Successful multimodal treatment of a breast cancer patient with a recurrence invading the chest wall.

We describe successful operative management of a solitary breast cancer metastasis in the chest wall after complete response with concomitant non-pegylated liposomal doxorubicin (NPLD) and docetaxel followed by sternal rib resection with prosthetic reconstruction. We report a case of a 41-year-old woman who had a breast cancer recurrence infiltrating neighboring osteo-cartilage of the left sternal body, the cartilaginous portion of the third and fourth ipsilateral ribs and was inseparable from the rear side pectoral reaching deep into contiguity with the pericardium. After 6 cycles of chemotherapy with NPLD plus docetaxel, sternal rib resection with prosthetic reconstruction was performed. Histological examination did not show any evidence of residual tumor. At 9 months of follow-up, the patient appears free of disease. Our case demonstrates that a multimodal approach in patients with chest wall recurrence of breast cancer without distant metastasis, may be safe and effective for maintaining a good quality of life.

[Predisposing factors for development of cardial adenocarcinoma]. / Fattori predisponenti l'adenocarcinoma del cardias.

After a careful revision of the various papers and on the basis of their personal experience, the persons responsible for this project analyse the factors that, today, influence the development of an adenocarcinoma in the region of the gastro-esophageal junction. They also study therapeutic strategies on the basis of new findings in anatomic-physiological matters of this region. From this analysis, specialists notice an increase in adenocarcinomas which affect the gastric region of the cardia, in comparison with carcinomas which affects the gastric region in toto. By considering Barrett, Hayward, Riedel and Ruol's studies, they maintain that the fundamental factor which causes the development of cardial adenocarcinoma is the gastroesophageal reflux. This reflux acts as a chronic irritative stimulus on the esophageal wall and therefore it provokes an increase in mucous secretion and the formation of metaplasia. This metaplasia is initially mucosecreting, acid-secreting and in the end it becomes intestinal. This also leads to the appearance of absorbent calciform cells; the absorption of toxic or mutagenic substance for the cell itself, will be the next step for the development of an adenocarcinoma. Nowadays the therapy of intestinal metaplasia provides for different therapeutic levels: from the endoscopic monitoring (which is used for the most serious cases of dysplasia), to the PPI medical treatment(today in disuse), to the surgical laparoscopic treatment with non-refluxing plasty (Nissen, Toupet). This last treatment is today associated with endoscopic esophageal mucosectomy in order to achieve a better effectiveness. This happens through the use of various methodologies, for example the multipolar electrocoagulation.

[Lung surgery in the elderly]. / La chirurgia polmonare dell'anziano.

Lung surgery in the elderly, once considered a major risk, to be avoided if possible has become more popular in recent years as a result of many factors. First: lung cancer incidence has increased significantly in every age group but mostly in the elderly. Second: diagnosis at an early stage of the disease is higher in patients over 70 due to more frequent medical control in old subjects. Third: we now have more and more humans over 80 and a life expectancy increasing over the years. Fourth: preoperative, operative and postoperative medical supports are now safer and more reliable than previously. Operability criteria in the elderly are substantially the same as in younger group of patients for lung cancer. There are no reasons to refuse surgery in a subject over 80 because he is old. Lobectomy is the procedure of choice for lung cancer even in the elderly. Pneumonectomy must be avoided preferring a less radical procedure (wedge resection) so avoiding the risk of a postoperative respiratory failure that is often fatal for a patient with in border line functional respiratory tests, as often happens in the elderly. Thoracoscopic atypical resections must be considered in patients when a wedge resection is indicated preoperatively and almost always metastatic pulmonary lesion.

[Duodeno-gastric reflux in gallbladder stones and after laparotomic cholecystectomy]. / Il reflusso duodeno-gastrico nella calcolosi della colecisti e doppo colecistectomia laparotomica.

