Image-defined Risk Factors Research Articles

Image-defined risk factor assessment of neurogenic tumors after neoadjuvant chemotherapy is useful for predicting intra-operative risk factors and the completeness of resection.

Patients with neuroblastoma are now stratified at diagnosis according to the presence and number of image-defined risk factors (IDRFs). We examined the added value of IDRF assessment after neoadjuvant chemotherapy for predicting surgical resection. From 2009-2012, 39 out of 91 patients operated on in our institution for neuroblastic tumors received neoadjuvant chemotherapy based on ongoing SIOPEN protocols or treatment guidelines. IDRFs were assessed both at diagnosis and preoperatively on CT and/or MRI. Median age at diagnosis was 30 months [range 2-191]. The tumor locations were adrenal (n = 20), paravertebral (n = 13) and perivascular (n = 6). INRGSS stages were L2 (n = 13), M (n = 25) and Ms (n = 1). Eleven tumors (28%) were MYCN-amplified. Chemotherapy reduced the number of IDRFs in 54% of patients overall (21/39): 61.5% (16/26) of M and Ms patients, and 38.5% (5/13) of non metastatic patients (P < 0.001). The number of IDRFs lost after chemotherapy was proportional to the degree of tumor shrinkage (P = 0.002), independent of the primary tumor location (P = 0.73), although the number was higher in patients with left versus right adrenal locations (P = 0.004). Patients with neuroblastoma on post-surgical histology lost more IDRFs (median: 1[0-9]) than patients with ganglioneuroblastoma (median: 0[0-4]) (P < 0.001). The completeness of resection was related only to the number of preoperative IDRFs (P = 0.028). IDRF assessment after neoadjuvant chemotherapy is useful for predicting completeness of resection of neurogenic tumors. A larger international study is needed to confirm these results and to explore a possible correlation between preoperative IDRF status and survival.

Influence of image-defined risk factors on the outcome of patients with localised neuroblastoma. A report from the LNESG1 study of the European International Society of Paediatric Oncology Neuroblastoma Group.

The European multicenter study LNESG1 was designed to evaluate the safety and efficacy of surgical treatment alone in patients with localised neuroblastoma. In a retrospective, observational study we examined the impact of image-defined risk factors (IDRF) on operative complications and survival (EFS and OS). 534 patients with localised, non-MYCN amplified neuroblastoma were recruited between 1995 and 1999. Group 1 consisted of 291 patients without IDRF (Stage L1 in the International Neuroblastoma Risk Group (INRG) staging system), all treated with primary surgery. Group 2: 118 patients with IDRF (INRG Stage L2), also treated with primary surgery. Group 3: 125 patients in whom primary surgery was not attempted, 106 receiving neo-adjuvant chemotherapy. In L1 patients (Group 1) 5-year EFS was 92% and OS 98%. In L2 patients (Group 2 and 3) EFS was 79% and OS 89%. The differences in both EFS and OS were significant. EFS and OS in Group 2 (86% and 95%) were significantly better than 73% and 83% in Group 3. In INSS stage 1, 2 and 3, EFS were respectively 94%, 81% and 76%. Except between stage 2 and 3 the differences were significant. OS were respectively 99%, 93% and 83%, all significantly different. The 17% operative complication rate in L2 patients was significantly higher than 5% in L1 patients. In localised neuroblastoma, IDRF at diagnosis are associated with worse survival rates and higher rates of operative complications. The impact of IDRF should become an integrated part of therapy planning.

