Leptin and adiponectin receptor expression in oesophageal cancer.

BACKGROUND: Oesophageal adenocarcinoma is an exemplar model of an obesity-associated adenocarcinoma. Altered secretion of adipokines by visceral fat is believed to play a key role in tumorigenesis. This study examined leptin receptor (ObR) and adiponectin receptor (AdipoR1 and AdipoR2) expression in oesophageal cancer, and its relationship with patient obesity status, clinicopathological data and patient survival. METHODS: Tissue microarrays were constructed from paraffin-embedded oesophagectomy specimens. ObR, AdipoR1 and AdipoR2 expression was quantified by immunohistochemistry. Anthropometric data were measured at the time of diagnosis, and obesity status was assessed using visceral fat area determined by computed tomography and body mass index. Receptor expression was correlated with various clinicopathological and anthropometric variables. Patient survival was estimated using the Kaplan-Meier method, and results compared between those with low versus high receptor expression. A Cox multivariable regression model was used to assess the relationship between survival and a number of co-variables. RESULTS: All 125 tumours analysed expressed AdipoR1 and AdipoR2, whereas 96·8 per cent expressed ObR. There was no significant difference in tumour pathological features or patient obesity status between tumours with low versus high ObR expression. A high level of AdipoR1 expression was significantly associated with increased patient age, obesity and less advanced tumour (T) category. Expression of AdipoR2 was inversely associated with T category (P = 0.043). Low AdipoR1 expression was an independent predictor of improved overall survival (hazard ratio 0.56, 95 per cent confidence interval 0.35 to 0.90; P = 0.017). CONCLUSION: The association between adiponectin receptor expression, obesity status and tumour category and survival suggests a potential mechanism linking obesity and oesophageal cancer.

Patterns of lymphatic drainage and lymph node involvement in esophageal cancer.

The esophagus has a complex pattern of lymphatic drainage. Lymph node involvement and number of lymph node metastases are very important prognostic factors, and the newly revised TNM staging system for esophageal cancer reflects this. Knowledge of the location and nomenclature of the common nodal stations in the thorax and upper abdomen is essential for the accurate staging of these patients. PET-CT and EUS are essential in the routine staging of esophageal cancer patients. The aim of this pictorial review is to present the nodal stations, nomenclature and location of regional lymph nodes in esophageal cancer using PET-CT and EUS images from selected patient cases. We will review the EUS and PET-CT imaging for a number of patients with esophageal cancer, using cases which highlight the advantages and diagnostic pitfalls for these imaging modalities.

Distinct neural signaling characteristics between fibromyalgia and provoked vestibulodynia revealed by means of functional magnetic resonance imaging in the brainstem and spinal cord.

Introduction: Fibromyalgia and provoked vestibulodynia are two chronic pain conditions that disproportionately affect women. The mechanisms underlying the pain in these conditions are still poorly understood, but there is speculation that both may be linked to altered central sensitization and autonomic regulation. Neuroimaging studies of these conditions focusing on the brainstem and spinal cord to explore changes in pain regulation and autonomic regulation are emerging, but none to date have directly compared pain and autonomic regulation in these conditions. This study compares groups of women with fibromyalgia and provoked vestibulodynia to healthy controls using a threat/safety paradigm with a predictable noxious heat stimulus. Methods: Functional magnetic resonance imaging data were acquired at 3 tesla in the cervical spinal cord and brainstem with previously established methods. Imaging data were analyzed with structural equation modeling and ANCOVA methods during: a period of noxious stimulation, and a period before the stimulation when participants were expecting the upcoming pain. Results: The results demonstrate several similarities and differences between brainstem/spinal cord connectivity related to autonomic and pain regulatory networks across the three groups in both time periods. Discussion: Based on the regions and connections involved in the differences, the altered pain processing in fibromyalgia appears to be related to changes in how autonomic and pain regulation networks are integrated, whereas altered pain processing in provoked vestibulodynia is linked in part to changes in arousal or salience networks as well as changes in affective components of pain regulation.

Metabolic syndrome and leptin are associated with adverse pathological features in male colorectal cancer patients.

