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Biomedical subjects

A Guglielmi

Publications and source records attributed to A Guglielmi.

At least 19 recordsLinked to original sources
PubMed2007

Tissue factor and vascular endothelial growth factor expression in colorectal cancer: relation with cancer recurrence.

OBJECTIVE: This study was undertaken to quantify tissue factor (TF) and vascular endothelial growth factor (VEGF) in colorectal cancer and to evaluate their possible relationship with recurrence. METHOD: TF and VEGF were measured by enzyme-linked immunosorbent assay in surgical tumour specimens and normal mucosa from 50 consecutive patients with colorectal cancer who were followed up for 3 years for the assessment of disease recurrence. RESULTS: TF and VEGF antigens were detected in all tumour samples. VEGF, but not TF, was much higher in tumour than in normal mucosa (P < 0.0001), as also confirmed by measurement of specific mRNAs. There was a strong correlation between TF and VEGF antigens (P < 0.0005) in tumour tissue but not in normal mucosa. Neither protein was related to tumour stage, grade or size. Local or distant recurrence was statistically related to pTNM stage. High VEGF, but not TF, levels in tumour extracts were associated with an increased risk of recurrence both by univariate (RR, 4.00, 95% CI: 1.45-11.0) and multivariate analyses (RR, 3.65, 95% CI: 1.33-10.0). CONCLUSION: These findings suggest that VEGF content in colorectal cancer is an independent risk factor for tumour recurrence and might help select patients who might benefit from adjuvant therapy.

Colorectal Neoplasms↗
PubMed2006

Total parenteral nutrition-related gastroenterological complications.

Total parenteral nutrition is a life saving therapy for patients with chronic gastrointestinal failure, being an effective method for supplying energy and nutrients when oral or enteral feeding is impossible or contraindicated. Clinical epidemiological data indicate that total parenteral nutrition may be associated with a variety of problems. Herein we reviewed data on the gastroenterological tract regarding: (i) total parenteral nutrition-related hepatobiliary complications; and (ii) total parenteral nutrition-related intestinal complications. In the first group, complications may vary from mildly elevated liver enzyme values to steatosis, steatohepatitis, cholestasis, fibrosis and cirrhosis. In particular, total parenteral nutrition is considered to be an absolute risk factor for the development of biliary sludge and gallstones and is often associated with hepatic steatosis and intrahepatic cholestasis. In general, the incidence of total parenteral nutrition-related hepatobiliary complications has been reported to be very high, ranging from 20 to 75% in adults. All these hepatobiliary complications are more likely to occur after long-term total parenteral nutrition, but they seem to be less frequent, and/or less severe in patients who are also receiving oral feeding. In addition, end-stage liver disease has been described in approximately 15-20% of patients receiving prolonged total parenteral nutrition. Total parenteral nutrition-related intestinal complications have not yet been adequately defined and described. Epidemiological studies intended to define the incidence of these complications, are still ongoing. Recent papers confirm that in both animals and humans, total parenteral nutrition-related intestinal complications are induced by the lack of enteral stimulation and are characterised by changes in the structure and function of the gut. Preventive suggestions and therapies for both these gastroenterological complications are reviewed and reported in the present review.

Animals↗
PubMed2006

Laparoscopic hepatic resection.

BACKGROUND: Although laparoscopy in general surgery is increasingly being performed, only recently has liver surgery been performed with laparoscopy. We critically review our experience with laparoscopic liver resections. METHODS: From January 2000 to April 2004, we performed laparoscopic hepatic resection in 16 patients with 18 hepatic lesions. Nine lesions were benign in seven patients (five hydatid cysts, three hemangiomas, and one simple cyst), five were malignant in five patients (five hepatocarcinoma), and four patients had an uncertain preoperative diagnosis (one suspected hemangioma and three suspected adenomas). The mean lesion size was 5.2 cm (range, 1-12). Twelve lesions were located in the left lobe, three were in segment VI, one was in segment V, one was in segment IV, and one was in the subcapsular part of segment VIII. RESULTS: The conversion rate was 6.2%; intraoperative bleeding requiring blood transfusions occurred in two patients. Mean operative time was 120 min. Mean hospital stay was 4 days (range, 2-7). There were no major postoperative complications and no mortality. CONCLUSIONS: Hepatic resection with laparoscopy is feasible in malignant and benign hepatic lesions located in the left lobe and anterior inferior right lobe segments (IV, V, and VI). Results are similar to those of the open surgical technique in carefully selected cases, although studies with large numbers of patients are necessary to drawn definite conclusions.