Neuroblastoma and nephroblastoma: an overview and comparison

Neuroblastoma (NBL) is the most common extra-cranial tumour in childhood [1] and commonly presents as an abdominal mass. Nephroblastoma, also more commonly known as a Wilms’ tumour, is the commonest renal tumour in childhood and also typically presents as abdominal pathology. The natural histories and typical clinical courses of these tumours are very different, thus early distinction is important. Both occur in early childhood, with Wilms’ having a slightly older peak incidence at between 3 – 4 years. Histologically, they are different diseases with NBLs arising from primordial neural crest cells [1] and Wilms’ being undifferentiated mesodermal tumours [2]. The heterogeneity of NBLs and their biological characteristics mean the prognosis is highly variable; tumour stage, patient age, tumour oncogenes and DNA content are all known to be implicated [3]. Wilms’ have two distinct histopathological types, favorable and unfavorable, with differing outcomes. NBLs are most commonly located within the adrenal gland, so typically present as palpable abdominal masses causing pain and distension [1,4]. Well described paraneoplastic syndromes include opsomyoclonus and excessive vasoactive intestinal peptide (VIP) production [1]. Metastatic disease is common on presentation [1]. Wilms’ usually present as a large, painless abdominal mass with few constitutional symptoms [2]. On ultrasound (US), NBLs are solid, heterogeneous masses with calcification and are rarely cystic [4]. With Wilms’, US also evaluates whether the mass is intra- or extra-renal, solid or cystic, and for the presence of vascular invasion [2]. MRI effectively assesses the extent of primary NBL disease, being superior to CT in assessing metastatic marrow disease, chest wall invasion and spinal canal involvement. On CT, NBLs are poorly marginated, heterogeneous masses that can cross the midline and enter adjacent body cavities. A key-defining feature is calcification, but this can have a variable appearance [4]. NBLs tend to encase and displace structures rather than invade them. Over 90% are MIBG-sensitive, but for primaries that are not, ⁹⁹mTc-diphosphonate bone scintigraphy is currently recommended to look for metastatic bony disease [1,3]. MRI is also useful at Wilms’ diagnosis, with contrast-enhanced sequences clearly demonstrating the ‘claw’ of normal renal tissue around the tumour. Tumours return low signal on T1W, with variable/high signal intensity on T2W. The non-cystic components typically restrict on diffusion sequences. In contrast to NBL, vessels are displaced rather than encased and vascular invasion occurs in approximately 5-10% of cases [4]. NBL staging has evolved with the simpler International Neuroblastoma Risk Group (INRG) system [3,5]. Imaging significantly contributes to this system. To enable consistent reporting, imaging defined risk factors have been identified by the INRG [3]. Unlike with NBL, chest CT is routinely done for Wilms’ staging. Management strategies for NBL include surgery, chemotherapy and radiotherapy, with additional myeloablative therapy and recently also immunotherapy for high-risk disease. A unilateral Wilms’ tumour is treated with nephrectomy and chemotherapy. With bilateral disease, pre-operative chemotherapy is vital as each kidney is staged separately, but the surgical approach is to preserve normal renal parenchyma.

Minimally invasive surgery of neuroblastic tumors in children: Indications depend on anatomical location and image-defined risk factors.

Minimally invasive surgery (MIS) is still not a well-accepted surgical approach to remove neuroblastic tumors. We aimed to assess the indications and limits of MIS in this childhood tumor according to tumor location and image-defined risk factors (IDRFs). Between 2006 and 2012, 39 patients underwent MIS for neuroblastic tumors, using thoracoscopic (n = 20), retroperitoneoscopic (n = 1) or laparoscopic approaches (n = 18). The tumor locations were paravertebral (n = 18; thoracic n = 15, lumbar n = 3), perivascular (n = 5; abdominal n = 2; thoracic n = 3), adrenal (n = 13), pleural (n = 2) and pelvic (n = 1). Two patients were treated for relapses. According to the INRG staging system, IDRFs were absent in 20 patients and present in 19 patients. Ten patients received chemotherapy preoperatively. Mean largest diameter was 35 mm for thoracic tumors (range: 7-85 mm) and 34 mm for abdominal tumors (range: 10-75 mm). Mean follow-up was 25 months (range: 5-116 months). Resection was macroscopically incomplete (R2) for six thoracic tumors and one adrenal tumor. Conversion was necessary for three thoracic L2 tumors. Postoperative complications consisted of chylothorax in three patients with L2 paravertebral thoracic tumors, Horner's syndrome in a patient with a cervicothoracic tumor, and renal atrophy in a patient with a L2 abdominal tumor. No perioperative or postoperative complications occurred in patients with adrenal and abdominal paravertebral tumors. The overall survival rate was 98%. In carefully selected cases, MIS permits safe and efficient resection of neuroblastic tumors in children. Open surgical approach should be considered if organ or vascular control or quality of resection is jeopardized. Pediatr Blood Cancer 2015;62:257-261. © 2014 Wiley Periodicals, Inc.

