Biomedical subjects

A Tamburini

Publications and source records attributed to A Tamburini.

At least 19 recordsLinked to original sources

PubMed2006

The kinetics of reduction of minimal residual disease impacts on duration of response and survival of patients with acute myeloid leukemia.

UNLABELLED: We assessed by multiparametric flow cytometry the levels of minimal residual disease (MRD) in 100 adult patients with acute myelogenous leukemia (AML) achieving complete remission after intensive chemotherapy. The aim of the study was to determine the optimal threshold, in terms of residual leukemic cells, and the time point of choice, that is, post-induction (post-Ind) or post-consolidation (post-Cons), able to better predict outcome. By applying the maximally selected log-rank statistics, the threshold discriminating MRD- from MRD+ cases was set at 3.5 x 10(-4) residual leukemic cells, a level that allowed the identification of distinct subgroups of patients, both at post-Ind and post-Cons time points. Post-Cons MRD- patients had a superior outcome in terms of relapse rate, overall survival (OS) and relapse-free survival (RFS) (P<0.001, for all comparisons), regardless of the MRD status after induction. In particular, patients entering MRD negativity only after consolidation showed the same outcome as those achieving early negativity after induction. Multivariate analysis, including karyotype, age, MDR1 phenotype, post-Ind and post-Cons MRD levels, indicated that the post-Cons MRD status independently affected relapse rate, OS and RFS (P<0.001, for all comparisons). IN CONCLUSION: (1) the threshold of 3.5 x 10(-4) is valid in discriminating risk categories in adult AML and (2) post-Cons MRD assessment is critical to predict disease outcome.

Adolescent↗

PubMed2006

Evaluation of biological features of cord blood units collected with different methods after cesarean section.

INTRODUCTION: Cord blood banks are established worldwide as a result of the increased use of umbilical cord blood (UCB) transplantation. The outcomes of this procedure relate to the cell dose of the UCB unit and the UCB collection. The aim of this study was to evaluate whether the mode of collection influenced the biological features of the UCB units. MATERIALS AND METHODS: We studied 151 UCB units consecutively collected in the cesarean setting with two different methods: in utero after infant delivery and before delivery of the placenta, and ex utero after delivery of placenta. RESULTS: Sixty-nine UCB units were collected in utero and 82 ex utero. The two groups were comparable for maternal and obstetric factors. The proportion of banked UCB units was similar in the two groups (38% vs 40%, respectively). No statistically significant differences were observed between the methods of collection in term of volume, white blood cell count, total nucleated cell content, CD34(+) cells, and CFU-GM. CONCLUSION: This preliminary study showed that the two methods of collection in the cesarean setting were overlapping and valid if performed according to standard operating procedures.

Cesarean Section↗

PubMed2006

Optimizing umbilical cord blood collection: impact of obstetric factors versus quality of cord blood units.

INTRODUCTION: The main limitation factor for wide use of umbilical cord blood units (UCBs) as a source of hematopoietic progenitors for transplantation is cell dose. International standard guidelines recommend 2 x 10(7)/kg as the minimal nucleated cell dose for UCB transplantation for adults and 3.7 x 10(7)/kg for children. Therefore it is important to the optimize donor selection and the collection method so as to achieve high cell doses. In this study our main purpose was to determine whether obstetric factors influence UCBs collected. STUDY DESIGN: The study involved 304 UCBs collected from January to December 2004. The UCBs were collected after donor selection based on international criteria for cord blood banking. We analyzed UCB biological features such as collected volume, total nucleated cells (TNC), and CD34-positive cells, and obstetric factors. RESULTS: First, our study showed by multivariate analysis that infant weight was the main factor that influenced biologic features of UCB collected such as total volume (P = .000), TNC (P = .000), CD34 total count (P = .003), and CFU-GM (P = .004). Placental weight > 600 g produced a better volume (P = .007) and increased TNC (P = .056). Gestational age > 39 weeks enhanced CD34% (P = .016). Regarding route of delivery, we found that cesarean section produced higher volume and reduced WBC count compared to vaginal delivery, regarding cord length, it increased TNC (P = .037). And last, we noticed that female infants increased WBC (P = .013) and CD34(+) total count (P = .019) more than male ones. CONCLUSIONS: Our results confirm that volume and TNC are influenced by several obstetric factors, such as greater infant and placental weight, predicting a better collection.