Adult↗
PubMed2005

High pathological response rate in locally advanced esophageal cancer after neoadjuvant combined modality therapy: dose finding of a weekly chemotherapy schedule with protracted venous infusion of 5-fluorouracil and dose escalation of cisplatin, docetaxel and concurrent radiotherapy.

BACKGROUND: This phase I study was aimed at defining the toxicity profile and pathological response rate of a neoadjuvant schedule including weekly docetaxel and cisplatin, protracted venous infusion (PVI) of 5-FU and concomitant radiotherapy (RT) in locally advanced esophageal cancer. PATIENTS AND METHODS: The schedule consisted of a first phase of chemotherapy alone and a second phase of concurrent chemoradiation. Initial doses were: docetaxel and cisplatin 20 mg/m2 on days 1, 8, 15, 29, 36 and 43 plus 5-FU 150 mg/m2 PVI on days 1-21 and 29-49; RT (40 Gy) started on day 29. In the following steps the doses were escalated up to docetaxel 35 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, 29, 36, 43, 50 and 57 plus 5-FU 180 mg/m2 PVI on days 1-21 and 150 mg/m2 PVI on days 29-63 concurrently with RT 50 Gy. RESULTS: Forty-seven patients were enrolled and 46 completed the planned treatment. During the concomitant phase, grade 3-4 hematological toxicities occurred in three patients (6.5%) (or 3/174 cycles) and non-hematological toxicities in six patients (13%) (or 7/179 cycles). A pathological downstaging was obtained in 59.6% of the cases (28/47): complete remission (pCR) in 14 patients, near pCR (residual microfoci on the primary pN0) in eight patients, pT2 pN0 in three patients and partial response on the primary with positive lymph nodes in three patients. Six (13%) and 13 (28%) patients were considered stable and non-responders, respectively. In the last dose level, eight pCR and four near-pCR were obtained out of 15 patients. The maximum tolerable dose was not formally defined because dose escalation was stopped at the last dose level. CONCLUSION: This schedule represents a feasible treatment and the high pathological response rate is extremely encouraging; the doses found in the last dose-level are the basis for an ongoing phase II study at our institution.

Adult↗
PubMed2005

Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism. Multicentre prospective study by the 'Nutritional Problems in Gastroenterology' Section of the Italian Society of Gastroenterology (SIGE).

BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.

Adult↗
PubMed2004

Phase II study of a triplet regimen in advanced colorectal cancer using methotrexate, oxaliplatin and 5-fluorouracil.

Building upon the concept of schedule-specific biochemical modulation of 5-fluorouracil (FU), which alternates bolus and continuous infusion (CI) FU, we have incorporated oxaliplatin (l-OHP) following the bolus part of the regimen to explore the activity of this new combination. Patients with advanced, untreated, measurable colorectal cancer received sequential methotrexate (MTX) (days 1 and 15)-->l-OHP+FU (days 2 and 16) (200, 85 and 600 mg m(-2), respectively) followed by 3 weeks of CI FU (200 mg m(-2) day(-1)) given from day 29 to 50, modulated by weekly leucovorin (LV) (20 mg m(-2)). After 1 week of rest, the second cycle was started. The treatment was continued until progression or patient's refusal. According to the intention-to-treat analysis on all 46 patients accrued, the response rate was 42% (95% CL=28-55%), with three complete responses and 16 partial responses. The median overall survival was 15.9 months and the median progression-free survival 6.9 months. Toxicity was very mild, with the bolus part of the regimen more toxic than the infusional part (24 vs 7% of grade III-IV, respectively). This new combination of MTX -->l-OHP-FU followed by FU CI is well tolerated, feasible and produces activity results similar to other more simple, but more toxic, regimens. Pros and cons of the different fluoropyrimidines-l-OHP combinations are discussed.

Adult↗
PubMed2004

Lack of correlation between immunohistochemical expression of E2F-1, thymidylate synthase expression and clinical response to 5-fluorouracil in advanced colorectal cancer.

