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Biomedical subjects

R Rosati

Publications and source records attributed to R Rosati.

121 records · Page 7Linked to original sources

Thoracoscopic esophagectomy: are there benefits?

Between 1991 and 1995, 18 patients affected by a resectable intramural tumor of the esophagus underwent esophagectomy with thoracoscopic dissection of the esophagus. All patients had a relative contraindication to transthoracic esophagectomy with radical lymphadenectomy. All esophagectomies were completed thoracoscopically and reconstruction of the digestive tract was performed in 17 cases through cervical gastroplasty, and in 1 case, through cervical coloplasty. One cirrhotic patient died in the postoperative period due to a cervical anastomotic leak. Six other patients experienced a postoperative complication (mortality rate, 5.5%; morbidity rate, 33.3%). After a median follow-up of 17 months, 14 patients are alive without evidence of disease. One patient, who had excision of a cutaneous metastasis at a trocar insertion site 6 months postoperatively, eventually died with locoregional recurrence 14 months postoperatively. Another patient died 20 months after surgery with mediastinal recurrence. One patient died 28 months postoperatively after massive hematemesis with a suspect abdominal recurrence. The results of the present series, and those reported by other authors, do not seem to indicate evident advantages at present for the minimally invasive procedure during resection of the esophagus for cancer. Currently, there is no indication that this procedure should be used for standard clinical use. Wider randomized trials, performed in selected centers only, and longer follow-up are needed to further evaluate the procedure.

Aged↗

Experience with living related liver transplantation in 63 children.

The incentive to develop intrafamilial living related liver transplantation (LRLT) originated from the shortage of cadaveric organ supply. We report our experience with LRLT in 63 children during 1993-1998 in the frame of a protocol approved by the Ethics Committee of our Institution. During this period, 152 potential intrafamilial (mostly parental) donors were evaluated; 44 (28.5%) were excluded because of surgical (n = 4), medical (n = 39) or psychosocial reason (n = 1). Out of 108 who matched all medical, surgical and psychological criteria of selection, 45 did not underwent living donation because their child received a cadaveric graft (n = 22; LRLT was their second option) or because one of the parents who had both been selected was chosen [by the surgical team because of more favourable anatomy (n = 8) or by mutual agreement between the two parents (n = 5)]. Sixty-three living donors (36 mothers, 24 fathers, one grand mother, one aunt and one uncle) underwent procurement of the left lobe (n = 52), the left lobe extended to part of segment IV (n = 8) or a left hepatectomy (n = 3) without mortality or any serious morbidity. Their median hospital stay was 7 days (range: 6-12); full physical rehabilitation and normalization of liver tests were usually obtained within three weeks. Their psychological follow-up did not disclose any longstanding serious sequellae. The median age of the recipients was 13 months (range 5-189); 30 were younger than one year at the time of transplant. Their median weight was 8.1 kg (range: 4.3 to 60); 36 had an actual weight under 10 kg. Fifty-two received an ABO identical and 11 received an ABO compatible transplant. The native liver diseases were similar to common data in children, with biliary atresia being the most frequent indication (74.6%). The median weight of the graft was 260 gr (range: 138-680) with a median ratio between the graft weight and the recipient body weight of 3.17% (range: 0.75-8.08). All grafts were implanted orthotopically with semi-microvascular reconstruction of the hepatic vein, portal vein and hepatic artery [end to end anastomosis in 58 (2 arteries were reconstructed in 7 patients) and interposition of an iliac arterial allograft from the infrarenal aorta in 5]. Base line immunosuppression consisted of a triple drug regimen including steroids, Azathioprine and either Cyclosporine-Sandimmun (n = 9), Cyclosporine Microemulsion formulation-Neoral (n = 13) or Tacrolimus-Prograft (n = 41). Biopsy-proved acute rejection was treated with intravenous bolus of steroids; steroid-resistant acute rejection was treated by a switch from Cyclosporine to Tacrolimus or addition of Mycophenolate-Mofetil (Cellcept) in Tacrolimus treated patients. Actuarial patient survival was 91.8% and 89.6% after LRLT at one and five years post-transplant, respectively, and 87.5% and 82.8% at one and five years, respectively, in 90 patients who received a cadaveric graft during the same interval. Actuarial graft survival was 91.8% and 84.1% after LRLT at one and five years, respectively, and 76.4% and 73.3% at one and five years, respectively, after cadaveric transplants. Vascular thrombosis was observed in 9.5% of the patients (arterial thrombosis: 1.6%; portal thrombosis: 7.9%) without graft loss. Biliary complications were observed in 26.9% (bile leak from cut surface in 3.1%, anastomotic stricture in 22.2% and intrahepatic stricture in 1.5%); two patients died from septic shock possibly related to uncompletely relieved anastomotic stricture; all other biliary complications were successfully treated either conservatively or surgically. The incidence of acute rejection was 90.9% in 22 patients with Cyclosporine-based immunosuppression; acute rejection was corticoresistant in 50%. It was 46.3% in 41 patients with Tacrolimus-based immunosuppression (64% with Prograft in capsules and 18.7% with Prograft in granules); no acute rejection was corticoresistant. (ABSTRACT TRUNCATED)

Adult↗

[Observations concerning an unusual presentation in a case of intestinal duplication].

