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Biomedical subjects

A Guglielmi

Publications and source records attributed to A Guglielmi.

At least 55 records · Page 3Linked to original sources
PubMed1997

[Prognostic value of histologic classifications of advanced stomach cancer: comparative study of Lauren's and Goseki's classifications].

Controversy exists about the prognostic value of the histological classifications of gastric cancer commonly used. Recently Goseki proposed a new classifying system based on intracellular mucus production and the degree of tubular differentiation. The aim of this study was to compare Lauren and Goseki classifications with particular emphasis on their prognostic significance. Eighty-nine patients, who underwent potentially curative resections (RO) and radical lymphadenectomy for advanced gastric cancer from September 1988 to April 1996 were analysed. Cox regression model was used to evaluate the prognostic significance of Goseki classification, Lauren classification, age, sex, type of lymphadenectomy, depth of tumour invasion (T), node metastases (N) and number of metastatic nodes. A statistically significant correlation between the different Goseki grades and histology according to Lauren was found (p < 0.001). By multivariate analysis the only parameters predictive of long term outcome were depth of tumour invasion, nodal status and histology according to the Lauren classification. Also after excluding the Lauren classification from the analysis, the Goseki histological grading system did not affect survival independently. This study on advanced gastric cancer patients identified depth of invasion, lymph node metastases and Lauren classification as significant independent pathological variables influencing survival. The classification proposed by Goseki did not add anything further to the prognostic informations provided by TNM staging and Lauren classification.

Adenocarcinoma↗
PubMed1996

Prognostic significance of lymph node dissection in gastric cancer.

The results for 162 patients who underwent curative gastrectomy for gastric cancer from January 1988 to June 1994 were analysed statistically with special reference to the effect of lymph node dissection. Median survival was 69.3 months and the overall cumulative 5-year survival rate was 50.2 (95 per cent confidence interval (c.i.) 41.6-58.1) per cent. By univariate analysis age, histology, depth of tumour invasion, node involvement, number of metastatic lymph nodes and type of lymphadenectomy were found to be significant factors related to survival time. Multivariate analysis with the Cox model and stratified for tumour node metastasis stage revealed that only the number of metastatic nodes (P = 0.04) and the extent of lymphadenectomy (P = 0.003) affected survival independently. With respect to D1 lymphadenectomy, the relative risk associated with D2 and D4 lymphadenectomy was respectively 0.61 (95 per cent c.i. 0.34-1.10) and 0.26 (95 per cent c.i. 0.12-0.60). The 5-year survival rate was 28 per cent for patients who had a D1 dissection, 63 per cent for those who had D2 and 68 per cent for those who had D4. These results suggest that extended lymphadenectomy (D2) and especially superextended lymphadenectomy (D4) can improve survival in patients with gastric cancer.

Aged↗
PubMed1996

Alternating bolus and continuous infusion 5-fluorouracil: a strategy to overcome resistance to this fluoropyrimidine in advanced colorectal cancer patients.

