Evaluation of risk factors for chemotherapy-induced nausea and vomiting in cisplatin and gemcitabine treatment for biliary tract cancer: acid suppressants do not prevent nausea.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most serious adverse effects of cancer therapy. Cancer patients frequently use acid suppressants (AS) for palliation of gastrointestinal symptoms associated with malignancy and/or anticancer therapy. AS are suggested as an additional option for CINV management in several antiemetic guidelines, although their efficacy remains unknown. The aim of this study was to determine whether AS administration affects CINV incidence in cisplatin and gemcitabine treatment for biliary tract cancer. The primary endpoint was to evaluate whether AS administration was associated with the incidence of all-grade nausea in the first administration by logistic analysis. The secondary endpoints were to assess factors associated with anorexia. Prophylactic antiemetics were based on current guidelines. Nausea occurred in 34.2% of patients (grade 1, 31.7%; grade 2, 2.5%). Patients exhibiting vomiting and anorexia represented 4.2% and 39.1%, respectively, without grade 3/4 symptoms. Multivariate analysis suggested that the independent risk factors for nausea as female sex, and no- or less-alcohol drinking habit and regular narcotics administration were associated with anorexia. In contrast, AS administration was not associated with nausea and anorexia incidence (odds ratio, 95% confidence interval: 1.43, 0.64-3.23; P =0.38 for nausea, 1.62, 0.71-3.68; P =0.25 for anorexia). In conclusion, we found that AS administration is not associated with CINV incidence, and female sex is a risk factor for nausea, and non-alcohol drinking habits and regular narcotic use are factors associated with anorexia in cisplatin and gemcitabine treatment for biliary tract cancer. We should correctly administer AS depending on the patient's situation. Successful CINV management needs effective monitoring and administration of prophylactic antiemetics and counter-measure medicines for patients at risk.

A general approach for the prediction of the intestinal absorption of drugs: regression analysis using the physicochemical properties and drug-membrane electrostatic interaction.

A general method for predicting the intestinal absorption of a wide range of drugs using multiple regression analysis of their physicochemical properties and the drug-membrane electrostatic interaction was developed. The absorption rates of tested drugs from rat jejunum were measured by the in situ single-pass perfusion technique. The drugs used in this study were divided into three groups for regression analysis, and a smaller "test" set of compounds was used to assess the predictive capacity of the regression equation. When the analysis was applied to each respective group of drugs (i.e., anionic, cationic, and nonionized compounds), obtained regression coefficients were 0.569, 0.821, 0.728 by using the organic solvent (n-octanol)/buffer partition coefficient, 0.730, 0.734, 0.914 using the permeation rate across a silicon membrane, and 0.790, 0.915, 0.941 using an EVA membrane, respectively. However, smaller regression coefficients of 0.377, 0. 468, and 0.718 were obtained when these three groups of drugs were put together for prediction. Meanwhile, correlation was improved remarkably when drug-membrane electrostatic interactions, namely, hydrogen-bonding donor (Halpha) and acceptor (Hbeta) activity or index of electricity (Ec), were added to the other parameters of lipophilicity and permeation rate across the EVA membrane (r = 0.880 and 0.883, respectively). Moreover, the equation obtained from these regression analyses was applicable even to the prediction of the absorption of the zwitterionic drugs. These results suggest that including the electrostatic interaction parameters in addition to lipophilicity and permeability across artificial membranes would afford a better prediction for the intestinal absorption of the vast majority of drugs.

Hepatitis C virus infection in patients with B-cell non-Hodgkin's lymphoma.