Duplications of the alimentary canal are an infrequent pathology and may be localised in any part of the digestive tract. According to reports by several authors, the jejunoileal localisation is the most frequent. The authors report the case of a 13-year-old patient with a duplicate ileal tract which remained asymptomatic until hospitalisation was required, whose symptoms at onset resembled the clinical manifestations of acute appendicitis.

Abdomen↗

Anastomotic healing in dogs under cortisone treatment. A pilot study comparing compression and stapled anastomosis.

Colonic anastomoses made both by a new Compression Anastomotic Device (CAD) and by a traditional stapler (Autosuture CDEEA) were evaluated in impaired anastomotic healing induced by systemic cortisone in the dog. Twenty dogs were given daily i.m. hydrocortisone (25 mg/kg) starting one month before surgery and then until sacrifice. Eight untreated dogs served as controls. Surgery consisted of colonic transection and anastomosis done with CAD-25 in half the cases and with CDEEA-25 in the remaining half. The dogs were sacrificed six and 13 days after surgery. Macroscopic assessment, bursting pressure test, and histology were performed on the anastomosis. One dog died from peritonitis due to anastomotic dehiscence. No other clinical complications were observed. Although the number of observations was too small to attain statistical significance, CAD anastomoses appeared better than stapled ones as regards peri-anastomotic adhesions, anastomotic index, and histology. This preliminary study suggests that compression is as reliable as the stapler in the construction of colon anastomosis even in such situations of delayed anastomotic healing. Further experience is required to substantiate this conclusion.

Anastomosis, Surgical↗

Preferential expression of the dbl proto-oncogene in some neuroectodermal tumors.

The dbl oncogene belongs to a unique class of human transforming genes. The dbl proto-oncogene is activated by substitution of the 5' portion of the gene with an unrelated human sequence. The proto-oncogene product is distributed between the soluble and membrane fractions of the cytoplasm and its function remains still unknown. In order to understand the biological role of dbl in human malignancies or during cell differentiation we have investigated the expression of the dbl oncogene in a wide number of human tumors of different embryological derivation. We found that dbl is preferentially expressed in a few neoplastic histiotypes of neuroectodermal origin. The transcript size of 5.3 Kb strongly suggests that the gene is not truncated in these tumors. These data, together with the information that the proto-oncogene has been found expressed in normal brain and adrenal medulla, indicate that dbl expression may be involved in cell differentiation of some tissues of neuroectodermic origin.

Gene Expression Regulation, Neoplastic↗

Surgical treatment of malignant tumors of the Oddian region.

From 1974 through 1984, 24 patients with malignancies of the Oddian region underwent surgery. Four ampullectomies were carried out with one more than 10-year survivor. Nineteen duodenopancreatectomies were performed with no operative mortality, a 21% complication rate and a 4% reoperation rate; mean survival was 42 months; 1-, 3- and 5-year survival was 95%, 53%, and 37% respectively. Nodal metastasis was the major determinant of long-term survival. Duodenopancreatectomy should be considered the operation of choice for malignancies of the Oddian region.

Adenoma, Bile Duct↗

Laparoscopic treatment of functional diseases of the esophagus.

The possibilities of laparoscopic surgery in the treatment of functional esophageal diseases (gastroesophageal reflux, achalasia and epiphrenic diverticula) are illustrated with special emphasis on the technical aspects, including intraoperative complications and postoperative care. Results are discussed on the ground of the following experience. Thirty-seven laparoscopic fundoplications were performed with 13% conversion rate, 2.7% postoperative morbidity (1 slipped Nissen requiring redo laparoscopic surgery). Median operative time was 140 min. One patient complained of dysphagia relieved by endoscopic dilation (2.7%). All patients are not asymptomatic after a median follow-up of 16 months although one has gastroesophageal reflux (GER) at 24-hrs pH monitoring. forty laparoscopic Heller-Dor procedures: 7% conversions, 5% postoperative morbidity. Median duration 120 min. One patient complained of persistent dysphagia requiring endoscopic dilation (2.5%) and asymptomatic GER was detected in 8% of patients. Finally, 2 patients underwent laparoscopic diverticulectomy, esophagomyotomy and Dor fundoplication without morbidity and excellent postoperative result. Laparoscopic treatment of functional diseases of the esophagus is safe and effective, provided it is performed by an experienced surgeon with respect for some important technical details. Further follow-up is needed to evaluate long-term results.

