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Carlo Staudacher

Publications and source records attributed to Carlo Staudacher.

15 recordsLinked to original sources

Killer cell Ig-like receptors ligand-mismatched, alloreactive natural killer cells lyse primary solid tumors.

BACKGROUND: Donor alloreactive natural killer (NK) cells have a potent antileukemic effect in haploidentical stem cell transplantation. Whether alloreactive NK cells are able to specifically kill fresh tumor cells from primary solid tumors was analyzed. METHODS: NK cells were purified from healthy donors for the expression of inhibitory killer cell immunoglobulin (Ig)-like receptors (KIRs), ex vivo expanded, and used as effector cells. Their cytotoxic effect on tumor cells freshly obtained from surgical specimens was assessed by means of a single-cell cytotoxic assay (SCCA). RESULTS: Tumor cells from 1 ovarian, 1 gastric, 3 colon, and 4 renal cell cancers were analyzed and found susceptible to alloreactive NK cell killing (>20% lysis at an effector cell to target cell [E:T] ratio of 10:1 for tumor cells not expressing at least 1 human lymphocyte antigen [HLA] class I KIR-ligand group). Remarkably, NK cells that recognized specific HLA-C group mismatches were able to kill HLA-C KIR ligand-mismatched tumor cells, whereas no lysis of target cells occurred with KIR ligand-matched tumor targets. CONCLUSIONS: Alloreactive NK-cell mediated antitumor effects might provide useful insights for designing new cell therapy approaches against solid tumors.

Antineoplastic Agents↗

Quality of life assessment in advanced pancreatic adenocarcinoma: results from a phase III randomized trial.

BACKGROUND: A phase III trial suggested that a PEFG (cisplatin, epirubicin, 5-fluorouracil, gemcitabine) regimen might improve the outcome compared to gemcitabine in advanced pancreatic adenocarcinoma. The analysis of treatment impact on quality of life (QOL) is reported. METHOD: Patients completed the European Organization for Research and Treatment of Cancer QLQ-C30 and PAN-26 questionnaires at baseline and every second month of treatment until disease progression. RESULTS: The largest differences between arms favored PEFG. Expressed as improvement > or =10 points from baseline (PEFG/gemcitabine), these were: emotional function (43/18%), fatigue (41/17%), QOL (55/29%), pain (64/41%), and flatulence (50/26%). Only change in sexual function favored gemcitabine (19/42%). Physical function, fatigue, appetite, and satisfaction with healthcare improved in 40-46% of partial responders compared with 0-12% of patients with stable disease. CONCLUSION: Clinically relevant improvement in QOL from baseline was observed more often after PEFG than after gemcitabine, suggesting that the PEFG regimen did not impair QOL, Partial response was associated with improved QOL suggesting that effective treatment of pancreatic adenocarcinoma may have an important role in these patients.

Adenocarcinoma↗

Comparison of glycerine trinitrate and botulinum toxin-a for the treatment of chronic anal fissure: long-term results.

PURPOSE: This study was designed to compare the efficacy of two different "chemical sphincterotomies" for chronic anal fissure. METHODS: From January to December 2001, 30 consecutive patients (17 males; mean age, 41.8 years) with chronic posterior anal fissure were enrolled. The patients were randomly assigned to receive 0.2 percent glycerine trinitrate ointment applied three times daily at the anal margin for eight weeks (Group A) or 20 units Botulinum toxin A injection into the internal anal sphincter on each side of the anterior midline (Group B). The patients were reviewed at 15 days, 1, 3, 6, 12, and every other 12 months. Follow-up ranged between 36 and 46 months. Patients in either group who failed to improve were referred for surgical treatment. RESULTS: Twelve patients in Group A and 11 in Group B had improvement or relief from symptoms at the first visit. The fissure was healed in ten patients in Group A and in eight in Group B within three months (66.7 and 57.1 percent). Recurrence of the fissure occurred in five patients in each group during the follow-up. The healing rate at three years was 40 and 33.3 percent for Group A and B, respectively. No patients in either group reported serious adverse effects; however, three patients in Group A (20 percent) had transient headache. None had fecal incontinence. CONCLUSION: Both treatments may be considered as first-line treatment even if less effective than surgery.

