A. K. C. Li

Selective internal radiation therapy for nonresectable hepatocellular carcinoma with intraarterial infusion of 90yttrium microspheres

PURPOSE To evaluate the efficacy of intraarterial 90yttrium (90Y) microspheres in nonresectable hepatocellular carcinoma (HCC). METHODS AND MATERIALS Patients with nonresectable HCC, but without extrahepatic disease, who also had lung shunting < 15% and tumor-to-normal ratio > or =2, as determined by simulation using (99m)technetium macroaggregated albumin, were entered into the study. The radiation dose delivered to the lungs, tumor, and normal liver was estimated by a partition model. 90Y microspheres were infused into the hepatic artery at the time of hepatic angiography or through an implanted arterial portacatheter under fluoroscopy. Repeated treatments were given for residual or recurrent tumor. Response to treatment was monitored by serum alpha-fetoprotein or ferritin levels, together with serial computed tomography. RESULTS Seventy-one patients, including 20 patients with postoperative recurrence, were initially treated with an activity of 0.8 to 5.0 Giga-Becquerel (GBq) (21.6-135.1 mCi) (median 3.0 GBq or 81.1 mCi) of 90Y microspheres. There was a 50% reduction in tumor volume in 19 (26.7%) patients after the first treatment. However, the overall objective response in terms of changes in alpha-fetoprotein levels was 89% [partial response (PR) 67%, complete response (CR) 22%] among the 46 patients with raised pretreatment levels. The serum ferritin level in the other 25 patients dropped by 34 to 99% after treatment. Treatment was repeated in 15 patients. The maximum number of treatments was 5 and the maximum total activity was 13.0 GBq (351.4 mCi), given in 3 treatments. The estimated radiation doses to the nontumorous liver ranged from 25 to 136 Gy (median 52 Gy) in the first treatment and the highest total radiation dose was estimated to be 324 Gy. For the tumors, the estimated radiation doses ranged from 83 to 748 Gy (median 225 Gy) in the initial treatment and the highest cumulative dose reached was 1580 Gy. The residual tumors were resected in 4 patients. Two of these had complete histological remission, but only occasional viable tumor cells were found in the necrotic centers of the tumors resected from the other 2 patients. The median survival of the 71 patients was 9.4 months (range 1.8 to 46.4 months). Treatment was well tolerated and there was no bone-marrow toxicity, or clinical evidence of radiation hepatitis or pneumonitis. CONCLUSIONS Selective internal radiation therapy using 90Y microspheres is effective for selected cases of nonresectable HCC and is well tolerated. The objective response rate in terms of drop in tumor marker levels is higher than that based on reduction in tumor volume shown by computed tomography. The nontumorous liver appears more tolerant to internal radiation than external beam radiation. Selective internal radiation treatment may convert nonresectable tumors to resectable ones.

A prospective randomized trial comparing R1 subtotal gastrectomy with R3 total gastrectomy for antral cancer.

ObjectiveThe authors determined if more radical surgery with extended lymphadenectomy improves the results of gastrectomy in patients with adenocarcinoma of the gastric antrum. Summary Background DataThe overall survival in patients with gastric cancer is disappointing. Improved survival has been reported by Japanese authors. Whether this is because of a higher number of early gastric cancers in the Japanese series, different biologic behavior in Asians, or the adoption of radical surgery with lymphadenectomy remains unclear. MethodsR1 subtotal gastrectomy with omentectomy and R3 total gastrectomy (omentectomy, splenectomy, distal pancreatectomy, lymphatic clearance of the celiac axis, and skeletonization of vessels in the porta hepatis) were evaluated in a prospective, randomized comparison. ResultsFifty-five patients were randomized—25 to the R1 group and 30 to the R3 group. The two groups were comparable for age, sex, tumor size, TNM stage, and length of follow-up. The R3 group had a longer operating time (140 vs. 260 min; p < 0.05), a greater transfusion requirement (0 vs. 2 units, p < 0.05) and a longer hospital stay (8 vs. 16 days; p < 0.05) (medians; Mann-Whitney U test). The only postoperative death was in the R3 group and was caused by intra-abdominal sepsis. Fourteen patients in the R3 group developed left subphrenic abscesses. There were no major complications in the R1 group. Overall survival was significantly better in the R1 group (median survival estimated by Kaplan-Meier method, 1511 vs. 922 days, p < 0.05, log-rank test). ConclusionsR3 total gastrectomy can be performed with a low mortality, but it has a high morbidity because of intra-abdominal sepsis. The data do not support the routine use of R3 total gastrectomy for treatment of patients with antral cancer.

