Variplex™ test system fails to reliably detect SARS-CoV-2 directly from respiratory samples without RNA extraction.

Diagnosis of COVID is performed by PCR methods, but their capacity is limited by the requirement of high-level facilities and instruments. The loop-mediated isothermal amplification (LAMP) method has been utilized for the detection of isolated virus-specific RNA. Preliminary data suggest the possibility of isothermal amplification directly from respiratory samples without RNA extraction. All patients admitted to our hospital were screened for SARS-CoV-2 by routine. Respiratory samples were tested by variplex system based on LAMP method directly without RNA extraction and by PCR. Primary endpoint was the false-negative rate of variplex test compared with PCR as gold standard. In 109 patients variplex test and PCR assay were performed simultaneously. Median age was 80 years and male/female ratio was 40/60%. The prevalence of PCR-confirmed COVID diagnosis was 43.1%. Variplex test was positive in 13.8%. False-negative rate of variplex test compared with PCR was 83.0%. The potential of LAMP technology using isolated RNA has been demonstrated impressively by others, and excellent sensitivity and specificity of detecting SARS-CoV-2 has been reported. However, without RNA extraction, the variplex test system failed to reliably detect SARS-CoV-2 directly in respiratory samples.

Comparison of cap-assisted endoscopy vs. side-viewing endoscopy for examination of the major duodenal papilla: a randomized, controlled, noninferiority crossover study.

BACKGROUND : Use of a side-viewing endoscope is currently mandatory to examine the major duodenal papilla; however, previous studies have used cap-assisted endoscopy for complete examination of the papilla. The aim of this study was to compare cap-assisted endoscopy with side-viewing endoscopy for examination of the major duodenal papilla. METHODS : This was a prospective, randomized, blinded, controlled, noninferiority crossover study. Patients were randomized to undergo either side-viewing endoscopy followed by cap-assisted endoscopy or cap-assisted endoscopy followed by side-viewing endoscope. Photographs of the major duodenal papilla were digitally edited to mask the cap area before they were evaluated by three blinded external examiners. Our primary end point was complete visualization of the major duodenal papilla. Secondary end points were the ability to examine the mucosal pattern, the overview of the periampullary region, overall satisfaction, and time to locate the papilla. RESULTS : 62 patients completed the study. Complete visualization of the major duodenal papilla was achieved in 60 examinations by side-viewing endoscopy and in 59 by cap-assisted endoscopy (97 % vs. 95 %). The difference between the two examinations was 1.6 % with a two-sided 95 % confidence interval of -4.0 % to 7.3 %, which did not exceed the noninferiority margin of 8 %. Cap-assisted endoscopy achieved better scores regarding the examination of mucosal pattern and overall satisfaction, whereas side-viewing endoscopy had a better overview score (P < 0.001, P = 0.004, and P < 0.001, respectively). There was no relevant difference in the median times to locate the major duodenal papilla. CONCLUSION : Cap-assisted endoscopy and side-viewing endoscopy had similar success rates for complete visualization of the major duodenal papilla. Cap-assisted endoscopy is superior to side-viewing endoscopy regarding the mucosal pattern and overall satisfaction. Side-viewing endoscopy gives a better overview of the periampullary region.

Mandatory criteria for the application of variability-based parameters of fluid responsiveness: a prospective study in different groups of ICU patients.

BACKGROUND AND OBJECTIVE: Stroke volume variation (SVV) has high sensitivity and specificity in predicting fluid responsiveness. However, sinus rhythm (SR) and controlled mechanical ventilation (CV) are mandatory for their application. Several studies suggest a limited applicability of SVV in intensive care unit (ICU) patients. We hypothesized that the applicability of SVV might be different over time and within certain subgroups of ICU patients. Therefore, we analysed the prevalence of SR and CV in ICU patients during the first 24 h of PiCCO-monitoring (primary endpoint) and during the total ICU stay. We also investigated the applicability of SVV in the subgroups of patients with sepsis, cirrhosis, and acute pancreatitis. METHODS: The prevalence of SR and CV was documented immediately before 1241 thermodilution measurements in 88 patients. RESULTS: In all measurements, SVV was applicable in about 24%. However, the applicability of SVV was time-dependent: the prevalence of both SR and CV was higher during the first 24 h compared to measurements thereafter (36.1% vs. 21.9%; P<0.001). Within different subgroups, the applicability during the first 24 h of monitoring ranged between 0% in acute pancreatitis, 25.5% in liver failure, and 48.9% in patients without pancreatitis, liver failure, pneumonia or sepsis. CONCLUSIONS: The applicability of SVV in a predominantly medical ICU is only about 25%-35%. The prevalence of both mandatory criteria decreases over time during the ICU stay. Furthermore, the applicability is particularly low in patients with acute pancreatitis and liver failure.

