Understanding the Benefit of Magnetic Resonance-guided Adaptive Radiotherapy in Rectal Cancer Patients: a Single-centre Study.

AIMS: Neoadjuvant chemoradiotherapy followed by surgery is the mainstay of treatment for patients with rectal cancer. Standard clinical target volume (CTV) to planning target volume (PTV) margins of 10 mm are used to accommodate inter- and intrafraction motion of target. Treating on magnetic resonance-integrated linear accelerators (MR-linacs) allows for online manual recontouring and adaptation (MRgART) enabling the reduction of PTV margins. The aim of this study was to investigate motion of the primary CTV (CTVA; gross tumour volume and macroscopic nodes with 10 mm expansion to cover microscopic disease) in order to develop a simultaneous integrated boost protocol for use on MR-linacs. MATERIALS AND METHODS: Patients suitable for neoadjuvant chemoradiotherapy were recruited for treatment on MR-linac using a two-phase technique; only the five phase 1 fractions on MR-linac were used for analysis. Intrafraction motion of CTVA was measured between pre-treatment and post-treatment MRI scans. In MRgART, isotropically expanded pre-treatment PTV margins from 1 to 10 mm were rigidly propagated to post-treatment MRI to determine overlap with 95% of CTVA. The PTV margin was considered acceptable if overlap was >95% in 90% of fractions. To understand the benefit of MRgART, the same methodology was repeated using a reference computed tomography planning scan for pre-treatment imaging. RESULTS: In total, nine patients were recruited between January 2018 and December 2020 with T3a-T4, N0-N2, M0 disease. Forty-five fractions were analysed in total. The median motion across all planes was 0 mm, demonstrating minimal intrafraction motion. A PTV margin of 3 and 5mm was found to be acceptable in 96 and 98% of fractions, respectively. When comparing to the computed tomography reference scan, the analysis found that PTV margins to 5 and 10 mm only acceptably covered 51 and 76% of fractions, respectively. CONCLUSION: PTV margins can be reduced to 3-5 mm in MRgART for rectal cancer treatment on MR-linac within an simultaneous integrated boost protocol.

Carbohydrate malabsorption and the effect of dietary restriction on symptoms of irritable bowel syndrome and functional bowel complaints.

BACKGROUND: Carbohydrate malabsorption of lactose, fructose and sorbitol has already been described in normal volunteers and in patients with functional bowel complaints including irritable bowel syndrome. Elimination of the offending sugar(s) should result in clinical improvement. OBJECTIVE: To examine the importance of carbohydrate malabsorption in outpatients previously diagnosed as having functional bowel disorders, and to estimate the degree of clinical improvement following dietary restriction of the malabsorbed sugar(s). METHODS: A cohort of 239 patients defined as functional bowel complaints was divided into a group of 94 patients who met the Rome criteria for irritable bowel syndrome and a second group of 145 patients who did not fulfill these criteria and were defined as functional complaints. Lactose (18 g), fructose (25 g) and a mixture of fructose (25 g) plus sorbitol (5 g) solutions were administered at weekly intervals. End-expiratory hydrogen and methane breath samples were collected at 30 minute intervals for 4 hours. Incomplete absorption was defined as an increment in breath hydrogen of at least 20 ppm, or its equivalent in methane of at least 5 ppm. All patients received a diet without the offending sugar(s) for one month. RESULTS: Only 7% of patients with IBS and 8% of patients with FC absorbed all three sugars normally. The frequency of isolated lactose malabsorption was 16% and 12% respectively. The association of lactose and fructose-sorbitol malabsorption occurred in 61% of both patient groups. The frequency of sugar malabsorption among patients in both groups was 78% for lactose malabsorption (IBS 82%, FC 75%), 44% for fructose malabsorption and 73% for fructose-sorbitol malabsorption (IBS 70%, FC 75%). A marked improvement occurred in 56% of IBS and 60% of FC patients following dietary restriction. The number of symptoms decreased significantly in both groups (P < 0.01) and correlated with the improvement index (IBS P < 0.05, FC P < 0.025). CONCLUSIONS: Combined sugar malabsorption patterns are common in functional bowel disorders and may contribute to symptomatology in most patients. Dietary restriction of the offending sugar(s) should be implemented before the institution of drug therapy.

Innovative communication in a biomedical engineering department.

