calculations and measurements, with fluctuations at maximum of 30 degrees in phases and 40% in amplitudes. CONCLUSIONS: The measurement method presented here turned out to be a practical tool for online registration of E-fields in phases and amplitudes along arbitrary curves in a water bolus or phantom. It can be utilized to evaluate antenna design and modeling calculations and leads, thus, to a better understanding of complicated multiantenna systems. In clinical routine, it can be employed as input for patient-specific hyperthermia planning and, finally, for the realization of online control with subsequent optimization of the power distribution in the patient.

Algorithms↗

PubMed1999

Hyperthermia for treatment of rectal cancer: evaluation for induction of multidrug resistance gene (mdr1) expression.

Environmental stress factors, such as heat, may induce multidrug resistance gene (mdr1) expression, which could result in the disadvantageous multidrug resistance (MDR) phenotype. To evaluate this possibility in a clinical situation, we investigated mdr1 gene expression in patients with locally advanced rectal cancer who underwent preoperative radio-chemo-thermo-therapy (RCTT). Patients were classified into groups according to the treatment schedule of RCTT vs. radio-chemo-therapy (RCT) without hyperthermia (control group). Expression of the mdr1 gene was analyzed in tumors and normal rectal tissues prior to and post-treatment (RCTT or RCT, respectively) by means of semi-quantitative and quantitative reverse transcription-polymerase chain reaction (RT-PCR). The data were correlated with therapeutic response and survival parameters. Based on our evaluation criteria, in 2 of 19 tumors of the RCTT group, mdr1 gene expression was increased more than 2-fold; in 3 of 19 tumors of this group, however, mdr1 expression was decreased more than 2-fold. In the patient control group, levels of mdr1 gene expression were reduced in 2 of 8 tumors. Thus, hyperthermia combined with RCT (RCTT) in comparison with RCT alone does not lead to an increase in mdr1 gene expression in patients with locally advanced rectal cancer within the preoperative treatment schedule. The risk of inducing the classical multidrug resistance phenotype by hyperthermia was thus minimal in this clinical setting. Subsequent adjuvant chemotherapy should thus not be hindered.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Experiences in HCV-NAT screening prior to releasing cellular components by the German Red Cross Blood Transfusion Service of Baden-Württemberg.

In this report we present the accumulated data on nucleic acid testing (NAT) for hepatitis C virus (HCV) RNA of blood donations by the Blood Transfusion Service of Baden-Württemberg in the period between March 1997 and March 1999. An extra barcoded blood sample was collected from each donor. Samples were tested by NAT in mini-pools of maximally 96 samples. First-time and repeat donors were tested separately. RT/HCV-PCR was performed with the COBAS HCV Amplicortrade mark, versions 1.0 and 2.0 from Roche Diagnostic Systems. Many modifications have been introduced to the original protocol since the implementation of NAT screening aiming at an increase in the sensitivity and specificity of the assay. NAT positive pools containing serologically positive samples were detected. Initially, reactive pools were identified that could not be confirmed by secondary pooling and single testing procedures. So far, no serologically negative but NAT positive sample has been found.

Blood Banks↗

PubMed1999

Accuracy of endorectal ultrasound after preoperative radiochemotherapy in locally advanced rectal cancer.

OBJECTIVES: Factors limiting the accuracy of endorectal ultrasound in staging, locally advanced primary rectal cancer after preoperative neoadjuvant radiochemotherapy (RCT) were evaluated. METHODS: Patients (n = 84) with initial locally advanced rectal cancer (uT3/uT4) undergoing R0 resection were investigated after preoperative treatment that combined radiotherapy up to 45 Gy with two cycles of chemotherapy (5-FU and leucovorin on d 1-5 and 22-28). At 4 to 6 weeks after completion of RCT and before tumor resection, preoperative endoluminal ultrasound was performed. RESULTS: The accuracy to predict the depth of tumor infiltration (T-category) was found to correlate with downstaging. The T-category was correctly staged before surgery in 15 of the 51 responders (29%) and in 27 of 33 nonresponders (82%), whereas misinterpretation occurred in 36 of the responders (71%) and in 6 of the nonresponders (18%) (p < 0.001). Neither tumor distance from anal verge nor tumor location correlated with the staging accuracy. Lymph node involvement was correctly assessed in 48 patients (57%). Wall invasion was correctly ascertained in 42 patients (50%), with under estimation in 11 patients (13%) and overestimation in 31 patients (37%). CONCLUSIONS: After radiochemotherapy, endosonography does not provide a satisfactory accuracy for preoperative staging of rectal cancer. New interpretation and diagnostic criteria are needed for the prediction of treatment response.

