Enhanced recovery protocol in esophagectomy, is it really worth it? A cost analysis related to team experience and protocol compliance.

Application of enhanced recovery protocols (ERP) in esophageal surgery seems to lead an advantage in terms of length of hospital staying and outcomes, but only few data exist on its cost effectiveness. Previous literature analyzed pre- and post-ERP groups, finding a cost reduction with the introduction of the pathway. We aimed to study the influence on costs of accumulating experience and compliance in an ERP group. Seventy-one patients have been treated at our institution from January 2014 to June 2017 with our ERP for Ivor-Lewis esophagectomy. Direct costs were divided into subcategories and were analyzed as a function of calendar year and compliance. Factor affecting costs were searched. Univariable analysis highlighted a significant reduction in costs over time. Increase in compliance led to a progressive cost reduction for each ERP item completed (€14 852-€11 045). While age was not found to significantly influence the cost (p = 0.341), complications seemed to nullify the effect of experience: the median was €11 507 in uncomplicated patients, and increased to €13 791 in Clavien-Dindo 3-4 (CD3-4) patients. Compliance and CD3-4 remained significant also in multivariable analysis, accomplished by quantile regression, while year of surgery lost its significance. Our results evidence how accumulating experience in ERP led to a cost reduction over time, which was mainly mediated by an increase in compliance. Indeed, compliance was the main factor in reducing ERP cost while CD3-4 complications were the most important factor in cost increasing, nullifying the benefit of compliance.

Enhanced recovery after surgery protocol in patients undergoing esophagectomy for cancer: a single center experience.

This article is about an emerging issue in esophageal surgery: enhanced recovery after surgery (ERAS) Few data are published in literature and its safety and feasibility is still debated. The focus of our paper is on the feasibility of an ERAS protocol for esophagectomy (including both the Ivor-Lewis and McKeown procedure) in a high volume center comparing to a standard perioperative protocol. We introduced a novelty item on this type of surgery: resume of oral feeding in the first postoperative day. We analyzed the dropout rate for each item and the postoperative morbidity. We studied 39 patients operated in the Upper GI division of Verona University Hospital between January 2013 and August 2014; 22 patients (ERAS group) were studied in a perspective way while 17 patients (standard group) were studied retrospectively. The enhanced recovery protocol included intraoperative fluid management, time of extubation after surgery, intensive care unit discharge, drains and nasogastric tube management, mobilization of the patient, oral food intake. We compared the results between the two groups in term of hospital stay, postoperative morbidity and mortality. We also calculated the percentage completion of the protocol, evaluating patient drop-out rates for each of the items. Patients showed an improvement in the ERAS group in terms of earlier extubation, earlier intensive care unit discharge (p < 0.01), earlier thoracic drain, urinary catheter (p < 0.01) and nasogastric tube removal (p = 0.02), earlier mobilization (p < 0.01), and resume of oral feeding (p < 0.01). Median length of hospital stays in the ERAS group was 9 days while in the standard group was 10 days (p = 0.23). Postoperative morbidity and mortality were comparable between the two groups. This study shows the feasibility and safety of an ERAS protocol for esophageal surgery in a high-volume center. These data strengthen the literature results on this argument calling for larger sample size studies.

Patterns of relapse and modalities of treatment of breast cancer: the 'IRIS' Project, a multicenter observational study.

OBJECTIVES: The aim of this study was to describe the patterns of breast cancer relapse and the factors influencing therapeutic choices in an unselected postmenopausal population. METHODS: Five hundred and thirty-nine patients were enrolled between October 1999 and March 2001. The majority (92.6%) underwent surgery for the primary tumor: there was no difference between general and university hospitals in terms of the type of mastectomy, but a slight difference was found between Southern and Northern Centers. RESULTS: At the time of first relapse, 61.6% of the patients had a good Karnofsky performance status. The median disease-free interval (DFI) was 34 months. More than half of the patients (62.3%) presented a single metastasis. Metastatic disease was treated with chemotherapy in 64.8% of cases (alone in 44.1%, and in combination with hormone therapy in 20.1%), hormone therapy alone was given in 30.8% of cases. The main reasons for choosing chemotherapy were age (31%), standard guidelines (19.4%) and the site of metastatic disease (14.3%), and those for selecting hormone therapy were age (26.6%), site of relapse (19.3%), standard guidelines (19.2%), biological tumor characteristics (14.3%) and the DFI (11.1%). Taxane-containing treatments accounted for 46.1% of the chemotherapies, whereas letrozole was the preferred hormone (41.2%). CONCLUSION: The first relapse of breast cancer is often single, at bone or viscera, and mainly diagnosed by instrumental screening examinations. The preferred chemo- and hormone therapies are taxane-containing regimens and letrozole, respectively.

