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L Staib

Publications and source records attributed to L Staib.

At least 37 records · Page 2Linked to original sources

Follow-up in colorectal cancer: cost-effectiveness analysis of established and novel concepts.

BACKGROUND: Follow-up programs in colorectal cancer have been under question recently due to their low efficacy. Some meta-analyses found a survival benefit and four randomized studies suggested the opposite. Therefore, this paper analyzes existing and proposed follow-up programs for costs and efficacy. METHODS: One thousand and fifty-four colorectal cancer patients intensively followed-up in Ulm (endoscopy, chest radiography, abdominal ultrasound, computed tomography (CT) pelvis) were prospectively evaluated for recurrence, salvage surgery rate, survival and costs. Costs were compared among existing and proposed international follow-up programs retrieved by a MedLine search. RESULTS: A total of 350/1,054 colorectal cancer patients (33.2%) relapsed asymptomatically, as detected by follow-up. 56/350 (local 47%, distant 53%) recurrences were resectable (16%), 21/350 patients survived (6%). The efficacy of follow-up was 21/1,054 patients (2%). Costs were, per patient, 2,220 euros (colon) or 4,851 euros (rectum). Costs in five randomized studies varied between 616 euros for minimal and 5,049 euros for intensive follow-up. Four proposed follow-up concepts include risk-adaption, which claim to reduce costs by 50-60% and range between 889 (colorectal) and 5,910 (high-risk, rectum) euros. The recommended German follow-up guideline costs 610 euros (low-risk, colorectal), 1,120 euros (high-risk, colon) or 2,252 euros (high-risk, rectum). CONCLUSION: Follow-up concepts for colorectal cancer should aim at the identification of curable patients with recurrence. Evidence-based concepts, including life quality tests, remain to be defined, but currently abdominal ultrasound, endoscopy and carcino-embryonic antigen (CEA) determination at 6-month intervals for 2 years and annual intervals for 3 years seem to identify this patient sub-group.

Carcinoembryonic Antigen↗

Is (18)F-fluorodeoxyglucose positron emission tomography in recurrent colorectal cancer a contribution to surgical decision making?

BACKGROUND: Accuracy of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and contribution to surgical decision making in recurrent or metastatic colorectal cancer were evaluated. METHODS: One hundred whole-body PET tests in colorectal cancer patients (1994 to 1998) were compared with computed tomography (CT), liver ultrasonography, and carcinoembryonic antigen (CEA) test. Mean follow-up was 12 months. RESULTS: Sensitivity, specificity, and accuracy of FDG-PET for malignant findings were, respectively, 98%, 90% and 95%; for 87 CT scans, 91%, 72%, and 82%; for 98 CEA tests, 76%, 90%, and 82%; for detection of liver metastases with PET, 100%, 99%, and 99%; and for 68 ultrasound tests, 87%, 96%, and 93%. PET accuracy for local recurrence was 96%. Additional information was provided by PET in 86% of cases (abdomen, thorax, liver). PET influenced surgical decisions in 61% of cases. CONCLUSION: FDG-PET adds relevant accuracy to the conventional staging of patients with colorectal cancer and may cost-effectively help to select the appropriate treatment.

Abdominal Neoplasms↗

Values and limitations of 18F-fluorodeoxyglucose-positron-emission tomography with preoperative evaluation of patients with pancreatic masses.

