Uracil-tegafur as an adjuvant for hepatocellular carcinoma: a randomized trial

Frequent recurrence of hepatocellular carcinoma (HCC) after surgery remains a major clinical problem. This randomized controlled trial evaluated whether postoperative adjuvant therapy with oral uracil-tegafur (UFT) prevents recurrence of HCC. A total of 160 patients who underwent curative hepatic resection for HCC were randomly assigned to receive either 300 mg/day of UFT for 1 year after surgery (n = 79, UFT group) or surgery alone (n = 80, control group). The primary endpoint was recurrence-free survival, and the secondary endpoint was overall survival. Other study variables included liver function and type of recurrence. During a median follow-up of 4.8 years (range: 0.5-7.9), recurrence-free survival curves in the groups were similar (P = .87). Overall survival was slightly but not significantly worse in the UFT group than in the control group (P = .08). The rates of recurrence-free and overall survival at 5 years were 29% and 58%, respectively, in the UFT group, as compared with 29% and 73%, respectively, in the control group. The hazard ratio for recurrence in the UFT group, relative to the control, was 1.01 (95% confidence interval: 0.84-1.22, P = .87). The proportion of patients with advanced recurrence (i.e., multiple, extrahepatic, or associated with vascular invasion) was significantly higher in the UFT group (74%, 43 of 58 patients with recurrence) than in the control group (53%, 30 of 57) (P = .02). In conclusion, our results offer no evidence to support potential benefits of adjuvant chemotherapy with UFT after surgery in patients with HCC and suggest that such treatment may even worsen overall survival.     

Endoscopic screening during 17 years for gastric stump carcinoma. A prospective clinical trial

In an attempt to reduce mortality in gastric stump carcinoma a defined cohort of operated peptic ulcer patients was followed up with an endoscopic screening programme. From 1930 and through 1960, 1575 patients were operated on for peptic ulcer disease at the Dept. of Surgery in Lund, Sweden. Of 838 still alive in January 1973, 682 were selected for geographical reasons and were offered endoscopic screening with biopsy at regular intervals. Three hundred and fifty-four patients came to the first examination. The follow-up programme was individualized thereafter with screening at 1- to 3-year intervals, depending on endoscopic and histologic findings. The remaining patients have, since then, constituted a control group, followed up only through death certificates and the Swedish Cancer Registry. By December 1989, 202 patients in the screening group had died and 320 in the control group. During the 17 years of follow-up 12 patients in the screening group died of gastric cancer, compared with 14 in the control group, even though 17 cases of early gastric cancer were diagnosed and operated on in the first group, compared with only 2 in the latter. We conclude that regular endoscopic screening does not reduce gastric cancer mortality and can thus not be recommended in asymptomatic patients previously subjected to partial gastric resection due to peptic ulcer disease.     

Total gastrectomy with or without abdominal drains. A prospective randomized trial.

The most common postoperative complications of total gastrectomy are esophagojejunal anastomotic leakage and subphrenic abscess. These complications are a cause of morbidity and mortality, relaparotomy, and longer postoperative stay. The use of abdominal drains is useful for the early diagnosis and management of anastomotic leaks. The aim of this study was to analyze our experience with total gastrectomy for gastric cancer in patients with and without abdominal drains, and to evaluate the results regarding postoperative morbidity, postoperative hospital stay, postoperative days for oral intake, relaparotomy and mortality. This prospective and randomized study examines the results in 60 consecutive patients (43 males and 17 females) with gastric cancer who underwent total gastrectomy in the Regional Clinical Hospital of Concepción, Chile, between 2000 and 2003. Patients were divided into two groups: group I (without drains) and group II (two drains). We found 31 patients in group I and 29 patients in group II. The mean length of postoperative stay was 12.9 days in group I and 18.8 days in group II (p = 0.0242, s.). Morbidity was 9.7% in group I and 37.9% in group II (p = 0.0242, s.). Re-explorations were more frequent in group II (24.1%) versus group I (9.7%) (p = 0.1239, n.s.). Postoperative days for oral intake were 9.4 in group I and 12.8 in group II (p = 0.0514, n.s.) Mortality was 0% in group I and 3.4% in group II (p = 0.4833, n.s.). In our experience, morbidity and postoperative hospital stay were statistically higher in the group of patients with abdominal drains.     

