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R Buzzoni,
S Pusceddu,
A Damato,
E Meroni,
A Cumali,
M Milione, V Mazzaferro,
F De Braud,
C Spreafico,
M Maccauro,
N Zaffaroni,
M R Castellani
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ABSTRACT: Pheochromocytoma and paraganglioma are rare neuroendocrine tumors. Knowledge about such neoplasms ameliorated in the last 10-15 years with the discovery of increasing number of germ line mutations even in apparently sporadic cases. Seemingly, genetic tests are going to be an integral part of diagnostic procedures. Standard therapies (advanced surgery, radiometabolic therapy, chemotherapy and radiotherapy) have revealed suboptimal results in tumor size reduction and survival. Currently, there is no standard therapeutic protocol and thus some patients end up with overtreatment while others are undertreated. An effective molecular target therapy aiming at permanent control of these highly complex neoplasms should be the aim of future efforts. In clinical setting investigatory trials with multiple drug therapies targeting a variety of different parallel pathways should be available. Successful management requires a multidisciplinary teamwork.
The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... 04/2013;
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C Chiesa,
M Mira,
M Maccauro,
R Romito,
C Spreafico,
C Sposito,
S Bhoori,
C Morosi,
S Pellizzari,
A Negri,
E Civelli,
R Lanocita,
T Camerini,
C Bampo,
M Carrara,
E Seregni,
A Marchianò, V Mazzaferro,
E Bombardieri
[show abstract]
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ABSTRACT: Aim: Our goal was to limit liver toxicity and to obtain good efficacy by developing a dosimetric treatment planning strategy. While several dosimetric evaluations are reported in literature, the main problem of the safety of the treatment is rarely addressed. Our work is the first proposal of a treatment planning method for glass spheres, including both liver toxicity and efficacy issues. Methods: Fifty-two patients (series 1) had been treated for intermediated/advanced hepatocellular carcinoma (HCC) with glass spheres, according to the Therasphere® prescription of 120 Gy averaged on the injected lobe. They were retrospectively evaluated with voxel dosimetry, adopting the local deposition hypothesis. Regions of interest on tumor and non tumor parenchyma were drawn to determine the parenchyma absorbed dose, averaged also on non irradiated voxels, excluding tumor voxels. The relationship between the mean non tumoral parenchyma absorbed dose D and observed liver decompensation was analyzed. Results: Basal Child-Pugh strongly affected the toxicity incidence, which was 22% for A5, 57% for A6, 89% for B7 patients. Restricting the analysis to our numerically richest class (basal Child-Pugh A5 patients), D median values were significantly different between toxic (median 90 Gy) and non toxic treatments (median 58 Gy) at a Mann-Withney test, (P=0.033). Using D as a marker for toxicity, the separation of the two populations in terms of area under ROC curve was 0.75, with 95% C.I. of [0.55-0.95]. The experimental Normal Tissue Complication Probability (NTCP) curve as a function of D resulted in the following values: 0%, 14%, 40%, 67% for D interval of [0-35] Gy, [35-70] Gy, [70-105] Gy, [105-140] Gy. Discussion. A limit of about 70 Gy for the mean absorbed dose to parenchyma was assumed for A5 patients, corresponding to a 14% risk of liver decompensation. This result is applicable only to our administration conditions: glass spheres after a decay interval of 3.75 days. Different safety limit (40 Gy) are published for resin spheres, characterized by higher number of particle per GBq (more uniform irradiation, bigger biological effect for the same absorbed dose). Conclusion: As result of this study we suggest a constraint of about 70 Gy mean absorbed dose to liver non tumoral parenchyma, corresponding to about 15% probability of radioinduced liver decompensation while still aiming at achieving an absorbed of several hundreds of Gy to lesions.
The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... 12/2012; 56(6):503-8.
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A W Avolio,
U Cillo,
M Salizzoni,
L De Carlis,
M Colledan,
G E Gerunda, V Mazzaferro,
G Tisone,
R Romagnoli,
L Caccamo,
M Rossi,
A Vitale,
A Cucchetti,
L Lupo,
S Gruttadauria,
N Nicolotti,
P Burra,
A Gasbarrini,
S Agnes
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ABSTRACT: Donor-recipient match is a matter of debate in liver transplantation. D-MELD (donor age × recipient biochemical model for end-stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3-year patient survival. D-MELD cutoff predictive of 5-year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D-MELD.com). Differences among D-MELD deciles allowed their regrouping into three D-MELD classes (A < 338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44-2.85) in D-MELD class C versus B. The OR was 0.40 (95% CI, 0.24-0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11-1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51-0.93), retransplant (OR = 1.82; 95% CI, 1.16-2.87) and low-volume center (OR = 1.48; 95% CI, 1.11-1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59-2.43) for D-MELD class C versus class B and 0.42 (95% CI, 0.29-0.60) for D-MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D-MELD ≥ 1750). The innovative approach offered by D-MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients.