AIM: Metabolic syndrome (MetS) describes a clustering of factors including central obesity, hypertension and raised plasma glucose, triglycerides and high-density lipoprotein (HDL) cholesterol. Central obesity is associated with a risk for colorectal cancer, but the impact of MetS on colorectal cancer biology and outcomes is unclear. METHOD: A prospective observational study of colorectal cancer patients was carried out in an Irish population. Patients underwent metabolic and anthropometric assessment before treatment, including measurement of serum hormones and adipokines and CT measurement of visceral fat. MetS was defined according to the International Diabetes Federation definition(3) . RESULTS: One-hundred and thirty consecutive colorectal cancer patients (66 men and 64 women) were recruited. MetS was diagnosed in 38% patients compared with the population norms reported at 21%(21) . Male patients had a significantly greater visceral fat area compared with female patients. MetS was associated with node-positive disease (P = 0.026), percentage nodal involvement (P = 0.033) and extramural vascular invasion (P = 0.049) in male patients but no significant association was observed in female patients. HDL cholesterol was also significantly associated with a more advanced pathological stage (P = 0.014) and node-positive disease (P = 0.028). Leptin was associated with nodal status (P = 0.036), microvascular invasion (P = 0.054), advanced pathological stage (P = 0.046) and more advanced Dukes stage (P = 0.042). CONCLUSION: We report a high prevalence of MetS and visceral obesity in a colorectal cancer population. MetS and plasma leptin are associated with a more aggressive tumour phenotype in male patients only.

Altered Pain in the Brainstem and Spinal Cord of Fibromyalgia Patients During the Anticipation and Experience of Experimental Pain.

Chronic pain associated with fibromyalgia (FM) affects a large portion of the population but the underlying mechanisms leading to this altered pain are still poorly understood. Evidence suggests that FM involves altered neural processes in the central nervous system and neuroimaging methods such as functional magnetic resonance imaging (fMRI) are used to reveal these underlying alterations. While many fMRI studies of FM have been conducted in the brain, recent evidence shows that the changes in pain processing in FM may be linked to autonomic and homeostatic dysregulation, thus requiring further investigation in the brainstem and spinal cord. Functional magnetic resonance imaging data from 15 women with FM and 15 healthy controls were obtained in the cervical spinal cord and brainstem at 3 tesla using previously established methods. In order to investigate differences in pain processing in these groups, participants underwent trials in which they anticipated and received a predictable painful stimulus, randomly interleaved with trials with no stimulus. Differences in functional connectivity between the groups were investigated by means of structural equation modeling. The results demonstrate significant differences in brainstem/spinal cord network connectivity between the FM and control groups which also correlated with individual differences in pain responses. The regions involved in these differences in connectivity included the LC, hypothalamus, PAG, and PBN, which are known to be associated with autonomic homeostatic regulation, including fight or flight responses. This study extends our understanding of altered neural processes associated with FM and the important link between sensory and autonomic regulation systems in this disorder.

T lymphocyte activation in visceral adipose tissue of patients with oesophageal adenocarcinoma.

BACKGROUND: Visceral adipose tissue may fuel obesity-associated chronic inflammation and tumorigenesis. T cells may be important in visceral adipose tissue in driving inflammation, but they have not yet been characterized in patients with cancer. This study aimed to characterize T lymphocytes in visceral adipose tissue and peripheral blood from patients with oesophageal adenocarcinoma. METHODS: Omental fat was taken from 35 patients with oesophageal adenocarcinoma at the start of surgery. Flow cytometry was performed to assess T cell activation status and cytokine production in omentum and peripheral blood. RESULTS: A large population of lymphocytes was present in the omentum. Omental CD4(+) and CD8(+) T cells displayed significantly enhanced expression of the T cell activation markers CD69 (P < 0·001) and CD107a (CD8(+) T cells: P < 0·01), and significantly decreased CD62L expression (P < 0·05), compared with blood. Significantly higher proportions of CD45RO(+) T cells compared with CD45RA(+) T cells were present in omentum (P < 0·001 and P = 0·012 for CD4(+) and CD8(+) cells respectively). Interferon γ was the most abundant cytokine expressed by omental T cells, with a significantly higher level than in blood and subcutaneous adipose tissue (P < 0·01). CONCLUSION: Visceral adipose tissue is a rich source of activated proinflammatory CD4(+) and CD8(+) T cells. It may fuel chronic inflammation via T cell-mediated pathways.

