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Biomedical subjects

F Stipa

Publications and source records attributed to F Stipa.

At least 19 recordsLinked to original sources

Outcomes for early rectal cancer managed with transanal endoscopic microsurgery: a 5-year follow-up study.

BACKGROUND: This study aimed to evaluate the long-term risk of local and distant recurrence as well as the survival of patients with early rectal cancer treated using transanal endoscopic microsurgery (TEM). METHODS: The study reviewed 69 patients with Tis/T1/T2 rectal cancer treated using full-thickness excision between 1991 and 1999. The pathology T-stages included 25 Tis, 23 T1, and 21 T2. The median follow-up period was 6.5 years (range 5-10.2 years). RESULTS: The overall local recurrence rate was 8.7%. The 5-year local recurrence rate was 8% for Tis, 8.6% for T1, and 9.5% for T2. All six patients with recurrence were managed surgically. The 5-year disease-specific survival rate was 100% for Tis, 100% for T1, and 70% for T2. The overall cancer-related mortality rate was 7.2%. CONCLUSIONS: After local excision of early rectal cancer, a substantial local recurrence rate is observed. Patients with recurrent Tis/T1 cancers who undergo a salvage operation may achieve good long-term outcome. Local treatment without adjuvant therapy for T2 rectal cancers appears inadequate.

Adult↗

The laparoscopic approach with antireflux surgery is superior to the thoracoscopic approach for the treatment of esophageal achalasia. Experience of a single surgical unit.

BACKGROUND: Since its first description in the early 1990s, minimally invasive Heller myotomy has become the treatment of choice for esophageal achalasia. We report the experience of a single unit with thoracoscopic Heller myotomy (THM) and laparoscopic Heller myotomy (LHM) and we analyze the short- and long-term surgical outcomes in patients treated by each of the two approaches. METHODS: We evaluated retrospectively 33 patients who underwent surgical treatment for achalasia. Sixteen patients underwent THM without an antireflux procedure, and 17 patients underwent LHM and partial anterior fundoplication (n = 10) or closure of the angle of His (n = 7). RESULTS: Mean operative time was significantly shorter for LHM than for THM (150 vs 222 min, respectively) (p = 0.0001). Mean hospital stay was significantly shorter after LHM than after THM (2.0 +/- 1.0 vs 5.1 +/- 2.2 days, respectively) (p = 0.0001). Six of 16 patients (37.5%) in the THM group experienced persistent or recurrent dysphagia compared to one of 17 patients (5.8%) in the LHM group (p = 0.04). Heartburn developed in five patients (31.2%) after THM and in one patient (5.8%) after LHM (p = 0.07). Regurgitation developed in four patients (25%) after THM and in one patient (5.8%) after LHM (p = 0.149). Lower esophageal sphincter (LES) basal pressure decreased significantly from 30.1 +/- 5.07 to 15.3 +/- 2.1 after THM and from 32.1 +/- 5.9 to 10.5 +/- 1.7 after LHM (p = 0.0001). Mean esophageal diameter was significantly reduced after LHM compared to THM (from 54.5 +/- 5.7 mm to 27.1 +/- 3.3 mm vs 50.8 +/- 7.6 mm to 37.2 +/- 6.9 mm, respectively) (p = 0.0001). CONCLUSION: In our experience, LHM is associated with a shorter operative time and a shorter hospital stay, and it is superior to THM in relieving dysphagia. LHM with partial anterior fundoplication should be considered the treatment of choice for achalasia.

Adolescent↗

[Local resection in treatment of rectal tumors].

We treated 160 patients (96 males, 64 females) with a mean age of 66 +/- 12 years. 63 patients presented adenomas (AD) and 97 adenocarcinomas (ADC). In the ADC group 32 patients received preoperative chemoradiation (RT + CT), and 15 postoperative RT. In 7 patients with RT + CT the tumor disappeared. No hospital mortality was recorded. Morbidity was observed in 13% of AD group and 18% of ADC group. Hospital stay was less than 7 days for 72% of patients. Stages were: 10 pTis, 40 pT1, 29 pT2, 18 pT3. Recurrence was observed in 7 (11%) of AD and 23/97 ADC (24%). 0 pTis, 12% pT1, 24% pT2, 61% pT3. No patient with RT + CT and negative margins had recurrence with a minimum follow-up of 2 years (11 patients). Five-year cumulative survival was 100% for pTis, 92% for pT1, 75% for pT2 and 69% for pT3.

