Antithrombin in severe sepsis--"new" indication of an "old" drug?
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Antithrombin III↗
Biomedical subjects
H Riess
Publications and source records attributed to H Riess.
A phase II trial of gemcitabine in combination with 5-fluorouracil (24-hour) and folinic acid in patients with chemonaive advanced pancreatic cancer.
BACKGROUND: Gemcitabine (Gemzar) and 5-fluorouracil (5-FU) plus folinic acid (FA) both have proven activity in the treatment of patients with advanced pancreatic cancer. The present study was initiated to investigate the efficacy of gemcitabine in combination with 5-FU-FA. PATIENTS AND METHODS: Thirty-eight patients, median age 60 years (range 34-70) with inoperable, stage IV, pancreatic cancer were enrolled into the study and treated on an outpatient basis. All except one patient received at least one cycle of treatment with gemcitabine (1000 mg/m2), followed by FA (200 mg/m2) and 5-FU (750 mg/m2) administered as a 24-hour continuous infusion on days 1, 8, 15 and 22 of a 42-day schedule. No patient had received prior chemotherapy or radiotherapy. All 38 patients were assessed for efficacy, toxicity and time to progressive disease. RESULTS: Two patients (5%), achieved a partial response and thirty-four patients (89%) achieved stable disease. There were two early deaths (< or = 4 weeks). The median time to progression was 7.1 months (range 0.4-18.1+; 95% confidence interval (95% CI): 5.3-7.9 months). Three patients had a progression-free interval of greater than 12 months and 12 of 38 patients (32%) survived longer than 12 months. The median overall survival was 9.3 months (range 0.5-26.5; 95% CI: 7.3-13.0 months). The incidence of grade 3 and 4 toxicities was low. CONCLUSIONS: The combination of gemcitabine and 5-FU-FA is active and well tolerated and seems to offer an improvement in progression-free interval over both gemcitabine monotherapy and 5-FU-FA therapy.
Adult↗
[Imaging of intra-arterial hepatic port catheter systems by power-doppler sonography using contrast media--preliminary results].
AIM: This study was designed to determine whether intra-arterial hepatic port catheter systems can be adequately detected by contrast-enhanced power-Doppler sonography. METHOD: 15 patients with a liver port system were investigated before chemotherapy. Examinations were performed with short bolus injections of the contrast medium Levovist in addition to angiographic imaging. RESULTS: Liver port systems were easily detected by the contrast-enhanced power-Doppler method. In 11 out of 15 patients a correct flow of the contrast medium via the port system was seen with both examination methods. One partially occluded hepatic artery was not identified by power-Doppler despite correct flow of the contrast fluid. In one of three patients showing an incorrect flow of the contrast medium the blood circulated primarily through the splenic artery due to a dislocation of the catheter tip. Circulation through both the hepatic and the splenic arteries was shown in a second patient and an occluded right hepatic artery was demonstrated in a third. All these findings were observed with both examination techniques. CONCLUSION: Power-Doppler sonography provides a reliable image of the port catheter system. This method can be used as a follow-up procedure to determine the state of arterial hepatic circulation during chemotherapy.
Aged↗
Paclitaxel as weekly second-line therapy in patients with advanced pancreatic carcinoma.
Although the prognosis for patients with pancreatic adenocarcinoma is still poor, gemcitabine has shown significant impact upon survival and quality of life. Our aim was to examine the potential effectiveness of a second- or third-line therapy with paclitaxel (Taxol) after confirmed progression with a gemcitabine-containing schedule for patients remaining in good clinical condition. Eighteen patients with stage IVb disease participated in this study. Pretreatment with gemcitabine was performed either as monotherapy and/or in combination with 5-fluorouracil (5-FU) and folic acid (FA). Paclitaxel was administered at weekly intervals on an outpatient basis. We observed 238 weekly treatments with a median number per patient of 12 treatments. The median dosage was 73 mg/m2 paclitaxel (range 55-88 mg/m2). Regarding toxicity, only one patient each presented with anemia and leukocytopenia of WHO grade III. Hepatotoxicity with a temporary increase in aminotransferase of WHO grade II occurred in three patients. Higher-grade symptomatic toxicity was rare, except alopecia. At this time, the median survival time is 17.5 weeks (range 7-88 weeks) since the start of therapy. Stable disease was observed in five patients. One patient achieved complete remission within 37 weeks. At this time, he has survived for more than 56 weeks after confirmed progression under first-line therapy. In conclusion, this schedule demonstrates that weekly therapy with paclitaxel after pretreatment can be effective with a low toxicity profile. This opens up an additional therapeutic option for a selected patient group with a poor prognosis so far.
Aged↗
The role of gemcitabine alone and in combination in the treatment of pancreatic cancer.