Adult↗

Laparoscopic central pancreatectomy.

BACKGROUND: The role of mini-invasive surgery in pancreatic surgery is still being debated. Indications and results are still controversial. Only a few centers in the world report on laparoscopic pancreatic resections. With the aim of improving the use of minimally invasive surgery, we have devised a novel laparoscopic procedure for surgical treatment of neuroendocrine tumor of the neck of the pancreas. METHODS: A central laparoscopic pancreatic resection was successfully performed. The pancreatic resection was performed using the harmonic scalpel. The duct was isolated and transected. The proximal duct stump was closed by an endoscopic stitch. The pancreaticojejunostomy was intracorporeally performed using a Roux-en-Y loop. RESULTS: Histologic findings showed a well differentiated neuroendocrine tumor. Operating time was 330 minutes and blood loss 300 mL. The postoperative course was uneventful. CONCLUSIONS: Laparoscopic central pancreatectomy is a feasible and safe procedure. The minimally invasive approach ensures an adequate treatment despite requiring the expertise of highly skilled laparoscopic surgeons.

Aged↗

Final results of a prospective trial of a PEFG (Cisplatin, Epirubicin, 5-Fluorouracil, Gemcitabine) regimen followed by radiotherapy after curative surgery for pancreatic adenocarcinoma.

BACKGROUND: Postoperative management of patients with pancreatic adenocarcinoma (PA) is controversial. METHODS: The aim of this pilot study was to assess the feasibility of postoperative combination chemotherapy followed by radiotherapy in patients aged 18-70 years with a histological diagnosis of PA, and Karnofsky performance status (KPS) > or =70. Cisplatin and epirubicin 40 mg/m2 on day 1, gemcitabine 600 mg/m2 on day 1 and 8, and 5-fluorouracil 200 mg/m2/day as protracted infusion (PEFG regimen) were delivered every 28 days for 4 cycles. Assuming a minimum one-year disease-free survival (DFS) of interest of 65% and a maximum of low interest of 45% (alpha 0.05; beta 0.10), the target enrollment was 51 patients, and the strategy would be considered to deserve further analysis if more than 29 patients were DF at one-year from surgery. RESULTS: Fifty-one patients, KPS >80: 29, median tumor size 3.5 cm, stage II/III/IVA: 2/34/13, grade 3-4: 22, positive resection margins: 26, node positive: 46, received 179 cycles of chemotherapy. Main grade 3/4 toxicity consisted of neutropenia (51%), thrombocytopenia (18%), and anemia (4%). One-year DFS was 67 +/- 7%. Two-year overall survival was 53 +/- 7%. CONCLUSION: Postoperative management of PA with this multimodality strategy was well tolerated and yielded a promising outcome.

Adenocarcinoma↗

Laparoscopic vs. open colectomies in octogenarians: a case-matched control study.

PURPOSE: The aim of this study was to define any benefits in terms of early outcome for laparoscopic colectomy in patients over 80 years old compared with open colectomy. METHODS: Sixty-one patients undergoing laparoscopic colectomy for colorectal cancer were matched to 61 open colectomy patients for gender, age, year of surgery, site of cancer, and comorbidity on admission. Independence status on admission and at discharge from the hospital was also evaluated. RESULTS: Mean (standard deviation) age was 82.3 (3.5) years in the laparoscopy group and 83.1 (3.3) years in the open group. Conversion rate was 6.1 percent. Operative time was 49 minutes longer in the laparoscopy group (P = 0.001). The overall mortality rate was 2.4 percent. The morbidity rate was 21.5 percent in the laparoscopy group and 31.1 percent in the open group (P = 0.30). Patients in the laparoscopy group had a faster recovery of bowel function (P = 0.01) and a significant reduction of the mean length of hospital stay (9.8 vs. 12.9 days for the open group, P = 0.001). Laparoscopy allowed a better preservation of postoperative independence status compared with the that of the open group (P = 0.02). CONCLUSION: Laparoscopic colectomy for cancer in octogenarians is safe and beneficial including preservation of postoperative independence and a reduction of length of hospital stay.

