Biomedical subjects

L Staib

Publications and source records attributed to L Staib.

35 records · Page 2Linked to original sources

PubMed1998

Ampullectomy for adenoma of the papilla and ampulla of Vater.

INTRODUCTION: The frequency of malignant adenomas of the papilla figures between 15 and 30%. Villous adenoma is considered to be a premalignant lesion. TREATMENT: Resection of the papilla is indicated in large tubular and small tubulovillous adenoma. Ampullectomy, however, is mandatory in villous adenoma with severe dysplasia and large villous or tubulovillous adenoma. If villous adenoma with a low-risk pT1 N0 M0 G1/2-cancer is treated by ampullectomy, local lymph dissection should also be performed. Ampullectomy includes extirpation of the ampulla of Vater and reinsertion of the common bile duct and the pancreatic main duct into the duodenal wall. RESULTS: Hospital mortality after ampullectomy is less than 0.4%, and surgical morbidity, e.g., cholangitis, below 10%.

Adenoma↗

PubMed1998

Adjuvant radiochemotherapy--what is the patients benefit?

BACKGROUND: Local relapse is a major problem after potentially curative rectal cancer surgery. Although the incidence of local recurrences may be reduced by specialized surgical techniques such as total mesorectal excision (TME), local relapse rates of 20% or higher are the surgical reality today. Studies using adjuvant postoperative radiotherapy, chemotherapy, radiochemotherapy or immunotherapy have tried to reduce local relapse rates and distant progression. Postoperative radiochemotherapy has been the recommended standard, after complete resection of Union Internationale Contra la Cancrum (UICC) stages II and III rectal cancers. In view of recent positive results with preoperative radiotherapy of TME without adjuvant therapy, we found it important to review the literature to update the recommendable adjuvant procedure in rectal cancer. METHOD/PATIENTS: The literature from 1985 to May 1998 was reviewed for studies trying to either confirm or improve adjuvant therapy in rectal cancer. Only randomized controlled trials were analyzed with regard to their effectiveness in reducing the absolute rates of local recurrence and improving survival. RESULTS: Two trials applying adjuvant radiotherapy were able to demonstrate the reduction of local relapse rates, one trial with marginal significance, both without impact on survival. Four trials involving 1104 patients with rectal cancer stages UICC II-III compared postoperative radiochemotherapy with either surgical controls, adjuvant radiotherapy or conventional radiochemotherapy. In these trials, local relapse rates were significantly reduced by 11-18%, and survival rates significantly improved by 10-14%. Severe acute toxicities occurred in 50-61% of the patients, compromising compatibility, and caused death in 0-1%. Small-bowel obstruction leading to surgery was noted in 2-6% and to death in up to 2% of the patients. Intraoperative radiotherapy (IORT) improved local control and survival after surgery of locally advanced disease/local relapse. CONCLUSION: In view of four trials demonstrating a significant benefit of postoperative radiochemotherapy and with regard to recent still-debatable results of preoperative short-term radiotherapy optimal surgery with lowest local relapse rates plus postoperative radiochemotherapy remains the actual recommendable standard for rectal cancer surgery in R0 resected tumors stages UICC II+III.

Chemotherapy, Adjuvant↗

PubMed1998

Endotoxin binding and elimination by monocytes: secretion of soluble CD14 represents an inducible mechanism counteracting reduced expression of membrane CD14 in patients with sepsis and in a patient with paroxysmal nocturnal hemoglobinuria.