Focusing our effort on the importance of FUra scheduling we have tested the hypothesis that pulse and continuous infusion (CI) of the fluoropyrimidine have different mechanisms of cytotoxicity. Our initial approach was to compare the mechanism of resistance of a cell line resistant to a short term exposure to FUra (HCT-8/FU4hR) to that of a cell line resistant to a prolonged exposure to the fluoropyrimidine (HCT-8/FU7dR). Cytotoxicity studies showed that HCT-8/FU4hR cells were still sensitive to FUra given as a 7-d exposure, suggesting different mechanisms of resistance. Indeed, rapid recovery of TS activity after drug removal was evident in the HTC-8/FU7dR cell line while HCT-8/FU4hR cells were similar to the parental cell line with regard to both the degree of in situ TS inhibition by FUra and duration of inhibition after FUra removal. In contrast, labelling studies with [3H-6]FUra(4 h exposure, 100 microM) showed that the incorporation of the fluoropyrimidine into RNA is significantly decreased in HCT-8/FU4hR cells as compared to parental HCT-8 cells. Given the lack of cross resistance between the two schedules in vitro, a pilot trial was done on patients with colorectal cancer refractory to bolus FUra. On 15 patients failing after FUra+LV or FUra alone 1 PR, 3 MR, 3 SD and 8 P were observed, confirming a certain degree of activity of CI FUra in patients clinically resistant to bolus FUra. Based on this rationale, a phase II trial of schedule-oriented biochemical modulation of FUra in advanced colorectal cancer patients was conducted, employing a hybrid regimen of 2 biweekly cycles of FUra bolus (600 mg/sqm), preceeded by (24 h interval) methotrexate, 200 mg/sqm (in order to maximize the RNA effect of the drug) alternating with Fura continuous infusion, 200 mg/sqm daily for 3 weeks, modulated by leucovorin, 20 mg/sqm weekly bolus (in order to maximize the DNA effect). Thirty-three consecutive patients (median ECOG PS 1) with advanced measurable colorectal cancer and no prior therapy for metastatic disease entered the study, from February 1992 to August 1993. Three complete and 13 partial responses were obtained among these 33 patients (RR = 48%, 95% confidence limits, 31-66%). After a median follow-up time of 23 months, 16 patients are still alive. The median progression free survival and overall survival were 9.6 and 20.8 months, respectively. No toxic deaths or grade 4 toxicity occurred. The incidence of grade 3 toxicity per patient in any cycle was: mucositis 6%, diarrhea 3% and vomiting 3% for the bolus part and 21%, 3% and 6% respectively, for the continuous infusion part of the regimen. Hand-foot syndrome occurred in 27% of the patients treated with the continuous infusion regimen. In conclusion, this experimental and clinical project has generated a novel regimen of schedule oriented biochemical modulation that is twice as active and half as toxic compared to bolus FU+LV given with either the daily x 5 or the weekly schedule. This high clinical activity is very encouraging, especially considering that 1) consecutive patients were entered, 2) the responses were independently reviewed, 3) the progression free survival and survival were much longer than those actually reported for this disease, 4) the toxicity of the program, in particular the bolus regimen, was relatively low allowing further intensification.

Adenocarcinoma↗
PubMed1996

[Ultrasonography mapping of peritoneal adhesions].

A previous laparotomy is still a contraindication to laparoscopy because of the possible presence of abdominal wall adhesions exposing the patient to the risk of a visceral injury when the pneumoperitoneum is created and/or the first trochar is inserted. We report the results of abdominal wall US exams performed preoperatively for the diagnosis of peritoneal adhesions: we investigated two distinct signs unrelated to one another, to minimize false-negative findings. Ultrasonography was performed on 141 patients subdivided into two groups: 81 patients with no previous abdominal surgery (group A) and 60 patients with a history of abdominal surgery (group B). For diagnostic purposes, the visceral movement sign according to Sigel, modified on the basis of preliminary observations, and the reflection band sign were studied. US data were included in the patient's record and compared with intraoperative findings. Overall diagnostic accuracy was 94% and sensitivity 100% in the two groups. To conclude, the preoperative US mapping of abdominal wall adhesions enabled us to establish adhesion-free areas unquestionably and thus to choose the safest and most suitable sites for risky maneuvers during laparoscopy in the patients with a history of previous abdominal surgery.

False Positive Reactions↗
PubMed1995

5-Fluorouracil plus 5-methyltetrahydrofolate in advanced pancreatic cancer. GLISP (Gruppo Ligure Studio Pancreas).

A total of 20 patients with advanced pancreatic adenocarcinoma were enrolled in a phase II trial testing the activity of 5-fluorouracil given at 370 mg/m2 as a rapid i.v. bolus for 5 consecutive days, preceded by a rapid i.v. bolus of 200 mg/m2 5-methyltetrahydrofolic acid. The treatment was repeated every 4 weeks. The median age of the patients was 68 years and their median Eastern Cooperative Oncology Group (ECOG) performance status was 1. There were 7 patients with locally advanced disease and 13 with distant metastases (median, 2 sites). A median of 3 monthly cycles of treatment (range, 1-7) were given, with a corresponding dose intensity of 396 mg/m2 per week (86% of that planned). No complete response, 1 partial response, and 8 cases of disease stabilization were obtained. In general the regimen was well tolerated, with only 2 patients suffering from grade 3 stomatitis or diarrhea; the most common toxicity was nausea, which was experienced by almost 50% of the patients. The combination of 5-methyltetrahydrofolate plus 5-fluorouracil appears as little effective in this disease as 5-fluorouracil plus 5-formyltetrahydrofolate (leucovorin). It is suggested that bolus 5-fluorouracil is so inactive as an "effector agent" against pancreatic cancer that its biochemical modulation with exogenous high-dose reduced folates cannot improve the therapeutic outcome produced by the fluoropyrimidine in these patients.