How fMRI Analysis Using Structural Equation Modeling Techniques Can Improve Our Understanding of Pain Processing in Fibromyalgia.

PURPOSE: The purpose of this study was to investigate the utility of data-driven analyses of functional magnetic resonance imaging (fMRI) data, by means of structural equation modeling, for the investigation of pain processing in fibromyalgia (FM). PATIENTS AND METHODS: Datasets from two separate pain fMRI studies involving healthy controls (HC) and participants with FM were re-analyzed using both a conventional model-driven approach and a data-driven approach, and the results from these analyses were compared. The first dataset contained 15 women with FM and 15 women as healthy controls. The second dataset contained 15 women with FM and 11 women as healthy controls. RESULTS: Consistent with previous studies, the model-driven analyses did not identify differences in pain processing between the HC and FM study groups in both datasets. On the other hand, the data-driven analyses identified significant group differences in both datasets. CONCLUSION: Data-driven analyses can enhance our understanding of pain processing in healthy controls and in clinical populations by identifying activity associated with pain processing specific to the clinical groups that conventional model-driven analyses may miss.

Associations between leptin and adiponectin receptor upregulation, visceral obesity and tumour stage in oesophageal and junctional adenocarcinoma.

BACKGROUND: Obesity is associated with oesophageal adenocarcinoma, but mechanisms linking fat and carcinogenesis remain poorly understood. Altered circulating adipocytokines may be important. This study aimed to identify pathways through which visceral fat impacts on tumour biology. METHODS: Seventy-five patients with oesophageal adenocarcinoma underwent anthropometric and radiological assessment of obesity. Expression of leptin receptor (ObR) and adiponectin receptors 1 and 2 (AdipR1, AdipR2) was quantified by real-time reverse transcriptase-polymerase chain reaction. The human oesophageal adenocarcinoma cell line OE33 was used as the calibrator sample. RESULTS: Ninety-one per cent of tumours expressed ObR, 95 per cent expressed AdipR1 and 100 per cent expressed AdipR2. Relative expression of ObR was upregulated in 67 per cent, and AdipR1 and AdipR2 were downregulated in 55 and 68 per cent respectively, relative to the calibrator sample. Upregulated ObR and AdipR2 expression was significantly associated with anthropometric and radiological measures of obesity. Upregulated ObR was associated with advanced tumour and node category (P = 0.036 and P = 0.025 respectively), and upregulated AdipR2 with nodal involvement (P = 0.037). CONCLUSION: Obesity is associated with upregulated ObR and AdipR2 expression in oesophageal adenocarcinoma. The association of ObR and AdipR2 with tumour stage suggest that pathways involving adipocytokines affect tumour biology.

Outcomes in achalasia from a surgical unit where pneumatic dilatation is first-line therapy.

The management of achalasia remains controversial, with little consensus on the optimal patient treatment pathway. In our own esophageal unit, we offer pneumatic dilatation as the initial therapy in most patients as first-line therapy. In this study, we aimed to examine the safety and efficacy of our own approach to the management of patients with a diagnosis of achalasia, examining symptomatic outcomes, patient satisfaction, and need for further intervention, as well as examining patient factors associated with treatment failure. Sixty-seven consecutive patients underwent pneumatic dilatation as first-line therapy (53% male, mean age 46 years). All attended regular outpatient follow-up (mean 37, range 3-132 months). Twenty-five percent of patients required a second intervention because of symptom recurrence, at a median period of 4.5 months. Symptomatic outcomes were excellent or good in 80%. Significant predictors of treatment failure and poor symptom score included a younger age at the time of diagnosis and increased esophageal diameter on barium swallow. This study suggests that pneumatic dilatation is a safe and effective approach as first-line therapy in patients with newly diagnosed achalasia.

Coordinated Human Brainstem and Spinal Cord Networks during the Expectation of Pain Have Elements Unique from Resting-State Effects.