American Journal of Transplantation 09/2011; 11(12):2724-36. · 6.39 Impact Factor
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ABSTRACT: Transarterial chemoembolization (TACE) is considered the gold standard for treating intermediate-stage hepatocellular carcinoma (HCC). However, intermediate-stage HCC includes a heterogeneous population of patients with varying tumour burdens, liver function (Child-Pugh A or B) and disease aetiology. This suggests that not all patients with intermediate-stage HCC will derive similar benefit from TACE, and that some patients may benefit from other treatment options. Results of an extensive literature review into the treatment of unresectable HCC with TACE were combined with our own clinical experience to identify factors that may predict survival after TACE. We also report contraindications to TACE and propose a treatment algorithm for the repetition of TACE. In addition, we have constructed a number of expert opinions that may be used as a guide to help physicians make treatment decisions for their patients with intermediate-stage HCC. The data included in the literature review related almost exclusively to conventional TACE, rather than to TACE with drug-eluting beads. Therefore, the findings and conclusions of the literature review are only applicable to the treatment of HCC with conventional TACE. Treating physicians may want to consider other treatment options for patients with intermediate-stage HCC who are not suitable for or do not respond to TACE. By distinguishing those patients who represent good candidates for TACE from those where little or no benefit might be expected, it may be possible to make better use of current treatment options and improve outcomes for patients.
Cancer treatment reviews 05/2011; 37(3):212-20. · 5.30 Impact Factor
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C Chiesa,
M Maccauro,
R Romito,
C Spreafico,
S Pellizzari,
A Negri,
C Sposito,
C Morosi,
E Civelli,
R Lanocita,
T Camerini,
C Bampo,
S Bhoori,
E Seregni,
A Marchianò, V Mazzaferro,
E Bombardieri
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ABSTRACT: In most centres, the choice of the optimal activity to be administered in selective intra-arterial radioembolization with microspheres is nowadays based on empirical models which do not take into account the evaluation of tumour and non tumour individual absorbed dose, despite plenty of published data which showed that local efficacy is correlated to tumour absorbed dose, and that the mean absorbed dose is a toxicity risk factor. A pitfall of the crudest, empirical tumour involvement method are 20 deaths in a single centre which adopted it to administer the whole liver, or the need of systematic 25% subjective reduction of activity prescribed with body surface area method. In order to develop a possibly safer and more effective strategy based on real individual dosimetry, we examine first external beam liver radiation therapy results. The half century experience has something to be borrowed: the volume effect, according to which the smaller the fraction of the irradiated liver volume, the higher the tolerated dose. Different tolerance for different underlying disease or previous non radiation treatment is to be expected. Radiobiological models experience also has to be inherited, but not their dose reference values. Then we report the published dosimetric experience about (90)Y microsphere radioembolization of primary and metastatic liver tumours. In addition we also present original data from our growing preliminary experience of more refined (99m)Tc MAA SPECT based calculations in hepatocarcinoma patients. This overcame the mean dose approach in favour of the evaluation of dose distribution at voxel level. An insight into dosimetry issues at microscopic level (lobule level) is also provided, from which the different radiobiological behaviour between resin and glass spheres can be understood. For tumour treatment, an attenuation corrected (99m)Tc- SPECT based treatment planning strategy can be proposed, although quantitative efficacy thresholds should be differentiated according to the kind of pathology and previous treatment. For non tumour liver parenchyma, data in favour of a relationship between absorbed dose and dangerous effects are encouraging. Unfortunately in hepato-cellular carcinoma, some confounding factors may hamper the adequate estimation of the risk of toxicity. First there is a lack of consensus about the exact definition of toxicity after (90)Y microsphere radioembolization. Second, for HCC patients, progression of both cancer and cirrhosis can simulate a radioinduced toxicity, making the analysis more complex.