OBJECTIVE: As a causative role of hepatitis C virus (HCV) in B-cell lymphoproliferative disorders (LPD) has been suggested by several reports, we investigated the prevalence of HCV infection among patients with LPD at our hospital with the aim of clarifying the clinical features and the outcome for HCV antibody-positive patients with non-Hodgkin's lymphoma (NHL). METHODS: Retrospective chart review. PATIENTS: A total of 123 patients with B-cell LPD (4 with chronic lymphocytic leukemia, 17 with multiple myeloma, and 100 with B-cell NHL), 38 patients with non-B-cell LPD (5 with adult T-cell lymphoma, 8 with Hodgkin's disease, and 25 with non-B-cell NHL) and 516 patients with miscellaneous diseases other than liver diseases or LPD (control) were studied. RESULTS: HCV infection was detected in 17 of 100 patients with B-cell NHL versus none of 25 patients with non-B-cell NHL (p=0.023) and in 34 patients (6.6%) in the control group with miscellaneous diseases (p=0.0011). In HCV-positive B-cell NHL, primary liver involvement was detected in 3 of 17 patients compared to none of 83 HCV-negative patients (p=0.0019). Intermediate-grade lymphoma (Working Formulation) was the most frequent histology. Eleven of 15 HCV-positive patients achieved complete remission after chemotherapy, and 6 of 7 deaths were caused by liver-related diseases. CONCLUSION: The prevalence of HCV infection was higher in patients with B-cell NHL than in those with non-B-cell NHL and the control group. Primary liver involvement and liver-related causes of death were frequent in HCV-positive patients with B-cell NHL.

[Fluoroscopic contrast medium percutaneous ethanol injection therapy (FCM-PEIT): newly developed clinical useful method for injecting ethanol into nodules of hepatocellular carcinoma].

We have performed fluoroscopic contrast medium percutaneous ethanol injection therapy (FCM-PEIT) total 266 times to 82 hepatocellular carcinoma (HCC) nodules in 44 HCC cases: FCM-PEIT is the newly developed method that HCC nodules are punctured by a needle and injected with ethanol mixed with water-soluble contrast medium (Iopamidol containing 370 mg/ml iodine) (vol/vol: 7/3) under the fluoroscopic observation as well as ultrasonic diagnostic equipment (US). Autopsy analyses have demonstrated nearly complete tumor necrosis by FCM-PEIT. We analyzed the detectable rate (%) of the contrast medium-mixed ethanol (CME) leakage out of HCC nodules by US-alone, fluoroscope-alone, and US-fluoroscope observation. The detectable rate of the leakage was 63% by US-fluoroscope, while was only 32% by US-alone. Particularly, all leakages into intra hepatic bile duct were missed by US-alone. The maximal CME-amount for injection without any leakage was not uniform and not related to the size of HCC nodules. The present results suggest that FCM-PEIT is clinically more useful method for the treatment of HCC compared to general PEIT that HCC nodules are injected with ethanol under the US-alone observation, since it is easy to confirm whether ethanol can be sufficiently injected into HCC nodules without any leakage.

Bleeding esophageal ulcers caused by NSAIDs.

This report describes four patients with NSAID-induced esophageal ulcers documented by endoscopy. The cause of injury was ibuprofen alone in two patients, aspirin in one patient, and a combination of aspirin and ibuprofen in one patient. The most common findings were anemia, retrosternal pain, and dysphagia. Three patients had bleeding esophageal ulcers requiring blood transfusions. One patient had massive bleeding which was controlled by endoscopic hemostasis. Three patients were followed up by endoscopy, which showed healing in 3-4 weeks. These NSAID-induced ulcers had characteristic endoscopic features, namely, a large, shallow, discrete ulcer in the midesophagus near the aortic arch with normal surrounding mucosa. These findings suggest that the injury resulted from mucosal contact with NSAIDs. A precise history and immediate endoscopic examination were most important in establishing the diagnosis of esophageal ulcer. Healing occurs if drug-induced injury is recognized early and treatment is appropriately started with antacids and H2 blockade. Offending medication should be discontinued and patients should be counseled to take pills in an upright posture with liberal amounts of fluids well before retiring for the night.

Perioperative hepatic functional risk assessed with technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin liver scintigraphy in patients undergoing pancreaticoduodenectomy complicated by obstructive jaundice.