BACKGROUND: Duodeno gastric reflux (DGR) is still a not well-defined condition, even though it has been the subject of different studies for many years. METHODS: The authors examine its relation with gallstones before and after the surgical removal of the gallbladder. After examining various study techniques, they present their experience of DRG. In this work the methodology used in a group of 40 patients suffering from gallstones and operated by laparotomic cholecystectomy is presented. All patients have been subjected to a clinical questionnaire in order to evaluate their symptoms, before and after cholecystectomy, and at the same time they have been subjected to an endoscopic exam. It s not easy to comment the RESULTS. RESULTS: Actually, of 32 patients (80%) showing DGR symptoms before surgical treatment, 20 showed their persistence, worsening, or the appearance of new symptoms after cholecystectomy, while 12 were completely asymptomatic. Of 8 patients with no symptoms before cholecystectomy, 3 developed a typical DGR symptomatology while 5 were asymptomatic. CONCLUSIONS: So 57% of patients were DGR symptomatic after surgical treatment. The compromised function of cholecystitis with calculi, antrum-pyloric-duodenal motility, continuous bile flux in the duodenum, surgical trauma all interact in determining DGR.

[Current diagnosis of gastroesophageal reflux disease: learning experience]. / Diagnosi attuale della malattia da reflusso gastroesofageo: esperienza di scuola.

The authors report their study on gastro-esophageal reflux disease, a pathology that has become increasingly common over the past years reflecting both a real increase and the use of new and more sophisticated and reliable diagnostic methods and tests. It can be included in the group of pathologies absorbing the largest proportion of financial resources, even exceeding biliary lithiasic disease according to American studies. The authors start by analysing the symptoms of gastroesophageal reflux disease, drawing a distinction between typical (heartburn, epigastric pain and postprandial regurgitation) and atypical symptoms (laryngotracheal symptoms, bronchopulmonary symptoms and esophageal motor incoordination). They outline the diagnostic iter and tests most widely used today to achieve a correct diagnosis. Lastly, they report their experience of 160 patients attending their esophageal diagnostic unit since January 1999 who underwent a number of different instrumental tests, the results of which are compared. Three different aspects are compared: the presence of symptoms, 24-hour pH-metry and endoscopic tests. All these are necessary for a correct diagnosis of gastroesophageal reflux disease and to evaluate the possibility and efficacy of surgery. They emphasise the diagnostic importance of 24-hour pH-measurement as the only test that can directly reveal gastroesophageal reflux. Positive pH results represent a discriminating element in deciding whether the patient should undergo surgery.

[Gastroduodenal reflux after laparotomic or laparoscopic cholecystectomy]. / Il reflusso duodeno-gastrico dopo colecistectomia laparotomica o laparoscopica.

BACKGROUND: The authors analyse gastroduodenal reflux (GDR) in the light of the progress made over the past ten years. The good results achieved using mini-invasive techniques in cholecystectomy prompted the authors to compare laparotomic and laparoscopic cholecystectomy in order to evaluate the influence of both techniques in determining GDR and clinical symptoms. METHODS: Symptoms were evaluated before and after surgery in 30 patients operated using a laparotomic technique and in 30 patients operated using a laparoscopic technique. Two groups of 10 patients, operated respectively using laparotomic and laparoscopic techniques, were studied both clinically and endoscopically before and after surgery. RESULTS: The analysis of the results shows a lower incidence of GDR and typical symptoms of GDR in patients undergoing laparoscopic surgery. The rationale underlying the lower incidence of GDR and its symptoms in these patients compared to the more conventional group is not completely clear. CONCLUSIONS: These results may be influenced by reduced surgical trauma and the careful selection of case or the laparoscopic technique, hence the exclusion of cases complicated by severe cholecystitis.

[Ileal occlusion caused by enterolith migrated from Meckel's diverticulum]. / Occlusione ileale da enterolita migrato da diverticolo di Meckel.