The aim of this study was to determine the value and limitations of 18F-fluorodeoxyglucose (FDG)-position-emission tomography (PET) for differentiating benign and malignant pancreatic disease and for staging malignant disease. One hundred fifty-nine patients with 89 malignant and 70 benign pancreatic lesions all received PET, computed tomography (CT), and endoscopic retrograde cholangiopancreatography (ERCP) before pancreatic surgery. The original reports were compared for all patients (group I; N = 159), for a subgroup that neither had fasting plasma glucose levels > or =130 mg/dL or known elevated levels of C-reactive protein ([CRP], group II; n = 123), and for the remaining patients (group III; n = 36). For group I, accuracy values (areas under receiver operating characteristic [ROC] curves) for differentiation of benign/malignant masses were 0.86 (PET), 0.93 (ERCP), 0.82 (CT), and 0.95 for ERCP + PET (N = 159). For group II, ROC areas increased to 0.92 (PET), 0.94 (p < 0.05; n = 123) (ERCP), 0.82 (CT), 0.97 (p < 0.05; n = 123) (ERCP + PET). The results for group III were 0.71 (PET), 0.81 (CT), and 0.93 (ERCP); (n = 36). With 54 patients of group II that either had contradictory or indeterminate/technically unsuccessful CT/ERCP, PET was correct in 43 patients (84%). Sensitivity/specificity for lymph node staging was 49%/63%, respectively. For patients with hepatic metastasis, PET was 70% sensitive and 95% specific, missing some metastasis that were <1 cm. PET detected peritoneal metastasis in 25% of patients, missing poorly localized microscopic spread. For selected patients who have indeterminate pancreatic masses but no hyperglycemia or serologic evidence of active inflammation, FDG-PET is an independent functional assay that significantly adds to the diagnostic accuracy of ERCP and CT in the differentiation of benign and malignant pancreatic disease. PET can reliably detect hepatic, peritoneal, and other distant metastases that are > or =1 cm.

Area Under Curve↗

Colorectal cancer vaccines: antiidiotypic antibody, recombinant protein, and viral vector.

The colorectal cancer antigen GA733 (also termed CO17-1A, KSI-4, Ep-CAM, KSA) has proved to be a useful target in passive immunotherapy with monoclonal antibody and in active immunotherapy with antiidiotypic antibodies in cancer patients. The GA733 antigen was molecularly cloned and expressed in baculovirus (BV), adenovirus (AV), and vaccinia virus (VV). Recombinant BV-, VV-, and AV-GA733 induced antigen-specific cytotoxic antibodies and proliferative and delayed-type hypersensitive lymphocytes. However, only the AV recombinant induced antigen-specific cytolytic T lymphocytes and regression of established tumors. Cured mice were protected against challenge with antigen-negative tumors, indicating antigen spreading of immune responses. In a model of active immunotherapy against the murine homologue of the human GA733 antigen, murine epithelial glycoprotein (mEGP), BV-derived mEGP protein in various adjuvants did not protect mice against a challenge with mEGP-positive tumors. AV mEGP, only when combined with interleukin-2, significantly inhibited growth of established mEGP-positive tumors. This is in contrast to the same vaccine expressing the human antigen that was effective without interleukin-2. AV GA733, in combination with interleukin-2, is a candidate vaccine for colorectal cancer patients.

Animals↗

Decreased benzodiazepine receptor binding in prefrontal cortex in combat-related posttraumatic stress disorder.

OBJECTIVE: Animals exposed to stress exhibit a decrease in benzodiazepine receptor binding in the frontal cortex. No studies have examined central benzodiazepine receptor binding in patients with posttraumatic stress disorder (PTSD). The purpose of this study was to examine measures of benzodiazepine receptor binding in PTSD. METHOD: From 13 patients with Vietnam combat-related PTSD and 13 case-matched healthy comparison subjects, a quantitative measure related to benzodiazepine receptor binding (distribution volume) was obtained with single photon emission computed tomography (SPECT) imaging of [(123)I]iomazenil binding and measurement of radioligand concentration in plasma. Distribution volume image data were analyzed by means of statistical parametric mapping. RESULTS: Lower distribution volumes were found in the prefrontal cortex (Brodmann's area 9) of PTSD patients than in comparison subjects. CONCLUSIONS: These findings of lower values for the benzodiazepine receptor binding measure of distribution volume are consistent with fewer benzodiazepine receptors and/or reduced affinity of receptor binding in the medial prefrontal cortex in patients with PTSD. Alterations in benzodiazepine receptor function in this area may underlie many of the symptoms of PTSD.

Adult↗

A minimax entropy registration framework for patient setup verification in radiotherapy.