Adenocarcinoma↗

Selection, establishment and characterization of cell lines derived from a chemically-induced rat mammary heterogeneous tumor, by flow cytometry, transmission electron microscopy, and immunohistochemistry.

In order to isolate, characterize, and establish culture cell lines with different diagnostic and prognostic significance, derived from multiclonal neoplasms, a ductal infiltrating mammary tumor was induced in rats by 7,12-dimethylbenz[a]anthracene. Clones with different DNA/protein content, being the DI of 1.16, 1.30, and 1.60, respectively, were observed in the primary tumor. Biparametric flow cytometry suggested that the clone at 1.30 is made up of two subpopulations with different protein and slightly different DNA contents. The culture, after a few passages, exhibited the presence of aneuploid cells and the absence of diploid components, demonstrating that only tumor cells survived. The limiting dilution method gave rise to four lines with DI of 1.16, 1.25, 1.30, and 1.50; a mean chromosome number of 45, 46, 47, and 88, respectively; and different morphological and ultrastructural features. These characteristics were stable during the experimental procedure, that is, for about 20 passages. Conversely, the detection of cytoskeletal proteins indicated that the tumor epithelial cells underwent early dedifferentiation into sarcoma-like cells showing markers of stromal cell type and thus exhibiting phenotypic instability in vitro, a feature reported in many advanced human breast cancers in vivo. In conclusion, this cellular model represents the in vivo situation and appears suitable for in vitro studies of tumor cell characteristics and might be used to predict clinical behavior.

Animals↗

In vitro proliferation and in vivo malignancy of cell lines simultaneously derived from a chemically-induced heterogeneous rat mammary tumor.

Identification of clones in primary tumors responsible for proliferation, invasion, and metastasis was carried out. Four different aneuploid established cell lines derived from a ductal infiltrating mammary rat tumor induced by 7,12-dimethylbenz[a]anthracene were studied for proliferative and growth features in vitro and for tumorigenic and metastatic potential in vivo in nude mice. Clones, named RM1, RM2, RM3, and RM4, were characterized by different proliferative activity. Clone RM1 showed the highest proliferative activity by both tritiated thymidine incorporation and S-phase flow cytometry, followed by clone RM4. Conversely, clones RM2 and RM3 showed a lower proliferation rate. Growth-promoting activity, tested on 3T3 Swiss cells, was high in all clones, although RM1 showed significantly lower growth factors-releasing activity. Nude mice tumorigenesis demonstrated a strong tumor induction of line RM1 (100% of the mice after 47 +/- 7 d) and a slightly lower tumor induction of line RM4 (70% of the mice after 69 +/- 9 d). Line RM3 showed tumor induction in 40% of the mice after 186 +/- 16 d. Lines RM2 showed no tumor induction. Metastasis occurred in mice treated with line RM1 only. Therefore, tumorigenesis and metastasis correlate with proliferation but not with the release of growth factors. In conclusion, flow cytometry monitoring of clones from heterogeneous primary tumors proved to be a suitable model for the study of in vivo malignancy and in vitro proliferation.

Animals↗

[Antibiotic prophylaxis in the surgical treatment of inguinal hernia: need or habit?].

BACKGROUND: Prophylactic antibiotics are recommended for clean-contaminated and selected contaminated surgery. In clean surgery antibiotics are suggested if the operation involves the insertion of prosthetic devices and a potential infection is expected to cause serious morbidity or mortality. Inguinal hernia repair is a clean operation, infections are rare; they can usually be cured without removing the prosthesis and recurrence is uncommon even after removal of the mesh. Aim of the study is to evaluate whether the lack of antimicrobial prophylaxis increases the risk of postoperative infections in patients treated for groin hernia, compared to those treated with prophylaxis. METHODS: One hundred and forty-eight patients underwent inguinal hernia repair with mesh: 64 patients (43%) received 2 g cefotaxime by intravenous bolus about 30 minutes before the operation, 84 patients (57%) did not receive any antimicrobic prophylaxis. Mean follow-up was 13 months (range 1-31 months) for both groups. RESULTS: We did not observe any major complication. Among both groups, no patient had developed infection at one week and one month after surgery. CONCLUSIONS: In personal experience, any advantage in terms of prevention of infections with antibiotic prophylaxis in patients operated on for groin hernia has been observed. A review of the literature showed no general agreement on this subject with different risk of infections in different trials. A new prospective randomized trial is necessary to clarify this topic.