Effective communication is one of the most important and often overlooked components of the functioning of a biomedical engineering department. The Biomedical Engineering Department (Biomed) at the VA Medical Center, Boston, Massachusetts uses innovative methods and resources to improve communication between Biomed and the Medical Center staff. While some changes have dealt directly with the information content communicated by Biomed, many improvements have also been made to the format in which information and ideas are presented. The latter changes serve the purpose of improving communication by ensuring that the presented information is both understood and retained. Improvements have been made in the areas of operator training, alerting users to actual and potential hazards and recalls, and staff education concerning Biomed's role in the Medical Center and the availability of Biomed to assist in technology issues.

Fish oil treatment of hyperlipidemia in children and adolescents receiving renal replacement therapy.

The effect of 8 weeks of daily oral fish oil supplementation in a dose of 3 to 8 g/d on serum lipid levels was studied in 16 patients, 7 to 8 years of age, who had end-stage renal disease and were receiving renal replacement therapy. Fasting serum cholesterol (CHOL), triglyceride (TG) levels, and lipoprotein profiles were measured before therapy, 8 weeks after fish oil supplementation, and 4 weeks after its cessation. During 8 weeks of treatment the mean serum CHOL level did not change. The mean serum TG level, however, decreased significantly (P less than .01) from 236 +/- 31 mg/dL to 171 +/- 21 mg/dL (27.5%). Four weeks after treatment was stopped, the mean serum TG level returned to a value not significantly different from the pretreatment level (208 +/- 30 mg/dL). In a subgroup of 11 excessively hyperlipidemic patients, with serum CHOL and TG levels greater than or equal to 50% of the 90th percentile for age and sex, the mean serum TG level decreased even more (30.8%), from 286 +/- 35 mg/dL to 198 +/- 24 mg/dL (P less than .01), and the mean CHOL/high-density lipoprotein CHOL ratio decreased from 8.4 +/- 1.2 to 7.4 +/- 1.3 (P less than .05). Blood pressure and platelet counts remained stable during the entire study period. Side effects of the treatment were minimal. These results show that dietary fish oil supplementation reduces serum TG levels in young patients receiving renal replacement therapy and improves their "atherogenic" serum lipoprotein profile.

Dietary-induced hyperlipidemia and renal function in the uremic rat.

Rats made uremic by 2-stage 5/6 nephrectomy and sham-operated control animals were fed either a normal laboratory chow, a high-sucrose (60%) or a high-fat (10% cholesterol; 20% olive oil) diet, all containing 21% protein and identical amounts of electrolytes, vitamins and trace elements. Serum creatinine levels remained unchanged in the control animals but rose in the 5/6 nephrectomised uremic animals by a factor of 2.7 from a mean of 0.44 +/- 0.05 mg/dl to 1.20 +/- 0.11 mg/dl at 8 weeks, without differences between the dietary groups. During 8 weeks of dietary regimen the high-sucrose and high-fat diets induced significant hypertriglyceridemia, generally similar in control and uremic rats. The uremic animals on a high-sucrose and high-fat diet had the most pronounced rise in serum triglycerides, 331.5 +/- 89.0 and 298.0 +/- 45.0 mg/dl, respectively (control: 159.9 +/- 14.0 mg/dl). After 4 and 8 weeks, only the animals on the high-fat diet had significant hypercholesterolemia, most pronounced in the uremic animals (356 +/- 56.3 mg/dl; control: 71.6 +/- 12.9 mg/dl). The animals in the latter group also had significant proteinuria and renal histologic abnormalities consisting of xanthoma-like glomerular lesions, infiltrates and fibrosis not seen in the other groups of animals. These data indicate that dietary-induced hyperlipidemia of short duration causes or aggravates renal damage in the rat with mild-moderate uremia, induced by ablation.

Isolated lipase and colipase deficiency in two brothers.

Two brothers of Arab origin, aged 15 and 10 years, with isolated congenital lipase and colipase deficiency are described. Both were normally developed with a history of passing greasy stools since early infancy. Both have remarkable steatorrhoea and low serum carotene and vitamin E concentrations. After exocrine pancreatic stimulation, lipase and colipase activities in the duodenal fluid were almost completely absent, while amylase trypsin, bile salt, and pH values were normal. No other aetiology for exocrine pancreatic insufficiency was found. This is the first report of congenital combined lipase and colipase deficiency in two brothers.

