Alfredo Guarnieri

A novel biweekly multidrug regimen of gemcitabine, oxaliplatin, 5-fluorouracil (5-FU), and folinic acid (FA) in pretreated patients with advanced colorectal carcinoma.

Previous results suggest that GEM affects 5-fluorouracil (5-FU) metabolism and pharmacokinetics in cancer patients, while combined with oxaliplatin, levo-folinic acid, and 5-FU (GOLF regimen), at doses achievable in cancer patients, determines high cytotoxic and proapoptotic antitumour activity in colon cancer cells in vitro. On these bases we designed a phase I–II clinical trial testing the GOLF regimen in patients with metastatic colorectal carcinoma, who had received at least a prior line of chemotherapy. In total, 29 patients (20 males and nine females) enrolled in the study received every 2 weeks, gemcitabine (patients #1–3 received 600 mg m−2; patients # 4–6 received 850 mg m−2; while patients # 7–29 received 1000 mg m−2) on the day 1, levo-folinic acid (100 mg m−2) on the days 1 and 2; 5-fluorouracil (400 mg m−2) in bolus injection, followed by a 22-h continuous infusion (800 mg m−2) on the days 1 and 2, and oxaliplatin (85 mg m−2), 6 h after the 5-FU bolus on day 2. The most frequent side effect was grade I–II haematological toxicity. In total, 28 patients were evaluable for response: three achieved a complete response, nine a partial response, 10 had a stable disease, and six progressed. The average time to progression and overall survival of the patients was, respectively, 7.26 and 22 months. Our GOLF combination is well tolerated and seems promising for the treatment of advanced colorectal cancer.

Prognostic Value of Extracapsular Extension of Axillary Lymph Node Metastases in T1 to T3 Breast Cancer

BackgroundThe importance of extracapsular extension (ECE) of axillary metastases as a risk factor for either local or distant recurrence and poorer survival in breast cancer has been suggested, but its prognostic value has not been uniformly confirmed.MethodsFrom a prospective database including 1142 breast cancer patients operated on at the Department of General Surgery and Surgical Oncology of the University of Siena, we selected 376 cases with pT1 to pT3 node-positive breast cancer. The prognostic significance of ECE of axillary metastases was evaluated with respect to disease-free survival, overall survival, and the patterns of disease recurrence. Such prognostic significance was then compared with that of other clinical and pathologic factors.ResultsWith a median follow-up of 103 months, factors with independent prognostic value for disease-free survival by multivariate analysis included absence of estrogen receptors (P < .0005), pN category (P < .01), presence of lymphovascular invasion (LVI; P < .005), and ECE (P < .0001). An independent negative prognostic effect on overall survival was observed for absence of estrogen and progesterone receptors (P < .05), pN category (P < .05), and presence of LVI (P < .005) and ECE (P < .0001). The presence of ECE was significantly related to an increased risk of regional (13.4% vs. 6.6%; P = .037) and distant (43% vs. 16.2%; P < .001) recurrences.ConclusionsECE demonstrated a stronger statistical significance in predicting prognosis than the pN category and was also related to an increased risk of distant recurrences. We suggest that the decision on adjuvant therapy should consider the presence of ECE of axillary metastases and peritumoral LVI as indicators of high biological aggressiveness.

Duodenal obstruction from isolated breast cancer metastasis: a case report.

Metastatic involvement of the upper gastrointestinal tract from breast cancer has been reported in autopsy series as occurring in more than 15% of patients, usually associated with extensive systemic spread; clinical manifestations from such metastases have been described in less than 1% of cases. Lobular infiltrating carcinoma seems to have a different metastatic pattern than the ductal type, with an apparent predilection for the gastrointestinal tract. Metastatic presentation as an isolated intestinal obstruction without other signs of metastatic spread is extremely rare. We present a case of isolated duodenal metastasis from breast cancer, associated with intestinal obstruction, as the first sign of metastatic spread.

Prediction of lymph node status by analysis of prognostic factors and possible indications for elective axillary dissection in T1 breast cancers.