Laparoscopic resection of adrenal neuroblastoma without image-defined risk factors: a prospective study on 21 consecutive pediatric patients

Over the last 20 years MIS has progressively gained popularity in children with cancer. We therefore aimed at evaluating the safety of Minimally Invasive Surgery (MIS) resection in a series of children affected by adrenal neuroblastoma (NB) presenting without Image-Defined Risk Factors (IDRFs). An Institutional protocol for MIS resection of adrenal NB in pediatric patients without IDRFs has been applied since 2008. Absence of IDRFs represented the main indication for MIS in NB, regardless of tumor size. All pediatric patients who underwent MIS for NB between January 2008 and May 2013 were included. Specific technical considerations, demographic data, and outcome have been recorded. Twenty-one patients underwent MIS resection for IDRFs-negative adrenal NB. Nine of these patients experienced preoperative downgrading of IDRFs after chemotherapy. Radiological median diameter of the mass was 30 mm (range 10-83 mm). Median operative time was 90 min. Median hospital stay was 4 days. All patients were treated successfully, without serious intraoperative complications. One mild intraoperative hemorrhage occurred and was treated without the need for conversion to open surgery nor blood transfusion was required. No postoperative complications, including port-site or peritoneal metastases were experienced. This study demonstrated the safety and effectiveness of MIS for the resection of adrenal NB without IDRFs in children. Pediatric surgeons dedicated to oncology should be aware of this alternative approach to open resection.

Pediatric robot-assisted laparoscopic radical adrenalectomy and lymph-node dissection for neuroblastoma in a 15-month-old.

Neuroblastoma (NB) is the most common extra-cranial solid tumor in children and the most common malignancy in infants, with complete resection being curative in low-stage disease. The previous standard of treatment for many abdominal NBs involving the adrenal gland had been open surgery; however, there have been numerous descriptions of the safety and feasibility of a laparoscopic approach to resect adrenal masses in the pediatric population in benign and malignant disease, including improved cosmetic results, decreased length of stay, decreased surgical morbidity, and comparable oncological outcomes to open surgery. Despite these reported advantages over open surgery, the newer robot-assisted laparoscopy (RAL) offers benefits over the conventional laparoscopic approach that could further improve outcomes and expand the use of minimally invasive surgical approaches for pediatric adrenal masses. RAL offers many additional advantages over conventional laparoscopy, such as 3D visualization, increased range of motion of surgical instruments, tremor control, and a shorter learning curve compared with traditional laparoscopic surgery, while still maintaining the advantages of minimally invasive surgery. The body of literature concerning robot-assisted oncological surgery involving the adrenal gland in children is quite small, and to our knowledge no case reports have been published describing robot-assisted removal of an adrenal NB in a pediatric patient. We present our experience and technique of an RAL approach for lymph-node dissection and radical resection of a low-stage NB involving the adrenal gland with no image-defined risk factors in a 15-month-old infant.

Role of Surgery in the Treatment of Patients With Stage 4 Neuroblastoma Age 18 Months or Older at Diagnosis

Although intensive multimodal treatment has improved the prognosis of patients with metastatic neuroblastoma, the impact of primary tumor resection on outcome is a matter of medical debate. Patients from the German prospective clinical trial NB97 with stage 4 neuroblastoma and age 18 months or older at diagnosis were included. Operation notes and imaging reports were reviewed by two independent experienced physicians. Finally, the extent of tumor resections was correlated with local control rate and outcome. A total of 278 patients were included in this study. Image-defined risk factors present at diagnosis were found to be predictive for the extent of tumor resection at first (P < .001) and best (P < .001) operation. No patient died from surgery. Before chemotherapy, complete resection, incomplete resection, and biopsy or no surgery were performed in 6.1%, 5.0%, and 88.5% of patients, respectively. The extent of first operation had no impact on event-free survival (EFS; P = .207), local progression-free survival (LPFS; P = .195), and overall survival (OS; P = .351). After induction chemotherapy, 54.7% of patients underwent complete resection of the primary tumor, 30.6% underwent incomplete resection, and 13.3% had only biopsy or no surgery of the primary tumor. The extent of best operation also had no impact on EFS (P = .877), LPFS (P = .299), and OS (P = .778). Moreover, multivariate analyses showed that surgery did not affect EFS, LPFS, and OS. In intensively treated patients with stage 4 neuroblastoma age 18 months or older at diagnosis, surgery of the primary tumor site has no impact on local control rate and outcome.