Adenocarcinoma↗

PubMed1999

Bacterial infection and extent of necrosis are determinants of organ failure in patients with acute necrotizing pancreatitis.

BACKGROUND: The risk factors predisposing to organ failure in patients with necrotizing pancreatitis remain unclear. The relationship between the extent of pancreatic necrosis, the presence of infection and the incidence of organ failure was analysed. METHODS: In a retrospective review, the occurrence of pulmonary insufficiency, renal insufficiency, shock, sepsis/sepsis-like syndrome (SLS) and coagulopathy was evaluated in 273 patients with necrotizing pancreatitis, and a comparison was made between patients with sterile or infected necrosis. Additionally, the relation between the incidence of organ failure and extent of pancreatic parenchymal necrosis was investigated by classifying the patients into three groups according to the amount of necrotic tissue found by contrast-enhanced computed tomography (group 1, extent less than 30 per cent; group 2, 30-50 per cent; group 3, more than 50 per cent). RESULTS: Organ failure was more frequent in patients with infected necrosis than in those with sterile necrosis. Differences were found in the incidence of pulmonary insufficiency, sepsis/SLS and coagulopathy. Organ failure occurred more frequently in group 3 than in group 2 or 1 (95 versus 79 and 66 per cent; P = 0.0004). The extent of infected necrosis was not related to the incidence of organ failure (group 1, 88 per cent; group 2, 86 per cent; group 3, 96 per cent). However, there was a relation between the incidence of organ failure and the extent of sterile necrosis (group 1, 59 per cent; group 2, 74 per cent; group 3, 94 per cent; P = 0.0001). Multivariate analysis confirmed the presence of infection and the extent of necrosis as independent determinants of organ failure. CONCLUSION: The incidence of organ failure is determined by both bacterial infection and extent of necrosis. The incidence of organ failure is determined by the extent of necrotic parenchyma in patients with sterile necrosis. Infected necrosis is associated with a high incidence of organ failure irrespective of the extent of necrosis.

Acute Kidney Injury↗

PubMed1999

Systemic lymphocyte activation modulates the severity of diet-induced acute pancreatitis in mice.

To examine the role of lymphocyte activation in the development of local and systemic complications in acute pancreatitis, we compared disease severity of choline-deficient, 0.5% ethionine supplemented (CDE) diet-induced acute pancreatitis in T- and B-cell deficient SCID mice and immunocompetent C.B-17 mice. Twenty-five female SCID and 17 female C.B-17 mice were fasted for 24 h and fed a CDE diet for 72 h. Twenty SCID and 12 C.B-17 mice were bled and their organs removed for histologic evaluation. Five control animals of both kinds were fed a regular diet for 6 days. Lung, kidney, and pancreas were examined microscopically, and pancreatic damage scored. Apoptosis was detected by DNA nick-end labeling and confirmed by DNA laddering. Trypsinogen-activation peptide was measured by enzyme-linked immunosorbent assay (ELISA), and the catalytic activity of PLA2 was determined by a radiometric assay. Four-day mortality was 10% in SCID and 33% in C.B-17 mice, and 10-day mortality was 0 in SCID and 60% in C.B-17 mice. SCID mice had mild pulmonary damage, whereas pulmonary injury was severe in C.B-17 mice. Pancreatic damage was severe in both groups. Even though in situ staining of apoptotic cells was found in all pancreatitis animals, apoptosis was confirmed by DNA laddering only in C.B-17 mice. In SCID mice, apoptotic cell staining positively correlated with necrosis (r = 0.91; p < 0.001). Plasma TAP and PLA2 catalytic activity did not differ significantly between the groups. In conclusion, the absence of T and B lymphocytes prevents severe pulmonary injury resulting from acute pancreatitis but does not influence pancreatic or renal damage. Our results suggest that systemic lymphocyte activation does not affect the initiating events that trigger pancreatic injury but modulates the systemic response, in particular, pulmonary injury caused by acute pancreatitis.

Acute Disease↗

PubMed1999

New approaches in surgical management of severe acute pancreatitis.