Activities of Daily Living↗

Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial.

BACKGROUND: Patients with advanced pancreatic adenocarcinoma have a poor response, progression-free survival, and overall survival with standard treatment. We aimed to assess whether a four-drug regimen could improve 4 month progression-free survival compared with gemcitabine alone. METHODS: In a randomised multicentre phase III trial, 52 patients were randomly assigned to 40 mg/m2 cisplatin and 40 mg/m2 epirubicin both given on day 1, 600 mg/m2 gemcitabine given intravenously over 1 h on days 1 and 8, and 200 mg/m2 fluorouracil a day given by continuous infusion on days 1-28 of a 4-week cycle (PEFG regimen), and 47 were assigned to 1000 mg/m2 gemcitabine given intravenously over 30 min once a week for 7 of 8 consecutive weeks in cycle 1 and for 3 of 4 weeks thereafter. The primary endpoint was 4-month progression-free survival. Secondary endpoints were overall survival, objective response, safety, and quality of life. Analyses were by intention to treat. FINDINGS: 51 patients assigned PEFG and 46 assigned gemcitabine alone had disease progression. 49 patients in the PEFG group and 46 in the gemcitabine group died from progressive disease. More patients allocated PEFG than gemcitabine alone were alive without progressive disease at 4 months (60% [95% CI 46-72] vs 28% [17-42]; hazard ratio [HR] 0.46 [0.26-0.79]). 1-year overall survival in the PEFG group was 38.5% (25.3-51.7) and in the gemcitabine group was 21.3% (9.6-33.0; HR 0.68 [0.42-1.09]). More patients assigned PEFG showed disease response than did those assigned gemcitabine (38.5% [25.3-51.7] vs 8.5% [0.5-16.5]; odds ratio 6.60 [2.11-20.60], p=0.0008). More patients in the PEFG group had grade 3-4 neutropenia and thrombocytopenia than in the gemcitabine group (p<0.0001). INTERPRETATION: The PEFG regimen could be considered for treatment of advanced pancreatic adenocarcinoma.

Adenocarcinoma↗

Morphological and functional differences in haemostatic axis between kidney transplanted and end-stage renal disease patients.

End-stage renal disease (ESRD) is characterized by several atherothrombotic abnormalities, and kidney transplant seems to improve most of them. However, because it is not clear which mechanism is responsible for such improvement, our purpose was to clarify that point.We conducted a cross sectional study involving 30 ESRD patients, 30 ESRD kidney-transplanted patients (Ktx) and 30 healthy controls (C) to evaluate platelet morphology and function, atherothrombotic profile, endothelial abnormalities and cytokine levels involved in the insulin resistance/endothelial dysfunction. (i) Platelet morphology: The ESRD group showed platelet size similar to the other two groups (ESRD=3518x10(3)+/-549x10(3) nm2, C=3075x10(3)+/-197x10(3) nm2, Ktx=2862x10(3)+/-205x10(3) nm2) with similar platelet granules and number. (ii) Platelet surface glycoprotein: The CD41 and P-Selectin were similar between groups. (iii) Platelet intracellular calcium: Resting intracellular calcium was statistically higher in ESRD compared to the C group (ESRD=182.1+/-34.5, Ktx=126.7+/-14.1, C=72.0+/-11.0 nM, P<0.01). (iv) Hypercoagulability markers and natural anticoagulants: The Ktx and ESRD groups showed higher levels of hypercoagulability markers compared to the C group. A reduction in antithrombin activity was evident in ESRD compared to the Ktx group (P=0.03). (v) Endothelial morphology: The ESRD group showed a thickened vessel basal membrane compared to the Ktx and C groups with more endothelial sufference. (vi) Insulin resistance and pro-inflammatory cytokine profile: The ESRD showed a higher homeostasis model assessment provided equations for estimating insulin resistance (HOMA-IR) compared to the Ktx and C groups (ESRD=2.6+/-0.3, Ktx=1.8+/-0.2, C=1.1+/-0.1, P=0.005) and increased soluble tumor neurosis factor alpha (sTNFalpha) (P<0.05) and soluble vascular cell adhesion molecule (sVCAM) levels (P<0.01). Positive correlations were evident among HOMA-IR and sTNFalpha (P<0.001) and sVCAM (P=0.01), respectively. In a small subgroup of ESRD who underwent Ktx (five pts), our findings were confirmed at 1 year of follow-up, suggesting an improvement of almost haemostatic abnormalities. Kidney transplant is associated with a better atherothrombotic profile in ESRD, platelet intracellular calcium and cytokines seem to be most influenced by the transplant, while most morphological abnormalities are retained.

