Impact of STIMUlant and osmotic LAXatives (STIMULAX trial) on gastrointestinal recovery after colorectal surgery: randomized clinical trial.

BACKGROUND: Recovery of gastrointestinal (GI) function is often delayed after colorectal surgery. Enhanced recovery protocols (ERPs) recommend routine laxative use, but evidence of benefit is unclear. This study aimed to investigate whether the addition of multimodal laxatives to an ERP improves return of GI function in patients undergoing colorectal surgery. METHODS: This was a single-centre, parallel, open-label RCT. All adult patients undergoing elective colorectal resection or having stoma formation or reversal at the Royal Adelaide Hospital between August 2018 and May 2020 were recruited into the study. The STIMULAX group received oral Coloxyl® with senna and macrogol, with a sodium phosphate enema in addition for right-sided operations. The control group received standard ERP postoperative care. The primary outcome was GI-2, a validated composite measure defined as the interval from surgery until first passage of stool and tolerance of solid intake for 24 h in the absence of vomiting. Secondary outcomes were the incidence of prolonged postoperative ileus (POI), duration of hospital stay, and postoperative complications. The analysis was performed on an intention-to-treat basis. RESULTS: Of a total of 170 participants, 85 were randomized to each group. Median GI-2 was 1 day shorter in the STIMULAX compared with the control group (median 2 (i.q.r. 1.5-4) versus 3 (2-5.5) days; 95 per cent c.i. -1 to 0 days; P = 0.029). The incidence of prolonged POI was lower in the STIMULAX group (22 versus 38 per cent; relative risk reduction 42 per cent; P = 0.030). There was no difference in duration of hospital day or 30-day postoperative complications (including anastomotic leak) between the STIMULAX and control groups. CONCLUSION: Routine postoperative use of multimodal laxatives after elective colorectal surgery results in earlier recovery of gastrointestinal function and reduces the incidence of prolonged POI. Registration number: ACTRN12618001261202 (www.anzctr.org.au).

Palliative pamidronate treatment in patients with bone metastases from breast cancer.

PURPOSE: An open, randomized study was performed to assess the effects of supportive pamidronate treatment on morbidity from bone metastases in breast cancer patients. PATIENTS AND METHODS: Eighty-one pamidronate patients and 80 control patients were monitored for a median of 18 and 21 months, respectively, for events of skeletal morbidity and the radiologic course of metastatic bone disease. The oral pamidronate dose was 600 mg/d (high dose [HD]) during the earliest study years, then changed to 300 mg/d (low dose [LD]) because of gastrointestinal toxicity. Twenty-nine of 81 pamidronate (HD/LD) patients first received 600 mg/d and were then changed to 300 mg/d; 52 of 81 pamidronate LD patients received 300 mg/d throughout the study. Tumor treatment was unrestricted. RESULTS: An overall intent-to-treat analysis was performed. In the pamidronate group, the occurrence of hypercalcemia, severe bone pain, and symptomatic impending fractures decreased by 65%, 30%, and 50%, respectively; event-rates of systemic treatment and radiotherapy decreased by 35% (P < or = .02). The event-free period (EFP), radiologic course of disease, and survival did not improve. Subgroup analyses suggested a dose-dependent treatment effect. Compared with their controls, in pamidronate HD/LD patients, events occurred 60% to 90% less frequently (P < or = .03) and the EFP was prolonged (P = .002). In pamidronate LD patients, event-rates decreased by 15% to 45% (P < or = .04). Gastrointestinal toxicity of pamidronate caused a 23% drop-out rate, but other cancer-associated factors seemed to contribute to this toxicity. CONCLUSION: Pamidronate treatment of breast cancer patients efficaciously reduced skeletal morbidity. The effect appeared to be dose-dependent. Further research on dose and mode of treatment is mandatory.

Generalized peliosis hepatis and cirrhosis after long-term use of oral contraceptives.

Peliosis hepatis, a condition characterized by the presence of blood-filled lacunar spaces in the liver, has been described primarily in patients on androgenic steroid medication and patients with tuberculosis. It has never been reported as a complication of the use of oral contraceptives, except in association with and localized in contraceptive-induced hepatic tumors. The present report concerns a 43-yr-old woman with generalized peliosis hepatis that developed during long-term use of oral contraceptives. Extensive examination did not reveal a hepatic tumor. Liver cirrhosis and portal hypertension developed, although the oral contraceptives had been withdrawn. She finally underwent successfully an orthotopic liver transplantation.

PIP: A case report is presented of a 43-year-old woman with generalized peliosis hepatitis that developed during longterm use of oral contraceptives (OCs). The patient had been in good health until the last 2 years when she began to experience vague epigastric pains and a feeling of abdominal distension. Several months prior to admission, she had started to complain of itching and fatigue. There was no history of dark urine, white stools, or hepatitis. On physical examination, no jaundice or cutaneous stigmata of chronic liver disease were observed. Laboratory studies showed a normal erythrocyte sedimentation rate and hematological blood count. A radionuclide study of the liver showed hepatomegaly; especially the left lobe was enlarged. A computerized tomographic scan of the liver showed multiple areas of decreased density in both of the enlarged lobes. There was no evidence of a tumor. Selective transfemoral angiography of the celiac artery also showed hepatic enlargement but no signs of a space-occupying lesion. At laparoscopy, the liver was grossly enlarged and had a lumpy appearance, but again there were no signs of a tumor. No evidence of veno-occlusive disease or hepatocellular adenoma was found. The diagnosis was peliosis hepatitis. The OCs were withdrawn, and the patient was discharged. Regular follow-up in the outpatient department showed no decrease in the size of the liver. The alkaline phosphatase level rose. The fatigue became worse, and cholestyramine was prescribed for progressive itching. In September 1980, the patient was admitted for reevaluation. A repeated CT scan and angiography of the liver again yielded no evidence of a tumor. Esophagoscopy showed the presence of varices grade 2. The liver at laparoscopy had the same appearance as it had in 1976. Histological examination of a biopsy specimen showed occasional dilated sinusoids and locally marked periportal and intralobular fibrosis. No regeneration nodules were found. The diagnosis was liver fibrosis. The patient's condition deteriorated gradually in the following years. She experienced increasing fatigue. Steatorrhea developed, and the patient lost weight. She needed increasing doses of cholestyramine and oral supplementation of vitamins A, D, and K. She was admitted for a 3rd time in February 1985. Esophagoscopy revealed varices grade 4. A CT scan of the liver showed no change. The patient successfully underwent an orthotopic liver transplantation in January 1987. The diagnosis of peliosis hepatis was well documented in this patient.