Effects of experimentally induced ametropia on the morphology and optical quality of the avian crystalline lens.

PURPOSE: To examine the effects of refractive error on avian lens morphology and optical quality. METHODS: Hatchling white leghorn chicks were unilaterally goggled for 7 days with either a form-deprivation goggle (n = 12), a -10 D defocus goggle (n = 12), or a +10 D defocus goggle (n = 12) to induce myopia and hyperopia. Optical quality of lenses (focal length and focal length variability) from treated and contralateral control eyes was assessed using a scanning laser apparatus. Lens morphology was examined by light and electron microscopy. RESULTS: Although the induction of refractive errors did not significantly alter lens size, shape, paraxial focal length, or average focal length, average focal length variability increased. Lenses from eyes goggled with form-deprivation and +10 D defocus goggles demonstrated a twofold increase in average focal length variability, when compared with their contralateral controls. The morphology of the lens is not altered by these experimental manipulations. CONCLUSIONS: This study provides evidence that the refractive development of the chick lens is not independent of the refractive development of the ocular globe and that chick lenticular development is influenced by both genetics and visual experience.

Relating clinical study design to basic research.

Devising any research study involves careful attention to its design, as well as the development of an appropriate research question and hypothesis. Together, these attributes ensure the validity of the study in question. In most clinical or epidemiological studies, the types of research designs are often explicitly noted, whereas in papers describing basic or biological research, they are couched in different terms or, more often, are ignored, thus potentially hindering communication between basic and clinical researchers. However, given that the framework for all valid scientific research is based on sound logic, it is proposed that for each study design, a direct homology exists between clinical and basic research paradigms, despite the problem of relating epidemiological vernacular to basic research. By applying examples of basic research protocols to traditional clinical study designs, this paper shows that parallels can be drawn between the two strategies, suggesting that in the absence of a conventional nomenclature to describe basic research study designs, the use of traditional clinical design jargon is valid in describing basic research protocols.

Effect of age on the morphology and optical quality of the avian crystalline lens.

The effect of age on the avian lens was examined using White Leghorn chickens of five age groups: hatchling (n =19), 7 day (n = 15), 34 week (n =10), 2 year (n =24), and 5 year (n =25). The chick lens grows steadily up to 34 weeks of age, after which, the rate of growth slows down. During growth, average focal length of the lens becomes longer. However, no significant changes were noted between 2 and 5 year old lenses. An age related increase in average lenticular focal length variability (FLV) was observed, revealing that the optical quality of the lens decreases with age. Scanning electron microscopy demonstrated that: (1) the suture region of the lens becomes more diffuse and less precise with age; (2) the central regions of younger lenses are oblate spheroids, while older lenses become more apple-shaped; (3) individual lens fibres in the young lens are crescent-shaped, while older lens fibres are square-bracket-like in shape; (4) the edges of individual lens fibres become more jagged and irregular with age; and (5) the layering of lens fibres is more disorderly in older lenses, in contrast to the parallel and organized layering of fibres in young lenses.

Spontaneous ureterocolic fistula: a rare complication of colonic diverticular disease.