BACKGROUND: The level of the enzyme thymidylate synthase (TS) is known to inversely correlate with the clinical activity of 5-fluorouracil (FU) in advanced colorectal cancer patients. Since the correlation is not very strong, we have retrospectively analyzed the expression of E2F-1 in tumor samples or metastases from 25 patients with advanced colorectal cancer, homogeneously treated with an FU-based regimen. E2F-1 is a transcription factor regulating the expression of TS along with other crucial DNA synthesis related enzymes. MATERIALS AND METHODS: E2F-1 expression was analyzed by immunohistochemistry using the anti-E2F-1 monoclonal antibody KH95, scoring 2000 cells/case. Expression of TS was evaluated by immunohistochemistry using a rabbit anti-human polyclonal antibody. RESULTS: The level of E2F-1 expression did not correlate with TS expression, although a trend for correlation between E2F-1 level and maximal tumor shrinkage was observed (r = 0.42; P = 0.054). CONCLUSIONS: In spite of previous reports demonstrating that E2F-1 quantified by rt-PCR and western blot correlates with TS and could be used as a predictor to select colorectal cancer patients more likely to respond to FU treatment, our data suggest that, under these experimental conditions, immunohistochemistry cannot be used for such selection.

Animals↗
PubMed2003

Pattern of recurrence after surgery in adenocarcinoma of the gastro-oesophageal junction.

AIMS: This study reports mode, timing and predictive factors of recurrence after curative surgery for cardia cancer. METHODS: A prospective study in a series of 92 curatively (R0) resected patients from 1988 to 2002. RESULTS: The 5-year recurrence rate was 71%. Lymph node involvement was the only predictor of recurrence. No patients with more than 6 metastatic nodes were free from relapse 2 years after surgery. Locoregional, peritoneal and haematogenous relapses showed a similar median recurrence time (12, 10 and 12 months, respectively), 80% occurred within 24 months. CONCLUSIONS: Few patients can be cured by surgery, lymph nodal involvement is the only predictor of recurrence.

Adenocarcinoma↗
PubMed2002

Risk assessment and prediction of rebleeding in bleeding gastroduodenal ulcer.

BACKGROUND AND STUDY AIMS: The aims of this study were to identify risk factors for recurrence of hemorrhage in bleeding gastroduodenal ulcers after endoscopic injection therapy, and to develop a simple and relevant prognostic score which could be used to assess the early risk of recurrence and the residual risk of rebleeding. PATIENTS AND METHODS: A prospective study was conducted from January 1995 to December 1998, in 738 patients who were admitted to our department for acute bleeding peptic ulcer and who underwent endoscopic examination. Ulcers with active bleeding or signs of recent bleeding were treated with injection therapy using epinephrine (1/10,000) and 1% polidocanol. RESULTS: Multivariate analysis revealed that liver cirrhosis, recent surgery, systolic blood pressure below 100 mmHg, hematemesis, Forrest classification, and ulcer size and site were significantly predictive variables for the recurrence of hemorrhage. Among these, Forrest classification was the most important. The overall accuracy of the predictive model was 71% (95% CI = 63 - 79%). The model showed a better sensitivity of 90% for early rebleeding (< 48 hours) than for late rebleeding (> or = 48 hours) where the sensitivity was 65 %. A prognostic score was obtained and patients were classified into four risk classes: very low (VL), low (L), high (H), and very high (VH). The rebleeding rates for the four classes were 0%, 7.9%, 31.8% and 67.9%, and the mortality rates were 5.9%, 8.6%, 13.9% and 35.7%, respectively. The residual risk of rebleeding after 48 hours was 0%, 3.3%, 10.4%, and 14.3% in the VL, L, H and VH classes, respectively. After 5 days the residual risk was under 4% in all classes. CONCLUSIONS: This study demonstrates that the proposed prognostic score, which is easily obtained after emergency endoscopy, is useful in clinical practice because it can identify patients with different levels of rebleeding risk. It can be helpful in patient management and decision making for discharge.

Aged↗
PubMed2001

5-fluorouracil modulated by leucovorin, methotrexate and mitomycin: highly effective, low-cost chemotherapy for advanced colorectal cancer.