Despite many prospective randomized clinical studies a specific pharmacotherapy for severe acute pancreatitis is not in sight. To date, the only possibility to influence the prognosis of this severe illness is early diagnosis and prevention of intra- and extrapancreatic necrosis and its subsequent infection. In severe necrotizing pancreatitis the incidence of infected necrosis amounts to 40-70% of all patients within 3 weeks. Thereby, the clinical picture often varies to large extent. Ultrasonographically or computer tomography-guided fine-needle aspiration (FNAC) is a fast and reliable technique for diagnosis with an overall sensitivity of 88% and specificity of 90%. This method should however not be applied too early in the course of necrotizing pancreatitis. Since infection of pancreatic necrosis determines significantly the prognosis of disease, various studies have assessed the efficacy of prophylactic antibiotic treatment in patients. Three prospective randomized studies have shown that prophylaxis significantly minimizes septic complications, only in one study, however, the mortality rate could be improved. Although randomized studies are still mandatory to resolve the controversy, it seems justified to recommend prophylaxis with antibiotics which are capable of penetrating the pancreatic tissue and juice. Sterile necrosis should be treated conservatively, with prophylactic antibiotic treatment for as long as possible. Only if patients worsen despite intensive care medicine, surgical debridement should be considered. In contrast, in patients with infected necrosis immediate surgery is in most cases mandatory. Although in one prospective study conservative treatment did not lead to an enhanced mortality rate, possible delay of surgical treatment may endanger the patient. In order to improve the prognosis of the disease, timely and adequate treatment in specialized units provides the best chances for a good prognosis whereby the severely ill patient should not be treated according to a scheme but to his/her individual needs.

Antibiotic Prophylaxis↗

PubMed1999

Preoperative treatment of rectal cancer with radiation, chemotherapy and hyperthermia: analysis of treatment efficacy and heat-shock response.

Preoperative treatment of locally advanced rectal cancer with radiation, chemotherapy and hyperthermia is analyzed with regard to heat-shock response. In 23 patients with locally advanced rectal cancer (uT3/uT4), hyperthermia was administered in combination with radiotherapy and chemotherapy. In parallel, the effect of the treatment on levels of the heat-shock proteins HSP27 and inducible HSP70 in tumors and surrounding tissues was investigated by Western blotting. The patients' sera were also examined for autoantibodies against HSPs. HSP27 and inducible HSP70 were detected in most rectal tumors and surrounding tissues before and after treatment. HSP27 and inducible HSP70 levels had changed in 10 tumors after treatment. However, prior to treatment, there existed an unexpected diversity in HSP levels in the tumors and surrounding tissue. Hyperthermia doses in cumulative minutes for which 90% of the tumor is above the reference temperature (cum min T90 > or = 15 min) led to increased survival and response compared to that of a control group of patients treated without or with low-dose hyperthermia (cum min T90 < 15 min). However, there was no correlation to different expression of the HSPs. Hyperthermia as used in this setting does not lead to any sustained expression of HSPs in either the tumor or the surrounding tissue.

Antibodies↗

PubMed1998

Rationale for using invasive thermometry for regional hyperthermia of pelvic tumors.

PURPOSE: Invasive thermometry for regional hyperthermia is time-consuming, uncomfortable, and risky for the patient. We tried to estimate the benefit/cost ratio of invasive thermometry in regional hyperthermia using the radiofrequency system BSD-2000. METHODS AND MATERIALS: We evaluated 182 patients with locally advanced pelvic tumors that underwent regional hyperthermia. In every patient a tumor-related temperature measurement point was obtained either by invasive or minimally invasive catheter measurement tracks. In the earlier period for every patient an intratumoral measurement point was decided as obligatory and intratumoral catheters were implanted intraoperatively, CT guided, or under fluoroscopy. In the later period, invasive thermometry often was avoided, if a measurement point in or near the tumor was reached by an endoluminally inserted catheter (rectal, vaginal, cervical, urethral, or vesical). For every patient side effects and complications referred to thermometry were evaluated and compared with the potential benefit of the invasively achieved temperature data. The suitability of endolumimally registered temperatures is analyzed to estimate local feasibility (specific absorption rate achieved) and local effectiveness (thermal parameters correlated with response). RESULTS: In 74 of 182 patients invasive thermometry was performed, at most CT-guided for soft tissue sarcomas and rectal recurrences. In 14 of 74 (19%) side effects such as local inflammation, pain, or abscess formation occurred that enforced removal of the catheter. However, local problems were strongly correlated with the dwell time of the catheter and nearly never occurred for dwell times less than 5 days. Fortunately, no fatal complications (e.g., bleeding or perforation) occurred during or after implantation which could be attributed to the invasive thermometry procedure. Endoluminal tumor-related temperature rises per time unit (to estimate power density) were correlated with intratumoral rises at the same patients (where both measurements were available). For a subgroup of patients pooled in two Phase II studies with rectal (n = 37) and cervical (n = 18) carcinomas thermal parameters derived from endoluminal measurements were correlated with response or local control, resp. CONCLUSIONS: If a tumor-related endoluminal temperature measurement point is available, additional invasive thermometry gives no further information to improve the power deposition pattern. For primary rectal and cervical cancer, and probably as well for prostate, bladder and anal cancer, endoluminal measurements are suitable to estimate local feasibility and effectiveness. Therefore, invasive thermometry is dispensable in the majority of patients. In some selected cases, temperature measurement in the tumor center is required to estimate the maximum temperature. In those cases, dwell time of catheters should be minimized--and it should be considered to perform invasive thermometry at the beginning (one or two heat treatments).