Chemotherapy and targeted therapy in advanced biliary tract carcinoma: a pooled analysis of clinical trials.

BACKGROUND: In biliary tract cancer, gemcitabine platinum (GP) doublet palliative chemotherapy is the current standard treatment. The aim of this study was to analyze recent trials, even those small and nonrandomized, and identify superior new regimens. METHODS: Trials published in English between January 2000 and January 2014 were analyzed, as well as ASCO abstracts from 2010 to 2013. RESULTS: In total, 161 trials comprising 6,337 patients were analyzed. The pooled results of standard therapy GP (no fluoropyrimidine, F, or other drug) were as follows: the median response rate (RR), tumor control rate (TCR), time to tumor progression (TTP) and overall survival (OS) were 25.9 and 63.5%, and 5.3 and 9.5 months, respectively. GFP triplets as well as G-based chemotherapy plus targeted therapy were significantly superior to GP concerning tumor control (TCR, TTP) and OS, with no difference in RR. CONCLUSION: Triplet combinations of GFP as well as G-based chemotherapy with (predominantly EGFR) targeted therapy are most effective concerning tumor control and survival.

Pancreatic and hepatobiliary cancers.

Morphology-based imaging modalities have replaced classical conventional nuclear medicine modalities for detection of liver or pancreatic lesions. With positron emission tomography and the glucose analog F-18 fluorodeoxyglucose (FDG), a sensitive and specific modality for the detection of hepatic metastases and extrahepatic tumor deposits from hepatocellular or pancreatic cancer is available. F-18 FDG PET can increase the accuracy of staging primary tumors of the liver or the pancreas, and can be used for response monitoring. Radiopharmaceuticals such as Ga-68 DOTATOC and F-18 DOPA allow the specific detection of neuroendocrine pancreatic tumors and their metastatic deposits. Hybrid scanners such as PET-CT integrate morphologic and metabolic information, and allow to increase the sensitivity and specificity of noninvasive imaging in many tumor entities. The development of specific radiopharmaceuticals and technical innovations such as SPECT-CT has increased the reliability of conventional scintigraphic imaging. This chapter focuses on the use of PET-CT in hepatobiliary and pancreatic cancers.

Imaging of proliferation in hepatocellular carcinoma with the in vivo marker 18F-fluorothymidine.

UNLABELLED: We determined the ability of PET with the thymidine analog 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) to detect hepatocellular carcinoma (HCC). METHODS: In this pilot study, (18)F-FLT PET was performed in 18 untreated patients with clinically suspected HCC. Routine diagnostic procedures included ultrasound, MRI, or contrast-enhanced spiral CT of the upper gastrointestinal tract in all patients. At 45-60 min after the intravenous injection of approximately 270-340 MBq of (18)F-FLT, emission and transmission scanning was performed with a high-resolution PET scanner. Tracer uptake in the tumor and surrounding liver tissue was evaluated semiquantitatively by calculation of mean and maximum standardized uptake values (SUVs). Results were correlated with those of the conventional imaging methods. RESULTS: A total of 13 of 18 tumors (sensitivity, 72%; 95% confidence interval [CI], 47%-90%) showed focal (18)F-FLT uptake higher than surrounding liver activity and were detectable as hot lesions. Five tumors were characterized as photopenic lesions or contained a mixture of hot and cold lesions exhibiting a comparable or lower (18)F-FLT uptake than the surrounding liver tissue. When all lesions were considered, the mean (18)F-FLT SUV was 7.8 (range, 2.5-11.1), and the maximum (18)F-FLT SUV was 9.3 (range, 2.9-14.3). Histology and clinical follow-up revealed HCC in 16 patients and cholangiocarcinoma in 2 patients. In the subgroup of HCC, the sensitivity for tumor detection was 69% (11/16; 95% CI, 41%-89%). Correlation analysis demonstrated a significant positive relationship between the proliferation marker MIB-1 and the mean SUV (r = 0.66, P = 0.02). Survival analysis (Cox proportional hazards regression) for initial (18)F-FLT uptake (mean and maximum SUVs) revealed increased hazard ratios (mean SUV, 1.20; maximum SUV, 1.12), but because of the small number of events, these results were not statistically significant. CONCLUSION: In this pilot study, HCC tumors showed a mixed uptake pattern for the in vivo proliferation marker (18)F-FLT. A total of 69% of the HCC lesions showed (18)F-FLT uptake higher than that of the surrounding liver tissue, whereas the remaining lesions were photopenic or contained a mixture of hot and cold lesions. High initial (18)F-FLT uptake seems to be associated with reduced overall survival and could be an important prognostic factor if this tendency can be confirmed in a larger prospective trial.