We have reported that an alternating regimen of bolus and continuous infusion 5-fluorouracil (FU) was superior to bolus FU in terms of response rate and progression-free survival in advanced colorectal cancer. Biochemical modulation was an essential part of this regimen and it was selective for the schedule of FU administration: bolus FU was in fact modulated by methotrexate (MTX) while continuous infusion FU was potentiated by 6-s-leucovorin (LV). Considering the low cost and the favourable report on the activity of mitomycin C (mito) added to CI FU, we have incorporated this agent in the infusional part of our treatment programme. 105 patients with untreated, advanced, measurable colorectal cancer were accrued from 13 Italian centres and treated with the following regimen. 2 biweekly cycles of FU bolus (600 mg/m(2)), modulated by MTX (24 h earlier, 200 mg/m(2)) were alternated with a 3-week continuous infusion of FU (200 mg/m(2)daily), modulated by LV (20 mg/m(2)weekly bolus). Mito, 7 mg/m(2), was given on the first day of the infusional period. After a 1 week rest, the whole cycle (8 weeks) was repeated, if indicated. 5 complete and 34 partial responses were obtained (response rate, 37% on the intention to treat basis; 95% confidence limits, 28-46%). After a median follow-up time of 26 months, 37 patients are still alive. The median progression-free survival is 7.7 months with an overall survival of 18.8 months and a 2-year survival rate of 30%. The regimen was very well tolerated with fewer than 13% of patients experiencing WHO grade III-IV toxicity. These results are consistent with those obtained by our group in 3 previous trials of schedule specific biochemical modulation of FU. They also indicate a highly active, little toxic, inexpensive regimen of old drugs to be used (a) as an alternative to the more expensive combinations including CPT-11 or oxaliplatin or (b) as the basis for combination programmes with these agents.

Adult↗
PubMed2001

Contribution of posture to the maintenance of anal continence.

The anorectal angle (ARA) is believed to provide one of the most important contributions to anal continence. The normal resting angle is approx. 90 degrees, but the erect position may modify the ARA and other parameters usually considered in a proctometrogram. We compared the proctometrogram in different postures to elucidate the role of changes in the ARA in maintaining fecal continence. Sixty-three patients with constipation underwent static proctography. Variations in the ARA, perineal descent, puborectalis muscle length, and pubococcygeal distance were determined during resting, squeezing, and pushing with the patient in the Sims' position (SP); further evaluations used radiographs in resting position but with straight legs, in erect and sitting positions. The resting mean ARA was 95.3 +/- 15 degrees in SP and 79.8 +/- 14 degrees standing erect; the latter value was also significantly less during squeezing (84 +/- 11 degrees). The mean ARA during pushing was 118 +/- 16 degrees. A systematic and statistically significant difference in the mean resting ARA was demonstrated using the baseline of the rectal shape instead of the major rectal axis when measuring the anorectal angle. When sitting on a toilet, the mean resting ARA was significantly wider than in SP. The length of the puborectalis sling at rest did not change but was significantly reduced during squeezing and increased during pushing. The descent of the perineum at rest was near to 0 (-0.089 +/- 1.76 cm) in SP and significantly less when standing (-0.65 +/- 1.9 cm) and during squeezing (-0.97 +/- 1.7 cm). Perineal descent during pushing was +2.94 +/- 2.2 cm. The mean pubococcygeal distance did not change significantly in SP and in the erect position. The erect position thus contributes significantly to the maintenance of fecal continence by sharpening the ARA. This effect is stronger than any active contraction of the puborectalis muscle and is not related to shortening of the puborectalis sling but is secondary to lifting of the pelvic floor.

Adult↗
PubMed2001

Chilaiditi's syndrome. Successful surgical correction by colopexy.

We describe the case of a patient affected by the Chilaiditi's syndrome, the interposition of the small or large bowel between the inferior face of the diaphragm and the liver, a rare anomaly, often asymptomatic. A 50-year-old man came to our outpatients clinic because of persistent pain in the right abdominal region. Two attempts to perform colonoscopy failed because of the impossibility of passing through the transverse colon. A double contrast enema indicated only sigmoid diverticulitis. Only after abdominal radiography was the abnormal position of the right colon noted. At surgery the right colon was totally intraperitoneal and positioned between the diaphragm and liver, which was smaller than normal. The right colon was repositioned and fixed to the anterior abdominal wall. The postoperative course was uneventful and the right abdominal pain disappeared completely. In conclusion, surgical treatment of Chilaiditi's syndrome may be required in cases of persistent abdominal pain.

Colon↗
PubMed2001

Fatigue: a main component of anemia symptomatology.