Adult↗

Surgery of rectal tumors.

The results of surgical treatment of carcinoma of the rectum have been improved in the last decades, because of the availability of stapling device, the increasing use of adjuvant or neoadjuvant treatment and the development of endoluminal surgery. Herein we present our thirty years experience in the treatment of rectal carcinoma. It deals with 690 patients operated on, 602 with conventional surgery (87%) and 88 with local excision (13%). As regards the first subgroup, in 63 patients (10.4%) the operation was considered palliative, because there were either hepatic metastases or residual tumor; 21% of the whole number had tumor in the upper third, 40% in the middle third and 39% in the lower third. Radical resection was performed in 538 patients (89.6%); 53% of the patients underwent anterior resection and 47% underwent abdomino-perineal resection. Ninety percent of tumors located in the lower rectum were managed with abdomino-perineal resection and 97% of tumors located in the upper rectum were managed with anterior resection. Tumor of the middle rectum were treated indifferently with anterior resection or abdomino-perineal resection. Mortality was 4%; the morbidity was 33%. No statistical difference was found between anterior resection and Miles operation. Mean follow up is 6.8 years. Local recurrence was observed in 17% of patients and was more frequent after Miles operation than after anterior resection. The 5- and 10-year survival is respectively 53% and 43%; according to staging, 5-year survival is 68% for stage I, 64% for stage II, 39% for stage III and 9% for stage IV (p < 0.0001). As regard local excision, lesions usually arised from lower or middle rectum and were less than 3 cm. in the maximum diameter. Sixty per cent of patients received adjuvant or neoadjuvant treatment; we observed complete response with disappearance of the tumor in 28% of T2 patients. The toxicity was low: 3% of patients developed erithema and 21% different grades of proctitis. Mean duration of operation was 179 +/- 98 min' and hospitalization was less than 7 days in most of the patients. No mortality was recorded, while morbidity was 16% (14 patients). On pathological examination we observed 10 Tis (11%), 32 T1 (36%)28 T2 (32%) and 18 T3 (21%). Mean follow up is 3.3 years; local recurrence was related to staging and was respectively 0%, 16%, 25% and 61% (p = 0.0008). We did not observe local recurrence whenever T2 patients had neoadjuvant treatment and negative margins at i.o. pathological examination. Our findings show that anterior resection represents the most appropriate treatment for tumors of the upper and middle rectum; Miles operation should be reserved to tumors located within 5 cm. from the anal verge. Small tumors, confined to the rectal wall, can be properly treated with local excision; local treatment should be always associated to preoperative chemoradiation in tumors involving the muscular layer of the rectal wall.

Chemotherapy, Adjuvant↗

Basic fibroblast growth factor and myointimal hyperplasia after experimental polytetrafluoroethylene arterial grafting.

OBJECTIVE: To assess the role of polyclonal antibodies to basic fibroblast growth factor (bFGF) in inhibiting myointimal hyperplasia after insertion of polytetrafluoroethylene (PTFE) grafts in rats. DESIGN: Experimental study. SETTING: University laboratory, Italy. ANIMALS: 24 inbred Lewis rats. INTERVENTIONS: A segment of PTFE I cm long was interposed in the abdominal aorta. The animals were randomised in two groups, n = 12 in each. The first were given polyclonal antibodies to bFGF at the time of operation, and for the first two postoperative days; and the second were given non-specific IgG at the same time periods. MAIN OUTCOME AND MEASURES: Two animals died during the immediate postoperative period of anaesthetic complications. 12 animals (6 in each group) were killed 7 days postoperatively (24 hours after injection of 5-bromo-deoxyuridine BrdU) to assess smooth muscle cell proliferation. The remaining 10 animals (5 in each group) were killed after 1 month to assess the degree of anastomotic myointimal hyperplasia. RESULTS: Antibodies to bFGF resulted in less smooth muscle cell proliferation at the anastomoses as well as anastomotic myointimal hyperplasia. Smooth muscle cell proliferation was reduced to about half in animals treated with anti-bFGF antibodies. Neointimal thickness was reduced in treated animals. CONCLUSIONS: We conclude that after PTFE arterial grafting there is increased production of bFGF at the anastomotic regions that leads to smooth muscle cell proliferation and formation of myointimal hyperplasia. Agents that reduce the production of bFGF may also reduce the development of myointimal hyperplasia after PTFE arterial grafting.