Argon plasma coagulation of cervical heterotopic gastric mucosa as an alternative treatment for globus sensations.

BACKGROUND & AIMS: Ablation of gastric inlet patches (GIP) in the cervical esophagus by argon plasma coagulation (APC) can alleviate chronic globus sensations in the throat. We investigated the efficacy of this therapy in a randomized, controlled multicenter trial. METHODS: Patients with chronic globus sensations and GIP were randomly assigned 1:1 to groups that were treated with APC or a sham procedure (controls). Patients and their referring physicians were blinded to therapy. All patients completed a standardized questionnaire about symptoms before and 3 months after the procedure. Thereafter, control patients were eligible for cross-over therapy. Long-term efficacy was assessed in all patients >or=6 months after APC. RESULTS: Improvement of symptoms was reported in 9 (82%) of 11 patients who received APC, compared with 0 (0%) of 10 patients in the control group (P = .002). Nine (90%) of 10 patients treated with APC had per protocol healing, compared with 0 (0%) of 9 controls (P < .001). Scores for symptom/globus assessment significantly improved in patients in the APC group, whereas patients in the control group did not perceive any symptom relief. Eight of the 10 patients who started in the control group crossed over to the APC group. Long-term efficacy (after a median follow-up of 17 months) was documented in 13 (76%) of 17 treated patients. CONCLUSIONS: Ablation of gastric inlet patches appears to be an effective therapy for alleviation of associated globus sensations. This new treatment modality might change the paradigm for treatment of these patients.

Interleukin 1 beta gene promoter SNPs are associated with risk of pancreatic cancer.

Epidemiological and experimental data demonstrate, that inflammation contributes significantly to pancreatic carcinogenesis. IL1beta, a pleiotropic cytokine produced by inflammatory cells and tumor cells, promotes cancer progression. Single nucleotide polymorphisms (SNPs) of the IL1beta promoter were found to be associated with an increased risk for certain cancers. In this case-control study we determined IL1beta promoter SNPs in 73 patients with pancreatic cancer and 235 controls. We found that the IL1beta -511CT/-31TC genotype was significantly associated with an increased risk for pancreatic cancer (OR 1.42, p=0.0456). Among pancreatic cancer cases, patients with the -511CT/-31TC genotype had less frequently resectable disease than patients with other IL1beta -511/-31 genotypes (p=0.0323). Furthermore, the IL1beta -511CT/-31TC genotype was more frequent observed in UICC stage IV (p=0.039) and undifferentiated tumors (G3) (p=0.019). In addition, we found that the proinflammatory IL1beta -511CT/-31TC alleles define an IL1beta secretory phenotype in pancreatic cancer cell lines in vitro. These findings provide a first evidence for an association of the IL1beta gene promoter SNPs with risk for pancreatic cancer.

In vivo characterization of proliferation for discriminating cancer from pancreatic pseudotumors.