The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... 04/2011; 55(2):168-97.
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A.W. Avolio,
S. Agnes,
M.C. Lirosi,
M. Salizzoni,
A.D. Pinna,
B. Gridelli,
L. De Carlis,
M. Colledan,
G.E. Gerunda,
U. Valente, [......],
T.M. Manzia,
V. Tondolo,
M. Rendina,
V. Scuderi,
A. Perrella,
M. Angelico,
P. Burra,
S. Fagiuoli,
A. Gasbarrini,
U. Cillo
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[hide abstract]
ABSTRACT: A prognosis calculator was implemented (www.D-MELD.com) using determinants obtained on a national retrospective Italian Liver Transplant (LT) database (5946 LTs, 2002-2009). D-MELD (donor age x biochemical MELD) and other factors were evaluated. Differences among D-MELD deciles allowed their regrouping into 3 D-MELD classes (A <338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95%CI, 1.44-2.85) in D-MELD class C versus B; the OR was 0.40 (95%CI 0.24-0.66) in class A versus B. Other predictors were HCV (OR=1.42; 95%CI 1.11-1.81), HBV (OR=0.69; 95%CI 0.51-0.93), re-transplant (OR=1.82; 95%CI 1.16-2.87) and low-volume Center (OR=1.48; 95%CI 1.11-1.99). The practical advantage of the D-MELD approach is that cases previously judged as risky, because of extreme-high MELD, can present a down-leveling of their risk when a young donor is matched (i.e., MELD=40, donor age=20 -> D-MELD=800); in the same way, when a extreme-high donor age is matched to a low- MELD candidate the risk wi
Hepatology. 01/2011; 54:670A.
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A.W. Avolio,
S. Agnes,
M.C. Lirosi,
M. Salizzoni,
A.D. Pinna,
B. Gridelli,
L. De Carlis,
M. Colledan,
G.E. Gerunda,
U. Valente, [......],
E. Tondolo,
M. Rendina,
A. Perrella,
E. Scuderi,
B. Antonelli,
C. De Waure,
T. De Feo,
P. Burra,
A. Gasbarrini,
U. Cillo
[show abstract]
[hide abstract]
ABSTRACT: Optimization of donor-recipient match represents one of the major challenges in liver transplantation. The variable donor organ quality and recipient liver disease severity explain the various types of match adopted. Sometimes the match or the mismatch is purely the results of chance. Nevertheless, in the majority of cases surgeons and hepatologists can take the opportunity to combine organ and recipient on the basis of specific risk assesment methods. In order to develop an algorithms able to guide organ allocation and avoid futile match (life-expectancy <50% at 5 years) a database was created and filled with data from 5946 liver transplants performed in 21 Italian Centers during the 2002-2009 period. A web-based prognostic calculator was developed using D-MELD (donor age x biochemical MELD) and other prognostic factors. The calculator is available online at the web address www.d-meld.com (ESOT password: D-MELD123). Using logistic regression at 3-years the following significant prognostic factors were
Transplant International. 01/2011; 24:33-34.
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A.W. Avolio,
S. Agnes,
M.C. Lirosi,
M. Salizzoni,
A.D. Pinna,
B. Gridelli,
L. De Carlis,
M. Colledan,
G.E. Gerunda,
U. Valente, [......],
T. Manzia,
E. Tondolo,
M. Rendina,
M. Barone,
A. Perrella,
M. Romano,
C. De Waure,
P. Burra,
A. Gasbarrini,
U. Cillo
[show abstract]
[hide abstract]
ABSTRACT: Intentional matching of liver transplant donor-recipient risk factors, supported by D-MELD (donor age null biochemical MELD), could offer a new therapeutic strategy with effects on survival. As yet, an extensive stratification of cases according to the futile transplant principle using a continous quantitative parameter has not been performed. To stratify the prognosis according to donor-recipient match and assess the predictive role of D-MELD together with covariates, a database detailing 5946 liver transplants performed in 21 Italian Centers (2002-2009) was analyzed. Primary endpoint was to evaluate the prognostic power of D-MELD and covariates in terms of 3-year patient survival. The futile-transplant cutoff (life-expectancy <50% at 5 years) was investigated. The database was divided into a training and a validation set. The adequacy of fit for both sets was tested using Hosmer-Lemeshow and C-statistics. Cases were stratified in ten D-MELD deciles. Significant differences among D-MELD deciles allowe
Journal of Hepatology. 01/2011; 54:S17.