Adolescent↗

Thoracoscopic dissection of the esophagus for cancer.

Eighteen patients affected by a resectable intramural tumor of the esophagus have undergone esophagectomy with thoracoscopic dissection of the esophagus in the last 4 years. All patients had a relative contraindication to transthoracic esophagectomy with radical lymphadenectomy. All esophagectomies were completed thoracoscopically and reconstruction of the digestive tract was performed in 17 cases through cervical gastroplasty and in 1 case through cervical coloplasty. One cirrhotic patient died in the postoperative period due to cervical anastomotic leak. Six other patients experienced a postoperative complication (mortality rate 5.5%; morbidity rate 33.3%). After a median follow up of 17 months, 14 patients are alive without evidence of disease. One patient, who had excision of a cutaneous metastasis at a trocar insertion site 6 months postoperatively, eventually died with locoregional recurrence 14 months postoperatively. Another patient died 20 months after surgery with mediastinal recurrence. One patient died 28 months postoperatively after massive hematemesis with a suspect abdominal recurrence. The results of the present series and those reported by other authors do not seem to indicate presently evident advantages from the minimally invasive procedure during resection of the esophagus for cancer. At the present time, no indication to this procedure exists for standard clinical use; wider randomized trials and longer follow-up to be performed only in selected centers are needed to further evaluate the procedure.

Adenocarcinoma↗

Dolastatin 15 induces apoptosis and BCL-2 phosphorylation in small cell lung cancer cell lines.

BACKGROUND: The dolastatins are natural peptides which inhibit microtubule assembly and induce apoptosis in a number of malignant cell types. In small cell lung cancer (SCLC), bcl-2 overexpression is very common and appears to be a mediator of cell growth and treatment-resistance, suggesting that bcl-2 is a rational target for novel anti-SCLC strategies. Since several other tubulin-binding agents have been reported to induce apoptosis in association with phosphorylation and inactivation of bcl-2, we evaluated the effects of dolastatin 10 and 15 in SCLC cells. METHODS: The growth inhibitory activity of dolastatin 10 and 15 was evaluated in four SCLC cell lines with an MTT assay. Cell cycle and the induction of apoptosis were evaluated by flow cytometry and fluorescent microscopy. Immunoblot analysis was used to determine bcl-2 expression and phosphorylation. RESULTS: Dolastatin 15 displayed growth inhibitory activity against all four SCLC cell lines (NCI-H69, NCI-H82, NCI-H345, NCI-H446) with IC50 values ranging from 0.039-28.8 nM, which were 2.7-9.2-fold higher than the values for dolastatin 10. All four SCLC cell lines underwent G2/M arrest within 24 hours of exposure to dolastatin 15, and three had morphologic evidence of apoptosis after 48 hours. Immunoblot analysis of dolastatin 15-treated cells which overexpressed bcl-2 revealed a pattern consistent with bcl-2 phosphorylation. CONCLUSION: Dolastatin 15 has in vitro activity against SCLC cells, but is less potent than dolastatin 10. This activity is associated with the induction of apoptosis and bcl-2 phosphorylation. These findings suggest that further evaluation of the activity of the dolastatins in SCLC is reasonable and that the pharmacologic modulation of apoptotic pathways deserves further study as a potential anticancer strategy.

Antineoplastic Agents↗

Activity of 9-cis-retinoic acid and receptor-selective retinoids in small cell lung cancer cell lines.

Dysregulation of retinoid signaling pathways appears to be an early event in the pathogenesis of small cell lung cancer (SCLC). We evaluated the activity of 9-cis-retinoic acid (9cRA), a pan- receptor agonist, and two synthetic retinoids, TTNPB and LG100153, which are RAR- and RXR- selective, respectively, against a panel of SCLC cell lines. LG100153 was the most potent agent with an IC50 < 1.0 microM in three cell lines. TTNPB had an IC50 < 1.0 microM in two lines, and 9cRA an IC50 < 1.0 microM in only one. By fluorescent microscopy, LG100153, TTNPB and 9cRA also induced morphologic evidence of apoptosis in three, two and one cell lines, respectively. Although the expression of RARs and RXRs varied widely between cell lines, there was no clear correlation between the level or pattern of receptor expression and retinoid activity. These data suggest that novel retinoids, especially RXR-selective agents, deserve further evaluation in the treatment of SCLC.

Alitretinoin↗