Birth Weight↗

PubMed2006

Diagnosis of acute foetal distress does not preclude banking of umbilical cord blood units.

Clinical diagnosis of acute foetal distress (AFD) is based on several parameters such as abnormal foetal heart rate (FHR) pattern and/or meconium liquid staining (MLS). Standards for cord blood (CB) banking indicate that AFD should be considered as exclusion criteria for CB collection, but precise guidelines on how to proceed with CB collection in the presence of AFD signs during labour are not available. We evaluated whether the presence of FHR abnormality and/or MLS during labour 1) reduced the CB collection activity; 2) were associated with the infant's acidaemia or asphyxia and 3) deteriorated the biological characteristics of CB units. Thirty-three units of CB were evaluated for biological parameters, gas values and newborn's Apgar score. The results were compared with a control group of 33 consecutive units previously banked. No differences were observed between the two groups and all but one newborn showed normal Apgar score and absence of metabolic acidaemia. The results showed that 1) AFD reduced the CB collection activity by 10% each year; 2) the majority of CB units collected in the presence of abnormal FHR and/or meconium have biological characteristics eligible for banking; 3) FHR alterations or meconium in the presence of normal gas analysis do not represent certain diagnosis of AFD.

Apgar Score↗

PubMed2003

Pretransplant minimal residual disease level predicts clinical outcome in patients with acute myeloid leukemia receiving high-dose chemotherapy and autologous stem cell transplantation.

A total of 31 adult patients with AML entered in the EORTC/GIMEMA AML-10 trial, who received autologous stem cell transplantation (ASCT) after induction and consolidation chemotherapy, were prospectively evaluated for minimal residual disease (MRD) by multidimensional flow cytometry (MFC). Using a cutoff level of 3.5 x 10(-4) leukemic cells pre-ASCT, 12 patients (39%) were stratified to MRD high-risk group and 19 (61%) into MRD low-risk group. During follow-up, all patients who were in the high-risk group relapsed at a median time of 7 months; in the low-risk group, five patients relapsed at a median time of 11 months and 14 remained in remission for 56 (range 7-80) months (P=0.00004). Longitudinal MFC determinations post-ASCT showed increased MRD levels in three of the five patients who underwent subsequent relapse, while disease recurrence was unpredicted in the remaining two cases. The pre-ASCT MRD status was the factor most strongly associated with relapse risk in the multivariate analysis (P=0.0014). We conclude that: (1) pre-ASCT MRD status predicts successful outcome in patients receiving ASCT; (2) high-dose chemotherapy conditioning regimen followed by ASCT has no impact on the unfavorable prognostic value of high pre-ASCT MRD level; and (3) sequential MRD monitoring post-ASCT may allow the prediction of impending relapse.

Acute Disease↗

PubMed2002

Laparoscopic cholecystectomy and common bile duct exploration are safe for older patients.