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Transplantation Proceedings 10/2007; 39(7):2271-3. · 1.00 Impact Factor
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ABSTRACT: Few studies have focused on neuropsychiatric symptoms like hallucinations or delusions occurring in the early posttransplant period. The aim of this study was to estimate the percentage of patients reporting neuropsychiatric symptoms in the immediate postoperative phase, to describe the phenomenology, and to evaluate the emotional impact of such disorders.
We studied 94 consecutive patients who underwent orthotopic liver transplant (OLT) for hepatocellular carcinoma at least 30 days prior. The presence of neuropsychiatric symptoms were retrospectively evaluated through a semistructured interview.
Overall 49 patients (52%) reported various postoperative neuropsychiatric symptoms. None of the demographic and clinical variables showed significant associations, except for barbiturate administration; patients using barbiturates showed a lower percentage of neuropsychiatric symptoms. It was a time-limited phenomenon that in most cases resolved by day 7 after transplantation. Interestingly, the most frequent emotion perceived was surprise and not fear; a nontrivial amount of patients reported happiness, while many patients reported no emotion.
The results of this study suggested the usefulness of a registry of the neurological and psychiatric complications after OLT that may help to clarify the pathogenic mechanisms of such complications and implement uniform protocols of prevention and treatment. In fact, better knowledge of the phenomenology of neuropsychiatric symptoms in OLT recipients could allow easier symptom recognition and therapy adjustments on the basis of the emotional impact of such symptoms on patients, family, and caregivers, as well as increase patients' awareness and capability to face this experience.
Transplantation Proceedings 07/2007; 39(5):1564-8. · 1.00 Impact Factor
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ABSTRACT: Cirrhotic patients after liver transplantation show a near-normal glucose homeostasis when in stable condition. In contrast, the basal and insulin-mediated whole-body protein metabolism remain altered several years after the graft. To examine whether the persisting defect of protein metabolism was due to the muscle, 7 non-diabetic liver-transplanted patients in stable condition were studied by means of the catheterization of the brachial artery and the deep forearm vein (to measure the balance across the forearm) and the infusion of labelled leucine and phenylalanine associated with indirect calorimetry. Whole-body proteolysis (as determined by endogenous leucine flux, ELF), protein synthesis (from non-oxidative leucine disposal, NOLD) and leucine oxidation (LO) were reduced in comparison to previously obtained values in a normal population. Insulin infusion (while maintaining euglycemia) induced a not significant variation of forearm phenylalanine Ra (24.4-->16.5 micromol/100 ml forearm min(-1); proteolysis) and Rd (18.5-->19.7; protein synthesis). In contrast, the whole-body insulin-dependent inhibitions of ELF (31.5-->21.8 micromol/m(2) min) and NOLD (27.3-->18.4) were impaired with respect to a normal population. On the basis of the present results, we conclude that skeletal muscle is not responsible for the alterations of leucine metabolism persisting after liver transplantation. By exclusion, this points to the liver as the major determinant of the leucine metabolism defect.
Acta Diabetologica 12/2002; 39(4):203-8. · 2.78 Impact Factor
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ABSTRACT: Peripheral insulin-resistance and impairment of the hepatocellular function are two major possible causes of diabetes mellitus in liver cirrhosis. The pathogenesis of insulin-resistance (receptorial or post-receptorial) is unknown but it represents an important complication because it has a profound impact on the pathology and natural history of the liver disease. The beta-cell capacity, to compensate the insulin-resistant state to avoid the onset of frank diabetes mellitus plays a critical importance. Many factors may induce a reduction of the beta-cell function in patients with liver cirrhosis: some are due to a predisposition to the development of diabetes: genetic or environmental, unrelated to the hepatic disease; some others are hepatic disease-dependent (excess liver and islet of Langerhans iron deposition, HCV infection rather than other hepatic infections, the co-presence of HCC) and may be crucial because additive to the previous. It is likely that the high prevalence of diabetes in liver cirrhosis is due to the early onset of strong insulin-resistance coupled to a deficient beta-cell function aggravated by hepatic disease-related factors.
Recenti progressi in medicina 01/2002; 92(12):757-61.