Little is known about the role of peripheral blood mononuclear cells (PBMCs) in lipopolysaccharide (LPS) elimination. We studied the endotoxin elimination capacities (EEC) of PBMCs of 15 healthy volunteers, 13 patients with sepsis, and 1 patient suffering from paroxysmal nocturnal hemoglobinuria (PNH). Although expression of CD14, the best-characterized receptor for LPS to date, was reduced from 93.6% +/- 0.8% in healthy subjects to 50.5% +/- 6.5% in patients with sepsis and was 0.3% in a patient with septic PNH, EEC were found to be unchanged. There was no difference in the amount of tumor necrosis factor alpha (TNF-alpha) released by PBMCs of healthy donors and patients with sepsis. Anti-CD14 antibodies (MEM-18) completely suppressed EEC, binding of fluorescein isothiocyanate-labeled LPS to monocytes as determined by FACScan analysis, and TNF-alpha release in all three groups studied. The concentrations of soluble CD14 (sCD14) secreted by endotoxin-stimulated PBMCs from healthy donors and patients with sepsis amounted to 4.5 +/- 0.4 and 20.1 +/- 1.8 ng/ml, respectively. Based on our results, we suggest that PBMCs eliminate LPS by at least two different mechanisms; in healthy subjects, the membrane CD14 (mCD14) receptor is the most important factor for LPS elimination, while in patients with sepsis (including the septic state of PNH), increased sCD14 participates in LPS elimination. Secretion of sCD14 is strongly enhanced under conditions of low expression of mCD14 in order to counteract the reduction of mCD14 and maintain the function of monocytes. This sCD14 may substitute the role of mCD14 in LPS elimination during sepsis. The elimination of LPS by PBMCs correlates with the binding reaction and the secretion of TNF-alpha.

Adult↗

PubMed1998

FDG PET: elevated plasma glucose reduces both uptake and detection rate of pancreatic malignancies.

UNLABELLED: The aim of the study was to evaluate the effects of elevated plasma glucose levels on tumor detection. METHODS: One-hundred and seventy-one fasted patients (100 malignant pancreatic tumors, 46 chronic pancreatitis and 25 patients with other benign pancreatic lesions) were studied with 18F-fluorodeoxyglucose (FDG) PET before planned resective pancreatic surgery. Nineteen of 171 patients had elevated plasma glucose levels above 130 mg/dl, and 24 of 171 had diabetes mellitus. Standard uptake values (SUVs) with and without glucose correction, tumor-to-muscle ratios and tumor-to-liver ratios were measured of the pancreatic lesion respective of the area with the highest uptake within the pancreas. The original qualitative PET reports concerning the dignity of the pancreatic lesion were translated into a five-point malignancy scale. Tumor detection rates and SUVs were compared according to plasma glucose levels above and below 130 mg/dl, the presence of diabetes and by using receiver operating characteristic (ROC) analysis. RESULTS: The detection rates (and mean SUVs) for pancreatic malignancies were 86% and 42% (4.2 and 2.3) if fasted plasma glucose levels were below and above 130 mg/dl, respectively. The sensitivities (and mean SUVs of malignant tumors) were 83% and 69% (3.3 and 2.5) for patients without and with known diabetes. Areas under ROC curves were nearly equal for glucose corrected SUV and visual qualitative results (0.86 and 0.85), followed by uncorrected SUV (0.83), tumor-to-liver ratios (0.80) and tumor-to-muscle ratios (0.79). SUVs for chronic pancreatitis, muscle and liver had a tendency to increase with elevated plasma glucose levels. CONCLUSION: Negative PET results of patients with elevated plasma glucose should be interpreted with caution.

Blood Glucose↗

PubMed1998

Multimodal therapy in rectal cancer.

The possibilities and results of multimodal treatment in rectal cancer were reviewed with respect to the results of surgical treatment only. Based on the results of 4 studies, reducing local relapse rates and increasing long-term survival rates significantly, postoperative radiochemotherapy (RCT) + chemotherapy (CT) should remain the recommended standard for R0 resected UICC II and III rectal cancers. Preoperative neoadjuvant radiotherapy (RT) reduced local relapse rates in 8 studies, and extended survival in one study that evaluated all eligible patients. Preoperative RT may evolve as standard, if the patient selection is improved and postoperative morbidity and long-term toxicity are reduced. Postoperative adjuvant RT reduced local relapses significantly in a single trial, and no impact on survival time is reported. Since postoperative RT is inferior to preoperative RT, this treatment cannot be recommended, if RT is chosen as a single treatment modality as an adjunct to surgery. Preoperative RCT + CT downstages resectable and nonresectable tumors and induces a higher sphincter preservation rate. This treatment may be routinely applied in nonresectable primary tumors or local relapses. Intraoperative RT could be added to this concept or be used together with preoperative/postoperative RT with the same indications. The results of local tumor excisions may be improved with pre- or postoperative RCT + CT.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1997

Magnetic resonance imaging-based measurement of hippocampal volume in posttraumatic stress disorder related to childhood physical and sexual abuse--a preliminary report.

