The prognostic importance of MRI detected extramural vascular invasion (mrEMVI) in locally advanced rectal cancer.

BACKGROUND: MRI detected extramural vascular invasion (mrEMVI) is a poor prognostic factor in rectal cancer patients. The objectives of this study were to assess survival outcomes in patients with and without mrEMVI and to compare the prognostic value of mrEMVI with other rectal cancer features. METHODS: In a Dutch high volume rectal cancer center cohort of sixty-seven locally advanced rectal cancer patients, an independent radiologist reviewed all primary staging MRI scans. The presence of mrEMVI was correlated to tumor specific and survival outcomes. RESULTS: 20/67 patients had mrEMVI positive rectal cancer. 55% (11/20) developed metachronous metastases, compared with 23% (11/47) in the mrEMVI negative group (OR 4.0, p = 0.01). Overall survival was also decreased with a Hazard ratio of 3.3 (p = 0.01). A multivariable logistic regression with a backward selection procedure was conducted including cT-stage, c-N-stage, extramural tumor invasion depth, mesorectal fascia involvement, distance to anorectal junction, tumor length, mrEMVI, CEA level, and synchronous metastases. After stepwise removal based on p value, only positive mrEMVI remained as a single significant predictor for metachronous metastases (OR: 4.16 , p < 0.05). CONCLUSION: Positive mrEMVI is a poor prognostic factor in locally advanced rectal cancer with a 4-fold increased risk of developing metachronous metastases after surgery and a worsened overall survival. mrEMVI also appeared an independent risk factor, with a stronger prediction for metachronous metastases than other MRI-detectable tumor characteristics. mrEMVI should be incorporated in all risk stratification guidelines for rectal cancer.

Alpha-1-antitrypsin deficiency (carrier) as possible risk factor for development of colonic diverticula. A multicentre prospective case-control study: the ALADDIN study.

AIM: Connective tissue changes due to ageing or diseases leading to changes in the colonic wall are one theory for the development of diverticula. Alpha-1-antitrypsin (A1AT), a protease inhibitor that protects connective tissue, possibly plays a role in the aetiology of diverticulosis. The aim of this study was to explore associations between the development of diverticula and A1AT deficiency. METHODS: This was a multicentre prospective case-control study. A total of 221 patients aged ≥ 60 years with acute abdominal pain undergoing abdominal CT were included and analysed. Patients with diverticula were defined as the research group, patients without diverticula as controls. Genotype analysis for A1AT deficiency was performed. RESULTS: Twenty-six of 221 (11.8%) patients were diagnosed with (being a carrier of) A1AT deficiency. A non-significant difference in prevalence between patients with and without diverticula was found, 20 (13.9%) of 144 vs 6 (7.8%) of 77, respectively, with a crude OR of 1.9 (95% CI 0.7-5.0; P = 0.186) and after adjustment for confounders an adjusted OR of 1.5 (95% CI 0.5-4.0; P = 0.466). A non-significant difference in 30-day mortality rate from acute diverticulitis between A1AT deficient patients (or carriers) and those without was observed: two (22.2%) of nine patients with A1AT deficiency vs 1 (1.8%) of 55 without. CONCLUSION: We found no convincing evidence that A1AT deficiency plays a role in the aetiology of diverticulitis, although deficient patients and carriers had a higher mortality when experiencing diverticulitis. Diverticulitis is a multifactorial disease and larger numbers may be needed to explore the role of A1AT deficiency among other contributing factors.

Meta-analysis of the role of colonoscopy after an episode of left-sided acute diverticulitis.

BACKGROUND: Routine colonoscopy was traditionally recommended after acute diverticulitis to exclude coexistent malignancy. Improved CT imaging may make routine colonoscopy less required over time but most guidelines still recommend it. The aim of this review was to assess the role of colonoscopy in patients with CT-proven acute diverticulitis. METHODS: PubMed and Embase were searched for studies reporting the prevalence of advanced colorectal neoplasia (ACN) or colorectal carcinoma in patients who underwent colonoscopy within 1 year after CT-proven left-sided acute diverticulitis. The prevalence was pooled using a random-effects model and, if possible, compared with that among asymptomatic controls. RESULTS: Seventeen studies with 3296 patients were included. The pooled prevalence of ACN was 6·9 (95 per cent c.i. 5·0 to 9·4) per cent and that of colorectal carcinoma was 2·1 (1·5 to 3·1) per cent. Only two studies reported a comparison with asymptomatic controls, showing comparable risks (risk ratio 1·80, 95 per cent c.i. 0·66 to 4·96). In subgroup analysis of patients with uncomplicated acute diverticulitis, the prevalence of colorectal carcinoma was only 0·5 (0·2 to 1·2) per cent. CONCLUSION: Routine colonoscopy may be omitted in patients with uncomplicated diverticulitis if CT imaging is otherwise clear. Patients with complicated disease or ongoing symptoms should undergo colonoscopy.

