Islet cell carcinomas of the pancreas: a twenty-year experience

Unlike its lethal exocrine counterpart, islet cell carcinoma of the pancreas is an indolent neuroendocrine neoplasm. The majority of these tumors are hormonally active. When functioning, a number of clinical syndromes (for example, hyperinsulinism, Zollinger-Ellison and Cushing's syndromes) may be evident. Fifty-eight patients surgically treated between 1965 and 1984 were retrospectively analyzed. The purpose of this study was to determine the distribution of functioning versus nonfunctioning tumors and the response to type of therapy. Mean postoperative follow-up was 7.4 years. Survival and prognostic indices were calculated by the Kaplan-Meier method and compared with log-rank tests. Of the group, 54% had functioning and 46% nonfunctioning tumors. Gastrinomas were the most common functioning tumors encountered (19%). Of interest was the finding that nonfunctioning tumors increased steadily during the last 15 years of the study (25% to 65%). Curative resections were performed in 15 (26%) and noncurative procedures in 43 patients (74%), with an overall operative mortality rate of 3%. Symptomatic improvement was achieved in 90% (curative) and 51% (noncurative). Survival at 3 years was 87% and 66% for the curative and noncurative groups, respectively (p less than 0.1), with an overall 5-year survival of 42%. The absence of hepatic metastases was a major predictor of survival at 3 years (82% vs 56%, p less than 0.05). Survival was statistically better at 3 years in those patients with gastrinomas compared with patients with nonfunctioning tumors (91% vs 58%, p less than 0.05). Although surgical cure is rare, significant long-term palliation may be achieved in a large percentage of patients with an aggressive surgical approach, occasional total gastrectomy, combination chemotherapy, H2 blockade, when indicated, and, most recently, with the new long-acting analogue of somatostatin.     

Antagonism of midazolam sedation by flumazenil: a placebo-controlled study in patients recovering from intravenous anaesthesia with high doses of midazolam

Twenty adult surgical patients were anaesthetized with high-dose midazolam and alfentanil by infusion, vecuronium, and intubated and ventilated with 50% N2O in O2. The midazolam and alfentanil infusions were stopped at the end of surgery. Residual neuromuscular blockade and ventilatory depression were antagonized and the patients extubated. In the recovery room, patients were randomly allocated to receive either flumazenil 1 mg of placebo i.v. Before, and until 2 h after injection, patients were asked to perform psychomotor tests. In addition, sedation, comprehension and orientation were scored. The flumazenil (n = 10) and the placebo (n = 10) groups were comparable. Prior to injection all patients were heavily sedated. After flumazenil all were awake within 2-3 min, but fell asleep again 15-60 min later. The improvement in test scores was sustained for a longer time. After placebo, patients awoke in 1-2 h. At 60 and 120 min, test scores in the two groups were similar. Heart rate, blood pressure and respiration rate did not change. No side-effects were observed or reported. It is concluded that flumazenil is an effective and safe antagonist of high dose midazolam, with a rapid onset but a short duration of action.     

Percutaneous nephrolithotomy. Experience with renal and proximal ureteral calculi at Tygerberg Hospital

Percutaneous nephrolithotomy (PCN) enables the urologist to remove upper urinary tract stones through a percutaneous nephrostomy tract. The principal advantages of PCN are the low morbidity, shortened hospital stay and rapid recovery. Percutaneous puncture failed in 5 (11%) of the first 44 patients with upper tract urolithiasis treated by PCN at Tygerberg Hospital. In 35 patients (80%) PCN cleared the kidney of stones but in 4 patients (9%) all stone fragments were not removed during the procedure. If the puncture and dilatation was successful, then 90% of patients were stone-free after PCN. Complications were minimal except for a diabetic who died of septicaemia. PCN is an alternative to open renal surgery in the management of most upper urinary tract stones. The technique is readily mastered by any urologist experienced in endoscopic surgery.     

Tear function parameters in keratoconjunctivitis sicca with and without the association of Sj?gren's syndrome

In a group of patients with keratoconjunctivitis sicca (KCS) associated with Sj?gren's syndrome (SJ) a significant decrease in tear fluid lactoferrin concentration and tear film break-up time was demonstrated in comparison with a matched group in which KCS was not associated with any systemic disease. The Schirmer values were also lower in the SJ of patients and these differences almost reached statistical significance. None of these parameters in itself appeared to be of any clinical value to differentiate between KCS that was or was not associated with SJ. The combination of the tear fluid lactoferrin concentration, the Schirmer I test values and the tear film break-up time, however, provide a basis for differential diagnosis that is clinically of some value.     

Ink and bytes]

Paper journals--and books--will continue to exist, despite the digital revolution. Electronic media are superior for storage and retrieval of information, but far less so for intellectual digestion. The Dutch Journal of Medicine is proud of its recently completed electronic archive, in the form of digital images (1857-1985) and full text (from 1986 onwards). At the same time the Journal's supporting Society cherishes a valuable book collection, with some 700 titles before the year 1800 alone. Recently, a curator and a professional librarian were appointed. Part of the Society's assets have been transferred to a special fund for the support of projects on the borderline between medicine and other disciplines, such as history, philosophy, sociology and art.     