We have previously reported smaller hippocampal volume and deficits in short-term memory in patients with combat-related posttraumatic stress disorder (PTSD) relative to comparison subjects. The purpose of this study was to compare hippocampal volume in adult survivors of childhood abuse to matched controls. Magnetic resonance imaging was used to measure volume of the hippocampus in adult survivors of childhood abuse (n = 17) and healthy subjects (n = 17) matched on a case-by-case basis for age, sex, race, handedness, years of education, body size, and years of alcohol abuse. All patients met criteria for PTSD secondary to childhood abuse. PTSD patients had a 12% smaller left hippocampal volume relative to the matched controls (p < .05), without smaller volumes of comparison regions (amygdala, caudate, and temporal lobe). The findings were significant after controlling for alcohol, age, and education, with multiple linear regression. These findings suggest that a decrease in left hippocampal volume is associated with abuse-related PTSD.

Adult↗

PubMed1997

[PET in pancreatic tumor of unknown origin--luxury or value?].

18FDG-positron emission tomography (PET) was performed preoperatively in 159 patients (89 pancreatic cancers, 48 inflammatory pancreatic tumors, 22 benign tumors) with pancreatic mass of unknown origin and its diagnostic value (ROC analysis) was compared with ERCP and computed tomography. In patients with normal fasted blood glucose level (< 130 mg%) and without active inflammation (n = 126), diagnostic value of PET was equal to ERCP (0.94) and higher than CT (0.84; p < 0.02); PET showed in 88% of cases no prediction of resectability or local tumor infiltration, no influence on explorative celiotomies, in 93% no increase of preoperative hospital stay, in 4% influence on surgical strategy, in 5% metastases as additional information. Though its additional information gain for the surgeon remains limited, PET is certainly a diagnostic achievement with high diagnostic value in preselected patients.

Cholangiopancreatography, Endoscopic Retrograde↗

PubMed1996

Intraperitoneal regional chemotherapy with mitroxantrone.

Pharmacokinetic considerations and tests with cell lines and individual cell suspensions from metastatic human solid tumor biopsies suggested testing the efficacy of mitoxantrone (NOV) in intraperitoneal regional chemotherapy (IPRC). Twenty-seven patients with intraperitoneal metastatic disease of various solid tumors received cyclic IPRC with NOV for treatment of malignant ascites (N = 16) or of peritoneal carcinomatosis (N = 11) at a NOV instillate concentration of 10 micrograms/ml. A total of 125 cycles (1-5 per patient) were applied. Response and toxicity were registered according to WHO criteria. The response rate (CR+PR) was 56 percent in malignant ascites, 45 percent in peritoneal carcinomatosis, and 52 percent overall. There were no systemic toxicities. Regional side effects were bacteriemia (4 of 125 cycles), pain (2 of 125 cycles), small bowel stricture (1 of 27 patients), and small bowel perforation (1 of 27 patients). From these results we can conclude that NOV appears to be effective in IPRC for malignant ascites and peritoneal carcinomatosis at tolerable toxicities.

Antineoplastic Agents↗

PubMed1996

Adjuvant treatment of colon and rectal cancer: impact of chemotherapy, radiotherapy, and immunotherapy on routine postsurgical patient management. Forschungsgruppe Onkologie Gastrointestinaler Tumoren (FOGT).

Colon cancer patients with UICC stage III or T4 N0 M0 stage II should receive postoperative adjuvant therapy, since relapse rates are high and surgical outcome has been improved by adjuvant treatment. The standard treatment is 5-fluourouracil plus levamisole; an alternative option is the combination of 5-fluourouracil and folinic acid. Stage II (T3 N0 M0) colon cancer patients should not receive adjuvant treatment outside of studies. Rectal cancer patients of stage II or III should receive postoperative radiochemotherapy with 45-54.4 Gy and 5-fluourouracil as standard treatment. Patients not eligible for radiotherapy may receive adjuvant chemotherapy only. Studies need to be conducted to improve adjuvant therapy in colorectal cancer. All qualified patients should be treated within these studies requiring sufficient patient numbers, as well as comparable surgical procedures, proper patient selection and stratification criteria, drug and dose intensities. Intraportal infusion may be as effective as systemic adjuvant treatment; the tumor type and stage for which benefit from this kind of treatment is consistently significant needs to be defined, since intraportal infusion of all resectable colorectal cancers is overtreatment. Both surgery and histopathological staging may be improved in some centers, and these require standardization and quality control.