Adenocarcinoma↗
PubMed1995

Oxygen saturation in premature neonates with bronchopulmonary dysplasia in a hammock.

Premature neonates with bronchopulmonary dysplasia (BPD) frequently present borderline hypoxemia and the risk for oxygen desaturation may increase in relation to the posture. Our aim was to see if infants with BPD experience severe hypoxemia (SaO2 < 85%) in a hammock, a 'containing' posture considered advantageous to neuromotor and relational development of the preterm. Fifteen pulse oximetry recordings (Ohmeda B105 3760 Pulse Oximeter) were obtained in 15 subjects (range of gestational age and postnatal age 27-30 and 33-48 weeks, respectively; range of birth weight and body weight at entrance to the study 0.64-1.35 and 0.97-2.24 kg, respectively) before, during and after placement in a hammock; each testing period lasted 15 min, and each baby served as his or her own control. BPD preterm infants were receiving oxygen therapy by continuous flow standard nasal cannulas (FiO2 > 25%, < 40%). The analysis of the data, that have a rough gaussian distribution, indicates a worsening of SaO2 in the hammock position. In fact, mean +/- SEM, median and range of the SaO2 values in pre- and posthammock position are comparable, but are significantly different at 99.9% confidence level (CL) in prehammock vs. hammock posture and at 98% CL in posthammock vs. hammock posture. Moreover, the percent of time with SaO2 < 85% during the periods recorded increased about 10 +/- 5% in a hammock (24 +/- 4%), in comparison to pre- (14 +/- 3%) and posthammock position (15 +/- 3%). These results suggest that oxygen-dependent BPD preterm infants in the hammock posture may experience severe hypoxemia that in part limits the possible advantages of the 'containment'.

Bronchopulmonary Dysplasia↗
PubMed1995

Methylxanthines increase renal calcium excretion in preterm infants.

To determine the effect of a short course of methylxanthines on renal function and on urinary calcium excretion, 20 premature neonates affected by apnea or moderate respiratory distress syndrome were randomly assigned to either a theophylline treatment or to a caffeine treatment group. The protocol included a 24-hour pretreatment study period (I) and a subsequent 24-hour period (II) following 5 days of theophylline (loading dose 5 mg/kg i.v., maintenance dose 2.5 mg/kg/12 h) or caffeine (loading dose 10 mg/kg i.v., maintenance dose 2.5 mg/kg/12 h) administration. Pre- and postxanthine treatment serum sodium, potassium, calcium and phosphorus remained stable, while serum creatinine decreased significantly (p < 0.05). Furthermore, from period I to period II, sodium urine excretion, fractional Na excretion and creatinine clearance remained statistically comparable in both study groups, along with a significant increase (p < 0.05) in calciuria, urinary Ca/creatinine and urinary Ca/Na. Predose caffeine and theophylline serum levels, assessed on the 5th day of treatment, were 12.8 +/- 1.8 and 7.9 +/- 1.7 micrograms/ml, respectively. Compared to control healthy untreated prematures, the studied premature infants showed a statistically significant increase in urine calcium excretion (10- to 15-fold), which was more evident in the theophylline group. Our data suggest further investigation to determine the long-term renal effects of methylxanthines in premature neonates, to improve assessment of the risk of nephrocalcinosis and osteopenia, in particular in association with various diuretic therapies.

Caffeine↗
PubMed1995

"Silent" patent ductus arteriosus and bronchopulmonary dysplasia in low birth weight infants.