UNLABELLED: We have determined the ability of PET with the thymidine analog 3'-deoxy-3'-(18)F-fluorothymidine (FLT) to detect pancreatic cancer and to differentiate malignant from benign pancreatic lesions. METHODS: In this prospective study, (18)F-FLT PET was performed on 31 patients with undefined pancreatic lesions. Routine diagnostic procedures included endoscopic ultrasound, MRI, or multislice helical CT of the upper gastrointestinal tract in all patients. Uptake of (18)F-FLT was evaluated semiquantitatively by calculation of mean and maximal standardized uptake values (SUVs). Results were correlated to the reference methods, which were histopathology (23/31) or cytology/clinical follow-up (8/31). RESULTS: All 10 benign pancreatic lesions were negative on (18)F-FLT PET and showed only background activity (specificity, 100%; 90% confidence interval, 74%-100%). On visual interpretation, 15 of 21 malignant tumors presented as focal (18)F-FLT uptake higher than the surrounding background (sensitivity, 71.4%; 90% confidence interval, 52%-89%). (18)F-FLT PET missed 4 well-differentiated and 2 T1 cancers. Mean (18)F-FLT uptake was 3.1 in all malignant tumors (median, 2.8; range, 1.3-8.5), 3.7 in tumors with visual tracer uptake (median, 3.2; range, 2.1-8.5), and significantly higher in malignant than in benign tumors (mean/median, 1.4; range, 1.2-1.7; P<0.001). For discriminating cancer from benign pancreatic lesions, receiver-operating-characteristic analysis indicated a sensitivity of 81% and specificity of 100% (area under the curve, 0.93) using a mean (18)F-FLT SUV cutoff of 1.8 (maximal (18)F-FLT SUV: area under the curve, 0.92; SUV cutoff, 2.1). CONCLUSION: In this pilot study, focal uptake of the in vivo proliferation marker (18)F-FLT was detected exclusively in malignant tumors. (18)F-FLT PET may therefore be useful as a diagnostic adjunct for differentiating cancer from benign pancreatic lesions.

Volume assessment in patients with necrotizing pancreatitis: a comparison of intrathoracic blood volume index, central venous pressure, and hematocrit, and their correlation to cardiac index and extravascular lung water index.

OBJECTIVE: Volume depletion and/or increased hematocrit are associated with poor prognosis in necrotizing pancreatitis. Several studies suggest that intrathoracic blood volume index (ITBI) might be superior to central venous pressure (CVP) with regard to preload assessment. Therefore, the aim of our study was to evaluate the predictive value of CVP and hematocrit with regard to ITBI, and to correlate these parameters to cardiac index (CI). DESIGN: Prospective study. SETTING: Medical intensive care unit, university hospital. PATIENTS AND INTERVENTIONS: Within 24 hrs of intensive care unit-admission, 96 hemodynamic measurements using the PiCCO system were performed in 24 patients with necrotizing pancreatitis. MAIN RESULTS: Mean CVP (12.11 +/- 5.97 mm Hg; median 11.5 normal: 1-9 mm Hg) was elevated, whereas mean ITBI (822.8 +/- 157.0 mL/m2; median 836 mL/m2; normal: 850-1000 mL/m2) was decreased. Fifty-one of 96 ITBI values were decreased (prevalence of hypovolemia of 53%). No CVP value was decreased. Fifty-three CVP measurements were elevated despite simultaneous ITBI levels indicating a normal or decreased preload. Sensitivity, specificity, positive predictive value, and negative predictive value of CVP with regard to volume depletion (ITBI <850 mL/m2), were 0%, 100%, 0%, and 47%, respectively. An increase in hematocrit (hematocrit >40% [female] or >44% [male]) was found in 11 of 51 measurements with decreased ITBI. Sensitivity, specificity, positive predictive value, and negative predictive value of an increase in hematocrit with regard to volume depletion according to ITBI were 22%, 82%, 58%, and 48%, respectively. ITBI and delta-ITBI significantly correlated to CI and delta-CI (r = .566, p < 0.001; r = .603, p < 0.001), respectively. CVP and delta-CVP did not correlate to CI and delta-CI, respectively. There was a significant correlation between ITBI and extravascular lung water index (r = .392; p < 0.001), but no correlation between CVP and extravascular lung water index (r = .074; p = 0.473). CONCLUSIONS: Volume depletion according to ITBI was found in more than half the patients. The predictive values of CVP and hematocrit with regard to volume depletion were low. ITBI and its changes significantly correlated to CI and its changes, which was not observed for CVP and delta-CVP. Therefore, ITBI appears to be more appropriate for volume management in necrotizing pancreatitis than CVP or hematocrit.

Emerging drugs for biliary cancer.