Analysis of Variance↗

Oxidised LDL (OxLDL) induces production of platelet derived growth factor AA (PDGF AA) from aortic smooth muscle cells.

OBJECTIVES: Elevated concentrations of oxidised low density lipoproteins (OxLDL) are associated with accelerated atherogenesis. The aim of our study was to determine the effect of OxLDL on the proliferation rate and platelet derived growth factor (PDGF) AA production on aortic smooth muscle cells. High density lipoproteins (HDL), which are known to have a protective effect against atherosclerosis, were used as control. MATERIALS AND METHODS: Bovine aortic smooth muscle cells were grown in presence of increased concentrations of OxLDL and HDL and in presence of control medium culture (DMEM). Proliferation rate was assessed by 3H-thymidine uptake. PDGF AA production was determined by ELISA and Western Blot Analysis. RESULTS: OxLDL increased the proliferation rate of aortic smooth muscle cells as compared to DMEM and HDL (p < 0.001). The mitogenic activity of OxLDL on smooth muscle cells was reduced adding anti-PDGF AA antibodies (p < 0.001). PDGF AA production by aortic smooth muscle cells was increased after exposure to OxLDL as compared to DMEM (p < 0.001). HDL significantly reduced the production of PDGF AA by aortic smooth muscle cells (p < 0.001). CONCLUSIONS: Part of the atherogenic effect of OxLDL is mediated through the autocrine production of PDGF AA from aortic smooth muscle cells.

Animals↗

Growth factors and myointimal hyperplasia in experimental aortic allografts.

OBJECTIVES: To analyse the role of growth factors (platelet derived growth factor, PDGF; basic fibroblast growth factor, bFGF; interleukin 1, IL-1) in the genesis of myointimal hyperplasia in arterial allografts. MATERIALS: Two groups of experiments were performed: isografts and allografts. The isograft group consisted of 15 inbred Lewis rats in which a 1 cm long segment of aorta was inserted as an abdominal aortic interposition graft. The aortic segments were obtained from syngenic Lewis rats. The allograft group consisted of 15 inbred Lewis rats, in which a 1 cm long segment of aorta was interposed at the abdominal aorta level. The aortic segments were obtained from allogenic Brown-Norway rats. CHIEF OUTCOME MEASURES: The animals were killed 4 weeks after surgery and were analysed by morphometric analysis (n = 3 for each group). In addition, production of PDGF, bFGF and IL-1 by aortic segments (n = 12 for each group) in organ culture was assessed. MAIN RESULTS: Allografts had more myointimal hyperplasia, than isografts (p < 0.05). PDGF and bFGF production, generally considered to be the cause of myointimal hyperplasia, was not increased in allografts. IL-1 production was higher in allografts (p < 0.001). MAIN CONCLUSIONS: Myointimal hyperplasia in aortic allografts is dependent on growth factors produced by the graft itself. These growth factors are different from PDGF and bFGF that generally have been implicated in the genesis of naturally occurring myointimal hyperplasia and atherosclerosis. IL-1 may have a principal role in the genesis of myointimal hyperplasia in arterial allografts.

3T3 Cells↗

Assessment of non-acid esophageal reflux: comparison between long-term reflux aspiration test and fiberoptic bilirubin monitoring.