We conducted a clinical study on the antecedents of bronchopulmonary dysplasia (BPD) in 290 premature RDS infants with < or = 1.75 kg birth weight (BW). They were enrolled in a prospective trial of indomethacin treatment for "silent" patent ductus arteriosus (PDA), screened by 2-D echocardiographic and pulsed Doppler evaluation on the third day of life. The trial took place at the NICU of the Pediatric Department of Padua University between January 1987 and December 1991. Out of 290 infants screened, 96 had evidence of "silent" PDA (33%) and 77 responded to indomethacin treatment (80%). Comprehensively 79 (27%) developed BPD, and from these the incidence of BPD was statistically increased in infants with "silent" PDA, 47 out of 96 (49 +/- 9%), with respect to 32 out of 194 (16 +/- 3%) preterm infants without PDA. Statistical analysis showed that in preterm infants with "silent" PDA the development of BPD was correlated at 99% C.L. to their low BWs (mean BW = 1.13 kg): in fact the mean and the mode of BW distributions were statistically lower in the presence of BPD, 1.03 kg versus 1.24 kg, and 0.88 kg versus 1.65 kg respectively. Moreover, the preterm infants with "silent" PDA unresponsive to the first course of indomethacin and/or submitted later to surgical closure, presented a statistically lower BW with respect to the early responders, 1.06 kg versus 1.18 kg, and at the same time a statistically higher incidence of BPD (63 +/- 20% versus 43 +/- 9%). From these data we conclude that, although "silent", PDA increase per se the incidence of BPD, even if benefits from an early induced closure. Furthermore, a lower BW of infants affected by "silent" PDA represents a contributing factor to the development of BPD.

Bronchopulmonary Dysplasia↗
PubMed1995

Adjuvant Treatment of Colorectal Cancer in the Elderly.

From March 1992 until January 1994, 1,014 patients radically resected for Dukes' B(2), B(3) or C colon cancer were randomized to receive FU plus levamisole or FU plus leucovorin (LV) plus levamisole. Only 41% of patients older than age 70 years, as compared to 53% of those younger, have completed the treatment as planned. This poorer compliance was not associated with a higher incidence or degree of toxicity. Only a small difference in percentages was detected between the age groups of patients requiring dose reductions or treatment delays, while the percentages of patients that had their treatment discontinued was markedly increased in the older age group, without a parallel increase in severe toxicity. Preliminary results suggest that adjuvant chemotherapy with FU plus levamisole or FU plus LV plus levamisole is well tolerated by elderly patients and is not associated with greater toxicity in patients over 70 years of age than in younger patients. The lower adherence to the treatment plans in older patients may be due to reluctance by physicians and families to administer chemotherapy due to the misconception that the elderly are more prone to adverse reactions.

Journal Article↗
PubMed1995

In vitro synergism between 5-fluorouracil and natural beta interferon in human colon carcinoma cells.

The combination of 5-fluorouracil (FUra) plus IFN-beta was studied in vitro using a human colon carcinoma cell line, HCT-8. Continuous exposure to high concentrations of IFN-beta is cytotoxic to these cells (ED50, 600 +/- 50 IU/ml). A strong synergism (P < 0.002) was observed when a short-term (1-h), high-concentration exposure to fluoropyrimidine (300 or 1000 microM) was followed by IFN-beta given continuously. In fact, the mean ratio between the expected (product of the survival of each agent alone) and the observed clonogenic cell survival rates of the combination was 3.4 (range, 2.4-4.9). Longer exposures to the fluoropyrimidine (24 h, 7 days) produced less than additive effects with IFN-beta, indicating strong schedule dependency for this synergism. The mechanism of interaction was studied at four levels. First, thymidylate synthase (TS) activity, inhibition, and recovery were measured by an in situ assay in cells treated with FUra, IFN-beta, and their combination. When the prolonged infusion of IFN-beta followed a 1-h exposure to FUra, the observed TS inhibition and recovery, at each time point, were very similar to the expected values, indicating that the interactions between these drugs at the level of TS are not the determinant of the synergism. Second, cell cycle analysis was done. During the continuous exposure to IFN-beta, a significant accumulation of HCT-8 cells in S-phase was observed at 24, 48, and 72 h compared to untreated controls (P = 0.003); however, under the same experimental conditions producing synergy in the clonogenic assay, no significant cell cycle perturbations were produced by the combination of FUra followed by IFN-beta compared to those caused by each agent alone. Third, using the alkaline elution test, we also demonstrated that the synergism is not due to enhanced FUra-induced DNA single-strand break frequency in high molecular weight DNA. Finally, nucleic acid incorporation experiments, using tritiated FUra, showed that the cytokine, given continuously (300 IU/ml), enhanced the amount of FUra incorporated into nucleic acids 24 h after a 1-h exposure to 300 and 1000 microM of FUra. The median percentage of enhancement values were 31.6 +/- 11.5%,m for the lower drug concentration and 18. 4 +/- 8.1% for the higher drug concentration tested. These results suggest that the mechanism of this synergism may be related to the ability of IFN-beta to promote the incorporation of intracellular FUra metabolites into nucleic acids and/or to inhibit the cleavage of FUra nucleotides from RNA/DNA.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Activity of continuous-infusion 5-fluorouracil in patients with advanced colorectal cancer clinically resistant to bolus 5-fluorouracil.