Biliary cancer comprise carcinoma of the gallbladder as well as the intrahepatic, hilar and extrahepatic bile ducts. Furthermore, many different etiologies and risk factors are contributing to the inhomogeneity of this disease. It is often diagnosed at an advanced stage when potentially curative resection is not feasible. Due to the lack of randomised Phase III studies, there is no standard regimen for chemotherapy in biliary cancer. Recent investigations into the underlying molecular mechanisms involved in biliary carcinogenesis and tumour growth have contributed greatly to our understanding of biliary cancer. Through a better understanding of these mechanisms, improved and more specific diagnostic, therapeutic and preventive strategies may be developed. Although fluoropyrimidines and gemcitabine remain the backbone of routine chemotherapy in advanced disease, new agents such as epidermal growth factor receptor blockers and angiogenesis inhibitors may hold promise for improving the outcome for patients with biliary cancer.

Role of meal carbohydrate content for the imbalance of plasma amino acids in patients with liver cirrhosis.

BACKGROUND AND AIM: Imbalance of circulating branched chain amino acids (BCAA) versus aromatic amino acids (AAA) and hyperinsulinemia are common metabolic alterations in patients with liver cirrhosis. The aim of this study was to characterize the effect of the carbohydrate component of a protein-rich mixed meal on postprandial plasma concentrations of 21 amino acids, insulin and C-peptide in patients with compensated liver cirrhosis. Furthermore, the effect of a dietary intervention on the metabolic alterations in cirrhotic patients was examined. METHODS: Eighteen patients with cirrhosis and 12 healthy volunteers received a protein-rich meal (pork filet 200 g) with or without carbohydrates (bread 50 g, glucose 20 g). A subgroup of four cirrhotic patients received an isoenergetic (117 kJ/kg bw) carbohydrate-enriched (60%) and -restricted (20%) diet for 7 days each. RESULTS: In the cirrhotic patients, basal plasma insulin and C-peptide concentrations were significantly elevated. The ingestion of a protein-rich meal without additional carbohydrates led to a significantly greater increase of insulin and C-peptide in the cirrhotic patients compared to controls. Postprandial increases of leucine and isoleucine were reduced, whereas those of phenylalanine were higher in cirrhotic patients. The addition of carbohydrates led to higher insulin and C-peptide plasma concentrations in cirrhotic patients. Postprandial BCAA increases were more impaired in the cirrhotic group after additional carbohydrate ingestion (46%vs 82%). After the carbohydrate-restricted diet for 7 days BCAA plasma levels increased but the BCAA/AAA ratio remained unaltered. CONCLUSIONS: The carbohydrate content of a meal enhances reduction of BCAA plasma concentrations in clinically stable cirrhotic patients. An imbalanced BCAA/AAA ratio cannot be avoided by a carbohydrate-reduced diet alone, supporting mandatory BCAA supplementation.

Effect of low-molecular-weight heparin on survival in patients with advanced pancreatic adenocarcinoma.

This retrospective analysis aimed to identify whether low-molecular-weight heparins (LMWH) might improve survival in patients receiving chemotherapeutic treatment for advanced pancreatic adenocarcinoma. Two hundred forty-three patients who had received chemotherapy for advanced pancreatic adenocarcinoma were identified from a prospectively maintained database. Of these, 30 patients had to be excluded from analysis due to insufficient documentation. Of the remaining 213 patients 94 patients had been treated with LMWH, whereas 119 patients served as controls. Outcome was assessed in relation to overall survival, which was calculated from the date of initiation of chemotherapy to the date of death. There was no significant difference (hazard ratio, 0.8; 95% confidence interval (CI), 0.6 to 1.1; P = 0,2) between the two groups in terms of overall survival. The median survival was 7.1 months (95% CI, 5.8-8.4 months) in the LMWH group and 5.9 months (95% CI, 5.1-6.7 months) in the non-LMWH group. A positive effect of LMWH was seen in patients with metastatic disease (hazard ratio for LMWH vs. non-LMWH, 0,6; 95% CI, 0,4 to 0,8; P = 0,006) in contrast to those without metastatic disease (hazard ratio for LMWH vs. non-LMWH, 1; 95% CI, 0.6 to 1.7; P = 0,96). The median survival of patients with metastatic disease was 6,6 months (95% CI, 5-8, 2 months) and 3.8 months (95% CI, 2.5-5.1 months) for the LMWH group and the non-LMWH group, respectively. In conclusion, we found for metastatic pancreatic adenocarcinoma a survival advantage for patients receiving LMWH. Nevertheless, our observations need confirmation by prospective randomized studies.