Fatigue is a common complaint of patients with cancer or other physical or mental disorders. In cancer patients, the estimated prevalence of fatigue is high (about 70% to 90% in different surveys). However, despite the high prevalence and widely recognized clinical relevance of fatigue, few studies have been performed to evaluate the putative causal factors and therapeutic approaches for this condition. The paucity of studies has been mainly because of the lack of proper instruments to quantify this clinical problem. Moreover, fatigue is multifactorial, which makes evaluation of precise relationships with other medical conditions difficult. In particular, fatigue is considered the cardinal symptom of anemia. The pathogenesis of anemia-related fatigue remains unclear, but some suggest that abnormalities in energy metabolism play a role in inducing fatigue. In cancer patients, this effect may be exacerbated by the increased metabolic needs associated with tumor growth. At the clinical level, the relationship between anemia and fatigue is universally accepted. However, early studies were unable to show a clear association between fatigue and hemoglobin levels. Recently, new insights were afforded by the implementation of innovative survey instruments that assess the effects of fatigue and other (nonfatigue) symptoms of anemia on the patient's well-being and quality of life. The use of these validated instruments has shown a direct effect of hemoglobin levels on fatigue and other quality of life parameters. Thus, amelioration of anemia and fatigue should be considered a primary endpoint of antineoplastic and supportive-care treatment of cancer patients. Accordingly, the search for new simplified methods of assessment of fatigue and other anemia-related symptoms and their treatment outcomes should be strongly encouraged.

Anemia↗
PubMed2001

Metastases to the para-aortic lymph nodes in adenocarcinoma of the cardia.

OBJECTIVE: To find out the extent of involvement of the para-aortic nodes in patients with adenocarcinoma of the gastric cardia. DESIGN: Open prospective study. SETTING: Teaching hospital, Italy. SUBJECTS: 23 patients with advanced adenocarcinoma of the cardia (type II, n = 10, and type III, n = 13) who were treated by total gastrectomy with resection of the distal oesophagus and extended lymphadenectomy (D4) between January 1997 and June 1999. These were compared with 21 patients with advanced carcinoma of the proximal third of the stomach who had total gastrectomy with D4 lymphadenectomy during the same period. Lymph nodes were retrieved immediately postoperatively and assigned to the appropriate station according to the classification of the Japanese Research Society for Gastric Cancer. MAIN OUTCOME MEASURES: Number of para-aortic and other nodes involved. RESULTS: 22 of the 23 patients had lymph node metastases, and in 5 the para-aortic nodes were involved (N4). N3 lymph nodes were involved in only 1 patient, despite involvement of para-aortic nodes. Among the 5 patients with N4 metastases, 1 had only N1 metastases in addition, with no involvement of N2 or N3 nodes. Patients with involved N4 nodes had more nodes involved overall than those who did not (mean (SD) 17 (5) compared with 8 (12)). CONCLUSIONS: 5/23 patients with advanced carcinoma of the cardia had involved para-aortic nodes. This may have some prognostic value, but larger studies of D4 lymphadenectomy specimens is required.

Adenocarcinoma↗
PubMed2001

Rhesus D-phenotype does not provide prognostic information additional to TNM staging in gastric cancer patients.

Recently, the Rhesus D-negative phenotype was identified in multivariate analysis as an important independent risk factor in gastric cancer patients who underwent curative resection. The distribution of Rhesus (Rh) D phenotype was investigated in a group of 268 patients who underwent gastrectomy for gastric cancer from June 1988 to April 1999. After excluding patients with short, potentially guaranteed follow-up or who deceased in the postoperative period, the prognostic significance of Rh D phenotype was evaluated in a subgroup of 239 patients by Cox regression model controlling for gender, age, site, histology, depth of tumor invasion (T), node metastasis (N), and type of resection (R). Two hundred and thirty-six patients (88.1%) presented an Rh+ phenotype and 32 (11.9%) presented an Rh- phenotype. A significant association was found between Rh D- phenotype and the presence of residual tumor after surgery (P = .01). The cumulative 5-year survival rate (95% confidence interval) was 37.3% (18.1-56.6) in patients with Rh- phenotype and 47.0% (39.2-54.4) in patients with Rh+ phenotype. The Rh D phenotype did not affect survival independently either in univariate analysis (P = .27) or in multivariate analysis (P = .55). The relative risk of death in D-negative versus D-positive patients decreased from 1.36 (95% confidence interval, 0.80-2.30) in univariate analysis to 0.84 (0.47-1.49) in multivariate analysis after controlling for depth of tumor invasion, lymph node metastases, and type of resection. Our study did not confirm the prognostic significance of Rh D phenotype in gastric cancer patients.

Adult↗