OBJECTIVE To identify those patients with T1 breast cancers with lower risk of nodal metastases who can safely be spared axillary dissection. DESIGN Retrospective study. SETTING University hospital, Italy. SUBJECTS Review of clinical records and histopathological slides of 547 patients with T1 breast cancer, operated on between 1984 and 1997. MAIN OUTCOME MEASURES Incidence of axillary metastases in relation to age, menopausal status, diameter and grade of tumour, vascular invasion, DNA ploidy, S-phase fraction and hormone receptor state, by univariate and multivariate analysis. RESULTS Axillary metastases were present in 159 patients (29%). On univariate analysis, diameter of tumour 10 mm or less (pT1a/pT1b cancers), no vascular invasion, and grade 1 tumour were significantly correlated with a lower risk of nodal metastases, but only vascular invasion (p = 0.0001, odds ratio = 3.1) and diameter of tumour (p = 0.04, odds ratio = 1.6) were independent predictors on multivariate analysis. Among 34 pT1a/pT1b cancers, with low grade of tumour and no vascular invasion, only 2 (6%) had axillary metastases. When only one favourable predictive factor was associated with diameter of tumour of 10 mm or less, the incidence of axillary metastases ranged from 12% for 43 patients with grade 1 cancers to 13% for 76 patients with no vascular invasion. CONCLUSIONS Axillary dissection may be avoided in pT1a and pT1b breast cancers (< or = 10 mm), with low grade of tumour or no vascular invasion. T1 breast cancers 10 mm or less in diameter should be treated by a two-step approach, first wide excision of the tumour and then axillary dissection or not depending on pathological examination of the primary tumour.

Weekly epirubicin in advanced breast cancer.

Twenty-nine advanced breast cancer patients, considered unable to tolerate conventional cytotoxic chemotherapy, were treated with a weekly schedule of epirubicin (15 mg/m2 i.v.). All patients were fully evaluable. A remission of 34.5 % was observed (2 CR; 8 PR), with a median duration of response of 9 months (range, 3–24 months). Side effects were mild, and on the whole the toxicity was negligible. This regimen showed a favorable therapeutic ratio in our series and seems active and well tolerated even in elderly and/or poor performance status patients.

Giant Sigmoid Diverticulum: A Rare Presentation of a Common Pathology

Although colonic diverticulum is a common disease, affecting about 35% of patients above the age of 60, giant sigmoid diverticulum is an uncommon variant of which only relatively few cases have been described in the literature. We report on our experience with a patient affected by giant sigmoid diverticulum who was treated with diverticulectomy. Resection of the diverticulum is a safe surgical procedure, provided that the colon section close to the lesion presents no sign of flogosis or diverticula; in addition, recurrences are not reported after 6-year follow-up.

Gemcitabine (GEM), 5-Fluorouracil (5-FU) and Folinic Acid (FA) in Patients with Different Gastroenteric Malignancies

Abstract This phase II clinical trial was performed in order to evaluate the pharmacokinetics, toxicity and anti-tumor activity of a novel combination of gemcitabine (GEM), 5-fluorouracil (5-FU) and folinic acid (FA) designed on a specific translational basis. Every 4 weeks, 44 patients with various gastroenteric malignancies, 29 of whom had pancreas carcinoma, received a short intravenous (i.v.) infusion of FA (100 mg/m2) and 5-FU (400 mg/m2) on days 1-5, and GEM 1000 mg/m2 on days 1, 8 and 16. Our results suggest that, although this treatment leads to hematological and gastroenteric toxicity, it is very active in patients with pancreatic carcinoma. We therefore believe that an improved version would merit further investigation in larger scale trials.

Initial Experience with Laparoscopic Adjustable Gastric Banding and Pouch Dilatation: Two Cases

Background: Late proximal pouch dilatation (LPPD) has occurred occasionally following gastric banding for morbid obesity. At present, laparoscopic conservative resetting and oversuturing of the band is considered the standard procedure for pouch dilatation without any important posterior component. Methods: Two cases of LPPD are presented, which occurred in our initial experience with the LapBand®, corrected via a laparoscopic approach. Results: The reintervention was necessary in both patients, with conservative laparoscopic repositioning and oversuturing of the band in the first case and laparoscopic substitution of the gastric band in the second. We have not observed further complications, and weight loss has been maintained in a midterm outcome in both cases (30 and 18 months follow-up). Conclusions: LPPD can be corrected with a conservative laparoscopic surgical approach, without complications and negative functional effects on mid-term outcome.