BACKGROUND: Laparoscopic common bile duct (CBD) exploration is a well-established treatment option in dedicated centers. However, few data are available on the results in elderly patients. METHODS: The outcome after laparoscopic CBD exploration in elderly patients (age <70 years) was compared with that in a concurrent control group of younger patients (age, <70 years). RESULTS: There were 77 elderly patients in group A and 207 younger patients in group B. American Society of Anesthesiology (ASA) III and IV patients and prior abdominal operations were more frequent in group A (p <0.001). Two patients from each group underwent conversion to open surgery. There was no significant difference frequency of use between the transcystic and choledochotomy approaches, although the latter tended to be more frequent in the group A because of larger stones, (group A 53.4%; group B, 37.6%). Minor and major morbidity (group A, 12%; group B, 13.6%), rate of recurrent stones (group A, 1.3%; group B, 1.9%), and mortality (group A, 1.3%; group B, 0%) were not significantly different between the two groups. The single death in group A involved a patient with acute toxic cholangitis who underwent emergency surgery after multiple failed attempts at endoscopic retrograde cholangiopancreatography/endoscopic sphincterotomy performed elsewhere. No CBD stenosis was observed at follow-up assessment. CONCLUSIONS: Elective laparoscopic CBD exploration is safe and effective. It may become the standard of care in both elderly and younger patients.

Adolescent↗

PubMed2001

Laparoscopic resection of a juxtaglomerular cell tumor of the right kidney.

Juxtaglomerular cell tumor is an extremely rare neoplasm of the kidney that causes blood hypertension. A 45-year-old man with persistent hypertension was referred to our department because of a solid mass of unclear origin (kidney? colon?) located in the right mesorenal region that had been detected by Computed tomography (CT) scan, ultrasonography, and colonoscopy. Serum levels of renin, plasma renin activity (PRA), and aldosterone were all normal. Operatively, four 10/12-mm ports were placed, ultrasonography confirmed a well-encapsulated lesion of the kidney. Ultrasonic shears and cautery were used to resect the lesion, including 5 mm of free renal tissue. Postoperatively, a prompt normalization of blood pressure was observed. The pathological findings showed a juxtaglomerular cell tumor. The definitive diagnosis of juxtaglomerular cell tumor is made on the basis of laboratory findings, and imaging studies, Its definitive treatment is surgical excision which can be accomplished successfully with minimally invasive surgery.

Adenocarcinoma↗

PubMed2001

Clinical significance of CD38 expression in chronic lymphocytic leukemia.

B-cell chronic lymphocytic leukemia (B-CLL) follows heterogeneous clinical courses, and several biological parameters need to be added to the current clinical staging systems to predict which patients will experience an indolent or an aggressive outcome. This study analyzed CD38 expression by flow cytometry and soluble APO1/Fas (sAPO1/Fas), Bcl-2 (sBcl-2), and CD23 (sCD23) proteins by immunoenzymatic methods to evaluate their effect on the clinical course of 168 unselected B-CLL patients. Intermediate/high risk modified Rai stages were characterized by a higher CD38(+) B-cell number (P =.0002) and higher sCD23 levels (P <.0001). Moreover, CD38(+) B-cell percentages were significantly and directly associated both with beta(2)-microglobulin and sCD23 concentrations (P <.0001 and P =.002, respectively). Both a higher tumor burden (lymphadenopathy/splenomegaly) and a lymphocyte doubling time less than 12 months were significantly associated with higher CD38(+) percentages (P <.0001 and P =.0001, respectively). With regard to clinical outcome, progression-free survival was significantly longer (75% versus 37% at 5 years; P =.00006) in patients with lower CD38(+) B-cell percentages. Furthermore, the risk of partial or no response to fludarabine increased with increasing CD38 expression (P =.003), and a shorter overall survival (50% versus 92% at 8 years; P <.00001) characterized patients with more than 30% CD38(+) B-cell number. The predictive value of CD38 expression was maintained among the patients within the Rai intermediate risk group and was confirmed in multivariate analysis. Thus, the percentage of CD38(+) B cells appears to be an accurate predictor of clinical outcome and therefore could be used to indicate when more novel chemotherapeutic approaches are needed.

ADP-ribosyl Cyclase↗

PubMed2001

Laparoscopic Heller myotomy relieves dysphagia in patients with achalasia and low LES pressure following pneumatic dilatation.