A novel transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma: a prospective randomized trial

Background

We designed a novel transcatheter arterial infusion chemotherapy (TAI) using iodized oil (lipiodol) and degradable starch microspheres (DSM) for hepatocellular carcinoma (HCC) patients. In this study, we investigated the efficacy of TAI using lipiodol and DSM in a prospective randomized trial.

Methods

We randomly divided 45 patients with HCC into 3 groups: TAI using lipiodol (lipiodol group, n?=?15), TAI using DSM (DSM group, n?=?15), and TAI using lipiodol and DSM (lipiodol?+?DSM group, n?=?15). In the lipiodol group, a mixture of cisplatin and lipiodol was administered. In the DSM group, a mixture of cisplatin and DSM was administered. In the lipiodol?+?DSM group, a mixture of cisplatin and lipiodol was administered, followed by DSM.

Results

The response rates were 40% in the lipiodol group, 53.4% in the DSM group, and 80% in the lipiodol?+?DSM group, respectively. The response rate tended to improve in the lipiodol?+?DSM group (lipiodol group vs. lipiodol?+?DSM group, P?=?0.07). The median progression-free survival time was 177?days in the lipiodol group, 287?days in the DSM group, and 377?days in the lipiodol?+?DSM group. The progression-free survival in the lipiodol?+?DSM group was significantly better than those in the DSM group (P?=?0.020) and the lipiodol group (P?=?0.035). There were no serious adverse effects among the 3 groups.

Conclusions

TAI using lipiodol and DSM was superior to TAI using lipiodol only and TAI using DSM only because of improvements in therapeutic effects and progression-free survival.     

Dexfenfluramine as adjuvant to a low-calorie formula diet in the treatment of obesity: a randomized clinical trial.

Dexfenfluramine (dF) was compared to placebo as adjuvant to a very energy-restricted diet (1.6-4.2 MJ/24 h). The diet was continued as long as possible or until a satisfactory weight loss had been achieved, and dietary efforts were continued throughout the study. Of the 37 females and five males included, 71 per cent could be followed up for 12 months. Initial BMI ranged from 28 to 54 kg/m2. The lowest body weight was reached 1 month earlier in the dF group (P = 0.037). Throughout the study, the reduction of excess weight (REW) was greater in dF patients (P less than 0.05 only at 4 and 6 months). At 6 months, excess weight had declined by 15 per cent more in the dF group than in the placebo group (95 per cent confidence limits of the median being 1-31 per cent). Between 6 and 12 months, both groups regained weight significantly, the rates of regain differing only insignificantly. At 12 months, excess weight showed a net decrease of only 8 per cent more in the dF group than in the placebo group (95 per cent confidence limits being -7 to +24 per cent). Therefore, REW showed no significant group difference after 12 months. Type of obesity (android or gynoid) as determined by waist to hip ratio had no significant impact on either weight loss, REW, reductions of waist and hip circumferences, or on waist to hip ratio changes. S-alkaline phosphatases and s-uric acid declined significantly in the dF group only. Side-effects were all mild and their prevalence showed no group difference.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intraoperative chemohyperthermic peritoneal perfusion as an adjuvant to gastric cancer: final results of a randomized controlled study