The authors present a case report of an intestinal obstruction due to a relatively big coprolite migrated from a large Meckel's diverticulum to the distal Ileum. The patients apparently healthy and a vegetarian, complained on admission of the absence of emission of faeces and gas since four days before with noticeable abdominal distension. In the physical examination he presented intestinal meteorism, a hard abdomen, painful on deep palpation in the median quadrants, especially in the epigastric and mesogastric ones. The abdominal X-RAY in the standing position confirms: an occlusive state with numerous liquid levels in the Ileum. Because of a worsening of the symptomatology and the appearance of generalized comprimission, two days later an exploratory laparotomy was performed. The intervention showed the presence of a Meckel's diverticulum with approximately 10 cm in length, with an ample neck, the distal Ileum for approximately 15 cm in dilation returned rapidly to a normal calibre, after a pastous endoluminal formation borne in the Meckel's diverticulum (Meckel resection presented actually a large niche at the fundus level with a eroded wall) and migrated in the distal Ileum where it could cause the obstruction. In the present case it is probably useful to perform a preoperative CT scan in order to get a precise etiology and perform an ascending Colonscopy, so avoiding a surgical procedure. According to the authors a CT scan is indicated in all cases of intestinal occlusion of unknown case, in order to have a more precise definition of the physiopathology of the occlusion.

[Surgery of large ventral hernias. Personal experience in 1990-1997]. / La chirurgia dei grandi laparoceli. Esperienza di scuola 1990-1997.

BACKGROUND: The surgical treatment of large wall defects conventionally defined as an extension over 10 cm is discussed. The difficulty to contain the bowels that have lost law of domicile in the abdominal hollow, constitutes motive for notable increase of the endo-abdominal Pressure with serious consequences in the postoperative course and this leads to the use of prothesis meshes that allow the closing of the abdominal hollow with the Tension-Free technique. METHODS: Personal experience embraces 45 patients, with large wall defects, divided into 21 patients with overumbilical location, 14 with umbilical location, 10 with periumbelical location; a simple suture has been used in 7 cases, the reconstruction of the wall according to Stoppa in 36 cases and the apposition of Goretex net internally and Marlex net externally in 2 cases. RESULTS: There have been neither mortality, neither recidivists of illness, but only some complications: 9 cases of superficial infection, 1 case of intestinal occlusion and 2 of subcutaneous seroma. CONCLUSIONS: According to their experience and wide literature review, the authors draw some conclusions: an accurate toilet and a careful evaluation of the respiratory functionality are fundamental; it's necessary to postpone surgical intervention in presence of local inflammation and, where this is improrogable it's opportune to avoid the use of prothesis meshes or refold on readsorbible prothesis; special care must be taken to the hemostasis and an aspirative drain for 24-48 hrs preserves from the risk of postoperative hematomas and following local infections. The submuscular mesh permits a Tension-Free suture and for this reason it would have nowdays a more extensive use. Finally it's pointed out the choice of a PTFEe mesh in contact with the intestinal skein.

[Secondary costal myxoid chondrosarcoma. Presentation of a clinical case]. / Condrosarcoma mixoide costale secondario. Presentazione di un caso clinico.

A type of malignant neoplasm of not frequent observation is reported and the difficulties concerning the distinction from the benign counterpart are underlined, for which a detailed instrumental study is made necessary, integrated with pre and, above all, postoperative histologic analysis. A white male patient of 83, affected by plurirecidivant chondromyxoma of the rib, was admitted for local recurrence. The lesion objectively appeared not dissimilar from the preceding ones, as an ovalar mass fixed on the underlying plains. Radiologic and ultrasonographic examinations seemed to confirm the admission diagnosis; at the end the patient underwent a new intervention. Histologic examination of the lesion yielded a diagnosis of chondromyxosarcoma. The clinical case is made even more interesting by the finding, through the TC technique, preoperatively performed, of a metastatic repetition on the opposite side. The authors examine the problem of the early recognition of a malignant neoplasm developing, in a patient with a clinical history of recidival chondromyxoma. Physical examination and laboratory analysis are not useful in the assessment of the occurring transformation. At molecular level chondromyxosarcoma is characterized by several genomic rearrangements and mutations. Though primitive chondromyxosarcoma often involves the ribs, chondromyxoma's transformation into its malignant counterpart is not a common event. The development of distant metastasis characterizes long term cases. Given the lack of encouraging results about chemo and radio-therapy efficacy in influencing the natural course of the disease, a systematic approach will be made necessary in patient management.