Colonic Neoplasms↗

PubMed1996

Regional chemotherapy directed by individual chemosensitivity testing in vitro: a prospective decision-aiding trial.

A prospective decision-aiding trial was performed to select drugs for regional chemotherapy of various liver tumors (n = 36) by individual drug testing. The drugs were chosen for hepatic artery infusion according to the individual chemosensitivity of tumor biopsies in the human tumor colony-forming assay (HTCA). In vitro HTCA sensitivity correlated with complete response (CR) + partial response (PR) + no change (NC) 93% of the time and with CR + PR 55% of the time. The test sensitivity was 90%, and the specificity was 67% for CR + PR + NC versus progressive disease (PD), whereas the sensitivity and specificity were 89% and 28%, respectively, for CR + PR versus NC + PD. The overall predictive accuracy of the test was 86% for CR + PR + NC versus PD and 58% for CR + PR versus NC + PD. Overall, 83% of this heterogenous patient group with various tumors achieved CR + PR + NC and a 50% clinical response (CR + PR). In vitro-sensitive patients showed a significantly lower intrahepatic progression rate (7% PD) than in vitro-resistant patients (57%; P < 0.05). These results indicate that the HTCA could identify active drugs for individualized hepatic artery infusion, and patients may profit from the use of in vitro-sensitive drugs.

Adult↗

PubMed1993

Protection against experimental cerebral metastases of murine melanoma B16 by active immunization.

Melanoma patients often develop brain metastases despite effective systemic immunotherapy against melanoma. We have attempted to establish a mouse model to develop strategies to combat this problem. Immunization of C57BL/6 (H-2b) mice with a combination of the syngeneic G3.12/BM2 melanoma (a B16 subclone) and the allogeneic Cloudman-S91 melanoma was effective in preventing the growth of 10,000 viable, s.c. injected G3.12 cells in 93% of the mice. Irradiated whole tumor cells pretreated with gamma-interferon for 2 days were most effective. A nonspecific adjuvant (DETOX) was injected routinely together with the tumor cells. Active immunization with 2 different doses of irradiated melanoma cells (1 x 10(5) or 2.5 x 10(6) cells/injection x 5 injections) protected against intracerebral challenge with 200 live G3.12 cells in 69% of the mice. This challenge caused the death of all control mice within 30 days. T-cell-mediated, tumor-specific cytotoxicity against G3.12 melanoma was demonstrated in the spleen of immunized mice. Histological observations in the brain, 80 days after tumor challenge, indicated complete eradication of the melanoma, but although CD4+ and CD8+ T-cells and macrophages were present, their number was low. Gliosis was present in both immunized and control animals. Thus, in this murine melanoma model syngeneic mice were protected from death by s.c. and intracerebrally inoculated tumor cells if pretreated with a sufficient number of irradiated syngeneic and allogeneic melanoma cells and an immunological adjuvant. Whether this regimen can treat established tumors of the brain, alone or in combination, is uncertain. Yet its success suggests that the "blood-brain barrier" impeding immunity to tumors may not be absolute.

Animals↗

PubMed1991

[Gallbladder carcinoma as an incidental finding].

Between March 1982 and December 1990, 903 patients underwent elective cholecystectomy. In 40 patients cholecystectomy was performed for gallbladder carcinoma. 15 malignomas (1.7%) were found incidentally. Preoperatively no anamnestic or diagnostic tumor signs were found in this group of patients. An en-bloc-resection of the gallbladder with resection of the bordering liver segments was performed when gallbladder carcinoma was diagnosed intraoperatively. When the diagnosis was established by postoperative histology, a relaparotomy with liver resection and lymphnode-dissection was done, except in one case (T-1a stage). Histology showed adenocarcinoma in 11 out of 15 cases. No significant difference in the course of the disease was observed in patients with gallbladder carcinoma of different types. The hospital mortality rate was 0% after curative and palliative surgical treatment of gallbladder carcinoma. Patients with T-1 and T-2 stage have survived without tumor-recurrence up to now. The median survival time after surgery for gallbladder carcinoma in T-3 stage was 17 months, and 8 months in T-4 stage. The morbidity rate after elective cholecystectomy is low and hospital mortality is 0%. According to the short survival times in advanced stages of gallbladder carcinoma, a prompt cholecystectomy in symptomatic gallbladder lithiasis or chronic cholecystitis is advocated.