Catheterization↗

PubMed1998

Radiochemotherapy and hyperthermia in the treatment of rectal cancer.

We evaluated the use of regional hyperthermia with radio-chemotherapy in a phase I/II study on locally advanced rectal carcinomas. Thirty-four patients with primary advanced (stage T3/T4) rectal carcinomas (24 patients) or recurring rectal carcinomas (6 patients) were treated using preoperative radiochemo-thermotherapy. Initial tumour staging was carried out clinically (degree of fixation) and using endorectal ultrasonography and CT. Radiotherapy was carried out with the patient prone (on a belly board) at 5 x 1.8 Gy per week up to 45 Gy at the reference point. 5-Fluorouracil (300-500 mg/m2) was administered with low-dose leucovorin (50 mg) on days 1-5 and 22-26. Patients were treated with regional hyperthermia each week prior to radiotherapy, using the Sigma-60 ring of the BSD-2000 system. Temperature/position curves and temperature/time curves were recorded via endocavitary catheters (tumour contact, bladder, vagina). Following endosonographic and clinical restaging, the operation was carried out 4-6 weeks after the end of preoperative therapy. In cases where tumours were unresectable, a boost of up to 60 Gy was given. Twenty-three of the 34 patients (68%) proved to be curatively resectable. Of these patients, 70% were downstaged endosonographically during preoperative therapy. The actuarial survival rates among these patients were 85% (primary rectal cancer) and 60% (recurrences) at 30 months. All in all, the preoperative multimodal therapy was well tolerated, and premature termination was necessary in only two cases. The quality of temperature distribution (T90, cum min T90 > 40.5 degrees C) depends on the power level and relative power density. The response (particularly downstaging) correlates significantly with the quality parameters of the temperature distributions. This regimen proved practical and effective, with encouraging downstaging rates and local control rates.

Adult↗

PubMed1998

[Phase II study on preoperative radio-chemo-thermotherapy in locally advanced rectal carcinoma].