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S Rossi,
F Garbagnati,
R Lencioni,
H P Allgaier,
A Marchianò,
F Fornari,
P Quaretti,
G D Tolla,
C Ambrosi, V Mazzaferro,
H E Blum,
C Bartolozzi
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ABSTRACT: To evaluate the usefulness of percutaneous radio-frequency (RF) thermal ablation of nonresectable hepatocellular carcinoma (HCC) after occlusion of the tumor arterial supply.
Sixty-two patients with cirrhosis and biopsy-proved HCC underwent RF ablation after interruption of the tumor arterial supply by means of occlusion of either the hepatic artery with a balloon catheter (40 patients) or the feeding arteries with gelatin sponge particles (22 patients).
After a single RF procedure in 56 patients and after two procedures in six patients, spiral computed tomography (CT) demonstrated a nonenhancing area corresponding in shape to the previously identified HCC, which was suggestive of complete necrosis. No major complications occurred. Two patients subsequently underwent surgical resection; the remaining 60 patients were followed up with spiral CT. During a mean follow-up of 12.1 months, 11 HCC nodules showed areas of local progression; 49 were identified as nonenhancing areas with a 40%-75% reduction in maximum diameter. The 1-year estimate of failure risk was 19% for local recurrence and 45% for overall intrahepatic recurrence. The estimated 1-year survival was 87%. Histopathologic analysis of one autopsy and two surgical specimens revealed more than 90% necrosis in one specimen and 100% necrosis in two.
HCC nodules 3.5-8.5 cm in diameter can be ablated in one or two RF sessions after occlusion of the tumor arterial supply.
Radiology 11/2000; 217(1):119-26. · 5.73 Impact Factor
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G Perseghin, V Mazzaferro,
L P Sereni,
E Regalia,
S Benedini,
E Bazzigaluppi,
A Pulvirenti,
A A Leão,
G Calori,
R Romito,
D Baratti,
L Luzi
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ABSTRACT: Diabetes mellitus frequently complicates cirrhosis but the pathogenic mechanisms are unknown. To assess the contribution of reduced insulin action and secretion, 24 cirrhotic-diabetic patients waiting for liver transplant because of an unresectable hepatocarcinoma underwent an oral glucose tolerance test (OGTT) to assess the beta-cell function and an insulin clamp combined with [3-(3)H]glucose infusion to measure whole body glucose metabolism before and 2 years after the transplant. Seven cirrhotic nondiabetic patients, 11 patients with chronic uveitis on similar immunosuppressive therapy, and 7 healthy subjects served as control groups. Cirrhotic patients showed a profound insulin resistance, and diabetics in addition also showed increased endogenous glucose production (P <.05) and insulin deficiency during the OGTT (P <.05). Liver transplantation normalized endogenous glucose production and insulin sensitivity but failed to cure diabetes in 8 of the 24 patients because a markedly low insulin response during the OGTT. Age, body mass index, family history of diabetes, immunosuppressive drugs, and pathogenesis of cirrhosis did not predict in whom liver transplant was going to cure diabetes. On the contrary, a reduced secretory response characterized the patients in whom the transplant would not be curative. In summary, insulin resistance was a primary event complicating cirrhosis but additional beta-cell secretory defects were crucial for development of diabetes. Liver transplantation, lessening insulin resistance, cured hepatogenous diabetes in 67% of cirrhotic-diabetic patients; nevertheless 33% were still diabetics because the persistence of a reduced beta-cell function, which makes these patients eventually eligible for combined islet transplantation.
Hepatology 03/2000; 31(3):694-703. · 11.66 Impact Factor
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ABSTRACT: The combination of radiotherapy and fluorouracil (5-FU) in patients with locally unresectable pancreatic carcinoma has led to a significant increase in survival in comparison with radiotherapy alone. Doxifluridine (5-DFUR) is an orally active fluoropyrimidine, and its cytotoxic metabolite (5-FU) may concentrate in areas of high tumor vascularization. This trial was carried out with the aims of improving locoregional control and making lesions resectable in patients with unresectable pancreatic cancer.
5-DFUR was given at a dose of 500 mg/m2 b.i.d. by way of mouth for 4 days every other week for a total of four courses, with leucovorin 25 mg b.i.d. orally being given 2 hours before each 5-DFUR administration. External beam RT was administered at a dose of 1000 cGy per week for 3 weeks, followed by a 2-week break and then by 1000 cGy per week for a further 2 weeks (a total dose of 5000 cGy). The patients were restaged 4 weeks after the end of treatment and explored for resection in cases of partial response (PR).