Effect of renal impairment on the pharmacokinetics and pharmacodynamics of desirudin.

OBJECTIVE: To investigate the pharmacokinetics and pharmacodynamics of desirudin in subjects with various degrees of renal impairment in comparison with subjects with normal renal function. METHODS: Eight subjects with normal renal function (creatinine clearance > 90 ml/min) received 0.5 mg/kg desirudin intravenously over 30 minutes. Four subjects with mild renal failure (creatinine clearance between 61 and 90 ml/min) received 0.5 mg/kg. Five subjects with moderate renal failure (creatinine clearance between 31 and 60 ml/min) received 0.25 mg/kg. Six subjects with severe renal failure (creatinine clearance < 31 ml/min) received 0.125 mg/kg. RESULTS: Specific maximum concentration values (maximum concentrations corrected to a dose of 1 mg/kg) increased slightly with decreasing creatinine clearance. Mean specific area under the plasma concentration-time curve increased by a factor of 1.15, 2.83, and 7.0 for subjects with mild, moderate, and severe renal failure, respectively, compared with healthy subjects. Total urinary excretion of desirudin was about 55% to 60% of the dose in all four groups; elimination was delayed for subjects with moderate and severe renal failure. Total and renal clearance of desirudin were proportional to creatinine clearance. Total plasma clearance of desirudin was proportional to renal clearance of the drug. Prolongation of activated partial thromboplastin time was increased among subjects with moderate and severe renal failure despite a dose reduction. Area under the dynamic activated partial thromboplastin time curve for subjects with moderate renal failure remained the same as that for healthy subjects despite a dose reduction by a factor of two. Area under the dynamic curve increased by a factor of about 1.5 for subjects with severe renal failure despite a dose reduction by a factor of four. CONCLUSION: A dose reduction by a factor of six is recommended for persons with severe renal failure.

The effect of valsartan on the angiotensin II pressor response in healthy normotensive male subjects.

OBJECTIVE: Valsartan is an oral antagonist of angiotensin II that competes with angiotensin II for the AT1-receptor and is being developed as an antihypertensive agent. This study assessed the ability of 80 mg valsartan to inhibit the pressor effect of exogenous angiotensin II in healthy normotensive men, first after a single dose and then after multiple doses once daily for 7 days. METHODS: This was a single-center, double-blind, placebo-controlled, randomized crossover study. Six healthy men underwent angiotensin II challenges to determine a suitable dose required to increase their systolic blood pressure by approximately 30 mm Hg. Each subject then received an 80 mg dose of valsartan or matching placebo. The inhibition of the angiotensin II pressor effect was determined by the systolic blood pressure response to repeated angiotensin II challenges at multiple time points. RESULTS: Systolic blood pressure responses to angiotensin II challenges after single and multiple doses of valsartan were significantly lower than placebo, indicating that valsartan blocked the blood pressure response to angiotensin II. The maximum blocking effect was observed within 2 to 3 hours. Mean data suggested that differences in effect between valsartan and placebo were similar after both single and multiple doses and persisted up to 24 hours after administration. The angiotensin II blocking effect was maintained up to this time, despite low plasma valsartan levels and minimal accumulation after multiple doses. CONCLUSION: Valsartan, 80 mg, is a potent angiotensin II antagonist with a rapid onset of action and persistent angiotensin II inhibition up to 24 hours. There is no attenuation of this effect after multiple doses.

Managing medication in the elderly.

The elderly receive 30% of all prescriptions and buy 40% of all OTC drugs. In addition to the potential pitfalls inherent to age-related changes in bioavailability and clearance, there are less well-known hazards in prescribing for the aged. Many drugs, for example, have powerful anticholinergic properties, and a generic agent may differ markedly from both the brand drug and another generic version.