BACKGROUND/AIMS: Although the most frequent cause of death after curative resection of advanced gastric cancer is peritoneal recurrence, there was no effective therapy for the prevention of peritoneal recurrence. This randomized trial sought to determine whether intraoperative chemohyperthermic peritoneal perfusion could eliminate microscopic residual disease and thereby improve survival of patients with advanced gastric cancer. METHODOLOGY: One-hundred and thirty-nine patients with T2-4 gastric cancer underwent curative gastrectomy with extended lymphadenectomy. These patients were randomly allocated into the following three groups. Patients in the CHPP group received surgery + chemohyperthermic peritoneal perfusion, and those in the CNPP group underwent surgery + chemonormothermic peritoneal perfusion. The third group was surgery alone group. In the CHPP and CNPP groups, peritoneal cavity was perfused with 6-8 liters of heated saline at, respectively, 42-43 degrees C and 37 degrees C with 30 mg of mitomycin C and 300 mg of cisplatin by a extracorporeal circulation machine. RESULTS: Major operative complication occurred in 19% (9/48), 14% (6/44) and 19% (9/47) of the CHPP, CNPP and surgery alone group, respectively. Complication which uniquely developed after chemohyperthermic peritoneal perfusion was bowel perforation. Mortality rates of each group were 4% (2/48), 0% (0/44) and 4% (2/47) in the CHPP, CNPP and surgery alone group, respectively. Overall 5-year survival rates of CHPP, CNPP and surgery alone groups were 61%, 43% and 42%, respectively. In a subset analysis, patients with gastric cancer having serosal invasion or lymph node metastasis have shown a statistically significant improvement in survival when treated with chemohyperthermic peritoneal perfusion. However, chemonormothermic peritoneal perfusion had no survival benefit. By analyzing with Cox proportional hazard model, chemohyperthermic peritoneal perfusion emerged as an independent prognostic factor for good survival. Surgery alone had three-fold higher risk of death than chemohyperthermic peritoneal perfusion. CONCLUSIONS: Chemohyperthermic peritoneal perfusion had an efficiency for the prophylaxis of recurrence after curative resection of advanced gastric cancer, and is indicated for patients with tumor infiltrating beyond serosal layer and node positive tumor.     

Antibiotic prophylaxis for percutaneous endoscopic gastrostomy. A prospective, randomized, double-blind clinical trial

Study Objective. To determine if prophylactic use of cefazolin reduces peristomal wound infection associated with percutaneous endoscopic gastrostomy. Design. Prospective, randomized, double-blind, placebo-controlled clinical trial. Setting. Academic medical center, referral-based, gastroenterology service. Patients. One hundred thirty hospitalized patients, 23 of whom were excluded. Of the remaining 107 patients, 52 (group I) were already using antibiotics at the time of randomization for gastrostomy, whereas 55 (group II) were not. Interventions. Patients received either intravenous saline as a placebo or intravenous cefazolin (1 g) 30 minutes before gastrostomy. Measurements and Main Results. For 1 week after gastrostomy, the peristomal area was evaluated and a score assigned each day for erythema (0 to 4), induration (0 to 3), and exudate (0 to 4). A maximum combined score of 8 or more or the development of pus was a criterion for infection. None of the patients in group I developed a wound infection. Only 2 of 27 group II patients given prophylaxis developed a wound infection, compared with 9 of 28 patients not given prophylaxis, a difference of 25% (95% confidence interval, 4.8 to 44.6%; p less than 0.025). The number of patients who developed a wound infection was 0 of 52 in group I and 2 of 27 in group II patients who received cefazolin, a difference of 7.4% (95% confidence interval, -2.5 to 17.3%; p = 0.07). Conclusion. Cefazolin prophylaxis significantly reduces the risk for peristomal wound infection associated with percutaneous endoscopic gastrostomy. It is needed, however, only for patients not already receiving antibiotic treatment at the time of gastrostomy.     

Efficacy of spinal cord stimulation as adjuvant therapy for intractable angina pectoris: A prospective,randomized clinical study

Objective. In a prospective, randomized study with an 8-week follow-up period, we evaluated the efficacy of spinal cord stimulation on exercise capacity and quality of life in patients with intractable angina.Background. Despite important achievements in therapy for ischemic heart disease, there remain patients with intractable symptoms of angina. In uncontrolled observations, several investigators have reported beneficial effects of spinal cord stimulation as an additional therapy for patients with angina pectoris.Methods. Seventeen patients were randomly assigned to the treatment (implantation within 2 weeks, eight patients) or control (implantation after 8 weeks, nine patients) group. Assessment of exercise capacity was performed by treadmill exercise testing. Quality of life was evaluated by daily and social activity scores and recording sublingual glyceryl trinitrate intake and angina pectoris attacks in a diary. After the 8-week study period, the control group also received the spinal cord stimulation device, and all patients were followed up for 12 months.Results. The treatment but not the control group demonstrated a significant increase in exercise duration (p < 0.02), rate-pressure product (p < 0.03) and time to angina (p < 0.04), with a decrease in ST segment depression (p < 0.05). This was associated with an increase in daily life (p < 0.008) and social activity (p < 0.005) scores and a reduction in glyceryl trinitrate intake (p < 0.004) and episodes of angina pectoris (p < 0.003). During the 1-year follow-up, improvement in an quality of life variables was linear for the entire group compared with baseline. The time to angina, exercise duration and ST segment depression showed a second-order trend.Conclusions. Spinal cord stimulation significantly improves exercise capacity and quality of life. On the basis of an increase in exercise capacity and rate-pressure product, the mechanism by which spinal cord stimulation acts may be related to improved oxygen supply to the heart combined with an analgesic effect.     