Prevalence of alpha-1-antitrypsin deficiency carriers in a population with and without colonic diverticula. A multicentre prospective case-control study: the ALADDIN study.

PURPOSE: The underling pathophysiological mechanisms that cause the formation of colonic diverticula (diverticulosis) remain unclear. Connective tissue changes due to ageing that cause changes in collagen structure of the colonic wall is one theory. Alpha-1-antitrypsin (A1AT) is a protease inhibitor known to protect connective tissue in other organs. Associations between (carriers of) A1AT deficiency and the development of colonic diverticula will be the main focus of this study. METHODS: A multicentre prospective case-controlled study. In total, 230 patients ≥ 60 years with acute abdominal pain undergoing an abdominal computed tomography (CT) will be included. The research group consists of patients with diverticulosis and/or diverticulitis; controls are patients without diverticula (0 to ≤ 5 diverticula). Genotype analysis for A1AT deficiency will be performed. RATIONALE: Hypothetically, connective tissue changes, in particular related to (carriers of) A1AT deficiency, can contribute to the development of diverticula and diverticulitis. We expect to find a higher prevalence of A1AT carriers in patients with diverticulosis compared to patients without diverticulosis. Having diverticulosis does not affect the general health of these individuals per se, when asymptomatic. Once an association is found, present findings can be the basis for a second study to assess the risk of developing acute diverticulitis and its disease course in carriers of A1AT deficiency. Because a large cohort is needed in the latter, we shall first perform a pilot study to investigate the likelihood of the primary hypothesis. TRIAL REGISTRATION: Netherlands Trial register, NTR6251, NL55016.094.15.

Is ultrasound-guided fine-needle aspiration cytology of adequate value in detecting breast cancer patients with three or more positive axillary lymph nodes?

This study evaluated the accuracy of ultrasound-guided fine-needle aspiration cytology of the sonographically most suspicious axillary lymph node (US/FNAC) to select early breast cancer patients with three or more tumour-positive axillary lymph nodes. Between 2004 and 2014, a total of 2130 patients with histologically proven early breast cancer were evaluated and treated in the Noordwest Clinics Alkmaar. US/FNAC was performed preoperatively in all these patients. We analysed the results of US/FNAC retrospectively. Pathological axillary node status (sentinel node biopsy and/or axillary lymph node dissection) was used as reference standard. A total of 634 (29.8 %) of 2130 patients had axillary lymph node metastases on final histology. 248 node positive patients (11.6 %) had three or more positive lymph nodes. The accuracy of US/FNAC to detect three or more positive lymph nodes was 89.8 %, sensitivity was 44.8 %, specificity was 95.7 %, PPV was 58.1 %, and NPV was 92.9 %. This study shows a more than adequate accuracy of preoperative US/FNAC to detect three or more positive lymph nodes (89.8 %). However, when US/FNAC was chosen as the only axillary staging method, 6.4 % of all patients (false negative group) would have been undertreated and 3.8 % of all patients (false positive group) would have been overtreated according to the ACOSOG Z0011 criteria.

The limited role of ultrasound in the diagnostic process of colonic diverticulitis.

BACKGROUND: Diverticulitis is commonly diagnosed using ultrasound (US), followed by computed tomography (CT). Our aim was to determine the diagnostic accuracy of US compared with CT for patients with uncomplicated and complicated diverticulitis. METHODS: We reviewed medical records of 232 patients admitted with diverticulitis via the emergency department between January 2009 and January 2011. Patients who had undergone US and a CT scan were identified and further analyzed. RESULTS: A total of 123 patients underwent an US and a CT scan. In 78/94 patients with uncomplicated diverticulitis, results of US and CT scan were compatible (83 %); in 6 of the remaining 29 patients both modalities showed a complicated diverticulitis (21 %). US misdiagnosed 17 % of patients with uncomplicated diverticulitis and 79 % with complicated diverticulitis. CONCLUSIONS: US is insufficient for diagnosing a complicated diverticulitis. Missing a complicated diverticulitis can have important clinical implications, and if diverticulitis is suspected, we suggest obtaining a CT scan to confirm diagnosis and to exclude complications.