BACKGROUND: Although pneumatic dilatation is said to relieve dysphagia in achalasia if it decreases lower esophageal sphincter (LES) pressure to 10 mmHg (n = 23); group C, no previous balloon dilatation and LES pressure >10 mmHg (n = 25). All patients underwent a laparoscopic Heller myotomy and Dor fundoplication. The severity of dysphagia was gauged on a scale of 0-4. RESULTS: In group A, LES pressure was 7 +/- 2 mmHg preoperatively and 8 +/- 3 mmHg postoperatively; the dysphagia score was 3.3 +/- 0.7 preoperatively and 0.9 +/- 1.1 postoperatively. Eighty-nine percent of patients had excellent or good results. In group B, LES pressure was 23 +/- 8 mmHg preoperatively and 10 +/- 1 mmHg postoperatively; the dysphagia score was 3.3 +/- 0.7 preoperatively and 0.3 +/- 0.5 postoperatively. All patients had excellent or good results. In group C, LES pressure was 23 +/- 11 mmHg preoperatively and 14 +/- 12 mmHg postoperatively; the dysphagia score was 3.6 +/- 0.6 preoperatively and 0.2 +/- 0.5 postoperatively. All patients had excellent or good results. CONCLUSIONS: These results show that (a) a LES pressure of <10 mmHg after pneumatic dilatation does not guarantee relief of dysphagia, and (b) laparoscopic Heller myotomy relieves dysphagia in most patients with a postdilatation LES pressure <10 mmHg. Thus, a laparoscopic Heller myotomy is indicated if dilatation does not relieve dysphagia, even if LES pressure has been decreased to <10 mmHg. Esophagectomy should be reserved for the occasional failure of this simpler operation.

Adolescent↗

PubMed2001

Neuroblastoma with symptomatic spinal cord compression at diagnosis: treatment and results with 76 cases.

PURPOSE: To report on the treatment of patients with newly diagnosed neuroblastoma presenting with spinal cord compression (SCC). PATIENTS AND METHODS: Of 1,462 children with neuroblastoma registered between 1979 and 1998, 76 (5.2%) presented with signs/symptoms of SCC, including motor deficit in 75 patients (mild in 43, moderate in 22, severe [ie, paraplegia] in 10), pain in 47, sphincteric deficit in 30, and sensory loss in 11. Treatment of SCC consisted of radiotherapy in 11 patients, laminectomy in 32, and chemotherapy in 33. Laminectomy was more frequently performed in cases with favorable disease stages and in those with severe motor deficit, whereas chemotherapy was preferred in patients with advanced disease. RESULTS: Thirty-three patients achieved full neurologic recovery, 14 improved, 22 remained stable, and eight worsened, including three who become paraplegic. None of the 10 patients with grade 3 motor deficit, eight of whom were treated by laminectomy, recovered or improved. In the other 66 patients, the neurologic response to treatment was comparable for the three therapeutic modalities. All 11 patients treated by radiotherapy and 26 of 32 patients treated by laminectomy, but only two of 33 treated by chemotherapy, received additional therapy for SCC. Fifty-four of 76 patients are alive at time of the analysis, with follow-up of 4 to 209 months (median, 139 months). Twenty-six (44%) of 54 survivors have late sequelae, mainly scoliosis and sphincteric deficit. CONCLUSION: Radiotherapy, laminectomy, and chemotherapy showed comparable ability to relieve or improve SCC. However, patients treated with chemotherapy usually did not require additional therapy, whereas patients treated either with radiotherapy or laminectomy commonly did. No patient presenting with (or developing) severe motor deficit recovered or improved. Sequelae were documented in 44% of surviving patients.

Adolescent↗

PubMed2001

Role of esophageal function tests in diagnosis of gastroesophageal reflux disease.