We have recently demonstrated that continuous-infusion (CI) 5-fluorouracil (FU) eradicates human colon carcinoma cells made resistant to bolus FU in vitro. In addition, in the same experimental system, the mechanisms of resistance to pulse and CI FU were found to be different. These observations led us to test the clinical activity of a standard regimen of CI FU (300 mg/m2 per day) in a cohort of 15 patients with advanced measurable colorectal cancer who were in progression after having failed to respond to bolus treatment with FU alone (3 patients) or FU combined with high-dose 6-S-leucovorin (LV) (12 patients). The median age of the patients was 68 years, and their median Eastern Cooperative Oncology Group performance status (ECOG PS) was 1. No myelotoxicity was observed. Mild diarrhea, mucositis, and vomiting occurred in 32%, 26%, and 19% of the patients, respectively, with no WHO grade 3 or 4 episodes being noted. In all, 6 of 15 patients complained of hand-foot syndrome, which was severe in 2 instances, lasting approximately 1 week. Overall, 1 partial response and 6 instances of disease stabilization, including 3 minor responses, were obtained both in patients who had been pretreated with pulse FU alone and in patients who had failed first-line treatment with FU + LV. Finally, 8 patients failed CI FU. In conclusion, these results, obtained in patients who were clearly progressing after having failed first-line treatment, support our experimental finding that resistance to bolus FU may be overcome by CI FU and extend this possibility to patients who are resistant to bolus treatment with FU + LV.

Aged↗
PubMed1993

"Silent" patent ductus arteriosus and bronchopulmonary dysplasia in low-birthweight twins.

During a screening protocol of early echocardiographic diagnosis (ATL MK 600) and treatment of "silent" PDA in RDS preterms with BW < or = 1.750 kg, clinical data on premature twins were collected, including diagnosis of both PDA and BPD, to investigate whether twin birth influences PDA incidence and BPD development. Out of the 290 RDS preterms evaluated, 96 (33%) showed evidence of PDA, and a total of 79 (27%) developed BPD, 47 (16%) with associated PDA and 32 (11%) without PDA. Out of 238 singletons, 74 (31%) presented "silent" PDA and a total of 75 (31%) developed BPD, 44 (18%) with associated PDA, and 31 (13%) without PDA. In 52 other twins (18% of the total number of babies studied), 22 (42% of this subgroup) presented evidence of "silent" PDA, and 4 (8% of the subgroup), developed BPD, 3 with associated PDA (6% of the subgroup), and 1 without PDA (2% of the subgroup). From these data, it is inferred that that low-birthweight twins are at high risk for PDA hemodynamic complications during RDS, and may benefit from early induced ductal closure. Instead, in RDS twins, BPD was statistically less frequent (at the 99% C.L.) probably because twinning enhances fetal lung maturity, influencing enzymatic and nonenzymatic protective systems of lung defence.

Bronchopulmonary Dysplasia↗
PubMed1993

Evaluation of the liver function of cirrhotic patients based on the formation of monoethylglycine xylidide (MEGX) from lidocaine.

Determination of the functional hepatic reserve is still controversial. Many tests have been proposed, but the assay based on formation of the lidocaine metabolite, monoethylglycine xylidide, seems to offer a promising approach to this problem. In this study we evaluated the effectiveness of the monoethylglycine xylidide test in the clinical evaluation of 31 cirrhotic patients submitted to three different therapeutic options (sclerotherapy, transjugular intrahepatic protosystemic shunt and surgical procedures) and in 1 patient submitted to right hepatectomy for giant hepatic angioma. We found a statistically significant difference between Child A and C patients and between Child B and C patients. The test did not differentiate Child A from Child B patients. We found no correlation between the Child-Pugh score, serum bilirubin, albumin and prothrombin time. There were no differences among the three groups of patients that could be statistically related to their therapy. The monoethylglycine xylidide test seems to be an attractive alternative to previous methods for the evaluation of the functional hepatic reserve, but further studies are necessary to assess the prognostic value of the test in cirrhotics, to separate the independent contribution of portosystemic shunting and hepatocyte dysfunction to monoethylglycine xylidide formation, and to evaluate the test as a prognostic index in cirrhotic patients submitted to general surgery.