Evolution of clinical nature, treatment and survival of locally recurrent rectal cancer: Comparative analysis of two national cross-sectional cohorts.

BACKGROUND: In the Netherlands, use of neoadjuvant radiotherapy for rectal cancer declined after guideline revision in 2014. This decline is thought to affect the clinical nature and treatability of locally recurrent rectal cancer (LRRC). Therefore, this study compared two national cross-sectional cohorts before and after the guideline revision with the aim to determine the changes in treatment and survival of LRRC patients over time. METHODS: Patients who underwent resection of primary rectal cancer in 2011 (n = 2094) and 2016 (n = 2855) from two nationwide cohorts with a 4-year follow up were included. Main outcomes included time to LRRC, synchronous metastases at time of LRRC diagnosis, intention of treatment and 2-year overall survival after LRRC. RESULTS: Use of neoadjuvant (chemo)radiotherapy for the primary tumour decreased from 88.5% to 60.0% from 2011 to 2016. The 3-year LRRC rate was not significantly different with 5.1% in 2011 (n = 114, median time to LRRC 16 months) and 6.3% in 2016 (n = 202, median time to LRRC 16 months). Synchronous metastasis rate did not significantly differ (27.2% vs 33.7%, p = 0.257). Treatment intent of the LRRC shifted towards more curative treatment (30.4% vs. 47.0%, p = 0.009). In the curatively treated group, two-year overall survival after LRRC diagnoses increased from 47.5% to 78.7% (p = 0.013). CONCLUSION: Primary rectal cancer patients in 2016 were treated less often with neoadjuvant (chemo)radiotherapy, while LRRC rates remained similar. Those who developed LRRC were more often candidate for curative intent treatment compared to the 2011 cohort, and survival after curative intent treatment also improved substantially.

Adherence to Enhanced Recovery After Surgery and length of stay after colonic resection.

AIM: The Enhanced Recovery After Surgery (ERAS) programme is a multimodal approach to improve peri-operative care in colon surgery. The aim of this study was to report on the adherence to and outcomes of ERAS in the first years after implementation. METHOD: Data of patients undergoing elective colon resections for malignancy in 2006 until 2010 were compared with patients receiving conventional care in 2005. Retrospective analysis was performed including length of stay (LOS), protocol adherence and complications. The predictive values of ERAS items and baseline characteristics on LOS and complications were analysed using univariate and multivariate analysis. RESULTS: Length of stay (LOS) was significantly shorter in 2006 and 2007 (P ≤ 0.009 and P ≤ 0.004) but not in 2008 and 2009. The mean adherence rate to the ERAS items was 84.1% in 2006 and 2007 and 72.4% in 2008 and 2009 (P < 0.001). In 2005, 2008 and 2009 LOS was significantly shorter for laparoscopically operated patients than for patients with open resections (P < 0.002, P < 0.001 and P < 0.004 respectively). Multivariate analysis showed that age, laparoscopic surgery, removal of nasogastric tube before extubation, mobilization within 24 h after surgery, starting nonsteroidal anti-inflammatory drugs at day 1 and removal of thoracic epidural analgesia at day 2 were independent predictors of LOS. CONCLUSION: Strict adherence to the ERAS protocol was associated with reduced LOS and improved outcome in elective colon surgery for malignancy. These benefits were lost when protocol adherence was lower. Embedding the ERAS protocol into an organization and repetitive education are vital to sustain its beneficial effects on LOS and outcome.

Fit4Surgery for cancer patients during covid-19 lockdown - A systematic review and meta-analysis.