Significance of Image-defined Risk Factors for Surgical Complications in Patients with Abdominal Neuroblastoma

Neuroblastoma (NB) is one of the most common malignant tumors in infancy. The commonly used International Neuroblastoma Staging System is not suitable for determining the surgical risks. To address this, we aimed to evaluate the correlation between so-called image-defined risk factors (IDRFs) and the surgical risks in abdominal neuroblastoma. We evaluated 60 cases who underwent surgical intervention and examined the pre-surgical radiological imaging to look for IDRFs and surgical complications in children with abdominal neuroblastoma. The MRI- and CT-scans showed a total of 122 IDRFs in 39 cases. Complete resection was carried out in 50%, partial excision in 32%, and biopsy in 18% of cases. Total resection was possible in 100% of cases with no IDRF. Where IDRFs were present, total resection was only possible in 26% of cases (p<0.0001). We found a highly significant, negative correlation between the number of IDRFs and the possibility of performing complete resection of NB (p<0.0001). 7 (11.6%) complications were detected, all in patients who showed at least one IDRF previously. Our findings indicate that IDRFs are useful indicators for predicting surgical risk and surgical outcome and thus should be taken into account when planning surgery.

Guidelines for Imaging and Staging of Neuroblastic Tumors: Consensus Report from the International Neuroblastoma Risk Group Project

Neuroblastoma is an enigmatic disease entity; some tumors disappear spontaneously without any therapy, while others progress with a fatal outcome despite the implementation of maximal modern therapy. However, strong prognostic factors can accurately predict whether children have "good" or "bad" disease at diagnosis, and the clinical stage is currently the most significant and clinically relevant prognostic factor. Therefore, for an individual patient, proper staging is of paramount importance for risk assessment and selection of optimal treatment. In 2009, the International Neuroblastoma Risk Group (INRG) Project proposed a new staging system designed for tumor staging before any treatment, including surgery. Compared with the focus of the International Neuroblastoma Staging System, which is currently the most used, the focus has now shifted from surgicopathologic findings to imaging findings. The new INRG Staging System includes two stages of localized disease, which are dependent on whether image-defined risk factors (IDRFs) are or are not present. IDRFs are features detected with imaging at the time of diagnosis. The present consensus report was written by the INRG Imaging Committee to optimize imaging and staging and reduce interobserver variability. The rationales for using imaging methods (ultrasonography, magnetic resonance imaging, computed tomography, and scintigraphy), as well as technical guidelines, are described. Definitions of the terms recommended for assessing IDRFs are provided with examples. It is anticipated that the use of standardized nomenclature will contribute substantially to more uniform staging and thereby facilitate comparisons of clinical trials conducted in different parts of the world.

Imaging neuroblastoma: what the radiologist needs to know

Neuroblastoma is the most common extracranial solid malignancy in children. The tumor has variable biological behavior that can be predicted by patient age, genetic features, tumor biology and extent of disease at diagnosis. Factors chosen by various cooperative groups to define risk of treatment failure have been non-uniform. Therefore, historically, it has been difficult to compare outcomes across clinical trials performed around the world. This has hindered the advancement of treatment strategies to improve survival of these patients. The International Neuroblastoma Risk Group (INRG) was established in 2004 to develop a consensus approach to pretreatment risk stratification. The result was the development of the INRG Staging System (INRGSS) which relies on imaging-defined risk factors (IDRFs) that are determined before surgery or other therapy. With the application of the INRGSS the radiologist's role in staging children with neuroblastoma is increased. This review provides an overview of the INRGSS and the IDRFs.