Efficacy and safety of balloon-occluded endoscopic injection sclerotherapy as a prophylactic treatment for high-risk gastric fundal varices: a prospective,randomized, comparative clinical trial

BACKGROUND: No single effective method has yet been established for the prophylactic treatment of gastric fundal varices at high risk for bleeding. A prospective, randomized trial was conducted to compare the efficacy and safety of a new technique, balloon-occluded endoscopic injection sclerotherapy (BO-EIS), to balloon-occluded retrograde transvenous obliteration (B-RTO) for treatment of high-risk gastric fundal varices. METHODS: Twenty consecutive patients with gastric variceal diameters of over 5 mm by color Doppler EUS were randomized to undergo either BO-EIS or B-RTO. All patients underwent color Doppler EUS 2 weeks after treatment and EGD every 3 months for assessment of sclerosing effect. RESULTS: The gastric varices in all patients except one in the B-RTO group were eradicated with either treatment. The volume of sclerosant used was significantly smaller in patients who underwent BO-EIS (p < 0.05). The endoscopic grade of esophageal varices in 4 of 9 patients worsened after treatment with B-RTO (p < 0.05). The method of randomization used resulted in an uneven distribution of women, although the difference between the groups was not statistically significant. When only men were compared, the results of the study were unchanged. CONCLUSIONS: BO-EIS is a safe and effective for treatment of high-risk gastric fundal varices. In contrast to B-RTO, it can be used even in patients without a gastrorenal shunt.     

Stop-flow thoracic perfusion for unresectable pulmonary carcinoma with or without inhalation IL-2 immunotherapy. A prospective randomized study.

BACKGROUND/AIMS: Pulmonary carcinoma, metastatic or primary, remains a challenging disease with a poor and dismal prognosis. This prospective randomized study compares the results of stop-flow thoracic perfusion and systemic chemotherapy with or without the addition of Interleukin-2 (IL-2) inhalation immunotherapy with respect to overall survival and quality of life. METHODOLOGY: From January 1996 to January 1999 stop-flow thoracic perfusion using two balloon-tipped catheters was carried out in combination with maintenance system chemotherapy, with (Group B) or without (Group A) inhalation IL-2 immunotherapy in 67 patients suffering from histologically diagnosed unresectable lung carcinoma. RESULTS: The mean survival for Group A patients was 12 months (M +/- SD: 12 +/- 8.82) while in Group B patients it was 19 months (M +/- SD: 19 +/- 8.47). CONCLUSIONS: Stop-flow thoracic perfusion in combination with systemic maintenance chemotherapy and IL-2 inhalation immunotherapy prolongs survival and ensures a good quality of life.     

Acetaminophen and diphenhydramine as premedication for platelet transfusions: a prospective randomized double-blind placebo-controlled trial

Non-hemolytic transfusion reactions (NHTR) occur in up to 30% of patients receiving platelet transfusions. Premedication with acetaminophen and diphenhydramine is a common strategy to prevent NHTR, but its efficacy has not been studied. In this prospective trial, transfusions in patients receiving pre-storage leukocyte-reduced single-donor apheresis platelets (SDP) were randomized to premedication with either acetaminophen 650 mg PO and diphenhydramine 25 mg IV, or placebo. Fifty-one patients received 98 transfusions. Thirteen patients had 15 NHTR: 15.4% (8/52) in the treatment arm and 15.2% (7/46) in the placebo arm. Premedication prior to transfusion of pre-storage leukocyte reduced SDP does not significantly lower the incidence of NHTR as compared to placebo.     