Pancreatic cancer, one of the most frequently reported gastrointestinal tumors, has a 5-year survival of less than 5%. Despite representing only 2-3% of the total cancer incidence, it is the fifth leading cause of cancer death. This is because it is commonly only diagnosed at an advanced stage. Until recently the traditional therapy for patients with advanced disease was palliative 5-fluorouracil (5-FU)-based chemotherapy. However, the novel antinucleoside gemcitabine (Gemzar) has demonstrated a survival benefit over 5-FU, and an improvement in disease-related symptoms and quality of life in patients with advanced disease. This review presents an overview of the clinical studies of gemcitabine, either alone or in combination, with other chemotherapeutic agents and/or radiation therapy, in the treatment of these patients. A comparison of these studies is made with those using alternative treatment regimens. The data suggest that gemcitabine in combination with biomodulated 5-FU should be considered the standard palliative treatment to which other new drug combinations or combined modality chemoradiation regimens should be compared.
Antimetabolites, Antineoplastic↗
Primary mucinous adenocarcinoma of the appendix: a rare entity in the differential diagnosis of ovarian cancer.
We report a 58-year-old female patient with the suspected diagnosis of ovarian cancer. Upon surgical exploration, examination of the appendix revealed the histological diagnosis of primary mucinous adenocarcinoma. This is an unusual consideration in the differential diagnosis of the ovarian cancer. We discuss the diagnosis, classification and treatment of the cancer of the appendix in relation to ovarian cancer.
Adenocarcinoma, Mucinous↗
Lack of point mutations in exons 11-23 of the retinoblastoma susceptibility gene RB-1 in liver metastases of colorectal carcinoma.
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Adolescent↗
[Regional chemotherapy of the liver after resection of liver metastases in colorectal carcinoma].
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Antineoplastic Combined Chemotherapy Protocols↗
[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↗
The effect of virus inactivation on coagulation factors in therapeutic plasma.
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Aged↗
Whole body hyperthermia: a secure procedure for patients with various malignancies?
OBJECTIVE: To establish the safety of systemic Cancer Multistep Therapy (sCMT) including whole body hyperthermia, by means of hemodynamic, laboratory and clinical investigations. DESIGN: Prospective study. SETTING: University clinic. PATIENTS: 12 patients with various cancers (with sCMT), a second group of 20 patients with colorectal carcinoma treated with chemotherapy (without sCMT). INTERVENTIONS: 25 treatments with sCMT for 60 min at 41.8 degrees C (including chemotherapy) were given in addition to induced hyperoxemia and hyperglycemia under general anesthesia. MEASUREMENTS AND RESULTS: Invasive monitoring of systemic and pulmonary hemodynamics as well as pulmonary gas exchange was used at 37 degrees C, 40 degrees C, 41.8 degrees C and 39 degrees C. In addition, laboratory parameters were measured before and within 4 days of therapy. At 41.8 degrees C, invasive monitoring showed characteristic signs of hyperdynamic circulation. In addition, right-to-left shunt, oxygen consumption, oxygen delivery and lactate levels were significantly different from pretreatment values. At the end of therapy, lactate levels and the extravascular lung water index increased, whereas all other parameters showed a clear tendency to return to initial values. Within the first day after sCMT, we measured a slight but significant reversible increase in serum creatinine compared to pretreatment values, but found no significant alterations of other chemical parameters. Between the sCMT group and controls, there was only a temporary significant difference in aspartate aminotransferase levels 2 days after therapy. CONCLUSIONS: sCMT, including whole body hyperthermia, accompanied by suitable anesthesiological management and monitoring, does not lead to any serious or sustained organ dysfunction and can therefore be regarded as a safe therapy.
Adult↗
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↗
Elevated reticulocyte count--a clue to the diagnosis of haemolytic-uraemic syndrome (HUS) associated with gemcitabine therapy for metastatic duodenal papillary carcinoma: a case report.
In adults, the haemolytic-uraemic syndrome (HUS) is associated with probable causative factors in the minority of all cases. Cytotoxic drugs are one of these potential causative agents. Although metastatic cancer by itself is a recognized risk-factor for the development of HUS, therapy with mitomycin-C, with cis-platinum, and with bleomycin carries a significant, albeit extremely small, risk for the development of HUS, compared with all other cytotoxic drugs. Gemcitabine is a novel cytotoxic drug with promising activity against pancreatic adenocarcinoma. We are reporting on one patient with metastatic duodenal papillary carcinoma developing HUS while on weekly gemcitabine therapy. The presenting features in this patient were non-cardiac pulmonary oedema, renal failure, thrombocytopenia and haemolytic anaemia. The diagnosis of HUS was made on the day of admission of the patient to this institution. Upon aggressive therapy, including one single haemodialysis and five plasmaphereses, the patient recovered uneventfully, with modestly elevated creatinine-values as a remnant of the acute illness. Re-exposure to gemcitabine 6 months after the episode of HUS instituted for progressive carcinoma, thus far has not caused another episode of HUS.
Adult↗
Activated protein C resistance shows an association with pregnancy-induced hypertension.