Clinicians typically make the diagnosis of gastroesophageal reflux disease (GERD) from the clinical findings and then prescribe acid-suppressing drugs. Endoscopy is usually done for persistent or severe symptoms. Esophageal function tests (EFTs: esophageal manometry and 24-hr pH monitoring) are generally reserved for patients who have the most severe disease, including those being considered for surgery. We hypothesized that EFTs are more accurate than symptoms and endoscopy in the diagnosis of GERD. This was a retrospective study undertaken in a university tertiary care center. Between October 1989 and November 1998, 822 patients with a clinical diagnosis of GERD (based on symptoms and endoscopic findings) were referred for EFTs. The patients were divided into two groups depending on whether the 24-hr pH monitoring score showed GERD (group A, GERD-; group B, GERD+). The groups were compared with respect to the incidence and severity of symptoms, presence of a hiatal hernia on barium x-rays, presence and severity of esophagitis on endoscopy, and esophageal motility. In all, 247 patients (30%) had normal reflux scores (group A, GERD-), and 575 patients (70%) had abnormal scores (Group B, GERD+). Eighty percent of group A and 88% of group B had been treated with acid-suppressing medications. The incidence of heartburn and regurgitation was similar in the two groups. Grade I-II esophagitis was diagnosed by endoscopy in 25% of group A and 35% of group B, and grade III esophagitis in 4% of group A and 11% of group B. Esophageal manometry showed that group B more often had esophageal dysmotility, consisting of a hypotensive lower esophageal sphincter and abnormal esophageal peristalsis. These data show that: (1) symptoms were unreliable for diagnosing GERD; (2) endoscopic evidence of grade I-II esophagitis was diagnostically nonspecific, and grade III was much less certain than claimed in other reports; and (3) pH monitoring identified patients with GERD and stratified them according to the severity of the disease. We conclude that esophageal manometry and pH monitoring are important in diagnosing GERD accurately. More liberal use of these tests early in patient management would avoid much improper and costly medical therapy and would help single out for special attention the patients with GERD who have the most severe disease.

Adolescent↗

PubMed2001

Laparoscopic common bile duct exploration.

BACKGROUND: Laparoscopic common bile duct (CBD) exploration is gaining favor in the treatment of patients with gallstones and CBD stones. Our aim is to report our results with this procedure, focusing on the technical aspects. PATIENTS AND METHODS: All patients with proven CBD stones undergo laparoscopic transcystic CBD exploration, preferably, or a choledochotomy if the former is not feasible. According to CBD stone load and diameter, a biliary drainage tube is positioned for postoperative biliary decompression. RESULTS: Among 284 patients who underwent laparoscopic CBD exploration, 4 (1.4%) were converted to open surgery. Transcystic CBD exploration was feasible in 163 cases (58.2%), but a choledochotomy was required in 117 (41.8%). Biliary drains were positioned in 204 patients (72.8%). Minor complications included hyperamylasemia (11; 3.9%) and minor subhepatic bile collection (7; 2.5%). Major complications were bile leakage (5; 1.8%), hemoperitoneum from cystic artery bleeding (2; 0.7%), subhepatic abscess (2; 0.7%), acute pancreatitis (1; 0.3%), and jejunal perforation (1; 0.3%). Retained CBD stones in 15 patients (5.3%) were removed through the biliary drainage sinus tract (8) or after endoscopy and sphincterotomy (6). In one patient, a small stone passed spontaneously (overall success rate 94.6%). Death from a cardiovascular complication was observed in one elderly high-risk patient (0.3%). Recurrent ductal stones in 5 patients (1.8%) were treated with ERCP and endoscopic sphincterotomy. One patient with re-recurrent ductal stones underwent hepaticojejunostomy. CONCLUSIONS: Laparoscopic CBD exploration during LC in unselected patients solves two problems during the same anesthesia with high success rates (94.6%), low minor (6.4%) and major (3.8%) morbidity rates, and a low mortality rate (0.3%). Standardization of the technique is mandatory to achieve high success rates.