Carbamazepine for prevention of oxaliplatin-related neurotoxicity in patients with advanced colorectal cancer: final results of a randomised, controlled, multicenter phase II study.

BACKGROUND: Oxaliplatin-induced neurotoxicity is a growing, relevant clinical problem. In this study we evaluated the efficacy and safety of carbamazepine for prevention of oxaliplatin-associated neuropathy in patients with advanced colorectal cancer. METHODS: Chemotherapeutic treatment consisted of oxaliplatin 85 mg/m(2) given biweekly and weekly folinic acid 500 mg/m(2) followed by a 24-h infusion of 5-FU 2000 mg/m(2) (FUFOX). One cycle consisted of six consecutive weeks of treatment followed by two weeks of rest (=Treatment B). For Treatment A carbamazepine was added in a dosage for targeted plasma levels of 4-6 mg/L. Neurotoxicity was regularly assessed using a specific scale. Moreover, an evaluation of chronic sensory symptoms and a neurologic examination including tests for vibrational sense, strength and deep tendon reflexes were added creating a peripheral neuropathy (PNP) score. RESULTS: The prospectively defined adequate number of patients needed to provide power for the primary outcome could not be achieved. 19 patients were assigned to Treatment A and 17 to Treatment B. At baseline, the distribution of all clinicopathologic variables was comparable between the two groups. Overall response rates were 16% and 24% and overall survival 15.1 months and 17.4 months for Treatment A and Treatment B, respectively. Between Treatment A and Treatment B there were no major differences when considering worst neurotoxicity during the study period (p=0.46). Grade 3/4 neurotoxicity occured in 4 patients with Treatment A vs. 6 patients with Treatment B. There were no major differences between both groups in each category of the PNP score. CONCLUSIONS: Based on the small number of patients and low statistical power of our study definite conclusions regarding efficacy and safety of carbamazepine for prevention of oxaliplatin-associated neuropathy in patients with advanced colorectal cancer cannot be drawn.

Pancreatic cancer: a review of recent advances.

Pancreatic cancer is one of the most common causes of cancer-related death. Despite the advances of the molecular pathogenesis, pancreatic cancer remains a major unsolved health problem. Overall, the 5-year survival rate is < 5% and only approximately 20% of the 10% of patients with resectable disease survive 5 years. Recently, the European Study Group for Pancreatic Cancer 1 trial demonstrated substantially increased survival from adjuvant chemotherapy with 5-fluorouracil-folinic acid and preliminary data showed prolonged disease-free survival from adjuvant gemcitabine. Current palliative therapeutic approaches mostly focused on evaluating chemotherapy regimens in which gemcitabine is combined with a second cytotoxic agent. Recently, large randomised trials of combinations of gemcitabine with either capecitabine or with erlotinib demonstrated prolonged survival and 1-year survival rates of approximately 25%. The advance of molecular biology has led to the elucidation of molecular events that are important for pancreatic carcinogenesis and has provided a foundation for the development of novel chemotherapeutic and biological agents that appear to be promising and are likely to play a future role in the treatment of patients with advanced pancreatic cancer.

Prophylaxis of contrast material-induced nephropathy in patients in intensive care: acetylcysteine, theophylline, or both? A randomized study.