Functional magnetic resonance imaging (fMRI) research on the human brainstem (BS) and spinal cord (SC) has identified extensive BS/SC resting-state networks (RSNs) by showing spontaneous coordinated blood oxygenation-level dependent (BOLD) signal fluctuations in the absence of a stimulus. Studies have shown that these networks can be influenced by participants' level of arousal or attention (e.g., watching a video), and linked network function to autonomic homeostatic regulation. Here we explore how the cognitive state of expecting pain can influence connectivity in these networks. Data from two studies (a predictable pain stimulus study, and a resting-state study) were compared to show the effects of expecting pain on BS/SC networks, and how networks differed from networks associated with the resting-state. In each study, BOLD fMRI data were obtained from the cervical SC and brainstem in healthy participants at 3 tesla using a T2-weighted single-shot fast spin-echo imaging method. Functional connectivity was investigated within the entire 3D volume by means of structural equation modeling (SEM) and analyses of covariance (ANCOVA). Results showed extensive connectivity within/across BS and SC regions during the expectation of pain, and ANCOVA analyses showed that connectivity in specific components of these networks varied with individual pain sensitivity. Comparing these results to RSN fluctuations revealed commonalities in coordination between BS and SC regions, and specific BS-BS connectivity fluctuations unique to the expectation of pain. Based on the regions involved, these results provide evidence of brainstem regulation specific to the expectation of pain.

A comparison of the effectiveness of functional MRI analysis methods for pain research: The new normal.

Studies of the neural basis of human pain processing present many challenges because of the subjective and variable nature of pain, and the inaccessibility of the central nervous system. Neuroimaging methods, such as functional magnetic resonance imaging (fMRI), have provided the ability to investigate these neural processes, and yet commonly used analysis methods may not be optimally adapted for studies of pain. Here we present a comparison of model-driven and data-driven analysis methods, specifically for the study of human pain processing. Methods are tested using data from healthy control participants in two previous studies, with separate data sets spanning the brain, and the brainstem and spinal cord. Data are analyzed by fitting time-series responses to predicted BOLD responses in order to identify significantly responding regions (model-driven), as well as with connectivity analyses (data-driven) based on temporal correlations between responses in spatially separated regions, and with connectivity analyses based on structural equation modeling, allowing for multiple source regions to explain the signal variations in each target region. The results are assessed in terms of the amount of signal variance that can be explained in each region, and in terms of the regions and connections that are identified as having BOLD responses of interest. The characteristics of BOLD responses in identified regions are also investigated. The results demonstrate that data-driven approaches are more effective than model-driven approaches for fMRI studies of pain.

Micron-scale restructuring of gelling silica subjected to shear.

HYPOTHESIS/OBJECTIVE: We examine the time dependent viscometric behavior of a well-defined system of gelling colloidal silica and how this behavior may be understood from a simple theoretical model which incorporates the microstructure of the gel. The ultra-small angle neutron scattering (USANS) technique is used to interrogate structure during the gelation process. EXPERIMENTS: The investigations focused on a system where both particles and interactions are well-defined: 7 nm silica particle acid-treated aqueous solution subjected to a constant applied shear in Couette geometry. Ultra-small angle neutron scattering (USANS) time-dependent scattering intensities were measured at wave vectors, q, in the range, 1.0 × 10-3 ≤ q/nm ≤ 7.3 × 10-2 coupled with viscosity data recorded simultaneously. The interpretation of the USANS scattering data is reliant on an isotropic sample. This assumption has been investigated, over a limited range of scattering vectors, using more suitable small angle neutron scattering (SANS) instrumentation with a restricted q-range. FINDINGS: The first recorded direct kinetic measurements of the micron-scale structure in a gelling system. A critical micro-structural feature of the intensity-viscosity time behavior of a gelling colloid subjected to a shear is the cluster size. A viscosity/intensity coupling observed at the time of a viscosity maximum that corresponds to a time-dependent critical stress and speculated to be independent of the wave vector over a wide q-range.

Conservative management resulting in complete resolution of a double intussusception in an adult haemophiliac.