Adult↗

Complications after percutaneous transaxillary implantation of a catheter for intraarterial chemotherapy of liver tumors: clinical relevance and management in 204 patients.

OBJECTIVE: The purposes of the study were to evaluate the complications of patients who underwent percutaneous transaxillary implantation of a permanent catheter-port system for intraarterial hepatic chemotherapy and determine their clinical relevance and specific management. SUBJECTS AND METHODS. Catheter-port systems were placed in 204 patients with liver tumors (86.7% from colorectal metastases). Under sonographic and fluoroscopic guidance, a 5.8-French catheter was placed in the hepatic artery and connected to a subcutaneous reservoir after embolization of the gastroduodenal and right gastric arteries. Floxuridine plus dexamethasone and systemic low-dose heparin were administered. During the follow-up period, complications were classified as clinically not significant (type 1), clinically significant not requiring interruption of intrahepatic chemotherapy (type 2), clinically significant needing temporary suppression of intrahepatic chemotherapy (type 3), and clinically significant causing permanent suppression of intrahepatic chemotherapy (type 4). RESULTS: No complications occurred during the implantation procedures. The mean number of intrahepatic chemotherapy cycles was 8.1. The mean follow-up period was 270 days. Primary and secondary patency rates of the system were 71.6% and 91.2%, respectively. Temporary suppression of intrahepatic chemotherapy was necessary in 19.6% of the patients and definitive suppression, in 8.8%. Hepatic artery thrombosis, not recanalized by local thrombolysis, was the main cause of permanent intrahepatic chemotherapy interruption (4.4%). Catheter occlusions and cerebral complications were not observed. In 91.2% of the patients, intrahepatic chemotherapy could be completed. CONCLUSION: Percutaneous implantation of a removable and reimplantable catheter-port system for intrahepatic chemotherapy can be a safe procedure to treat unresectable liver metastases from colorectal cancer. Technical and pharmacologic complications with variable clinical relevance occurred, and various specific management strategies were necessary to reduce their incidence.

Adult↗

Magnetic resonance with manganese-DPDP (mangafodipir) of focal solid pancreatic lesions.