Adenocarcinoma↗

PubMedDate not supplied

In vitro concentration response studies and in vitro phase II tests as the experimental basis for regional chemotherapeutic protocols.

The theoretical pharmacologic benefit of regional vs. systemic chemotherapy is defined and the concentration response behavior of cytostatic drugs and their optimal exposure times are described with human cancer cell lines (HT29, NMG64/84) and fresh human tumor cell suspensions in the human tumor colony assay (HTCA). The theoretical pharmacological advantages are 5.8 to 6 for adriamycin (ADM), 8 for cisplatinum (CDDP), 6.3 for epidoxorubicin (EPI), 22 to 58 for 5-fluorouracil (5FU), 4.6 for mitomycin C (MMC), and 6.3 for mitoxantrone (NOV). The drugs differed in their cytotoxic potency in vitro and thus also potential efficacy for regional chemotherapy; however, all but 5-fluorodeoxyuridine (5FUDR) exerted cytotoxicity dependent on exposure time and concentration. On average, elevation of the test concentrations by 1 lg doubled responses in fresh human tumor cell suspensions. From these results and clinical considerations, optimal times were defined for the regional chemotherapy strategies of hepatic artery infusion, intraperitoneal instillation, and chemoembolisation as performed at our institution.

Antineoplastic Agents↗

PubMedDate not supplied

Anti-idiotypic antibody and recombinant antigen vaccines in colorectal cancer patients.

The colorectal carcinoma (CRC)-associated GA733 antigen (also known as CO17-1A, KS1-4, KSA or EpCAM) has been the target of a phase II/III randomized trial of passive immunotherapy with monoclonal antibody CO17-1A and phase I active immunotherapy trials with polyclonal anti-idiotypic antibodies mimicking the CO17-1A or GA733 epitope on the antigen. The CO17-1A antigen was molecularly cloned and the extracellular domain expressed in baculovirus (BV) GA733-2E. Whereas, anti-idiotypic antibody mimics a single epitope on the antigen, BV GA733-2E expresses multiple potentially immunogenic epitopes. In animals, the immunogenicity of BV GA733-2E in aluminum hydroxide was superior to that of anti-idiotype in the same adjuvant. Here, we compared the immunogenicity of anti-idiotypic antibody and GA733-2E antigen in CRC patients. These studies indicate that the antigen is superior to the anti-idiotype antibody in inducing humoral and cellular immunity in CRC patients.

Antibodies, Anti-Idiotypic↗

PubMedDate not supplied

Toxicity and effects of adjuvant therapy in colon cancer: results of the German prospective, controlled randomized multicenter trial FOGT-1.