Acute abdominal pain in haemophiliacs should be approached as haemorrhage until proven otherwise. With advancements in factor repletion and coagulopathic management a conservative approach should be considered. We describe a case of double colo-colonic intussusception lead by an intramural haematoma occurring spontaneously and resolving with conservative management in a young haemophiliac. This demonstrates that intussusception in these cases may be transient, and does not require surgical intervention.

Efficacy of argon plasma coagulation compared to topical formalin application for chronic radiation proctopathy.

BACKGROUND: Chronic radiation proctopathy (CRP) is a troublesome complication of radiotherapy to the pelvis for which current treatment modalities are suboptimal. Currently, the application of formalin to the rectal mucosa (AFR) and thermal ablation with argon plasma coagulation (APC) are the most promising options. OBJECTIVE: To compare the efficacy and safety of AFR with APC for CRP. PATIENTS AND METHODS: Records of 22 patients (male to female ratio, 19:3; mean age, 74 years) who received either APC or AFR for chronic hematochezia caused by CRP, and who were evaluated and treated between May 1998 and April 2002, were reviewed. Complete evaluations were made three months after completion of each therapeutic modality. Patients were considered to be responders if there was a 10% increase in hemoglobin from baseline or complete normalization of hemoglobin (male patients, higher than 130 g/L; female patients, higher than 115 g/L) without the requirement for blood transfusion. RESULTS: The mean hemoglobin level before therapy was 107 g/L. Patients received an average of 1.78 sessions for APC and 1.81 sessions for AFR. Eleven patients (50%) were treated with APC alone, eight patients (36%) with AFR alone and three (14%) with both modalities (two with AFR followed by APC, and one with APC followed by AFR). Eleven of 14 patients (79%) in the APC group were responders, compared with three of 11 patients (27%) in the AFR group (P=0.017). In the APC group, seven of 11 responders required only a single session, while in the AFR group, only one patient responded after a single session. Adverse events (nausea, vomiting, flushing, abdominal cramps, rectal pain and fever) occurred in two patients after APC and in nine patients after AFR (P=0.001). In the APC group, the mean hemoglobin level increase was 20 g/L at three months follow-up, compared with 14 g/L in the AFR group. CONCLUSION: This retrospective study suggests that APC is more effective and safe than topical AFR to control hematochezia caused by CRP. Further studies are needed to confirm this observation.

Conception rates and serum progesterone concentration in dairy cattle administered gonadotropin releasing hormone 5 days after artificial insemination.

The objectives of this study were to determine the effect of administration of exogenous GnRH 5days after artificial insemination (AI) on ovarian structures, serum progesterone concentration, and conception rates in lactating dairy cows. In experiment 1, 23 Holstein cows were synchronized using the Ovsynch protocol. Five days after AI (day 0) cows were assigned randomly to receive either saline (saline; n=11) or 100microg GnRH (GnRH; n=12). To examine ovarian structures, ultrasonography was performed on day 1 and every other day beginning on day 5 until day 13. On days 5 and 13 blood samples were obtained to measure serum progesterone concentrations. All cows in the GnRH-treated group developed an accessory corpus luteum (CL), whereas cows in the saline group did not. Mean serum progesterone concentrations did not differ between GnRH and saline groups on day 5 (1.64+/-0.46ng/ml versus 2.04+/-0.48ng/ml). On day 13 serum progesterone concentrations were greater (P<0.05) in the GnRH group compared with saline (5.22+/-0.46ng/ml versus 3.36+/-0.48ng/ml). In experiment 2, 542 lactating cows, at two different commercial dairies, were used to test the effect of administering GnRH 5 days after AI on conception rates. Cows were synchronized and detected for estrus according to tail chalk removal. Cows detected in estrus received AI within 1h after detection of estrus. Five days after AI, cows were assigned randomly to receive either GnRH (n=266) or saline (n=276). Pregnancy status was determined by palpation per rectum of uterine contents approximately 40 days after AI. There was no effect of farm on conception rate. There was no effect of treatment as conception rates did not differ between GnRH and saline groups (26.7% GnRH versus 24.3% saline). Regardless of treatment, days in milk, parity, milk yield, and number of services had no effect on the odds ratio of pregnancy. In summary, the results of this study indicated that GnRH administered 5 days after AI increased serum progesterone by developing an accessory CL but did not improve conception rates in dairy cattle.