Comparative pharmacokinetics and bioavailability of nitroglycerin and its metabolites from Transderm-Nitro, Nitrodisc, and Nitro-Dur II systems using a stable-isotope technique.

The pharmacokinetics and bioavailability of nitroglycerin (GTN) and its metabolites, 1,2-glyceryl dinitrate (1,2-GDN) and 1,3-glyceryl dinitrate (1,3-GDN), were compared after a single 14-hour application of Transderm-Nitro (Ciba-Geigy, Summit, NJ), Nitrodisc (GD Searle, Chicago, IL), and Nitro-Dur II (Key Pharmaceuticals, Kenilworth, NJ) systems to 18 healthy male subjects on 3 separate occasions. A 14-hour intravenous infusion of 15N-labeled GTN was given simultaneously to correct for changes in systemic clearance during the application of each system. Plasma concentrations of 15N-labeled GTN, unlabeled GTN, and their corresponding dinitrate metabolites were measured using a gas chromatography/mass spectrometry method. Results showed that the plasma concentration profiles of nitroglycerin and its metabolites for the three systems were similar during and after system removal. Mean (SD) total amounts (AUCp x CLiv) of GTN transdermally available after adjustment for 15N-labeled GTN clearance were 5.3 (2.1), 5.3 (2.0), and 5.4 (2.6) mg for Transderm-Nitro, Nitrodisc, and Nitro-Dur II, respectively. Mean (SD) AUC values for 1,2-GDN were 44.6 (15.8), 44.3 (16.1), and 42.8 (19.3) ng.h/mL for the 3 systems. Corresponding AUC values for 1,3-GDN were 9.3 (2.9), 9.7 (2.9), and 8.7 (3.0) ng.h/mL. Statistical analysis of the log-transformed data based on 90% conventional confidence interval showed that all 3 systems delivered equivalent amounts of nitroglycerin into the systemic circulation. The AUC ratios for 1,3-GDN to GTN, but not 1,2-GDN to GTN, were statistically different for the intravenous and transdermal routes during all 3 system applications, indicating that the formation and metabolism of 1,3-GDN was dependent on route of administration.

Inhibition of angiotensin-converting enzyme with libenzapril in normotensive males.

The effect of intravenous (i.v.) libenzapril was studied in six healthy males by administering i.v. angiotensin I (AI) administered in stepwise increments of 20 ng/kg/5 min until the subjects' systolic blood pressure (SBP) had increased 20-30 mm Hg above baseline. The mean baseline infusion of 63 ng/kg/5 min resulted in a significant (P < 0.05) increase in the ratio of AII to AI plasma levels from 0.52 +/- 0.46 to 7.92 +/- 4.48 and a SBP increase of 120 +/- 7.1 to 147 +/- 5.6. Within 15 minutes of starting the 1-mg infusion of libenzapril over 1.5 hours, the AII/AI ratio decreased to baseline values, and the SBP had returned to baseline in 1 hour. Repeat AI challenges at 3.5 and 5 hours postdose did not increase SBP significantly. Even the 6.5-hour challenge demonstrated only a slight increase in SBP, with an AII/AI ratio of 0.26. At 24 hours, SBP was only 40% of the baseline response, demonstrating that libenzapril is a potent long-acting ACE inhibitor.

Pharmacodynamics of a continuous intravenous infusion of CGP-35126 recombinant human insulin-like growth factor-I (rhIGF-I) on glucose and insulin levels in healthy males.

Recombinant human insulin-like growth factor-I (rhIGF-I) was evaluated in 7 healthy males to determine the pharmacodynamics on glucose and insulin levels. Each subject received an initial intravenous infusion of normal saline and on the following day, rhIGF-I at a rate of 21.4 micrograms/kg/h over 7 hours. The subjects' fasting baseline glucose and insulin levels were not statistically different (p > 0.05) from their pre-dose levels. Compared to the saline (control) infusion, glucose levels were statistically lower (p < 0.05) 2 hours into the rhIGF-I infusion, and were suppressed until the subjects consumed a standard lunch (4 hours into the infusion). Insulin levels demonstrated a similar response to rhIGF-I, but decreases in insulin levels occurred after the rhIGF-I hypoglycemic effect. Therefore, suppression of insulin levels may be due to hypoglycemia rather than a direct action of rhIGF-I. This trial demonstrated the desired rhIGF-I effect of lowering subjects' glucose levels without clinically significant hypoglycemia. This finding suggests that rhIGF-I may have potential clinical utility in hyperglycemic or insulin resistant states.