PURPOSE: To assess the accuracy of magnetic resonance (MR) with Mangafodipir (Mn-DPDP) in the identification of focal solid pancreatic lesions. The possibility of lesion characterisation based on quantification of Mn uptake was also investigated. MATERIALS AND METHODS: Thirty-four patients (11 females, 23 males, aged 21-75, mean age 57) selected at sonography (US) and spiral CT (SCT) for clinically suspected focal solid pancreatic lesion, were studied between June 2000 and July 2001. Patients eligible for surgery underwent MR imaging (1.5 T) before and after infusion of 5 micromol/kg of Mn-DPDP (0.5 ml/kg Teslascan, Nycomed Amersham Health, Oslo, Norway). The baseline examination included FSE T2-weighted sequences and fat-saturated and non fat-saturated breath-hold gradient-echo T1-weighted sequences (FMP SPGR). After Teslascan infusion, fat-saturated and non fat-saturated FMP SPGR sequences were repeated. Thirty of the 34 patients had a definitive diagnosis provided by reference standards such as post-operative histology (22 cases), cytology (FNAB) and/or a follow-up period of at least 6 months (8 patients). As regards lesion characterisation, the signal-to-noise ratio (S/N ratio) and contrast-to-noise ratio (C/N ratio) of lesions compared to the pancreatic parenchyma were calculated using ROIs before and after contrast infusion. RESULTS: The definitive diagnosis was pancreatic malignancy in 18 patients, focal pancreatitis in 5 and neuroendocrine tumours in 3. Four patients with suspected lesions at US and/or SCT were free of focal pancreatic disease. Mn-DPDP MR identified 17/18 malignancies, 2/3 endocrine neoplasms 5/5 focal pancreatitis; the 4 patients with no pancreatic lesions were correctly identified. The Mn-DPDP MR accuracy in detecting focal pancreatic solid lesions was 93%. MR missed 1 small adenocarcinoma (the only pT1 in our group) and 1 insulinoma (with Mn uptake similar to the surrounding parenchyma). Due to the small number of inflammatory lesions included in the study, no significant differences were found in signal intensity and Mn-DPDP uptake between focal pancreatitis and neoplasms. CONCLUSIONS: MR with Mn-DPDP is very accurate in the identification of focal solid pancreatic lesions. Mangafodi-pir is also very useful for excluding the presence of pancreatic lesions suspected at US or CT. The characterisation of lesions, in particular of inflammatory versus neoplastic lesions, remains problematic and requires further investigation.

Adult↗

Hemorrhage from a right hepatic artery pseudoaneurysm: endovascular treatment with a coronary stent-graft.

PURPOSE: To report a novel case demonstrating the successful endovascular treatment of a right hepatic artery pseudoaneurysm using a balloon-expandable coronary stent-graft. CASE REPORT: A 60-year-old woman underwent surgical treatment for a Klatskin tumor, but her postoperative course was complicated by serious blood loss. An emergent celiac angiogram through a right transfemoral approach demonstrated a small iatrogenic pseudoaneurysm in the proximal right hepatic artery. A 7-F guiding catheter was positioned at the origin of the celiac trunk, and a Jostent coronary stent-graft mounted on a 2.7-F, 4-mm x 30-mm balloon catheter was successfully placed across the aneurysm neck. The final angiogram demonstrated total exclusion of the pseudoaneurysm with preservation of the arterial lumen. The hemodynamic condition of the patient became stable. At 12-month follow-up, duplex scanning confirmed regular right hepatic artery patency and absence of thrombotic tissue or signs of infection around the stent-graft. CONCLUSION: For hepatic artery pseudoaneurysms, endovascular repair using small covered stents may be a viable alternative to transcatheter embolization. The use of coronary instruments facilitates treatment of vascular lesions in small caliber visceral vessels.

Aneurysm, False↗

[Laparoscopic pancreatic resection: preliminary experience].

The aim of the study was to evaluate the results of laparoscopic pancreatectomy for pancreatic tumours. Four women and three men underwent laparoscopic pancreatectomy and were recruited into the study retrospectively over the period from June 2002 to February 2004. Pancreaticoduodenectomy (n = 4), intermediate pancreatectomy (n = 1) and distal pancreatic resection with splenectomy (n = 2) were successfully performed. Operative mortality was nil. The postoperative morbidity included two low-output pancreatic leaks. Mean operating time, blood loss and hospital stay were 342 minutes, 289 mL and 14 days, respectively. The pathological diagnosis was ductal adenocarcinoma in one, neuroendocrine tumour in five and metastatic melanoma in one. All patients are still well after a median follow-up of 7 months (range: 1-20 months). The patients appear to benefit from laparoscopic pancreatectomy for pancreatic tumours. The minimally invasive approach ensures adequate treatment but requires the expertise of highly skilled laparoscopic surgeons.

Adult↗

[Prognostic factors for long-term outcome of hepatic resection for colorectal liver metastases].