CONCLUSION: Liver scintigraphy with technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin (Tc-GSA) can be used to predict outcome of biliary drainage and hepatic function after pancreaticoduodenectomy in patients with pancreatic, biliary, and ampullary carcinomas complicated by obstructive jaundice. BACKGROUND: Preoperative obstructive jaundice has been reported as a crucial risk factor for serious postoperative complications in patients undergoing pancreaticoduodenectomy. The aim of the present study was to investigate whether Tc-GSA liver scintigraphy can assess hepatic functional risk in patients with pancreatic, biliary, and ampullary carcinomas complicated by obstructive jaundice. METHODS: Liver scintigraphy was performed before biliary drainage in 18 patients with obstructive jaundice. The maximum removal rate of Tc-GSA (GSA-Rmax; standard normal value > or = 0.60) was calculated. These patients underwent pancreaticoduodenectomy with wide lymphadenectomy. The efficacy of preoperative biliary drainage was assessed with the decrease in serum bilirubin concentration in the first week after biliary drainage. Postoperative liver function was assessed with the increase in serum bilirubin concentration, which was the difference between the immediate preoperative and maximal postoperative bilirubin concentrations. RESULTS: Serum bilirubin decreased more in the first week after biliary drainage in patients with GSA-Rmax > or = 0.60 (7.64 +/- 1.09 mg/Dl/wk) than in patients with GSA-Rmax < 0.60 (3.56 +/- 1.25 mg/DL/wk, p = 0.042). Postoperative bilirubin increased less in patients with GSA-Rmax > or = 0.60 (0.81 +/- 0.30 mg/dL) than in patients with GSA-Rmax < 0.60 (4.00 +/- 0.69 mg/DL, p = 0.0012). Multivariate analysis showed that GSA-Rmax significantly predicted the postoperative bilirubin increase (p = 0.020).

Experimental studies of thermal therapy for severe nonvariceal bleeding in dogs.

BACKGROUND: There are several methods of achieving endoscopic hemostasis for nonvariceal hemorrhage, including use of a heater probe, bipolar electrocoagulation, use of a Gold probe, and injection therapy with epinephrine or ethyl alcohol. However, due to clinical variations, clinical studies comparing thermal with injection therapy have yielded conflicting results. Therefore, we used a canine model of acute bleeding from gastric serosal vessels to examine the efficacy of the heater probe and the Gold probe in achieving hemostasis and to compare the injurious effects of these methods with injection therapy. METHODS: Seven mongrel dogs were used in the study. Four were assigned to acute experiments in which transected blood vessels were allowed to bleed profusely. Two dogs of this group were treated with either a large or small Gold probe, while the other two were treated with either a large or small heater probe. In the other three dogs, we tested the chronic effects of the heater probe, the Gold probe, and injection therapy with dilute epinephrine. RESULTS: Complete hemostasis was achieved for all four dogs in the acute experiments. Dogs treated with either a large or small heater probe had coagulation necrosis that extended to the serosa and muscularis but not to the mucosa. The large Gold probe had similar results, but the small Gold probe caused tissue damage to the serosa, muscularis, submucosa, and mucosa at several of the application sites. Both probes caused scarring of the gastric wall. In the chronic experiments, we found that the Gold probe caused larger mucosal ulcers than the heater probe. All ulcers healed in 3 weeks. The epinephrine injection caused localized swelling and discoloration, but after 1 week the tissue returned to normal. CONCLUSIONS: Both the heater probe and the Gold probe are effective in achieving hemostasis in a canine model of nonvariceal hemorrhage, and both methods are superior to injection therapy. For active bleeding ulcers, we currently recommend a combination therapy, using first injection therapy and then a heater or Gold probe. However, clinicians should be aware of the potential for tissue damage.

Influence of continuous venovenous haemodiafiltration on the pharmacokinetics of tacrolimus in liver transplant recipients with small-for-size grafts.