Uricosuric effect of CGS-12970, a new thromboxane synthase inhibitor.

3-Methyl-2-(3-pyridyl)-1-indoleoctanoic acid (CGS-12970) is a reversible thromboxane synthase inhibitor that was noted to lower serum uric acid during preliminary trials in humans. Our clinical research unit studied 20 healthy male volunteers who received two doses of CGS-12970 12 hours apart (100, 200, 300, or 400 mg twice a day). Four subjects received placebo as a control. Serum uric acid concentrations decreased between 34% and 47%. Urinary excretion of uric acid increased between 28% and 134% within 12 hours of the first dose. Urinary excretion of uric acid returned to baseline within 24 hours after the last dose. In vitro study of bovine-creme xanthine oxidase inhibitor activity revealed minimal inhibition of xanthine oxidase by either CGS-12970 or its metabolite, CGS-12961. CGS-12970 appears to be a potent reversible uricosuric agent. We hypothesize that the uricosuric effect may be attributable to the acidic properties of CGS-12970 rather than to its inhibition of thromboxane synthase.

Hypoglycemic and insulin response to a continuous intravenous infusion of CGP-35126 recombinant human insulin-like growth factor-I (rhIGF-I) in healthy males.

Recombinant human insulin-like growth factor-I (rhIGF-I) produced by expression in a yeast vector was evaluated in seven normal men to determine effects on plasma glucose and insulin levels. Each subject received an initial intravenous infusion of normal saline and on the following day, rhIGF-I at a rate of 21.4 micrograms/kg/hour. Each infusion lasted for 7 hours. The subjects' fasting baseline glucose and insulin levels were not statistically different (P > .05) from their pre-dose levels. Compared with the saline (control) infusion, serum glucose levels were statistically lower (P < .05) 2 hours into the rhIGF-I infusion. These lower glucose levels were maintained until the subjects consumed a standard lunch (4 hours into the infusion). Insulin levels demonstrated a similar response to rhIGF-I, but decreases in insulin levels occurred after the rhIGF-I hypoglycemic effect. This observation suggests that suppression of insulin levels may be due to secondary hypoglycemia rather than to a direct rhIGF-I effect. This study demonstrated the desired rhIGF-I effect of lowering subjects' glucose levels without clinically significant hypoglycemia. This finding suggests that rhIGF-I may have potential clinical utility in hyperglycemic states.

Pharmacokinetic disposition of multiple-dose transdermal nicotine in healthy adult smokers.

The pharmacokinetics and cardiovascular effects of nicotine and its major metabolite, cotinine, were characterized during repeated once-daily application for 5 days of a 30-cm2 nicotine transdermal system, Nicotine TTS (Habitrol), to nine healthy, black, adult, male smokers. Subjects abstained from smoking throughout the study. Pharmacokinetic analysis indicated that nicotine was delivered from Nicotine TTS for the 24-hr application period averaging 0.76 mg/cm2/24 hr, and at a relatively constant rate compared to other modes of drug administration. The transdermal clearance of nicotine, 1351 ml/min, coincided with reported values following intravenous nicotine administration; however, the terminal-phase half-life, 5.0 hr, did not. An analysis of the components of variance contributing to the variability in nicotine delivery from repetitive application of Nicotine TTS indicated that the in vivo transdermal permeation of nicotine is rate limited by both the device and the intrinsic skin conductivity. Clinical cardiovascular side effects were negligible as an apparent result of subclinical vasopressive nicotine concentrations, although drug activity with regard to other effects was manifested.