Antibacterial Treatment of Gastric Ulcers Associated with Helicobacter pylori

BACKGROUND There is a strong association between infection with Helicobacter pylori and gastric ulcers that are unrelated to the use of nonsteroidal antiinflammatory medications. We studied the efficacy of antibacterial therapy without medication to suppress gastric acid for the treatment of patients with H. pylori infection and gastric ulcers unrelated to the use of nonsteroidal agents. METHODS Patients with gastric ulcers seen on endoscopy and with H. pylori infection confirmed by smear or culture were randomly assigned to receive either a one-week course of antibacterial agents (120 mg of bismuth subcitrate, 500 mg of tetracycline, and 400 mg of metronidazole, each given orally four times a day) or a four-week course of omeprazole (20 mg orally per day). Follow-up endoscopies were performed after five and nine weeks. The patients and their physicians were aware of the treatment assignments, but the endoscopists were not. RESULTS A total of 100 patients were randomly assigned to treatment, and 85 completed the trial. At five weeks, H. pylori had been eradicated in 41 of the 45 patients in the antibacterial-treatment group (91.1 percent; 95 percent confidence interval, 82.9 to 99.3) and in 5 of the 40 in the omeprazole group (12.5 percent; 95 percent confidence interval, 2.3 to 22.7; P < 0.001). The gastric ulcers were healed in 38 of the patients treated with antibacterial drugs (84.4 percent; 95 percent confidence interval, 73.9 to 95.0) and in 29 of those treated with omeprazole (72.5 percent; 95 percent confidence interval, 58.6 to 86.4; P = 0.28). At nine weeks, ulcer healing was confirmed in 43 of the patients receiving antibacterial therapy and in 37 of those receiving omeprazole (P = 1.0). The mean (+/- SD) duration of pain during the first week of treatment was 1.9 +/- 2.6 days in the omeprazole group, as compared with 3.6 +/- 3.0 days in the antibacterial-treatment group (P = 0.004). One year after treatment, recurrent gastric ulcers were detected in 1 of 22 patients (4.5 percent) in the antibacterial-treatment group and in 12 of 23 (52.2 percent) in the omeprazole group (P = 0.001). H. pylori was detected in the 1 patient with a recurrent ulcer who had received antibacterial treatment and in 10 of the 12 patients with recurrent ulcers who had received omeprazole. CONCLUSIONS In patients with H. pylori infection and gastric ulcers unrelated to the use of nonsteroidal antiinflammatory drugs, one week of antibacterial therapy without acid suppression heals the ulcers as well as omeprazole and reduces the rate of their recurrence.

Duodenal ulcer healing by eradication of Helicobacter pylori without anti-acid treatment: randomised controlled trial

Randomised trials have shown that duodenal ulcers treated by H2 blockers heal faster if Helicobacter pylori is eradicated concurrently. It remains unknown whether eradication of H pylori without suppression of acid-secretion, is sufficient to allow healing. 153 patients with H pylori infection and duodenal ulcer were randomised to receive either a 1-week course of bismuth subcitrate, tetracycline, and metronidazole (76), or omeprazole for 4 weeks with the same three-drug regimen for the first week (77). Endoscopy and antral biopsies were done at entry and 4 weeks after treatment. 132 patients were suitable for analysis. Duodenal ulcers healed in 60 (92%; 95% CI 86-100%) patients taking bismuth, tetracycline, and metronidazole compared with 63 (95%; 88-100%) taking omeprazole in addition to the three other drugs. H pylori was eradicated in 61 (94%; 88-100%) who received only three drugs compared with 66 (98%; 96-100%) who received omeprazole as well. Symptoms were reduced more effectively during the first week in patients who received omeprazole (p = 0.003). We conclude that a 1-week regimen of bismuth, tetracycline, and metronidazole for patients with H pylori and duodenal ulcer eradicates the organism and heals the ulcer in most patients. Concurrent administration of omeprazole reduces ulcer pain more rapidly but has no effect on ulcer healing.

Radiation pneumonitis after selective internal radiation treatment with intraarterial 90Yttrium-microspheres for inoperable hepatic tumors