In this adjuvant three-arm multicenter trial, we studied whether modulating the standard 5-fluorouracil (5-FU) treatment with either folinic acid (FA) or interferon-alpha-2a (IFN-alpha) was superior to the recommended standard of adjuvant treatment in R0 resected colon cancer, 5-FU plus levamisole (LEV) for 12 months, in terms of toxicity and outcome. From July 1992 to October 1999, a total of 813 patients with resected colon cancer in stage II (T4N0M0; n = 63) or stage III (TxN1-3M0; n = 750) were randomized into three treatment groups and stratified according to N stage and participating centers (64 hospitals). The patients received a postoperative loading dose of 5-FU (450 mg/m2 on days 1 to 5 [arms A and C]) or 5-FU (450 mg/m2) plus FA (Rescuvolin, Medac, Hamburg, Germany, 200 mg/m2 on days 1 to 5 [arm B]). After completion of the first chemotherapy cycle, LEV was administered orally at a dosage of 150 mg per day on days 1 to 3, once every 2 weeks. After a 4-week chemotherapy-free interval, the treatment was continued weekly for 52 weeks. Treatment in one arm A ("standard") (n = 279) consisted of 5-FU intravenously (450 mg/m2 on day 1, once a week) plus LEV. 5-FU plus LEV was modulated in arm B (n = 283) with FA (200 mg/m2 on day 1, once a week) and in arm C (n = 251) with IFN-alpha at 6 million units three times a week repeated weekly. Treatment dosages were adjusted if toxic events above WHO grade 2 occurred. Patients were closely followed to determine recurrence and survival; the latter was calculated according to Kaplan-Meier analysis. Toxic events above WHO grade 2, mainly leukopenia, diarrhea, and nausea, occurred in 113 (14%) of 649 patients who had completed treatment in arms A (8.4%), B (13.5%), and C (31.7%). Discontinuance rates were as follows: 28% for all patients, 29% in arm A, 21% in arm B, and 34% in arm C. Overall relapse rates were 27% for all patients, 30% in arm A, 24% in arm B, and 28% in arm C. Relapses were local (8%), distant (78%), or combined (12%). Four-year overall survival rates in arms A, B, and C were 66.1%, 77.5%, and 66.2%, respectively. The 4-year survival rate in arm B was significantly higher compared to arm A (P <0.02, log-rank test) with arm A being equal to arm C. Adjuvant therapy with 5-FU plus FA plus LEV for 12 months is superior to the recommended standard (5-FU + LEV for 12 months). IFN-alpha modulation of 5-FU (plus LEV) adds to the toxicity with no therapeutic benefit.

Adjuvants, Immunologic↗

PubMedDate not supplied

PathMaster: content-based cell image retrieval using automated feature extraction.

OBJECTIVE: Currently, when cytopathology images are archived, they are typically stored with a limited text-based description of their content. Such a description inherently fails to quantify the properties of an image and refers to an extremely small fraction of its information content. This paper describes a method for automatically indexing images of individual cells and their associated diagnoses by computationally derived cell descriptors. This methodology may serve to better index data contained in digital image databases, thereby enabling cytologists and pathologists to cross-reference cells of unknown etiology or nature. DESIGN: The indexing method, implemented in a program called PathMaster, uses a series of computer-based feature extraction routines. Descriptors of individual cell characteristics generated by these routines are employed as indexes of cell morphology, texture, color, and spatial orientation. MEASUREMENTS: The indexing fidelity of the program was tested after populating its database with images of 152 lymphocytes/lymphoma cells captured from lymph node touch preparations stained with hematoxylin and eosin. Images of "unknown" lymphoid cells, previously unprocessed, were then submitted for feature extraction and diagnostic cross-referencing analysis. RESULTS: PathMaster listed the correct diagnosis as its first differential in 94 percent of recognition trials. In the remaining 6 percent of trials, PathMaster listed the correct diagnosis within the first three "differentials." CONCLUSION: PathMaster is a pilot cell image indexing program/search engine that creates an indexed reference of images. Use of such a reference may provide assistance in the diagnostic/prognostic process by furnishing a prioritized list of possible identifications for a cell of uncertain etiology.

Abstracting and Indexing↗

PubMedDate not supplied

Uptake and displacement of [3H]-propranolol and [3H]-chlorpromazine in isolated, recirculating perfused guinea-pig lungs.

The pulmonary uptake of tritium labelled propranolol and chlorpromazine and their displacement by amphiphilic drugs has been studied in isolated guinea-pig lungs. Lungs were perfused by recirculation with 60 ml tyrode solution (carbogen gassed, 37 degrees C, 6% hydroxy-ethyl-starch) at a flow rate of 10 ml/min. In uptake experiments, a steady state was reached within 20 min with 95% of 10(-9) M propranolol and 90% of 10(-9) M chlorpromazine removed from the perfusate. Using 10(-4) M propranolol, a saturation process became evident, whereas no concentration dependency was observed for chlorpromazine uptake. Kinetic analysis revealed similar uptake rates, but different capacities for both compounds. In displacement experiments, 10(-9) M propranolol was displaced by 10(-4) M amphiphilic drugs in the order: chlorpromazine greater than propranolol greater than alprenolol greater than tetracaine. No displacement occurred by practolol, indomethacin or phenylbutazone. The results indicate that the lungs have a large binding capacity for amphiphilic drugs. These compounds can interfere with each other, according to their lipophilicity, their steric configuration and charges.

Animals↗