Hormone replacement therapy and cobalamin status in elderly women.

Serum cobalamin concentrations are frequently low in the elderly but the cause is often not apparent. Because oral contraceptives have been associated with low cobalamin concentrations in young women, we compared hormone use with cobalamin status in elderly women to determine whether it could account for their unexplained low cobalamin concentrations. Thirty-eight of the 111 women had abnormal cobalamin status (defined by low cobalamin, elevated methylmalonic acid, and/or elevated homocysteine concentrations) and 73 had normal status. There was no difference in hormone use between the two groups: 7 (18.4%) of the 38 cobalamin-deficient subjects used estrogens compared with 20 (27.4%) of the 73 control subjects. No differences in hormone use were apparent either when analysis was confined to abnormal serum cobalamin concentrations alone. Similarly, the 27 women taking hormones and the 84 women not taking hormones did not have significantly different serum cobalamin or serum total homocysteine concentrations. Indeed, hormone users had slightly, though not significantly, higher cobalamin concentrations and lower homocysteine concentrations than nonusers; furthermore, hormone users also had significantly lower serum methylmalonic acid concentrations. Thus, neither cobalamin concentrations nor cobalamin metabolic status were significantly worse in elderly women taking estrogen than in those not taking it (and, if anything, may have been slightly better). Hormone use does not appear to be a significant contributor to the low cobalamin concentrations or the mild metabolic evidence of cobalamin deficiency so often seen in the elderly.

Famotidine in the therapy of gastric hypersecretory states.

The histamine (H2)-receptor antagonist famotidine was compared with ranitidine and cimetidine in its ability to control gastric acid hypersecretion in 33 patients with gastric hypersecretory states (32 patients with Zollinger-Ellison syndrome and one patient with idiopathic hypersecretion). Equipotent doses of each drug were determined in nine patients and used to determine relative onset of action, duration of action, and potency. Each drug had a similar time course of onset with a maximal effect at three to four hours after oral ingestion. The duration of action of famotidine was 30 percent longer than that of either cimetidine or ranitidine. In terms of relative potency, famotidine was nine times more potent than ranitidine and 32 times more potent than cimetidine. Thirty-two patients underwent long-term famotidine treatment for up to 34 months (mean, 10 months) with a duration in 21 patients of at least six months, in nine patients of at least 12 months, and in six patients of at least 24 months. The mean daily maintenance dose with famotidine was 0.33 g per day (range, 0.05 to 0.8 g). Prior to famotidine therapy, 27 patients were taking ranitidine and the mean daily dose required was 2.3 g per day (range, 0.6 to 5.4 g), whereas six patients were taking cimetidine and the mean daily dose was 4.6 g per day (range, 1.2 to 9.0 g). Fourteen of the 32 patients required an anticholinergic agent in addition to ranitidine or cimetidine to maintain control, whereas only five patients required an anticholinergic agent with famotidine. Gastric acid hypersecretion was controlled in seven patients with less frequent dosing with famotidine than with cimetidine or ranitidine. Long-term treatment with famotidine was not associated with any hematologic or biochemical toxicity or clinical side effects. These results demonstrate that famotidine has a similar onset of action to other H2-receptor antagonists but has a 30 percent longer duration of action and is nine times more potent than ranitidine and 32 times more potent than cimetidine. Famotidine is safe and highly effective in the long-term treatment of gastric hypersecretory states.

Prospective study of the standard meal provocative test in Zollinger-Ellison syndrome.