Noradrenaline in upper gastrointestinal haemorrhage. A prospective, randomized, double blind controlled clinical trial

The effect of noradrenaline (8 mg in 100 ml cold saline) gastric lavage was compared with that of cold saline alone in 42 patients with upper gastrointestinal haemorrhage in a prospective, randomized, double blind study. Fifty three per cent (11/21) of the patients given noradrenaline stopped bleeding within two hours of treatment compared with 14% (3/21) of those given saline alone. We suggest that noradrenaline gastric lavage is a simple, safe and effective method for controlling upper gastrointestinal haemorrhage and could be used with advantage in peripheral hospitals in tropical countries.     

Surgery or surveillance for mild asymptomatic primary hyperparathyroidism: a prospective, randomized clinical trial

CONTEXT: It is unclear whether patients with asymptomatic primary hyperparathyroidism (PHPT) do better with parathyroidectomy (PTx) as compared with conservative medical management. OBJECTIVE: The aim of the study was to evaluate the beneficial effect of PTx vs. conservative management in patients with mild asymptomatic PHPT. DESIGN: We conducted a prospective, randomized study. SETTING: The study took place at a referral center. PATIENTS: We studied 50 patients who did not meet any guidelines for parathyroid surgery as recommended by the National Institutes of Health Consensus Development Conference on Asymptomatic PHPT. INTERVENTION: Patients were randomly assigned to PTx or no PTx and were evaluated at 6 months and at 1 yr. MAIN OUTCOME MEASURES: We compared changes (percentage of basal) of lumbar spine bone mineral density (BMD) between the two groups at 1 yr. RESULTS: The change in BMD at lumbar spine was greater after PTx (+4.16 +/- 1.13 for PTx vs. -1.12 +/- 0.71 for no PTx; P = 0.0002). The change in BMD at the total hip was also significantly greater in the PTx group (+2.61 +/- 0.71 for PTx vs. -1.88 +/- 0.60 for no PTx; P = 0.0001). There was no difference in BMD after 1 yr between both groups at the one-third radius site. In comparison with those who did not undergo surgery, the PTx subjects, after 1 yr, showed significant differences in four quality of life measures as determined by the 36-item short form health survey scale: bodily pain (P = 0.001), general health (P = 0.008), vitality (P = 0.003), and mental health (P = 0.017). CONCLUSIONS: In patients with mild asymptomatic PHPT, successful PTx is followed by an improvement in BMD and quality of life. Most patients followed without surgery did not show evidence of progression.     

Combination chemotherapy for advanced ovarian cancer: a prospective randomized trial comparing hexamethylmelamine and cyclophosphamide to doxorubicin and cyclophosphamide

Forty-three patients with advanced stage III and IV epithelial cancers of the ovary were entered in a prospective randomized study comparing doxorubicin and cyclophosphamide to hexamethylmelamine and cyclophosphamide chemotherapy. No statistical difference in the overall response rates or survival times was demonstrated. However, the combination of doxorubicin and cyclophosphamide was more effective in inducing a response in histologically poorly differentiated cancers than in well-differentiated and moderately differentiated cancers, and the therapeutic implications of this observation are discussed.     

Conventional cutting vs. internal anal sphincter-preserving seton for high trans-sphincteric fistula: a prospective randomized manometric and clinical trial

Abstract. Background: Cutting setons have been used in complicated perirectal sepsis with good effect, although there is a moderately high incidence of fecal leakage after their use. The aim of this study was to compare a modified cutting seton, which repaired the internal anal sphincter muscle and re-routed the seton through the intersphincteric space, with a conventional cutting seton. Methods: A total of 34 patients were randomized between 1998 and 2002. They were prospectively assessed by continence score and anorectal manometry, and for anal function, clinical sepsis and fistula recurrence. Results: There was no difference in postoperative continence score, incidence of recurrent fistula or healing time between groups after a mean follow-up of 12 months. Resting anal manometric pressures and vector volumes were consistently higher with the modified seton (although not statistically significant), as was the area under the inhibitory curve during elicitation of the rectoanal inhibitory reflex across the full sphincter length. (p<0.05). Conclusion: A larger prospective study of internal anal sphincter-preserving seton use in cryptogenic high transshincteric fistula-in-ano appears justified.