Interstitial and vascular pancreas rejection in relation to graft survival

To examine the incidence of interstitial and vascular rejection in pancreas allografts and its impact on graft survival, we studied 36 percutaneous pancreas biopsies and 10 pancreas transplantectomy specimens from 32 patients who had undergone simultaneous pancreas-kidney transplantation. Interstitial rejection (IR) was predominantly found in the biopsies, while vascular rejection (VR) was most prominent in the transplantectomies. Pancreas graft survival was significantly decreased for pancreas grafts that had suffered from vascular rejection when compared to those with only interstitial rejection. Potential rejection markers, i. e., serum amylase, glucose, creatinine, and urinary amylase, did not correlate with histological signs of rejection, although increased levels of serum amylase were, in all but one case, associated with rejection.We conclude that a percutaneous pancreas biopsy remains the most reliable method to determine pancreas rejection, and that by distinguishing between IR andVR, a pancreas biopsy may provide important diagnostic as well as prognostic information. Received: 6 March 1997 Received after revision: 5 June 1997 Accepted: 30 June 1997     

Toe temperature versus transcutaneous oxygen tension monitoring during acute circulatory failure

Measurements of toe temperature and transcutaneous PO₂ (P_tcO₂) have been both suggested for non-invasive assessment of peripheral blood flow in acute circulatory failure. The underlying principle of the two methods is that cutaneous vasoconstriction occurs early when tissue perfusion is altered. In 15 patients, we compared the two measurements during cardiogenic shock (27 measurements) or septic shock (29 measurements). Toe-ambiant temperature gradient and P_tcO₂ correlated well together (r=0.66, p(0.001) especially in hyperkinetic septic shock (r=0.79, p(0.001). In cardiogenic shock, toe-ambiant temperature correlated well with cardiac index (r=0.63), stroke index (r=0.64) and oxygen transport (r=0.65), and these correlations were stronger than for P_tcO₂. In septic shock, both techniques were poor indicators of blood flow indexes but P_tcO₂ rather correlated with arterial pressure (r=0.66) and left ventricular work (r=0.66). Trend evaluation of data revealed in cardiogenic shock that the increase in toe temperature usually preceded the increase in P_tcO₂. Since measurement of P_tcO₂ is technically more complicated, correlates less well with standard hemodynamic parameters and later reflects cardiovascular improvement, it has no advantage over measurement of toe temperature in circulatory shock. In cardiogenic shock, measurements of toe temperature can reliably track cardiac output changes. In septic states, however, non-invasive assessment of skin perfusion is of limited interest.     

A comparative study on the diagnostic value of prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) in patients with carcinoma of the prostate gland

Serum prostatic-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined simultaneously in 241 patients presented to the Urology Department. The patients consisted of 140 prostatic carcinoma patients (34 newly diagnosed and 106 previously treated) and 101 patients with benign prostatic hypertrophy (BPH). Prostatic acid phosphatase was measured by two different methods, an enzymatic method (PAP-EA, Boehringer) with tartrate inhibition and an immunoenzymetric assay (PAP-IEMA, Hybritech). The concentration of prostatic specific antigen in serum was measured using a recently introduced immunoradiometric assay (PSA-IRMA, Hybritech). Receiver operating characteristic curves were constructed to compare the diagnostic value of the different tests at different cutoff values. The diagnostic efficiencies of the PAP-EA and the PAP-IEMA appeared to be similar. A better diagnostic efficiency for PSA compared to PAP was found independent of the cutoff value. The upper-normal limit of 2.7 micrograms/l for PSA, as suggested by the manufacturer and mentioned in the literature introduces too many false-positive results. We therefore selected 10 micrograms/l as the upper-normal limit for PSA (sensitivity 57%, specificity 88%). Combined sensitivity found for PAP + PSA was 37% with a specificity of 97%. A literature survey is included to allow better comparison with data published elsewhere.     

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10IUml ^-1), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10–20 IUml ^-1) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors'practice is now to start GH replacement at less than the usual recommended dose of 14IUm-² week^-1 in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilledema does not exclude the diagnosis.     

Dexfenfluramine in the treatment of severe obesity: a placebo-controlled investigation of the effects on weight loss, cardiovascular risk factors, food intake and eating behaviour.

Dexenfluramine, an effective and safe serotoninergic drug with anorectic and possible food-selection-tuning properties, was investigated in a placebo-controlled study of 1 year's duration in severe and refractory obesity. The aim of the study was to assess weight loss, and changes in cardiovascular risk factors, food intake and eating behaviour. Dexfenfluramine- and placebo-treated patients achieved a similar weight loss (greater than 10% of initial weight, by 39.5 and 30.0%, greater than 20% of initial overweight by 42.1% and 32.5% and greater than 10 kg by 41.4 and 33.3%, respectively, of the initial cohorts). Furthermore, the decreases in weight (10.7 vs. 8.0 kg), in body mass index (3.9 vs. 2.9 kg m2) and in waist/hip ratio (0.04 vs. 0.02) were not significantly different. After discontinuation of the drug, the increase in weight (2.8 vs. 1.0 kg) was significantly higher in the dexfenfluramine-treated group. Except for a borderline better effect on glucose of dexfenfluramine, both groups showed similar beneficial changes in food intake and cardiovascular risk factors. Eating behaviour in response to emotional and external stimuli was comparable in the two groups, but placebo-treated patients had to restrain their eating more in order to achieve the same weight loss. Notwithstanding the fact that weight losses and an associated amelioration of health-risk factors were of similar magnitude in dexfenfluramine- and placebo-treated patients, dexfenfluramine might have a useful role in promoting a less stressed adherence to prolonged restriction of energy intake in the severe and refractory obese subject.