BACKGROUND: Recent studies show that preoperative radio-chemotherapy can increase resectability and local control of locally advanced rectal carcinomas. Additional regional hyperthermia might increase remission rates and tumor response. We therefore tested regional hyperthermia together with radio-chemotherapy in a phase-II study on locally advanced rectal carcinomas. PATIENTS AND METHODS: Thirty-seven patients with primary advanced stage uT3/T4 rectal carcinomas were treated with preoperative radio-chemo-thermo-therapy. The initial tumor depth was determined using endosonography, CT, and MRI. Radiotherapy was carried out in prone position (on a belly board) using standard techniques, with 5 x 1.8 Gy per week up to 45 Gy at the reference point. 5-Fluorouracil (300 to 500 mg/m2) was administered with low doses of leucovorin (50 mg) on days 1 to 5 and 22 to 28. The patients were treated with regional hyperthermia each week prior to radiotherapy and simultaneously with chemotherapy, using the Sigma 60 ring from the BSD-2000 system. Temperature/position curves and temperature/time curves were recorded in endocavitary (endorectal) catheters in tumor contact and as well in bladder and vagina. Following endosonographic restaging, the operation was carried out 4 to 6 weeks after the end of preoperative therapy and adjuvant chemotherapy continued in four cycles. In cases where tumors were non-resectable, a boost up to 64 Gy was aimed. RESULTS: Thirty-one of the 37 patients (84%) with primary carcinoma proved locally R0-resectable. In addition we had 1 R1-resection (3%) and 5 non-resectable tumors (13%). Among the resected tumors, 53% experienced a reduction of depth infiltration from the initial endosonographic stage during preoperative therapy. The actuarial survival rate after 4 years is 65% (free of progression 57%). The actuarial 4-year survival rate was particularly favorable for the group of responders. Overall, the preoperative multimodal therapy was well tolerated, and premature termination was only necessary in 1 case (3%). Grade III/IV toxicities in the intestine and skin were reduced as far as possible by field blockings and cooling of the perineal region. They occurred only in 5/37 patients (13%) at the intestine and in 6/37 patients (16%) at the skin. The thermal data were subjected to a statistical analysis. The quality of temperature distribution (T90, cum min T90 > or = 40.5 degrees C) depends on the power level and relative power density. The response (reduction of tumor size or depth infiltration) correlated significantly with quality parameters of the temperature distributions. This dependency is found as a trend for progression-free survival, too. CONCLUSIONS: Preoperative radio-chemo-thermo-therapy proved to be practical and effective, with encouraging remission rates and excellent local control rates. For this reason, a phase-III study to test regional hyperthermia has been initiated. At the same time, certain technical improvements are still under development for regional hyperthermia.

Adult↗

PubMed1998

Video-assisted thoracic surgery. Staging and management of thoracic tumors.

BACKGROUND: This prospective study was conducted to investigate the value of video-assisted thoracic surgery (VATS) for staging and therapy of thoracic tumors. METHODS: VATS was performed in 86 patients presenting peripheral pulmonary nodules. Indications for thoracoscopy included diagnosis of indeterminated pulmonary lesions (n = 55), staging of disseminated disease (n = 24), and therapeutic interventions (n = 7). Previous or simultaneous tumors belonged to gastrointestinal tract (n = 27), sarcoma (n = 19), breast (n = 12), and miscellaneous. VATS was carried out under general anesthesia using double lumen intubation. RESULTS: VATS was successfully performed in 78% of patients. It was converted in 19 patients (22%) because of adhesions (n = 12), technical problems (n = 3), and lesions not to be found (n = 4). VATS revealed malignancy in 81% and benign lesions in 19%. Additional information compared to conventional staging was obtained in 48%, resulting in therapeutic consequences in 34% of the patients. Postoperative complications related to VATS were observed in nine patients. CONCLUSIONS: In this study, VATS proved to be a sensitive technique for staging of pulmonary lesions. Thoracoscopic wedge resection may have significant impact on the operative management of carefully selected patients with peripheral pulmonary lesions.

Adolescent↗

PubMed1998

The role of staging laparoscopy for multimodal therapy of gastrointestinal cancer.

BACKGROUND: This prospective study was conducted to evaluate the accuracy and the therapeutic relevance of staging laparoscopy. METHODS: Between June 1993 and February 1997 staging laparoscopy was performed in 389 patients with various neoplasms. Additionally, 144 selected patients of this group were examined with laparoscopic ultrasound using a semiflexible ultrasound probe (7.5 MHz). RESULTS: Compared to conventional imaging methods, laparoscopy and laparoscopic ultrasound improved the accuracy of staging in 158 of 389 patients (41%). Statistical subgroup analysis of 131 patients with gastric cancer showed that the accuracy of staging laparoscopy in the detection of distant metastases (68%) was significantly higher (p < 0.01) than that of ultrasound (63%) or computed tomography (58%). In the whole group, laparoscopy alone disclosed intraabdominal tumor dissemination or nonresectable disease in 111 patients. Laparoscopic ultrasound displayed additional metastases-i. e., liver metastases (n = 9), M1 lymph nodes (n = 15), or nonresectable tumors (n = 6) in 30 patients. Although metastastic disease was suggested by preoperative imaging, benign lesions were found in five patients with laparoscopy and in a further 12 patients with ultrasonography. The findings of staging laparoscopy changed the treatment strategy in 45% of the patients. Conversion to open surgery was necessary in 5% of the cases, and complications related to laparoscopy occured in 4% of the patients. CONCLUSIONS: Laparoscopy with laparoscopic ultrasound improves the staging of gastrointestinal tumors and has a significant impact on a stage-adapted surgical therapy.

Adolescent↗