Adolescent↗

PubMed2001

Effects of a nonforage diet on milk production, energy, and nitrogen metabolism in dairy goats throughout lactation.

The objective of the experiment was to compare a silage-based control diet (C) with a nonforage diet (NF) in dairy goats throughout lactation in terms of animal performance and energy utilization. Eight Saanen goats were divided into two groups and fed C or NF, a commercial blend that included sunflower meal, cassava, coconut meal, and whole cottonseeds as the main ingredients that was characterized by a small particle size and a high crude protein content. In early, mid, and late lactation (44, 100, and 219 days in milk) the goats were individually tested for dry matter intake (DMI), digestibility, milk yield and composition, milk renneting properties, rumen and plasma parameters, and nitrogen and energy utilization (open circuit respiration chambers). During early and mid lactation, the NF fed goats had a very high DMI: 2946 and 2915 g/d, respectively. Nevertheless, milk yield was similar for the two treatments: 4369 vs. 4342 and 3882 vs. 3841 g/d for goats fed diets C and NF during the first and second periods, respectively. Milk fat content was not statistically different between the two diets. The protein content and rheological parameters of milk were similar for the two diets. Nonprotein nitrogen and urea levels in milk of goats fed NF were significantly higher than goats fed C. Ruminal ammonia and plasma urea nitrogen were also significantly increased by diet NF, due to its high protein content. Plasma glucose, beta-hydroxybutyrate, and nonesterified fatty acids and ruminal volatile fatty acids were not influenced by dietary treatment. Dietary NF significantly decreased energy digestibility (74.5 vs. 65.8%, on average for the lactation, for C and NF, respectively) and had a significantly lower metabolizability (metabolizable energy/intake energy; 66.6 vs 58.0%, on average); however, the efficiency of utilization of metabolizable energy was unaffected by the diet. In conclusion, goats were fed a nonforage diet during the entire lactation without detrimental effect on their health and productive performance.

Animal Feed↗

PubMed2001

Quantitative analysis of Fas and bcl-2 expression in hematopoietic precursors.

BACKGROUND AND OBJECTIVES: We investigated the expression of bcl-2 and CD95 (Apo1-/Fas) on CD34+ cells obtained from bone marrow (BM), mobilized peripheral blood (MPB), and umbilical cord blood (UCB) samples. The expression of bcl-2 and Fas was then compared with that of other markers usually associated with immaturity; functional tests using the agonistic antibody anti- Fas CH11 were also carried out. DESIGN AND METHODS: The analysis was performed by flow cytometry on purified CD34+ cells in a three (CD95 PE, CD34 APC and CD71 FITC) and in a four (CD38 PE, HLA-DR PerCP, CD34 APC and bcl-2 FITC) fluorescence assay. RESULTS: The results were expressed as mean fluorescence index (MFI); bcl-2 expression was significantly higher (p < 0.001) in BM (3.73 +/- 0.63) than in MPB (2.47 +/- 0.39) and UCB (2.38 +/- 0.58); Fas was significantly less expressed (p < 0.001) in UCB (1.27 +/- 0.78) than in MBP (3.63 +/- 2.19) and BM (4.56 +/- 1.69). CD34 expression was significantly (p < 0.001) brighter in UCB compared to in MBP and BM, while CD38 and CD71 were significantly (p = 0.005 and p < 0.001, respectively) more expressed in BM than in MPB and UCB. Fas values were directly correlated to CD38; both Fas and bcl-2 were directly related to CD71 and inversely to CD34. Culture assays showed that hematopoietic precursor cells from BM, MPB and UCB had a low susceptibility to undergo Fas-mediated apoptosis. INTERPRETATION AND CONCLUSIONS: In conclusion, bcl-2 and Fas are less expressed in UCB than in MPB and BM; early hematopoietic precursor cells are relatively resistant to CD95-triggered apoptosis; the observed correlation between Fas/bcl-2 and markers of immaturity suggests that they may be determinants of commitment in early hematopoietic precursors.