PURPOSE: The purpose of this work was to evaluate the proposed usefulness of a standard meal-stimulated gastrin provocative test in: (1) distinguishing Zollinger-Ellison syndrome (ZES) from antral syndromes; (2) localizing duodenal gastrinomas; or (3) suggesting that patients with multiple endocrine neoplasia type I (MEN-I) may have an increased incidence of antral syndromes. PATIENTS AND METHODS: Seventy-four consecutive patients with ZES referred to the National Institutes of Health were studied prospectively. The extent and location of gastrinomas, acid secretory studies, and the presence or absence of MEN-I were determined and correlated with the results of the gastrin response to standard meal provocative testing. RESULTS: For patients with fasting serum gastrin levels less than 1,000 pg/mL (n = 43), only 44% had a less than 50% increase over the pre-meal value, which is reported to be the typical response in ZES, and 40% had a 50% to 99% increase. Furthermore 16% had a 100% or greater increase, 9% a 150% or greater increase, and 5% a 200% or greater increase, which overlaps with values reported to be characteristic of 98%, 92%, and 46% of patients with antral syndromes. Results did not differ for patients with or without MEN-I, depend on the extent of the gastrinoma (duodenal versus pancreatic gastrinomas), the presence of previous gastric surgery or type of gastric surgery, or for patients with fasting serum gastrin concentrations greater than or equal to 1,000 pg/mL or less than 1,000 pg/mL. studies of four patients before and after resection of the gastrinoma, who prior to surgery had a greater than 100% increase in gastrin secretion after the meal, demonstrated that all patients had a less than 100% increase postoperatively even though no gastric resection was done. CONCLUSIONS: Approximately half of the patients with ZES have a greater than 50% increase in serum gastrin concentration following a standard test meal and one fifth have a 100% or greater increase. Therefore, they cannot be distinguished on this basis from patients with antral syndromes. The increased serum gastrin level after the meal in these patients with ZES appears to be due to the gastrinoma. Furthermore, the current study provides no evidence for the proposals that antral syndromes are more common in patients with MEN-I, that gastric surgery affects the meal response in patients with gastrinomas, or that the meal test is useful in localizing duodenal gastrinomas.

Comparison of the effectiveness of ranitidine and cimetidine in inhibiting acid secretion in patients with gastric hypersecretory states.

The H2-histamine receptor antagonists ranitidine and cimetidine were compared for their abilities to control gastric acid hypersecretion on a short- and long-term basis in 22 patients with gastric acid hypersecretory states. Nineteen patients had Zollinger-Ellison syndrome, one patient had systemic mastocytosis, and two patients had idiopathic hypersecretion. The rates of onset of the action of cimetidine and ranitidine were the same. The actions of both drugs were increased by anticholinergic agents, and there was a close correlation between the daily maintenance dose of each drug needed to control acid secretion. However, ranitidine was threefold more potent than cimetidine both in acute inhibition studies and in the median maintenance dose needed (1.2 g per day for ranitidine and 3.6 g per day for cimetidine). Sixty percent of the males developed breast changes or impotence while taking cimetidine and in all cases these changes disappeared when cimetidine was replaced by ranitidine. Treatment with high doses of cimetidine (one to 60 months; median, 11 months) or ranitidine (two to 31 months; median, 14 months) was not associated with hepatic or hematologic toxicity or alterations of serum gastrin concentrations, but ranitidine therapy was associated with a significantly lower serum creatinine level than seen with cimetidine therapy. The results show that both drugs can adequately inhibit acid secretion in patients with gastric hypersecretory states. Both are safe at high doses, but ranitidine is threefold more potent and does not cause the antiandrogen side effects frequently seen with high doses of cimetidine.

Treatment of cancer of the pancreas by precision high dose (PHD) external photon beam and intraoperative electron beam therapy (IOEBT).

Twenty-five patients with a diagnosis of unresectable adenocarcinoma of the pancreas were explored in the Clement O. Miniger (COMROC) IOEBT operating amphitheater at the Medical College of Ohio. Seventeen were treated with IOEBT (20-30 Gy, 15 or 18 meV electrons) PHD external beam radiation therapy (40-60 Gy, 1.8 Gy per fraction) plus appropriate operative biliary and gastrointestinal bypass procedures. No intraoperative complications were observed. Two patients died of causes that may have been treatment-related. Two patients developed abdominocutaneous fistulae. Pain was ameliorated in eleven of twelve patients. Jaundice was relieved in all patients. Four of ten patients with weight loss showed a reversal of that trend. Patient survival was not significantly different from that of patients treated with high-dose precision therapy alone.