BACKGROUND: Prehabilitation is a promising method to enhance postoperative recovery, especially in patients suffering from cancer. Particularly during times of social distancing, providing home-based programmes may have become a suitable solution to increase compliance and effectiveness. METHODS: In line with the PRISMA guidelines, a systematic review was conducted including trials that investigated the effect of home-based prehabilitation (HBP) in patients undergoing surgery for cancer. The primary outcome was postoperative functional capacity (6 min walk test, 6MWT). Secondary outcomes were postoperative complications and compliance. RESULTS: Five randomized controlled trials were included with 351 patients undergoing surgery for colorectal cancer, oesophagogastric cancer, bladder cancer and non-small cell lung cancer. Three studies presented results of significant progress after eight weeks. The meta-analysis showed a significant improvement of the 6MWT in the prehabilitation group compared to the control group preoperatively (MD 35.06; 95% CI 11.58 to 58.54; p = .003) and eight weeks postoperatively (MD 44.91; 95% CI 6.04 to 83.79; p = .02) compared to baseline. Compliance rate varied from 63% to 83% with no significant difference between prehabilitation and control groups. These data must be interpreted with caution because of a high amount of heterogeneity and small sample sizes. DISCUSSION: In conclusion, HBP may enhance overall functional capacity of patients receiving oncological surgery compared to standard of care. This could be a promising alternative to hospital-based prehabilitation regarding the current pandemic and further digitalization in the future. In order to increase accessibility and effectiveness of prehabilitation, home-based solutions should be further investigated.

Patient-reported outcomes after incisional hernia repair.

PURPOSE: Patient-reported outcomes (PROs) are pivotal to evaluate the efficacy of surgical management. Debate persists on the optimal surgical technique to repair incisional hernias. Assessment of PROs can guide the selection of the best management of patients with incisional hernias. The objective of this cohort study was to present the PROs after incisional hernia repair at long term follow-up. METHODS: Patients with a history of incisional hernia repair were seen at the out-patient clinic to collect PROs. Patients were asked about the preoperative indication for repair and postoperative symptoms, such as pain, feelings of discomfort, and bulging of the abdominal wall. Additionally, degree of satisfaction was asked and Carolina Comfort Scales were completed. RESULTS: Two hundred and ten patients after incisional hernia repair were included with a median follow-up of 3.2 years. The main indication for incisional hernia repair was the presence of a bulge (60%). Other main reasons for repair were pain (19%) or discomfort (5%). One hundred and thirty-two patients (63%) reported that the overall status of their abdominal wall had improved after the operation. Postoperative symptoms were reported by 133 patients (63%), such as feelings of discomfort, pain and bulging. Twenty percent of patients reported that the overall status of their abdominal wall was the same, and 17% reported a worse status, compared to before the operation. Ten percent of the patients would not opt for operation in hindsight. CONCLUSION: This study showed that a majority of the patients after incisional hernia repair still report pain or symptoms such as feelings of discomfort, pain, and bulging of the abdominal wall 3 years after surgery. Embedding patients' expectations and PROs in the preoperative counseling discussion is needed to improve decision-making in incisional hernia surgery.

Breast cancer in the elderly: retrospective study on diagnosis and treatment according to national guidelines.

We set out to investigate the level of accordance of diagnosis and treatment of elderly breast cancer patients with national guidelines and to study predictors of deviation. Data on patient and tumor variables were collected from charts of 166 patients aged 70 years and older, diagnosed at our hospital in 2002-2004. Diagnostic work-up and treatment were compared with guidelines and reasons for deviation were recorded; 122 (74%) patients were diagnosed and treated in accordance with guidelines. Diagnosis was incomplete in 19 patients (11%). Surgery, radiotherapy, and hormonal therapy were withheld in 19 (11%), 11 (7%), and 9 (5%) patients, respectively. Guideline deviation was motivated in 18 patients (11%) (comorbidity n=11, patients' preferences n=5, age n=2), unmotivated in 18 (11%), and undeliberate in 8 (5%). Our study demonstrates that deviation from guidelines in elderly breast cancer patients mainly occurs due to a deliberate adjustment to patient's comorbidity and preference.

[A woman with a red, painful breast]. / Een vrouw met een rode, pijnlijke borst.

A 79-year-old woman presented with swelling and pain in her right breast after re-excision of a melanoma and an axillary sentinel lymph node biopsy. The cellulitis was caused by Clostridium perfringens, a rare cause of a postoperative infection.

Impact of health care organization on surgical lung cancer care.