PURPOSE To investigate the clinical, histopathological, and radiological features of radiation pneumonitis arising as a complication of selective internal radiation treatment for liver tumors. To correlate the development of radiation pneumonitis with the degree of lung shunting as assessed by 99mTechnetium-labeled macroaggregated albumin (Tc-MAA) scan. METHODS AND MATERIALS Five out of 80 patients who had inoperable hepatic tumors and underwent treatment with intraarterial 90Yttrium- (90Y)-microspheres, developed progressive restrictive ventilatory dysfunction without an infective or cardiovascular cause. Histopathological evidence of a pneumonitis and the presence of microspheres in the lung tissue suggested a diagnosis of radiation pneumonitis. The clinical course, radiological and histopathological findings, percentage tumor shunting to the lungs (lung shunting, as predicted by gamma camera scanning after intraarterial Tc-MAA), and the estimated radiation dose to the lungs were analyzed. In an attempt to reduce pulmonary shunting of the microspheres, three patients received partial hepatic embolization with inert particles before selective internal radiation therapy. RESULTS In the five patients who developed radiation pneumonitis, lung shunting percentages (as predicted by Tc-MAA scan) ranged from 13.1 to 45.6% (median 23.7%). The estimated whole lung radiation dose ranged from 10.43 Gy to 36.44 Gy (median 25.04 Gy). Among 75 patients who did not develop radiation pneumonitis, the percentage lung shunting ranged from less than 1% to 15% (median 6%). Nine patients had lung shunting greater than 13% and five of them developed radiation pneumonitis, whereas this developed in none of those in whom shunting was below 13%. The onset of radiation pneumonitis ranged from 1 to 6 months after internal radiation treatment. All five patients exhibited characteristic plain radiographic and computerized tomographic changes comprising extensive consolidation with well-defined lateral margins. Clinical improvement after corticosteroid treatment was seen in two patients. Three patients died from respiratory failure and two from other causes. Partial hepatic arterial embolization reduced the degree of lung shunting to less than 13%, but did not prevent the development of radiation pneumonitis. CONCLUSION Radiation pneumonitis may become a complication after intraarterial 90Y-microspheres treatment when lung shunting, as assessed by Tc-MAA scan, is high (above 13%). Prescribed activity of 90Y and lung shunting of Tc-MAA should be considered together before giving selective internal radiation (SIR) therapy for hepatic tumors, and preferably avoided if the lung shunting is above 13%.

A randomized study comparing laparoscopic versus open repair of perforated peptic ulcer using suture or sutureless technique.

OBJECTIVE This study compares laparoscopic versus open repair and suture versus sutureless repair of perforated duodenal and juxtapyloric ulcers. BACKGROUND DATA The place of laparoscopic repair of perforated peptic ulcer followed by peritoneal toilet of the peritoneal cavity has been established. Whether repair of the perforated peptic ulcer by the laparoscopic approach is better than conventional open repair and whether sutured repair is better than sutureless repair are both undetermined. METHODS One hundred three patients were randomly allocated to laparoscopic suture repair, laparoscopic sutureless repair, open suture repair, and open sutureless repair. RESULTS Laparoscopic repair of perforated peptic ulcer (groups 1 and 2) took significantly longer than open repair (groups 3 and 4; 94.3 +/ 40.3 vs. 53.7 +/ 42.6 minutes: Students test, p < 0.001), but the amount of analgesic required after laparoscopic repair was significantly less than in open surgery (median 1 dose vs. 3 doses) (Mann-Whitney U test, p = 0.03). There was no significant difference in the four groups of patients in terms of duration of nasogastric aspiration, duration of intravenous drip, total hospital stay, time to resume normal diet, visual analogue scale score for pain in the first 24 hours after surgery, morbidity, reoperation, and mortality rates. CONCLUSIONS Laparoscopic repair of perforated peptic ulcer is a viable option. Sutureless repair is as safe as suture repair and it takes less time to perform.

A Randomized Trial of Nonoperative Treatment for Perforated Peptic Ulcer

To determine whether surgery could be avoided in some patients with perforated peptic ulcer, we conducted a prospective randomized trial comparing the outcome of nonoperative treatment with that of emergency surgery in patients with a clinical diagnosis of perforated peptic ulcer. Of the 83 patients entered in the study over a 13-month period, 40 were randomly assigned to conservative treatment, which consisted of resuscitation with intravenous fluids, institution of nasogastric suction, and intravenous administration of antibiotics (cefuroxime, ampicillin, and metronidazole) and ranitidine. Eleven of these patients (28 percent) had no clinical improvement after 12 hours and required an operation. Two of the 11 had a perforated gastric carcinoma, and 1 had a perforated sigmoid carcinoma. The other 43 patients were assigned to immediate laparotomy and repair of the perforation. One of these patients was found to have a perforated gastric carcinoma. The overall mortality rates in the two groups were similar (two deaths in each, 5 percent), and did not differ significantly in the morbidity (infection, cardiac failure, or renal failure) rates (40 percent in the surgical group and 50 percent in the nonsurgical group). The hospital stay was 35 percent longer in the group treated conservatively. Patients over 70 years old were less likely to respond to conservative treatment than younger patients (P less than 0.05). We conclude that in patients with perforated peptic ulcer, an initial period of nonoperative treatment with careful observation may be safely allowed except in patients over 70 years old, and that the use of such an observation period can obviate the need for emergency surgery in more than 70 percent of patients.

Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer

Radiation doses to the tumour and non-tumorous liver compartments from yttrium-90 microspheres in the treatment of hepatic cancer, as estimated by a partition model, have been verified by correlation with the actual doses measured with a beta probe at open surgery. The validity of the doses to the lungs, the tumour and non-tumorous liver compartment as estimated by the partition model was further evaluated in clinical settings. On the basis of the observation that one of three patients who received more than 30 Gy from a single treatment and one of two patients who received more than 50 Gy from multiple treatments developed radiation pneumonitis, it was deduced that an estimated lung dose <30 Gy from a single treatment and a cumulative lung dose <50 Gy from multiple treatments were probably the tolerance limits of the lungs. Three of five patients who received lung doses >30 Gy as estimated by the partition model and were predicted to develop radiation pneumonitis, did so despite the use of partial hepatic embolization to reduce the degree of lung shunting. Furthermore, a higher radiological response rate and prolonged survival were found in the group of patients who received higher tumour doses, as estimated by the partition model, than in the group with lower estimated tumour doses. Thus the radiation doses estimated by the partition model can be used to predict (a) complication rate, (b) response rate and (c) duration of survival in the same manner as the actual radiation doses measured with a beta probe at open surgery. The partition model has made selective internal radiation therapy using90Y microspheres safe and repeatable without laparotomy.

Treatment of inoperable hepatocellular carcinoma with intrahepatic arterial yttrium-90 microspheres: a phase I and II study.

Eighteen patients with inoperable hepatocellular carcinoma (HCC) were treated with intrahepatic arterial yttrium-90 microspheres. All these patients showed a lung shunting below 15% and a tumour-to-normal ratio higher than 2 as determined by diagnostic technetium-99m macroaggregated albumin (Tc-MAA) gamma scintigraphy. The treatment was given through an arterial port placed during laparotomy. The radiation doses to the liver and tumour were determined intraoperatively with a beta probe and liquid scintillation counting of multiple liver biopsies. The treatment was well tolerated without major complications. In all patients the tumour marker fell to a level which ranged from 41% to 0.2% of the pretreatment level. Tumour regression was found to be dose related. Progressive or static disease occurred in a higher proportion of patients whose tumours received < 120 Gy (P = 0.005). Survival was better in those whose tumours received > 120 Gy (median survival = 55.9 weeks) than those whose tumours received lower doses (median survival = 26.2 weeks). This difference is statistically significant with P = 0.005. We conclude that yttrium-90 microsphere therapy is safe and that tumour response is dose related. A tumour dose of > 120 Gy is recommended.

Randomised comparison between adrenaline injection alone and adrenaline injection plus heat probe treatment for actively bleeding ulcers

Abstract Objective: To compare endoscopic adrenaline injection alone and adrenaline injection plus heat probe for the treatment of actively bleeding peptic ulcers. Design: Randomised prospective study of patients admitted with actively bleeding peptic ulcers. Setting: One university hospital. Subjects: 276 patients with actively bleeding ulcers detected by endoscopy within 24 hours of admission: 136 patients were randomised to endoscopic adrenaline injection alone and 140 to adrenaline injection plus heat probe treatment. Main outcome measures: Initial endoscopic haemostasis; clinical rebleeding; requirement for operation; requirement for blood transfusion; hospital stay, ulcer healing at four weeks; and mortality in hospital. Results: Initial haemostasis was achieved in 131/134 patients (98%) who received adrenaline injection alone and 135/136 patients (99%) who received additional heat probe treatment (P = 0.33). Outcome as measured by clinical rebleeding (12 v 5), requirement for emergency operation (14 v 8), blood transfusion (2 v 3 units), hospital stay (4 v 4 days), ulcer healing at four weeks (79.1% v 74%), and in hospital mortality (7 v 8) were not significantly different in the two groups. In the subgroup of patients with spurting haemorrhage 8/27 (29.6%; 14.5% to 50.3%) patients from the adrenaline injection alone group and 2/31 (6.5%; 1.1% to 22.9%) patients from the dual treatment group required operative intervention. The relative risk of this was lower in the dual treatment group (0.17; 0.03 to 0.87). Hospital stay was significantly shorter in the dual treatment group than the adrenaline injection alone group (4 v 6 days, P = 0.01). Conclusion: The addition of heat probe treatment after endoscopic adrenaline injection confers an advantage in ulcers with spurting haemorrhage. Key messages Endoscopic injection of adrenaline alone is effective in stopping bleeding peptic ulcers Further bleeding after adrenaline injection alone, however, occurs in 15-20% of patients, and the addition of heat probe thermocoagulation may improve permanent haemostasis and therefore patient outcome When compared with adrenaline injection alone the dual treatment significantly reduced the requirement for operative intervention and the length of hospital stay in the subgroup of patients with spurting ulcer haemorrhage In the endoscopic treatment of spurting ulcer haemorrhage heat probe thermocoagulation should be added after adrenaline injection