A common mutation in the factor V gene, the Leiden mutation, is the most frequent genetic cause of resistance to activated protein C (APC). Recent studies have shown that the prevalence of APC resistance is associated with severe pregnancy-induced hypertension (PIH). Our objective was to determine whether the factor V Leiden mutation is more prevalent in patients who developed severe PIH than in normotensive pregnant women. In 70 women with a history of severe PIH, of whom 15 had pre-eclampsia, we investigated common coagulation factors as well as APC resistance (factor V related). We found that seven of these 70 women showed low values for APC. Out of these, five were heterozygous and none was homozygous for factor V Leiden mutation. In a control group of normotensive pregnant women we found a 3.0% rate of APC resistance and a 3.0% rate of carriers of the Leiden mutation. These results indicate a significantly higher prevalence of both APC resistance and factor V Leiden mutation in women with severe PIH. Placental infarctions and micro-embolisms are considered to be one of the principle pathophysiological changes in severe PIH. Our results suggest that APC resistance is a risk factor for severe PIH, in addition to its well-known role in macrothrombo-embolism.
Adult↗
Phase I trial of gemcitabine (Gemzar), 24 h infusion 5-fluorouracil and folinic acid in patients with inoperable pancreatic cancer.
Gemcitabine (Gemzar) has a significant impact upon survival and quality of life for patients with pancreatic cancer, compared with 5-fluorouracil (5-FU). This phase I study was initiated to define the recommended dose of 5-FU delivered as a 24 h infusion in combination with gemcitabine (1000 mg/m2) and folinic acid (200 mg/m2) in patients with inoperable pancreatic cancer, treated on an outpatient basis. Drugs were administered weekly for 4 weeks out of 6 weeks. Sixteen chemonaive patients (median age 59 years, range 51-66) were enrolled, 15 had stage IV and one stage III disease. The median Karnofsky performance score (KPS) was 70 (range 60-80). Six patients received 5-FU 750 mg/m2, eight received 5-FU 1000 mg/m2 and two received 5-FU 1250 mg/m2. The maximum tolerated dose of 5-FU was 1000 mg/m2. Hepatotoxicity was dose limiting. One patient who received 5-FU 1250 mg/m2 died as a result of hepatorenal failure. There was one partial response, nine patients had stable disease for more than 3 months and 13 patients had improved KPS. The median time to progressive disease was 31 weeks (range 5-50 weeks). A phase 11 trial is underway to further assess the activity of this combination at the recommended dose of 750 mg/m2 5-FU.
Adult↗
Expression of bomapin, a novel human serpin, in normal/malignant hematopoiesis and in the monocytic cell lines THP-1 and AML-193.
Our group recently cloned the cDNA-encoding bomapin, a member of the serine protease inhibitor (serpin) superfamily, from a human bone marrow cDNA library (J Biol Chem 270:2675, 1995). To understand its expression within the hematopoietic compartment, RNA extracted from bone marrow or peripheral blood from normal donors and patients with leukemia was reverse transcribed and analyzed by polymerase chain reaction (PCR). Bomapin PCR products were readily detected in normal bone marrow, which was designated as a medium mRNA level. In peripheral blood, bomapin expression was low or undetectable in normal donors (n = 6) and patients with chronic lymphocytic leukemia (n = 6). Blood from patients with chronic myeloid leukemia (n = 6), chronic myelomonocytic leukemia (n = 6), acute myeloid leukemia (n = 5), and acute lymphocytic leukemia (n = 5) exhibited low to medium levels of bomapin expression. Furthermore, a high level of bomapin expression was detected in one individual with acute monocytic leukemia. These data suggest that bomapin expression may be elevated in hematopoietic cells of monocytic lineage. Therefore, we analyzed the expression of bomapin within cell lines that exhibited characteristics of the monocytic lineage. Bomapin PCR products were detected in the monocytic THP-1 and AML-193 cell lines but not in CRL 7607, CRL 7541, KG-1, or K562 cells. Induction of bomapin transcripts was not detected in the latter series of cell lines following a 24-hour treatment with phorbol myristate acetate (PMA, 10(-8) mol/L) or tumor necrosis factor-alpha (TNF-alpha, 30 U/mL), whereas treatment of THP-1 or AML-193 cells with these agents reduced the intensity of the bomapin PCR products. Northern blotting confirmed these results and showed that the expression of bomapin in THP-1 cells was downregulated over a 4-day period by PMA and, to a lesser extent, TNF-alpha. Immunoblotting was used to show the presence of a 40-kD protein in THP-1 cytosol preparations. Bomapin antigen levels were correspondingly reduced after treatment with PMA. Because PMA and TNF-alpha induce monocytic differentiation in THP-1 and AML-193 cells, these data increase the possibility that bomapin may play a role in the regulation of protease activities specifically in early stages of cellular differentiation.
Cell Differentiation↗
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↗
[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↗