Ornithine decarboxylase: an unreliable marker for the identification of population groups at risk for colonic neoplasia.

Ornithine decarboxylase (ODC) is the first and rate-limiting enzyme in the polyamine biosynthetic pathway. Polyamines have been studied as potential markers of neoplastic diseases, including colonic cancer. Previous studies have pointed out the possible value of this enzyme as a biochemical marker of colonic neoplasia, we studied 100 patients undergoing diagnostic total colonoscopy. There were 40 normal controls and 20 patients in each of the following groups: 1) family members of patients diagnosed as having colonic tumors, 2) patients with adenomas, and 3) patients with colonic adenocarcinoma. Six forceps biopsies were obtained from the normal-appearing sigmoid mucosa for the analysis of ODC. No difference was found among the four groups studied. We therefore conclude that ODC is unreliable for clinical use as a biochemical marker for the identification of population groups at risk for colonic neoplasia.

Absorption of medium chain triglycerides in the stomach of the human infant.

Following previous observations that medium chain triglycerides (MCT) are absorbed from the stomach of suckling rats, this study was devoted to studying absorption of MCTs in human infants. Four groups of patients were studied: (a) infants suffering from pyloric stenosis, (b) premature infants, (c) children suffering from cystic fibrosis, (d) infants with miscellaneous conditions. Infant formulae with known amounts of MCT were introduced by gastric tube and samples were removed at 0, 20, 40, and 60 min. In patients with pyloric stenosis there was an 18.1% decrease in MCT during the first 20 min. No significant changes in MCT took place during the subsequent 40 min. A similar response was observed in the group of premature infants. Older infants with miscellaneous diagnoses and children with cystic fibrosis showed an even rate of disappearance of MCT during the 60-min test period, and approximately 30% of the original MCTs present disappeared during this period. We conclude that MCTs are absorbed in the stomach of infants and children. Absorption appears to improve with age. Because MCT are an important constituent of formulae for premature infants and children with defects of small intestinal digestion and absorption of fat, these observations have practical implications.

Plasma vitamin E levels in uremic children and adolescents.

We studied plasma vitamin E levels in children/adolescents 3-19 years of age (10.9 +/- 4.5; mean +/- 1 SD) with chronic renal failure treated conservatively, on hemodialysis, on continuous ambulatory peritoneal dialysis and after renal transplantation. In all 4 groups of patients vitamin E levels (0.66-0.90 mg/dl) were within the normal range (0.76 +/- 0.19 mg/dl). The lowest levels of vitamin E (0.59 +/- 0.1 mg/dl) were found in nonuremic patients with a good functioning renal transplant. These data do not support the notion that uremia is accompanied by vitamin E malabsorption.

Intestinal fat malabsorption in the uremic rat.

In the past we have shown that patients with chronic renal failure (CRF) on hemodialysis show evidence of intestinal malabsorption of fat. The present study was designed to verify this finding in an animal model. Male rats weighing +/- 200 g were studied. Uremia (U) was induced by 2-stage subtotal (5/6) nephrectomy. Control (C) animals were sham-operated. Fat absorption was studied after 6 weeks of uremia with the oral fat loading test. Twenty percent intralipid (0.25 g/100 gBW) was given by gastric tube feeding to fasting animals and the appearance of chylomicrons (CHYL) and the rise of triglycerides (TG) in the serum was followed for 5 hrs. In order to isolate the effect of fat absorption, an additional group of U and C animals was pretreated with orotic acid and triton, thus blocking hepatic TG synthesis and neutralizing peripheral lipoprotein lipase activity. The absorption of CHYL was significantly (p less than 0.01) impaired in all U animals and averaged 43 and 70 percent of that of the C animals, 1 and 2 hrs after the load respectively. The rise in serum TG did not differ from C in mildly U animals (Scr 1.0 +/- 0.04). In the more severely uremic animals (Scr 2.6 +/- 0.2), however, pretreated with orotic acid and triton, the rise in serum TG was far less (p less than 0.01) than in C animals (111 +/- 26-903 +/- 111 delta % V.780 +/- 170-5032 +/- 746 delta %) 1 and 5 hrs after the load.(ABSTRACT TRUNCATED AT 250 WORDS)

Natriuretic response to i.v. saline loading after acute poststreptococcal glomerulonephritis.