Adult↗

PubMed2000

Level of minimal residual disease after consolidation therapy predicts outcome in acute myeloid leukemia.

We used flow cytometry to quantify minimal residual disease (MRD) in 56 patients with acute myeloid leukemia (AML) expressing a leukemia-associated phenotype. Thirty-four patients aged 18 to 60 years were entered into the AML-10 protocol (induction, consolidation, and autologous stem-cell transplantation [ASCT]), whereas 22 patients older than 60 years received the AML-13 protocol (induction, consolidation, and consolidation II). After induction, the level of MRD that was best associated with treatment outcome was 4.5 x 10(-4) residual leukemic cells. However, the outcome in patients with at least 4.5 x 10(-4) cells (n = 26) was not significantly different from that in patients with fewer leukemic cells (n = 30); there were 15 (58%) relapses in the first group and 12 (40%) relapses in the second. After consolidation, the most predictive MRD cutoff value was 3.5 x 10(-4) cells: 22 patients had an MRD level of 3.5 x 10(-4) cells or higher and 17 (77%) of these patients had relapse, compared with 5 of 29 patients (17%) with lower MRD levels (P <.001). An MRD level of 3.5 x 10(-4) cells or higher after consolidation was significantly correlated with poor or intermediate-risk cytogenetic findings, a multidrug resistance 1 (MDR1) phenotype, short duration of overall survival, and short duration of relapse-free survival (P =.014,.031,.00022, and.00014, respectively). In multivariate analysis, this MRD status was significantly associated with a high frequency of relapse (P <.001) and a short duration of overall (P =.025) and relapse-free survival (P =.007). ASCT did not alter the prognostic effect of high MRD levels after consolidation: the relapse rate after transplantation was 70%. Thus, we found that an MRD level of 3.5 x 10(-4) cells or higher at the end of consolidation strongly predicts relapse and is significantly associated with an MDR1 phenotype and intermediate or unfavorable cytogenetic findings. (Blood. 2000;96:3948-3952)

Actuarial Analysis↗

PubMed2000

In vivo cytoreduction studies and cell sorting--enhanced tumor-cell detection in high-risk neuroblastoma patients: implications for leukapheresis strategies.

PURPOSE: To improve autologous leukapheresis strategies in high-risk neuroblastoma (NB) patients with extensive bone marrow involvement at diagnosis. PATIENTS AND METHODS: Anti-G(D2) immunocytochemistry (sensitivity, 1 in 10(5) to 10(6) leukocytes) was used to evaluate blood and bone marrow disease at diagnosis and during the recovery phase of the first six chemotherapy cycles in 57 patients with stage 4 NB and bone marrow disease at diagnosis. A total of 42 leukapheresis samples from the same patients were evaluated with immunocytology, and in 24 of these patients, an anti-G(D2) immunomagnetic enrichment step was used to enhance tumor-cell detection. RESULTS: Tumor cytoreduction was much faster in blood compared with bone marrow (3.2 logs after the first cycle and 2.1 logs after the first two cycles, respectively). Bone marrow disease was often detectable throughout induction, with a trend to plateau after the fourth cycle. By direct anti-G(D2) immunocytology, a positive leukapheresis sample was obtained in 7% of patients after either the fifth or sixth cycle; when NB cell immunomagnetic enrichment was applied, 25% of patients had a positive leukapheresis sample (sensitivity, 1 in 10(7) to 10(8) leukocytes). CONCLUSION: Standard chemotherapy seems to deliver most of its in vivo purging effect within the first four cycles. In patients with overt marrow disease at diagnosis, postponing hematopoietic stem-cell collection beyond this point may not be justified. Tumor-cell clearance in blood seems to be quite rapid, and earlier collections via peripheral-blood leukapheresis might be feasible. Immunomagnetically enhanced NB cell detection can be highly sensitive and can indicate whether ex vivo purging should be considered.