Reflux esophagitis may result from the action of both acid and non-acid agents. The aim of this study was to test a new system able to measure the quantity of the bilirubin contained in the esophageal lumen. The analysis of esophageal reflux composition was conducted in two phases. In the first bile and pancreatic enzyme, concentration of 136 fluid samples obtained with ambulatory esophageal long-term reflux aspiration test were measured. For the second, the total bilirubin content of each sample was measured in vitro with a fiberoptic probe (Bilitec 2000, Synetics Medical Inc., Sweden). Studies were performed on 48 subjects: 43 patients with esophageal reflux and five healthy volunteers. The results of both techniques were then compared. Higher concentration of bile and pancreatic enzymes were found in esophageal fluid samples of patients with endoscopic esophagitis. Bile and pancreatic enzyme concentrations of esophageal fluid samples were higher in patients after gastrectomy compared to patients with intact stomachs. There was a significant correlation between the total bilirubin concentration of fluid specimens and the fiberoptic probe reading of bilirubin (r = 0.72, P < 0.001). The presence of bilirubin and bile acids within the esophageal refluxate can be determined reliably with continuous fiberoptic measurement. The correlation between total bilirubin content and the concentrations of pancreatic enzymes contained in the esophageal refluxate suggests that bilirubin is a good tracer for non-acid, duodenal or intestinal reflux in the esophagus.

Adolescent↗

Changes in hepatic portal resistance and in liver morphology during regeneration: in vitro study in rats.

OBJECTIVE: To study the effects of liver regeneration on hepatic portal resistance and on the morphology of liver sinusoids. DESIGN: Experimental in vitro study. SETTING: University laboratory, Hong Kong. ANIMALS: 10 Groups of 6 male Sprague Dawley rats each. INTERVENTIONS: Two thirds hepatectomy, with subsequent re-hepatectomy for measurements 0, 1, 3, 7, 21 and 56 days later. Perfusion of isolated livers and histomorphometry. MAIN OUTCOME MEASURES: Hepatic portal resistance and measurement of width and length of sinusoids. RESULTS: Liver weight was restored within 7 days of hepatectomy. Hepatic portal resistance/g of liver increased, reaching a maximum at 3 and 7 days of hepatectomy, and subsequently returned to initial values after 56 days. Width of sinusoids decreased to a minimum within 3 to 7 days of hepatectomy, and subsequently returned close to initial values within 56 days of hepatectomy. The changes in hepatic portal resistance occurred in phase with the changes in the width of liver sinusoids. CONCLUSIONS: There is a transient increase in hepatic portal resistance/g of liver during regeneration; transient narrowing of sinusoids may contribute to this change.

Animals↗

Growth factor production by arterial and vein grafts: relevance to coronary artery bypass grafting.

BACKGROUND: Occlusion caused by myointimal hyperplasia, atherosclerosis, or both is the main reason for late failure of saphenous vein coronary artery bypass grafts. On the other hand, internal mammary artery grafts are usually spared from atherosclerosis. Evidence exists that platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) are involved in the genesis of myointimal hyperplasia and atherosclerosis. The aim of this study was to assess the production of PDGF and bFGF by arterial and vein grafts. METHODS: In 20 inbred Lewis rats alpha 1 cm long segment of arterial graft was interposed at the level of the abdominal aorta. In a control group of 20 Lewis rats alpha 1 cm long segment of vein graft was implanted at the level of the abdominal aorta. Animals were killed 4 weeks after operation, and the grafts were studied in serum-free organ culture to assess the production of PDGF and bFGF. RESULTS. Arterial grafts produced a smaller quantity of PDGF and bFGF than vein grafts (p < 0.01) Higher mitogenic activity was present in the conditioned media from vein grafts than in the conditioned media from arterial grafts (p < 0.001). A large amount of myointimal hyperplasia was present in all vein grafts. CONCLUSIONS: This phenomenon could explain the rarity of atherosclerotic changes in internal mammary coronary bypass grafts.

3T3 Cells↗

Growth factor production after polytetrafluoroethylene and vein arterial grafting: an experimental study.