The outcome of acute poststreptococcal glomerulonephritis (APSGN) is still controversial. Whereas many studies show a good prognosis, particularly in children, late morphologic and functional renal abnormalities have been described. To verify this latter finding, we evaluated the sodium handling of the kidney several years after APSGN. Eleven subjects (9 children and adolescents and 2 adults) were studied 2 to 3 years after APSGN. At the time of the study all patients were well, without pathologic urinary findings and with normal blood pressures. Five healthy subjects (3 adults and 2 children) served as controls. Following two control periods of 30 min, an i.v. saline load (2.5% NaCl, 1 l/1.73 m2 body surface area) was administered over 45 min. Sodium excretion was measured during the control and salt-loading periods, and during four additional 30-min collection periods. No exaggerated natriuresis was found. We therefore conclude that epidemic APSGN in Israel carries not only an excellent clinical but also a good renal functional prognosis.

The fatty meal test: an alternative to stool fat analysis.

In view of the technical difficulties inherent in using stool fat estimations as a parameter of malabsorption, we used a fatty meal absorption test. Children under investigation for failure to thrive were divided into two groups, those having a normal stool fat output (less than 3.2 g/day) constituting the control group, and those having steatorrhea. After a fatty meal containing 25 g of margarine and 25 g of butter fat, we measured the rise of serum triglycerides and chylomicrons hourly for 5 h. Serum triglyceride rise of less than 100 mg/dl or less than 100% above basal values and the appearance of less than 7% of chylomicrons were considered pathological. Of our control group 95% had a normal rise of triglycerides; and 96% of our patients with steatorrhea had an abnormal rise. This test was more reliable than the two-point triglyceride test previously described for the diagnosis of fat malabsorption. The fatty meal test as described here is considered to be a useful test of absorptive function.

Impaired intestinal fat absorption in chronic renal failure.

We performed oral fat loading tests in 10 patients with chronic renal failure (CRF) on hemodialysis (5 children and 5 adults). Fat absorption was measured by hourly determination of serum triglycerides (TG), cholesterol (CHOL), and lipoproteins (LP) after oral administration of a 'milkshake' containing 50 g of fat of dairy origin. 10 age-matched healthy volunteers with normal fasting serum TG levels and 10 subjects with fasting hypertriglyceridemia served as controls. Mean fasting serum TG levels in CRF patients were elevated compared to normal controls (177.6 +/- 14.6 mg/dl, 2.0 +/- 17 mmol/l vs. 91.0 +/- 10.5 mg/dl, 1.03 +/- 12 mmol/l). 6 patients (4 adults, 2 children) had type IV LP patterns and 2 patients (both children) showed type IIb hyperlipidemia. In only 2 patients, 1 child and 1 adult were TG, CHOL and LP electrophoresis all normal. The oral fat loading test in all CRF patients showed delayed appearance of TG and chylomicrons (CHYL) in the bloodstream i.c. impaired or slow absorption of fat from the gut. In contrast to normal and hypertriglyceridemic controls, TG and CHYL levels in CRF did not decrease by 5 h after the oral fat load. This study demonstrates impaired intestinal fat absorption in children and adults with CRF.

Intestinal absorption of 47Ca in elderly patients with osteoporosis, Paget's disease and osteomalacia. Effects of calcitonin, oestrogen and vitamin D2.

The intestinal absorption of 47Ca was studied in elderly patients. A standard dose of 10 muCi of 47Ca was given orally. The radioactivity was measured in the plasma, and expressed as percentage of the administered dose per litre plasma. As a control group served 12 patients aged 60-80 years, hospitalized for observation for various reasons, receiving no medical treatment and not suffering from any known metabolic bone diseases or other metabolic pathological conditions. Results of kinetic curves demonstrate in elderly patients a decreased absorption with maximum specific activity in plasma reached at 120 min, when compared to data from the literature referring to a group of young people with a mean age of 35 years. Oestrogen treatment, given as ethinyl oestradiol 10 mug once daily per os for 10 days proved to increase 47Ca absorption as was demonstrated in 2 patients with osteoporosis. The effect of calcitonin (160 MRC units given 45 min before the test) on calcium absorption, in 5 patients with Paget's disease or osteoporosis appears as biphasic: in the first hour depressing calcium absorption and then in the second and third hours increasing the absorption, suggesting a hyperparathyroid state secondary to the calcitonin effect. The vitamin D2 treatment proved to increase calcium absorption.