PURPOSE: To prospectively compare the protective effect of acetylcysteine, theophylline, and both agents combined in patients who are admitted to the intensive care unit with at least one risk factor for contrast material-induced nephropathy and who receive at least 100 mL of iodinated contrast medium. MATERIALS AND METHODS: Institutional ethics review board approval and informed consent were obtained. A total of 91 patients (mean age, 58.5 years+/-14.8 [standard deviation]; 31 women, 60 men; 150 examinations) were admitted to the intensive care unit with at least one risk factor for contrast-induced nephropathy and received either (a) 200 mg theophylline 30 minutes before contrast medium administration (group T), (b) 600 mg acetylcysteine twice daily on the day of and (if possible) the day before the examination (group A), or (c) both agents combined (group AT). The primary endpoint for this study was the incidence of contrast-induced nephropathy (chi2 test). RESULTS: Groups T, A, and AT were comparable with regard to baseline creatinine levels and the amount of contrast medium administered. The incidence of contrast-induced nephropathy in groups T, A, and AT was 2%, 12%, and 4%, respectively, and was significantly lower in group T than in group A (P=.047). There was no significant difference in the incidence of contrast-induced nephropathy between groups A and AT (P=.148) or between groups T and AT (P=.53). For group A, serum creatinine did not change after 12, 24, or 48 hours compared with baseline. Creatinine levels in group T decreased 12 hours (1.19 mg/dL+/-0.58; P=.008) and 48 hours (1.16 mg/dL+/-0.55; P=.034) after contrast material injection compared with baseline (1.25 mg/dL+/-0.61). In group AT, creatinine significantly decreased 24 hours (1.21 mg/dL+/-0.74; P=.003) and 48 hours (1.17 mg/dL+/-0.69; P<.001) after contrast material injection compared with baseline (1.28 mg/dL+/-0.74). Group A had significantly higher maximal increases in creatinine than groups T and AT (P=.014). CONCLUSION: For prophylaxis of contrast-induced nephropathy in patients who are admitted to the intensive care unit and who receive 100 mL or more of contrast medium, theophylline is superior to acetylcysteine.

Phase II trial of weekly 24-hour infusion of gemcitabine in patients with advanced gallbladder and biliary tract carcinoma.

BACKGROUND: Patients with advanced gallbladder and biliary tract carcinoma face a dismal prognosis, as no effective palliative chemotherapy exists. The antitumor effect of gemcitabine is schedule-dependent rather than dose-dependent. We evaluated the activity of a prolonged infusion of gemcitabine in advanced gallbladder and biliary tract carcinomas. METHODS: Nineteen consecutive eligible patients were enrolled. All patients were required to have histologically confirmed diagnosis and measurable disease. Gemcitabine was infused over 24 hours at a dose of 100 mg/m2 on days 1, 8, and 15. Treatment was repeated every 28 days until progression of disease or limiting toxicity. Tumor response was evaluated every second course by computed tomography (CT) scans. RESULTS: Eighteen patients were evaluable for response. A total of 89 cycles of therapy were administered. One partial response was observed (6%; 95% confidence interval (CI): 0-27%) and ten additional patients had stable disease for at least two months (disease control rate 61%; 95% CI: 36-83%). The therapy was well tolerated, with moderate myelosuppression as the main toxicity. The median time to tumor progression and median overall survival was 3.6 months (95% CI 2.6-4.6 months) and 7.5 months (95% CI 6.5-8.5 months), respectively. CONCLUSION: Weekly 24-hour gemcitabine at a dose of 100 mg/m2 is well tolerated. There was a relatively high rate of disease control for a median duration of 5.3 months (range 2.8-18.8 months). However, the objective response rate of this regimen in gallbladder and biliary tract carcinomas was limited.

Phase II trial of a 24-hour infusion of gemcitabine in previously untreated patients with advanced pancreatic adenocarcinoma.

The antitumor effect of gemcitabine is not dose-response related but schedule dependent. Here we report a phase II trial of a weekly 24-hour infusion of gemcitabine in previously untreated patients with advanced pancreatic cancer. Patients with histologically proven, measurable, and irresectable pancreatic adenocarcinoma were treated with gemcitabine at a dose of 100 mg/m2 infused over 24 hr on days 1, 8, and 15. Treatment was repeated every 28 days until progression of disease or limiting toxicity. All 18 patients enrolled were evaluable for response. Neutropenia and thrombocytopenia grade 3 occurred in 1 patient each. One partial response and two minor responses were observed. Median time to progression of disease was 4.4 months. Improvement of the European Organization for Research and Treatment of Cancer C30 scores was observed in 6 patients (pain and overall symptom score, respectively) and in 3 patients (overall functioning score and global quality of life, respectively). Weekly 24-hr gemcitabine was well tolerated in previously untreated patients with advanced pancreatic cancer. It shows marginal antitumor activity in terms of response rate. However, the 24-hr infusion at a dose of 100 mg/m2 seems to be as active as the standard 30-min gemcitabine at a dose of 1000 mg/m2. Relatively long median time to progression of disease and improvement of symptom and quality-of-life scores suggest, that patients may benefit from 24-hr gemcitabine.