The aim of the study was to analyse the prognostic factors for long-term outcome of liver resections for metastases from colorectal cancer. The retrospective analysis included 297 liver resections for colorectal carcinoma liver metastases. The following prognostic factors were considered: age, gender, stage and grade of differentiation of the primary tumour, node metastases, site of the primary colorectal cancer, number and diameter of the hepatic lesions, time interval from primary cancer to liver metastases, preoperative CEA level, adjuvant chemotherapy after hepatic resection, type of hepatic resection, use of intraoperative ultrasound and portal triad clamping, blood loss and transfusions, postoperative complications and hospital stay, tumour-free surgical margins, clinical risk score (as defined by the Memorial Sloan-Kettering Cancer Centre group, MSKCC-CRS). Overall survival rates were estimated according to the Kaplan-Meier method and were compared at univariate analysis using the log-rank test. Multivariate analysis was performed including significant variables at univariate analysis using the Cox regression model. Differences were considered significant at p < 0.05. The 1, 3, 5 and 10-year overall survival rates were 90.6%, 51%, 27.5%, and 16.9%, respectively. The univariate analysis revealed a statistically significant difference (p < 0.05) in overall survival in relation to: grade of differentiation of the primary cancer (5-year survival of grades G1-G2 vs grades G3-G4: 30.7% vs 14.4%, p = 0.0016), preoperative CEA level > 5 and > 200 ng/ml (5-year survival of CEA < 5 ng/ml vs CEA > 5 ng/ml: 51.1% vs 15.5%, p = 0.0016; 5-year survival of CEA < 200 ng/ml vs CEA > 200 ng/ml: 27.9% vs 17.4%, p = 0.0001), diameter of major lesions > 5 cm (5-year survival of diameter < or = 5 cm vs > 5 cm: 30.0% vs 18.8%, p = 0.0074), disease-free interval between primary tumour and liver metastases longer than 12 months (5-year survival of patients with disease-free interval < or = 12 months vs > 12 months: 23.0% vs 36.1%, p = 0.042), high MSKCC-CRS (5-year survival of MKSCC-CRS 0-1-2 vs 3-4-5: 36.4% vs 1 6.3%, p = 0.017). The multivariate analysis showed three independent negative prognostic factors: G3-G4 primary cancer, CEA level > 5 ng/ml, and high MSKCC-CRS class. No single prognostic factor turned out to be associated with such disappointing outcomes after hepatic surgery for colorectal liver metastases as to permit the identification of specific subgroups of patients to be excluded on principle from undergoing liver resection. However, in the presence of a number of specific prognostic factors (G3-G4 grade of differentiation of the primary tumour, preoperative CEA level > 5 ng/ml, high MSKCC-CRS) enrolment of the patient in trials exploring new diagnostic tools or new adjuvant treatments may be suggested to improve the preoperative staging of the disease and reduce the incidence of tumour recurrence after liver resection.

Age Factors↗

Operative and long-term results after one-stage surgery for obstructing colonic cancer.

BACKGROUND/AIMS: To analyze retrospectively the operative results and five-year survival after single-stage resection and primary anastomosis for right- or left-sided colonic malignant obstruction. METHODOLOGY: From 1994 to 2002, 83 patients with acute obstruction due to primary cancer underwent a one-stage procedure, 36 (43.3%) for cancer of the right and 47 (56.7%) of the left colon. Of the 47 patients with left acute obstruction, 45 were treated with intraoperative colonic on-table lavage for decompression and wash-out before resection and anastomosis. Long-term survival was compared with the outcome of 369 patients with colonic cancer without obstruction 144 (39%) right and 225 (61%) left. RESULTS: Overall operative morbidity and mortality were 25.3% and 6%, respectively. Overall anastomotic leakage rate was 6%. Kaplan-Meier curves showed five-year survival rates poorer for patients operated on for obstructing malignancy than those observed for patients without obstruction (p=0.0001, Log-Rank test), obstructing malignancy was associated with more advanced age (p<0.0005) and staging of the cancer. CONCLUSIONS: One-stage resection and primary anastomosis can be applied to the majority of patients with malignant colonic obstruction and it allows achieving excellent operative results. Obstructing colonic cancer proved to be associated to a worse long-term survival.

Adenocarcinoma↗