OBJECTIVES: Organization and governance of national healthcare might play an important role in decision-making and outcomes in patients with lung cancer. Both Denmark and the Netherlands have a high level of healthcare but a different financial coverage, governance and level of centralization. By using both national databases we analyzed the consequences of these differences on patterns of care and outcomes with a focus on morbidity, mortality and clinical staging. MATERIALS AND METHODS: General numbers on both healthcare systems were requested. All patients who had surgery for lung cancer from 2013 to 2016 were included. Mortality, morbidity and clinical staging were analyzed for patients with NSCLC without metastases, only one operation and no neo-adjuvant therapy. RESULTS: In 2016 annual budget as share of gross national product was 10.4% for both countries. In Denmark 4 hospitals performed lung surgery in 2016, compared to 43 hospitals in the Netherlands. We included 4030 Danish and 8286 Dutch patients. In the subgroup 30-day mortality was 1.5% in Denmark compared to 1.9% in the Netherlands. The percentage of patients with a complicated course was 24.4% and 34.8% respectively (p < 0.05). Accuracy between cTNM and pTNM was 53.0% in Denmark and 52.9% in the Netherlands. CONCLUSION: Surgery for lung cancer is at a high level in both countries, reflected by low mortality-rates. Centralization has been implemented successfully in Denmark, which might explain the lower rate of patients with a complicated post-operative course, although different definitions preclude firm conclusions. In both countries correct clinical staging of lung cancer remains a challenge.

Effects of a Carbohydrate-, Glutamine-, and Antioxidant-Enriched Oral Nutrition Supplement on Major Surgery-Induced Insulin Resistance: A Randomized Pilot Study.

BACKGROUND: Insulin resistance after surgery hampers recovery. Oxidative stress is shown to be involved in the occurrence of postoperative insulin resistance. Preoperative carbohydrate-rich oral nutrition supplements reduce but do not prevent insulin resistance. The aim of the present study was to investigate the effect of a carbohydrate-, glutamine-, and antioxidant-enriched preoperative oral nutrition supplement on postoperative insulin resistance. METHODS: A double-blind randomized controlled pilot study in 18 patients with rectal cancer, who received either the supplement (S) or the placebo (P) 15, 11, and 4 hours preoperatively, was conducted. Insulin sensitivity was studied prior to surgery and on the first postoperative day using a hyperinsulinemic euglycemic 2-step clamp. RESULTS: Hepatic insulin sensitivity (insulin-mediated suppression of glucose production) decreased significantly after surgery in both groups, with no differences between the groups. Peripheral insulin sensitivity (glucose rate of disappearance, Rd) was significantly decreased after surgery in both groups (S: 37.2 [19.1-50.9] vs 20.6 [13.9-27.9]; P: 23.8 [15.7-35.5] vs 15.3 [12.6-19.1] µmol/kg·min) but less pronounced in the supplemented group (P = .04). The percentage decrease in glucose Rd did not differ between the groups. Adipose tissue insulin sensitivity (insulin-mediated suppression of plasma free fatty acids) decreased to the same extent after surgery in both groups. CONCLUSION: Rectal cancer surgery induced profound insulin resistance, affecting glucose and fatty acid metabolism. The preoperative nutrition supplement somewhat attenuated but did not prevent postoperative peripheral insulin resistance.

Evaluation of preoperative geriatric assessment of elderly patients with colorectal carcinoma. A retrospective study.

AIMS: Elderly patients with colorectal carcinoma are screened with the Identification of Seniors at Risk (ISAR) questionnaire to identify frail patients. These patients are more at risk for mortality and morbidity and are referred to the geriatric specialist for assessment (Dutch acronym: DOG). The DOG assessment aims to preoperatively optimize the patient in order to improve postoperative outcomes. This study evaluates if the DOG assessment influences postoperative outcome after colorectal surgery. METHODS: Retrospective cohort and match-control study. Elderly patients who underwent elective resection between 01-01-2008 and 01-08-2013 in the Medical Centre Alkmaar were included. Patients with a positive ISAR score were referred to the geriatric specialists for DOG assessment (DOG patients). DOG assessment encompassed comprehensive geriatric assessment and interventions. PRIMARY OUTCOMES: Mortality, delirium and length of hospital stay. SECONDARY OUTCOMES: postoperative complications. COHORT COMPARISON: Cohort ISAR- (2008-2010, no ISAR questionnaire) is compared with cohort ISAR+ (2011-2013, ISAR questionnaire). Match-control comparison: DOG patients are compared with matched controls from cohort ISAR-. RESULTS: Compared to their matched controls, DOG patients were older and had a higher prevalence of certain risk factors for postoperative delirium. In both comparisons, no statistical significant differences were found between the groups in mortality and postoperative delirium. Length of stay was significantly shorter in cohort ISAR+. CONCLUSIONS: While the DOG patients were significantly more at risk for postoperative complications, the DOG patients had comparable postoperative outcomes as their matched controls. We therefore conclude that the DOG assessment has a positive influence on the postoperative outcomes after colorectal surgery.