Spontaneous ureterocolic fistula is rare and usually caused by urinary calculi. We present the fifth reported case of spontaneous ureterocolic fistula caused by diverticular disease of the colon. Review of these cases revealed a preponderance of women (3:1 ratio), with mean age of 77 years. These patients may have a protracted course before an accurate diagnosis is made (up to 10 years) because of the typical vague presentation. Urologic symptoms predominate, especially urinary tract infection (100%), fecaluria (75%), and abdominal (75%) or flank pain (50%). Barium enema is the most reliable diagnostic test in demonstrating the fistula (75%) compared with intravenous pyelogram (33%) or retrograde pyelogram (25%). The left ureter is usually involved (75%). Surgical intervention is generally directed towards resection of the diseased bowel with primary anastomosis when feasible. Surgical manipulation of the urinary system is unnecessary except for removing a non-functioning, infected kidney. Results of surgery were excellent, with 100 per cent cure and one unrelated mortality on long term follow-up. We recognize the potential for increase in this type of internal fistula, given the increasing lifespan and the established increase in incidence of colonic diverticular disease with advancing age. The correct diagnosis can often be determined preoperatively (75%), and surgical intervention is routinely successful.

Serious or fatal complications after inadvertent administration of ionic water-soluble contrast media in myelography.

The consequences of the inadvertent administration, by the intrathecal route, of ionic contrast media instead of iopamidol in seven subjects are reported. The ionic compounds were diatrizoate, iodamide and ioxitalamate. The outcome was fatal in three out of seven subjects, and it depended on the type and the dose of the administered contrast agent. The serious or fatal reactions observed are a tragic confirmation of the predictive power of neurotoxicity data obtained in animal studies with various iodinated water-soluble compounds. The margin of safety, represented by the ratio of LD50 i.ce. in mice to clinical dose in humans, both normalized to bodyweight, appears to reliably reflect the risk of toxic reactions after intrathecal administration of iodinated contrast agents.

Iopamidol in cardioangiography: a retrospective, multicenter study. Part I. Adult patients.

To evaluate the occurrence of complications during diagnostic or interventional catheterization a retrospective analysis of catheterization procedures in 12 Italian laboratories using the nonionic contrast medium (CM) iopamidol (370 mgI/ml) was performed. Data obtained on 26,219 patients greater than or equal to 14 years are presented. The overall complication rate was 1.89% (485/26,219). The overall mortality rate was 0.1% (27/26,219). Procedure related complications were 389 (1.48%) and CM related complications were 106 (0.4%). No death was attributed to CM. Ventricular fibrillation (VF) rate was 0.11% comparable to the low rate observed with nonionic CM in other studies and less than the rate observed in surveys concerning the use of ionic CM. Fifty-seven thrombotic events were recorded (0.22%), a rate comparable with other surveys with ionic and nonionic CM. The total complication rate (6.1%), the rates of coronary occlusion (1.34%), myocardial infarction (0.37%) and urgent coronary artery by-pass grafting (0.5%) in 1,348 coronary angioplasties were lower than those recorded in previous surveys. These data confirm a good tolerability and no increased risk of VF and thrombotic events with iopamidol in cardiac catheterization.

Iopamidol in cardioangiography: a retrospective, multicentre study. Part II. Paediatric patients.

To evaluate the complication rate in paediatric cardioangiography with the nonionic contrast medium iopamidol data on 8,166 procedures were retrospectively collected in 12 centres. The overall complication rate was 3.78% (309/8,166). 3.44% were related to the procedure, and 0.34% to the contrast medium. The mortality rate varied with age. It was higher in patients less than 2 months (0.38%) than in patients greater than 2 months-2 years (0.06%) and in patients older than 2 years (0.03%). The total complication rate was higher than the one observed in a similar retrospective analysis performed in adult patients (1.89%). This difference is probably due to higher risk conditions of the younger patients. However the contrast medium related complication rate (0.34% vs 0.4%) and the mortality rate (0.11% vs 0.1%) were comparable, confirming the good tolerability of iopamidol in cardiac catheterisation also in paediatric patients.

Comparison of the new alpha 1-blocker alfuzosin with propranolol as first-line therapy in hypertension.