In adult-to-adult living donor liver transplantation (LDLT), the graft volume is inevitably much smaller than the ideal liver mass (standard liver volume) for the recipient's metabolic demand. Patients with small-for-size grafts are treated with continuous venovenous haemodiafiltration (CVVHD) for the artificial liver support. However, little is known about the influence of CVVHD on the elimination of tacrolimus. The objective of this study was to elucidate the effect of CVVHD on the pharmacokinetics of tacrolimus in recipients of LDLT with small-for-size grafts. Three liver transplant recipients (one male and two females) and donors (two males and one female) were enrolled in this study. Blood samples from inflow port and outflow port were obtained on the first day at the start of CVVHD. Whole-blood concentrations of tacrolimus were measured immediately using the microparticle enzyme immunoassay (MEIA; Abbott Laboratories). There was no significant difference between concentrations of tacrolimus in blood sampled at inflow port and outflow port sites and t(1/2)-values of tacrolimus in the three recipients were 29.9, 63.6 and 28.8 h. CVVHD did not cause a decrease in the blood tacrolimus concentration. Adjustment to the dose or dosing interval is not required for patients treated with tacrolimus during CVVHD.

Effective fluconazole therapy for liver transplant recipients during continuous hemodiafiltration.

Fungal infections are still one of the main causes of death and complications after solid organ and bone marrow transplants. The authors evaluated the effect of continuous hemodiafiltration (CHDF) on the pharmacokinetics of fluconazole in liver transplant recipients. Six liver transplant patients (primary biliary cirrhosis, n = 2; fulminant hepatitis, n = 2; viral hepatitis, n = 2) were enrolled in this study. In one patient not receiving CHDF, the fluconazole levels increased with increasing dosages. In contrast, in patients undergoing CHDF, the dosage of fluconazole was increased from 100 mg/d to 200 mg/d, but fluconazole did not reach the targeted levels. It appears that the targeted trough level cannot be achieved by administration of fluconazole at a dosage of 100 to 200 mg/d during CHDF. A higher dosage (600-1000 mg/d) of fluconazole may be required to achieve the therapeutic drug level in patients undergoing CHDF. In patients undergoing CHDF, fluconazole was given at a dosage of 800 mg/d and reached the targeted levels. In addition, after CHDF, the dosage of fluconazole was decreased to 100 mg/d, and fluconazole reached the near-targeted trough level. These results demonstrate that CHDF removes fluconazole from the blood at an efficiently high rate, resulting in its ineffective blood level. To guarantee safe and effective fluconazole therapy, the trough levels should be monitored routinely during CHDF.

Endoscopic management of Dieulafoy lesions of the stomach: a case study of 26 patients.

BACKGROUND AND STUDY AIMS: We studied the clinical features and therapeutic outcome in patients with a diagnosis of Dieulafoy lesion. PATIENTS AND METHODS: Twenty-six patients who had upper gastrointestinal bleeding from Dieulafoy lesions received endoscopic therapy. The clinical and endoscopic features, and the outcome of therapy, were analysed retrospectively. RESULTS: Hemostasis was attempted by hemoclipping in 18 patients, heater probe in six patients and ethanol injection in two patients. The initial therapy was successful in 22 (84.6%) cases. Hemostasis was achieved with additional endoscopic therapy in three cases (11,5%). Surgical treatment was needed only in one case, owing to uncontrolled bleeding. One patient died during the hospital stay from a cause unrelated to the Dieulafoy lesion. There were no side effects related to endoscopic therapy. None of these patients presented with rebleeding from Dieulafoy lesions over a mean long-term follow-up of 36 months. CONCLUSIONS: Bleeding from Dieulafoy lesions can be managed successfully by endoscopic methods, and these should be regarded as the first choice in their management. We emphasize the role of hemoclipping, a mechanical method, for the endoscopic treatment of these lesions.