PURPOSE: Occlusion caused by myointimal hyperplasia appears to be the main reason of late failure of polytetrafluoroethylene (PTFE) arterial bypass grafts. Evidence exists that growth factors are involved in the genesis of myointimal hyperplasia. The aim of this study was to assess the release of platelet-derived growth factor (PDGF) and basic fibroblastic growth factor (bFGF) by PTFE arterial grafts. METHODS: In 15 inbred Lewis rats a 1 cm long segment of PTFE was interposed at the level of the abdominal aorta. In a control of another 15 Lewis rats in a vein graft was implanted at the level of the abdominal aorta. Animals were killed four weeks after implantation and the tissue was studied in organ culture for release of PDGF AA, PDGF BB, and bFGF. RESULTS: PTFE grafts released a greater quantity of PDGF AA than did control vein grafts (28 +/- 4 ng/cm2/72 hr vs 7 +/- 2 ng/cm2/72 hr). Similarly, PTFE grafts released a greater quantity of bFGF than did arterial vein grafts (308 +/- 22 ng/cm(2)/72hr vs 204 +/- 20 ng/cm2/72 hr). CONCLUSIONS: We conclude that PTFE arterial grafts released a high quantity of growth factor, which could explain, in part, the occurrence of distal anastomotic myointimal hyperplasia.

Anastomosis, Surgical↗

Progression and regression of myointimal hyperplasia in experimental vein grafts depends on platelet-derived growth factor and basic fibroblastic growth factor production.

PURPOSE: The factors that lead to myointimal hyperplasia (MH) in arterial vein grafts (AVGs) are unknown. Platelet-derived growth factor (PDGF) and basic fibroblastic growth factor (bFGF) are two powerful mitogens for smooth muscle cells that have been implicated in the genesis of MH. The aim of this study was to analyze the correlation between progression and regression of MH and production of PDGF and bFGF in experimental vein grafts. MATERIALS: In 64 inbred Lewis rats, a 1-cm segment of inferior vena cava was inserted at the level of the abdominal aorta. The segments of inferior vena cava were obtained from syngenic rats. In 48 rats, the AVG was explanted 3 days (n = 8), 7 days (n = 8), 4 weeks (n = 24), and 12 weeks (n = 8) after surgery. In 16 rats the vein graft was explanted after being in the arterial system for 4 weeks and was reimplanted as a venous-venous bypass in syngenic Lewis rats. Reimplanted vein grafts (RVGs) were explanted 2 weeks (n = 8) and 8 weeks (n = 8) later. Grafts were analyzed by light and electron microscopy, morphometry, and histochemistry, and were put in organ culture to assess PDGF and bFGF production and mitogenic activity. RESULTS: We observed MH formation in AVGs and MH regression in RVGs (p < 0.001).PDGF and bFGF production correlated with the degree of MH (p < 0.01). Histochemistry showed PDGF and bFGF in the area of MH in AVG, which disappeared in RVG. Conditioned media from AVG had greater mitogenic activity than RVG or control veins. CONCLUSION: MH formation and regression in experimental vein grafts correlate with PDGF and bFGF production.

3T3 Cells↗

The degree of porosity influences the release of growth factors by healing polytetrafluoroethylene (PTFE) grafts.

OBJECTIVES: The aim of this study was to determine the influence of the degree of porosity on the release of growth factors (PDGF AA, PDGF BB, bFGF) by healing PTFE grafts. DESIGN AND SETTING: Laboratory animal study. MATERIALS: 1 cm long segments of non-reinforced PTFE grafts (30 microns fibril length, 2 mm internal diameter, 0.39 mm thick) were placed as an abdominal aortic interposition in Lewis rats. Fifteen grafts served as control (Group A; porous grafts); in eight rats (Group B; non porous grafts) the PTFE graft was completely wrapped by a non-porous plastic envelope. Animals were killed 4 weeks after surgery. OUTCOME MEASURES: The release of PDGF AA, PDGF BB and bFGF was assessed by Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: The release of PDGF AA, PDGF BB and bFGF was statistically higher in porous grafts. The only histological difference between the two groups was that porous PTFE grafts were invaded by many tufts of capillaries from the surrounding tissue, whereas this phenomenon was absent in non porous PTFE grafts. CONCLUSIONS: The degree of porosity influences the release of growth factors by healing PTFE grafts. This fact may have implication in the endothelisation of PTFE grafts and in myointimal hyperplasia formation as well.

Animals↗