The new alpha 1-blocker alfuzosin was compared with propranolol as monotherapy for hypertension in a double-blind, parallel group study of 8-week duration in 40 patients with essential hypertension. The patients (11 males, 29 females; mean age 47.8 +/- 2.2 years in the alfuzosin group and 46.6 +/- 2.4 years in the propranolol group) randomly received either alfuzosin from 2.5 mg b.i.d. up to 10 mg b.i.d. or propranolol from 40 mg b.i.d. up to 160 mg b.i.d. according to an individualized dose-titration schedule. The two groups were comparable with respect to disease history, cardiovascular risk factors, concomitant diseases, previous treatments and end-placebo blood pressure and heart rate values. Four patients did not complete the study, two patients in the alfuzosin group: one patient because of postural hypotension and the second one because of breast cancer; and two patients in the propranolol group: one patient for inefficacy and the second one lost to follow-up. At the end of the 8-week trial the mean daily doses were 12.2 +/- 0.61 mg and 196 +/- 9.82 mg for alfuzosin and propranolol, respectively. The antihypertensive effects of the two drugs were comparable. Upright and supine blood pressures decreased significantly with both treatments from the second week on (P less than 0.001 for all BP values). At the end of the 8-week double-blind trial, 83% of alfuzosin patients and 67% of propranolol patients were normalized. The two treatments differed significantly with respect to their effect on heart rate. Alfuzosin did not induce marked changes in heart rate: only a slight increase was observed. In contrast, propranolol caused bradycardia, more marked in the upright position. Palpitations, headache, asthenia and orthostatic hypotension were reported in the alfuzosin group. Asthenia and decreased libido were reported in the propranolol group. These data prove that alfuzosin has antihypertensive effects equivalent to propranolol and it is an interesting agent for the therapy of essential hypertension. It can be used as a first agent at doses between 5 and 20 mg/day with satisfactory therapeutic response and without relevant side-effects.

[Lymph node localization of gastrinoma. Diagnosis and treatment]. / Gastrinoma a localizzazione linfonodale. Diagnosi e trattamento.

The case of a 48-year old woman with a lymph node localization of gastrinoma is reported. The preoperative workup (US-scan, TC-scan and NMR) made it possible to detect and localize the lesion. A conservative surgical approach was decided according to the latest literature reports which showed a favourable course in patients with lymph node gastrinoma. Surgical resection has been accomplished. The patient's hormone level was normal at one-year follow-up.

[A case of cryptogenic bleeding: degenerative cystic angiodysplasia of the right colon]. / Un caso di sanguinamento criptogenetico: l'angiodisplasia cistica degenerativa del colon destro.

The authors report a case of gastro-intestinal bleeding due to arteriovenous malformation of the right colon: the angiodysplasia (AVMs-Moore's type 1). The investigations usually adopted in case of G.I. bleeding (x-Ray-examinations and endoscopy) are often unable to define the diagnosis. In this report the diagnostic importance of selective angiography in patients with lower intestinal blood loss is emphasized.

Intravenous diltiazem in patients with paroxysmal re-entrant supraventricular tachycardia.

The electrophysiologic effects and efficacy of diltiazem were evaluated with programmed electrical stimulation of the heart in 12 patients with supraventricular re-entrant tachycardia (five with atrioventricular nodal tachycardia and seven with circus movement tachycardia the accessory pathway being concealed in 4). Diltiazem was infused over 1 minute at the dose of 0.25 mg/kg and the electrophysiologic parameters were evaluated at 5 and 30 minutes. Diltiazem prolonged the AH interval from 83.5 +/- 58 to 99 +/- 55 msec (P less than 0.05), effective and functional refractory periods of atrioventricular node from 244 +/- 40 to 268 +/- 56 msec (P less than 0.05) and from 432 +/- 124 to 468 +/- 130 msec (P less than 0.005) respectively, lowered the atrial pacing rate inducing second-degree atrioventricular block from 159 +/- 32 to 134 +/- 33 beats/min (P less than 0.005) and decreased systolic and diastolic blood pressure from 143.5 +/- 33 to 132.5 +/- 22 mm Hg (P less than 0.05) and from 90 +/- 15 to 82.5 +/- 9 (P less than 0.05), respectively. Diltiazem prevented the reinduction of the tachycardia in 4 of 5 patients with atrioventricular nodal tachycardia and in 4 of 7 with circus movement tachycardia. The mechanism of action of diltiazem consisted of depression of conduction in atrioventricular node in anterograde fashion while there were no effects on refractoriness of the accessory pathway. The drug was well tolerated with no adverse effects. Diltiazem, therefore, appears an effective and safe drug in the acute treatment of re-entrant supraventricular tachycardia.