The PRECious trial PREdiction of Complications, a step-up approach, CRP first followed by CT-scan imaging to ensure quality control after major abdominal surgery: study protocol for a stepped-wedge trial.

BACKGROUND: After major abdominal surgery (MAS), 20% of patients endure major complications, which require invasive treatment and are associated with increased morbidity and mortality. A quality control algorithm after major abdominal surgery aimed at early identification of patients at risk of developing major complications can decrease associated morbidity and mortality. Literature studies show promising results for C-reactive protein (CRP) as an early marker for postoperative complications, however clinical significance has yet to be determined. METHODS: A multicenter, stepped wedge, prospective clinical trial including all adult patients planned to undergo elective MAS. The first period consists of standard postoperative monitoring, which entails on demand additional examinations. This is followed by a period with implementation of postoperative control according to the PRECious protocol, which implicates standardized measurement of CRP levels. If CRP levels exceed 140 mg/L on postoperative day 3,4 or 5, an enhanced CT-scan is performed. Primary outcome in this study is a combined primary outcome, entailing all morbidity and mortality due to postoperative complications. Complications are graded according to the Clavien-Dindo classification. Secondary outcomes are hospital length of stay, patients reported outcome measures (PROMs) and cost-effectiveness. Data will be collected during admission, three months and one year postoperatively. Approval by the medical ethics committee of the VU University Medical Center was obtained (ID 2015.114). DISCUSSION: the PRECious trial is a stepped-wedge, multicenter, open label, prospective clinical trial to determine the effect of a standardized postoperative quality control algorithm on postoperative morbidity and mortality, and cost-effectiveness. TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT02102217. Registered 5 February 2015.

Intestinal beta-carotene absorption and cleavage in men: response of beta-carotene and retinyl esters in the triglyceride-rich lipoprotein fraction after a single oral dose of beta-carotene.

Postprandial response curves of beta-carotene and retinyl esters in a triglyceride-rich lipoprotein (TRL) fraction were evaluated as a potential measure of beta-carotene uptake and cleavage. beta-Carotene, retinyl ester, and triglyceride concentrations in the TRL fraction (density < 1.006 kg/L) and plasma were measured in 10 men for 8 or 16 h after an oral dose of 15 mg beta-carotene. The beta-carotene response, unlike the triglyceride and retinyl ester response, can be evaluated in the TRL fraction but not in plasma. Intraindividual variations in the triglyceride-adjusted response of beta-carotene and retinyl palmitate in TRL fractions were 23% and 20% and interindividual variations were 42% and 36%, respectively. A low beta-carotene response was associated with a high ratio between retinyl palmitate and beta-carotene responses (r = -0.56, P = 0.013). In conclusion, the measurement of beta-carotene and retinyl esters in the TRL fraction after a dose of beta-carotene with a vitamin A-free meal may be an appropriate method to study beta-carotene uptake and cleavage.

Are proteinase inhibitors a factor for the derangement of homoeostasis in protein-energy malnutrition?

In protein-energy malnutrition essential amino acids for the synthesis of proteins are derived from the mobilization of endogenous proteins in order to maintain homoeostasis. Data are presented to support the hypothesis that proteinase inhibitors, which increase rapidly at the onset of infection, interrupt this catabolic effect which is the normal adaptive response to protein-energy malnutrition.

Vitamin A intervention: short-term effects of a single, oral, massive dose on iron metabolism.

A group of 134 school children aged 3-9 y, with signs of conjunctival xerosis, from the rural area of the Sakorn Nakhon province in Northeast Thailand were selected for a controlled study on the short-term effect (2 wk) of a single, oral high dose of vitamin A on iron metabolism. After collection of the baseline data, children within villages were randomly assigned to receive the capsules (n = 65) or serve as control subjects (n = 69). Two weeks after supplementation significant increases of retinol, retinol-binding protein, hemoglobin, hematocrit, serum iron, and saturation of transferrin were found in the supplemented group. Ferritin concentrations did not change significantly. These short-term changes completely exclude seasonal effects and change in morbidity. This study provides further evidence of a causal association between vitamin A and iron metabolism. In areas where vitamin A deficiency is endemic, periodic massive vitamin A dose programs can also improve iron status of the population.