Adolescent↗

PubMed2000

A phase-II trial of all trans retinoic acid and low-dose cytosine arabinoside for the treatment of high-risk myelodysplastic syndromes.

Twenty-two patients with high-risk myelodysplastic syndrome (HRMDS) were treated with a 10-day course of oral all trans retinoic acid (45 mg/m2) and s.c. low-dose cytosine arabinoside (LDARAc) given at the dose of 20 mg twice per day. The courses were repeated monthly until response or progression, in the case of response, the therapy was administered until relapse. Morphologic diagnoses were refractory anemia with excess blasts (RAEB) in nine, RAEB in transformation (RAEB-t) in nine, and chronic myelomonocytic leukemia (CMMoL) in four patients; in all cases, bone-marrow blast infiltration was greater than 10% (median 20%, range 12-30%). When the international prognostic scoring system was applied, all the cases qualified as intermediate/high-risk categories. Nineteen patients were males and three were females; the median age was 69 years (range 25-90 years); three patients had previously been treated with conventional chemotherapy, and one of them had also undergone autologous bone-marrow transplantation. The criteria of response were defined as follows: (1) complete response: normalization of blood counts and bone-marrow blasts (<5%), and (2) partial response: decrease in bone-marrow blast infiltration by 50%, and two of the following parameters - improvement in hemoglobin level by 1.5 g/dl or decrease by 50% in transfusional requirement, increase by 50% in absolute neutrophil count, and increase by 50% in platelet count. Overall, 7 (32%) of 22 patients achieved a response, with 5 (23%) being classified as complete responders and 2 (9%) as partial responders. Fifteen (68%) patients did not achieve any response, and 14 died of progressive disease or infectious disease. The overall median survival was 8 months (range 1-27 months), whereas the median survival of responders was 16 months (range 8-27 months); the median duration of response was 11 months (range 2-21 months). Moderate to severe hematological toxicity and infections were the most common side effects. In conclusion, it seems that the association of ATRA and LDARA-C may be effective in approximately 30% of HRMDS patients. Optimizing this approach might be pursued by selecting, on a biological basis, those cases more likely to respond or by incorporating other differentiating agents or growth factors.

Administration, Oral↗

PubMed1999

Laparoscopic Heller myotomy relieves dysphagia in achalasia when the esophagus is dilated.

BACKGROUND: It has been said that a Heller myotomy cannot improve dysphagia in achalasia when the esophagus is markedly dilated or sigmoid shaped. Those who hold this belief recommend esophagectomy as the primary treatment in such cases. This study aimed to compare the results of laparoscopic Heller myotomy combined with Dor fundoplication in 66 patients with and without esophageal dilatation, all of whom had achalasia. METHODS: On the basis of the maximal diameter of the esophageal lumen and the shape of the esophagus, the patients were placed into four groups: group A (esophageal diameter <4.0 cm; 26 patients), group B (diameter 4.0-6.0 cm; 21 patients), group C1 (diameter >6.0 cm and straight esophageal axis; 12 patients), and group C2 (diameter >6.0 cm and sigmoid-shaped esophagus; 7 patients). All patients underwent a laparoscopic Heller myotomy and Dor fundoplication. RESULTS: The duration of the operation and the length of hospital stay were similar among the four groups. Excellent or good results were obtained in 88% of group A, 100% of group B, 83% of group C1, and 100% of group C2. No patient in this consecutive series ultimately required an esophagectomy. CONCLUSIONS: In patients with achalasia who have esophageal dilation, a laparoscopic Heller myotomy and Dor fundoplication (a) took no longer and was no more difficult, (b) was associated with no more postoperative complications, and (c) gave just as good relief of dysphagia. We conclude that esophageal dilation by itself should rarely serve as an indication for esophagectomy rather than myotomy as the initial surgical treatment.

Adolescent↗