Dose-titration study of alfuzosin, a new alpha 1-adrenoceptor blocker, in essential hypertension.

An open, dose-titration study of alfuzosin, a new selective post-synaptic alpha 1-adrenoceptor antagonist with additional direct vasodilator properties has been performed. After a 3-week run-in placebo period, 12 patients with essential hypertension received alfuzosin 5 mg oral b.d., and then the dose was doubled every week, up to a maximum of 20 mg q.i.d. if the supine diastolic blood pressure was greater than 90 mm Hg. The study lasted for 4 weeks. Supine blood pressure (SBP) decreased from 160/102 (Day 0) to 148/89 mm Hg and upright blood pressure (UBP) from 151/102 (Day 0) to 137/84 mm Hg. Alfuzosin did not cause any significant change in supine or upright heart rate. In addition, after the first dose of alfuzosin, supine and upright blood pressure and heart rate (SHR and UHR) were measured every 30 min for 5 h. The fall in blood pressure was significant after 90 min and it lasted up to the 5th hour; the maximum effect was observed after 3 h: SBP decreased from 159/103 (time 0) to 137/84 mm Hg and UBP from 150/102 (time 0) to 123/79 mm Hg. SHR was increased from 72 (time 0) to 81 beats/min at the 5th hour and UHR from 87 to 101 beats/min at the 4th hour. A weak but significant correlation was observed between the hypotensive effect 12 h after drug intake and the plasma concentration of the drug at that time. A 10% decrease in supine diastolic blood pressure was found at a drug plasma concentration higher than 7 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Dose-response relationship of prizidilol hydrochloride (SK&F 92657): a comparison between acute and chronic effects in patients with essential hypertension.

Three different doses (50, 100 and 200 mg) of prizidilol hydrochloride (SK&F 92657), a novel antihypertensive agent with vasodilating and beta-adrenoreceptor blocking properties, were given to three (n = 5) groups of essential hypertensive patients in order to evaluate hypotensive dose-response relationship of the drug and its beta-adrenoreceptor blocking properties. Irrespective of the dose given, acute administration of prizidilol did not effectively decrease blood pressure; however after one-week of treatment prizidilol was effective in reducing blood pressure at both the 100 and the 200 mg b.i.d. schedules. At these doses the drug decreased resting heart rate and plasma renin activity for the first 4-6 h after both acute and steady-state dosing. Similarly postdynamic exercise tachycardia was reduced to a significant extent by the drug; after acute administration this effect lasted 2 h with the lowest dose and 4 h with the highest one. After chronic administration this effect lasted up to 10 h for both the 100 and 200 mg doses. These data indicate that: chronic prizidilol treatment can achieve a satisfactory control of blood pressure in patients with mild-moderate essential hypertension; when prizidilol is administered chronically in hypertensive patients, an equally effective control of blood pressure can be obtained with either a 200 mg b.i.d. or a 100 mg b.i.d. schedule; prizidilol possesses beta-adrenoceptor blocking properties in man which can contribute to its pharmacodynamic activity.

Effects of prizidilol (SKF 92657) on blood pressure, haemodynamics, sympathetic nervous system activity and plasma volume in essential hypertension.

1. The antihypertensive effect of 4 weeks' treatment with prizidilol (SKF 92657) (mean dosage 520 mg once or twice daily) was studied in ten essential hypertensive patients. 2. Both systolic and diastolic blood pressure were significantly reduced in all cases. Supine heart rate did not change, and in the erect position heart rate was significantly lowered. 3. Blood pressure reduction was due to peripheral vasodilatation, as the cardiac index increased after 4 weeks of prizidilol treatment. 4. After prizidilol plasma noradrenaline and adrenaline increased significantly, and PRA and plasma aldosterone were reduced. Although plasma volume increased, body weight did not change. 5. Cardiac performance, as evaluated by the PEP/LVET ratio, improved after treatment with prizidilol.