Adult↗
PubMed1992

Acute cholecystitis: ultrasonographic staging and percutaneous cholecystostomy.

Experience in the treatment of acute cholecystitis with percutaneous cholecystostomy in 29 high-risk and elderly patients is reported. The treatment group included 14 men and 15 women, 21 of whom were over 70 years of age. The suspected clinical diagnosis of acute cholecystitis was confirmed in all cases by ultrasonography (accuracy: 95.6%). The percutaneous cholecystostomy was successful in 27 of 29 cases and these patients had a sudden improvement in their clinical condition; failure of the procedure was due in one patient to dislodgement of the catheter and in another patient to the guide-wire slipping out of the gallbladder. Six patients complained of pain radiating to the right shoulder which disappeared within 30-60 minutes after the procedure. Twenty-three of the 27 patients subsequently underwent elective cholecystectomy. In 22 patients the ultrasonographic findings were compared with the histology; thus enabling us to establish an ultrasonographic staging of acute cholecystitis related to the seriousness of the disease. Percutaneous cholecystostomy is the treatment of choice in high-risk patients, in the elderly, as well as in young patients with impending perforation.

Acute Disease↗
PubMed1992

Randomised comparison of weekly bolus 5-fluorouracil with or without leucovorin in metastatic colorectal carcinoma.

148 patients with advanced untreated colorectal cancer were randomised to receive a weekly bolus of 5-fluorouracil (5-FU) 600 mg/m2 alone, with or without leucovorin (LV) 500 mg/m2. 5-FU plus LV produced a higher response rate than 5-FU alone: 23% (5 complete response, 11 partial response) vs. 8% (2 complete response, 4 partial response) (P = 0.03) out of 70 and 72 evaluable patients, respectively. Median survival was 11 months in both groups and median time to progression was not significantly different (P = 0.08). The combined regimen was more toxic than 5-FU alone, as evidenced by (a) a higher percentage of grade 3-4 diarrhoea, 19.5% vs. 8.5% (P = 0.045) and conjunctivitis, 26.5% vs. 5.6% (P = 0.0025); (b) the recording of one toxic death in the combined arm; and (c) the reduction of the median dose intensity of 5-FU actually delivered during the first 2 months of treatment. We conclude that 5-FU plus LV at a price of a higher toxicity is more active than 5-FU alone without improving survival and progression-free survival.

Adult↗
PubMed1992

Phase II study of 5-fluorouracil plus leucovorin and interferon alpha 2b in advanced colorectal cancer.

15 untreated patients with advanced measurable colorectal cancer along with other 29 patients in progression after failing first line chemotherapy with fluoropyrimidines received 5-fluorouracil (5FU) 500 mg/m2 given as a weekly bolus at mid-infusion of leucovorin (LV), 500 mg/m2 administered intravenously over 2 h and interferon alpha 2b (IFN) 3 x 10(6) U given intramuscularly every other day. All patients had their previous chemotherapy at least 4 weeks prior to 5FU-LV-IFN. 5 patients discontinued the three drug regimen due to toxicity (intense weakness, fever and influenza-like symptoms in 4 patients; diarrhoea in 1 patient) however no grade IV toxicity was observed. IFN administration was reduced to twice/weekly in 5 patients due to influenza-like symptoms. 1 complete response and 5 partial responses were observed (13.6% response rate); the complete response was obtained in a patient resistant to 5FU: the response rate was only twice as much in untreated patients (3/15 patients, 20%) compared with that in patients previously treated with fluoropyrimidines (3/29 patients, 10.3%). Therefore, modulation of 5FU with LV plus IFN at the doses and schedules employed in this study may rarely overcome clinical resistance to the fluoropyrimidine and the addition of IFN does not appear to enhance the activity of 5FU plus LV.

Antineoplastic Combined Chemotherapy Protocols↗