Excellent Outcome With Reduced Treatment in Infants With Nonmetastatic and Unresectable Neuroblastoma Without MYCN Amplification: Results of the Prospective INES 99.1

To evaluate the efficacy of low-dose chemotherapy in infants with nonmetastatic and unresectable neuroblastoma (NB) without MYCN amplification. Infants with localized NB and no MYCN amplification were eligible in the SIOPEN Infant Neuroblastoma European Study 99.1 study. Primary tumor was deemed unresectable according to imaging defined risk factors. Diagnostic procedures and staging were carried out according to International Staging System recommendations. Children without threatening symptoms received low-dose cyclophosphamide (5 mg/kg/d × 5 days) and vincristine (0.05 mg/kg at day 1; CyV), repeated once to three times every 2 weeks until surgical excision could be safely performed. Children with either one threatening symptom or insufficient response to CyV were given carboplatin and etoposide (CaE), sometimes followed by vincristine, cyclophosphamide, and doxorubicin. No postoperative treatment was to be administered. Between December 1999 and April 2004, 120 infants were included in the study. Eighty-eight had no threatening symptoms and 79 received CyV. CaE was given to 49 of them because of insufficient response. Thirty-two children had threatening symptoms, 30 of whom received CaE. Anthracyclines were given to 46 children. Surgery was attempted in 102 patients, leading to gross surgical excision in 93. Relapse occurred in 12 patients (nine local and three metastatic). Five-year overall and event-free survivals were 99% ± 1% and 90% ± 3%, respectively, with a median follow-up of 6.1 years (range, 1.6 to 9.1). Low-dose chemotherapy without anthracyclines is effective in 62% of infants with an unresectable NB and no MYCN amplification, allowing excellent survival rates without jeopardizing their long-term outcome.

Whole-body MRI of neuroblastoma

Whole-body MRI (WBMRI) is an emerging imaging method that has a great potential in pediatric oncologic imaging. It appears useful in staging and monitoring neuroblastoma although its clinical impact has not been thoroughly evaluated. Among various imaging techniques currently available for WBMRI, coronal and sagittal STIR imaging with a quadrature body coil at 1.5T MR system is recommended for a standard protocol. Nevertheless, further technical improvements are anticipated at 3.0T MR system and multi-channel surface coil system. Scan time of WBMRI is reasonably short ranging from 20 min to 60 min. In localized neuroblatoma, WBMRI may help in predicting surgical risks by evaluating image-defined risk factors accurately. In addition, WBMRI is quite useful in detecting distant metastasis, assessing initial treatment responses, and identifying tumor recurrence of neuroblastoma. We should understand limitations of WBMRI in the evaluation of lymph node involvement, in the differentiation between viable tumor and non-viable residual lesion, and in the detection of calcified lesion. Diffusion-weighted imaging may improve diagnostic accuracy of WBMRI. Complementary use of WBMRI and other metabolic imaging method such as MIBG scintigraphy or PET probably increases diagnostic accuracy and, subsequently, improves clinical outcome of children with neuroblastoma.

The Drama of the Gifted Disease

The Drama of the Gifted Disease

The International Neuroblastoma Risk Group (INRG) staging system: an INRG Task Force report.

The International Neuroblastoma Risk Group (INRG) classification system was developed to establish a consensus approach for pretreatment risk stratification. Because the International Neuroblastoma Staging System (INSS) is a postsurgical staging system, a new clinical staging system was required for the INRG pretreatment risk classification system. To stage patients before any treatment, the INRG Task Force, consisting of neuroblastoma experts from Australia/New Zealand, China, Europe, Japan, and North America, developed a new INRG staging system (INRGSS) based on clinical criteria and image-defined risk factors (IDRFs). To investigate the impact of IDRFs on outcome, survival analyses were performed on 661 European patients with INSS stages 1, 2, or 3 disease for whom IDRFs were known. In the INGRSS, locoregional tumors are staged L1 or L2 based on the absence or presence of one or more of 20 IDRFs, respectively. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, IDRFs were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease (78% +/- 4% v 90% +/- 3%; P = .0010). Use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world.

Review of image defined risk factors in localized neuroblastoma patients: Results of the GPOH NB97 trial