In external beam radiotherapy (EBRT), patient setup verification over the entire course of fractionated treatment is necessary for accurate delivery of a specified dose to the tumor. We are working on the development of a minimax entropy registration framework for patient setup verification using dual portal images and the treatment planning 3D CT dataset. In this paper, we present an overview of our registration framework, where an iteratively and automatically estimated segmentation of the portal image is utilized to more accurately and robustly register the portal image to the 3D treatment-planning CT data. In addition, we describe initial testing of this approach. We note that, due to low resolution and low contrast of the portal images, this registration presents a difficult problem. We also note that the registration of the images in our proposed method is guided by the bony structure visible in the portal and the 3D CT images. However, since the prostate can move with respect to the pelvic bone, we propose using ultrasound images to quantify this movement.

Algorithms↗

Immunotherapy in pancreatic cancer - current status and future.

BACKGROUND: In pancreatic cancer, multimodal protocols, involving chemotherapy, radiation, or regional treatment, are initiated to improve oncological outcome. Since pancreatic adenocarcinoma has been shown to be susceptible to immune stimulation, several immunotherapy approaches have been investigated to define the role of immunotherapy in pancreatic cancer. METHOD: A review of current and past data concerning experimental and clinical immunotherapy in pancreatic cancer is presented in the context of basic immunotherapeutic principles. Past pitfalls and future developments are analyzed and a synthesis of immune stimulation and immune suppression is deduced on the basis of published data. RESULTS: Preclinical and initial clinical studies with monoclonal antibodies CO17-1A, BW494/32 and anti-epidermal growth factor receptor (EGFR) have been conducted, and various targets suitable for immunotherapy have been identified involving new molecular and gene technology. Targets on pancreatic cancer cells currently under investigation are mucins (MUC-1), glycoproteins (GA733), ras peptides and EGFRs. Side effects are minor and rarely auto-immune reactive. Another approach combines randomized regional with systemic chemoimmunotherapy (mitomycin C, 5-fluorouracil, folinic acid, carboplatin, epirubicin; interferon-gamma, interleukin-2) in nonresectable pancreatic cancer and obtains significant differences in median survival rates (14 months vs 4.5 months in controls) and quality of life. CONCLUSION: Although single remarkable improvements in the immunological approach to treatment of pancreatic cancer have been made, immunotherapy in pancreatic cancer is still experimental. On the basis of reliable preclinical data, new immunotherapy protocols will have to be evaluated clinically. Careful monitoring of immune responses and side effects, and assessment of quality of life will ensure identification of effective immunotherapy protocols for human pancreatic cancer in the near future.

Animals↗

Detection of liver metastases from pancreatic cancer using FDG PET.

UNLABELLED: We evaluated the potential of the glucose analog [18F]fluorodeoxyglucose (FDG) as a PET tracer for the hepatic staging in 168 patients designated for resective pancreatic surgery. METHODS: Metastatic liver disease was confirmed or excluded during surgery or with CT follow-up for at least 6 mo. Proven metastases were then retrospectively identified on preoperative CT (gold standard). Hepatic PET scans of all patients were interpreted blindly. Any focal FDG uptake was considered malignant. Both proven hepatic metastases and suspicious hepatic PET lesions were then compared, lesion by lesion, with CT. Standardized uptake values (SUV) and tumor-to-liver ratios (T/L) were determined for the most intense lesion of each patient. RESULTS: Sensitivity of FDG PET was 68% (15 of 22 patients). The lesion detection rate was 97% (28 of 29 metastases) for lesions >1 cm and 43% (16 of 37 metastases) for lesions < or = 1 cm. Specificity was 95% (138 of 146 patients). Six of eight patients with false-positive results had marked intrahepatic cholestasis (versus 3 of 15 patients with true-positive lesions), one had an infrahepatic abscess and one had a right basal pulmonary metastasis. The SUV and T/L were 4.6+/-1.4 and 2.3+/-1.1, respectively, for malignant lesions and 4.1+/-1.5 and 1.9+/-0.3, respectively, for false-positive lesions and therefore are of limited value. CONCLUSION: FDG PET provides reliable hepatic staging for lesions >1 cm. False-positive results are associated with the presence of marked intrahepatic cholestasis. For lesions < or = 1 cm, FDG PET can define malignancy in 43% of suspicious CT lesions in the absence of dilated bile ducts.

Aged↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

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↗

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↗