Recently, an international expert group proposed revision of the International Neuroblastoma Staging System (INSS). Localized disease can be classified as L1 without and as L2 with image defined risk factors (IDRF published in JCO 2005; 23:8483-8489). Our aim was to evaluate IDRF for the prediction of resectability, complications, and outcome. Records of 520 localized neuroblastoma patients of the NB97 trial were reviewed. Patients were retrospectively classified as having IDRF or not. A total of 366 evaluable patients were then analyzed for extent and complications of surgery and the prognostic value of IDRF. Any IDRF was present in 26/160 of stage 1, 49/113 of stage 2, and 64/93 of stage 3 patients. Complete primary resection was achieved in 156/227 patients without IDRF and 43/139 patients with IDRF (P < 0.001). The frequency of complications was higher if any IDRF was present: 37/139 versus 33/227 (P = 0.006). Lack of IDRF was associated with better event free survival (3-year-EFS 86 +/- 2% vs. 75 +/- 4%, P = 0.010), whereas overall survival was similar (3-year-OS 98 +/- 1% vs. 96 +/- 2%, P = 0.462). EFS clearly depended on INSS stage (3-year-EFS 93 +/- 2% in stage 1, 78 +/- 4% in stage 2, and 69 +/- 5% in stage 3, P < 0.001). OS was not different (3-year-OS 98 +/- 1% vs. 99 +/- 1% vs. 94 +/- 2%, P = 0.056). Multivariate analysis demonstrated an impact of INSS stage on EFS only. IDRF were not shown to be significant for predicting EFS or OS. IDRF were useful in predicting risk and completeness of operation. IDRF failed as independent risk predictors in localized neuroblastoma. INSS more precisely identified patients with poor prognosis.

Update on the development of the international neuroblastoma risk group (INRG) classification schema

9503 Background: Modern treatment strategies for neuroblastoma (NB) are tailored according to patient risk. However, it is not currently possible to compare the results of clinical studies conducted around the globe because the criteria used to define risk are not uniform. A committee of international investigators with expertise in NB have worked during the past 2 years to develop a uniform International NB Risk Group (INRG) Classification System for pre-treatment stratification. Methods: Investigators from North America and Australia (COG); Europe (SIOPEN and Germany), and Japan collated data on 8,800 children with NB diagnosed between 1990 and 2002. Survival tree regression analyses tested 13 potential prognostic factors. Tumor differentiation, MKI, and diagnostic category were evaluated individually in lieu of the International NB Pathology Classification (INPC) system to determine if these histologic features had prognostic value independent from age. To stage patients at the time of diagnosis prior to surgery, a new staging system was developed (INRGSS) based on the presence or absence of image-defined risk factors (IDRFs) and metastases. Results: Since statistical analyses demonstrated support for an optimal age cut- off between 14–19 months, 18 months was selected. In addition to age, stage, MYCN amplification, tumor differentiation, ploidy, and genetic aberrations of 11q were found to be the most highly prognostically significant factors. These clinical and biological factors were combined to define 15 INRG pre-treatment groups. Patients with low- (3 groups), intermediate- (4 groups), high- (4 groups), or ultra-high-risk NB (4 groups) had EFS of ≥85%, &gt;70–85%, &gt;50–70%, or &lt;50%, respectively. Conclusion: International collaborative studies in NB will be greatly facilitated by the INRG classification system which will allow comparisons of different risk-based therapeutic approaches in homogeneous patient cohorts. No significant financial relationships to disclose.

Effect of prostacyclin (PGI2) on water and solute transport in the human jejunum.

Prostacyclin is an arachidonic acid metabolite, synthesised throughout the gastrointestinal tract, which has different effects on water and electrolyte transport across a variety of mammalian gastrointestinal epithelia. Using a perfusion technique in the human jejunum of 11 healthy subjects in vivo, the effect of intravenous prostacyclin, 4 ng/kg/min, on jejunal water and solute transport from a glucose electrolyte solution was investigated. In the prostacyclin group (n = 5), prostacyclin was infused intravenously from 70-150 minutes, and buffer administered iv from 0-70 and 150-210 minutes. In the buffer group (n = 6), iv buffer was administered from 0-210 minutes. In the prostacyclin group, net jejunal absorption of water was inhibited from 90-120 min (p less than 0.05), 150-180 min (p less than 0.01) and 180-210 min (p less than 0.01), of sodium was inhibited from 90-120 min (p less than 0.05), 120-150 min (p less than 0.05), 150-180 min (p less than 0.01) and 180-210 min (p less than 0.01), and of chloride was inhibited from 90-120 min (p less than 0.05), 120-150 min (p less than 0.005), 150-180 min (p less than 0.01) and 180-210 min (p less than 0.01). Prostacyclin had no effect on net movement of glucose, potassium or bicarbonate. These results are consistent with a role for prostacyclin in the endogenous humoral regulation of water and electrolyte transport in the human jejunum.