A total of 32 patients were treated between 1992 and 1997. Ab initio unresectability was shown by laparotomy (16 cases) or computed tomography (16 cases), and was due to vascular invasion in 27 patients, massive regional nodal metastases in nine, and both in four. The median age was 63 years (range 36-71); performance status (PS) (ECOG): 0-1 = 28 and PS 2 = 4. All the patients had measurable disease and were evaluable for response. There were seven PR (22%), 10 SD (31%), and 15 PD (47%). All of the responders underwent surgical exploration, and radical resection was possible in 5. Three of these patients are still disease-free with a follow-up of 18, 27, and 65 months; the other two cases relapsed 11 and 14 months after surgery. The median survival time was 9 months for the entire group, and 1-year survival rate was 31%. The treatment was never stopped because of toxicity. There were no CTC-NCI grade 3 or 4 toxic events; grade 1-2 diarrhea was observed in 10 cases.
This preoperative regimen was feasible and led to a successful surgical resection in 16% of otherwise inoperable cases. The median survival was comparable with the results obtained after 5-FU infusion plus radiotherapy. The resectability rate, and the benefit in terms of survival in the resected patients, make these results worthy of confirmation by larger studies.
International Journal of Radiation OncologyBiologyPhysics 10/1999; 45(2):285-9. · 4.11 Impact Factor
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ABSTRACT: Desmoid tumors are locally invasive fibromatous tumors, which, in patients with Gardner's syndrome, usually occur in the abdominal wall or intra-abdominally. After excision, they tend to recur, often leading to multiple bowel resections.
This is a report of the clinical course of a patient with Gardner's syndrome and desmoid tumor who had multiple enterectomies and gradually developed short-gut syndrome. He required prolonged parenteral nutrition, which damaged the liver. The patient underwent a multivisceral transplantation as a life-saving procedure.
After the transplant, the desmoid tumor recurred in the thoracic wall twice and was successfully resected. It also recurred in the abdominal cavity, compressing the intestinal loops; the tumor was excised uneventfully, leaving the graft intact. The recurrent tumors were all of recipient origin.
Intestinal and multivisceral transplantation could be considered in patients with short-gut syndrome caused by recurrent desmoid tumor. In the case of posttransplant tumor recurrence, resection is the only option recommended.
Transplantation 05/1999; 67(8):1197-9. · 4.00 Impact Factor
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A Battezzati,
D Bonfatti,
S Benedini,
G Calori,
R Caldara, V Mazzaferro,
A Elli,
A Secchi,
V Di Carlo,
G Pozza,
L Luzi
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ABSTRACT: Hypoglycaemia is an important complication of insulin treatment in Type 1 diabetes mellitus (DM). Pancreas transplantation couples glucose sensing and insulin secretion, attaining a distinctive advantage over insulin treatment. We tested whether successful transplantation can avoid hypoglycaemia in Type 1 DM. Combined kidney and pancreas transplanted Type 1 DM who complied with good function criteria (KP-Tx, n = 55), and isolated kidney or liver transplanted non-diabetic subjects on the same immunosuppressive regimen (CON-Tx, n = 14), underwent 1-day metabolic profiles in the first 3 years after transplantation, sampling plasma glucose (PG) and pancreatic hormones every 2 hours. KP-Tx had lower PG than CON-Tx in the night and in the morning and higher insulin concentrations throughout the day. KP-Tx had lower PG nadirs than CON-Tx (4.40+/-0.05 vs 4.96+/-0.16 mmol l(-1), ANOVA p = 0.001). Nine per cent of KP-Tx had hypoglycaemic values (PG < or = 3.0 mmol l(-1)) in the profiles, both postprandial and postabsorptive, whereas none of CON-Tx did (p < 0.02). In conclusion, after pancreas transplantation, mild hypoglycaemia is frequent, although its clinical impact is limited. Compared to insulin treatment in Type 1 DM, pancreas transplantation improves but cannot eliminate hypoglycaemia.
Diabetic Medicine 12/1998; 15(12):991-6. · 2.90 Impact Factor
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Transplantation Proceedings 09/1998; 30(5):1868. · 1.00 Impact Factor
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ABSTRACT: To study retinol binding protein variation in the serum of patients who have undergone liver transplantation.
Retinol binding protein was retrospectively determined by the immunonephelometric method on serum from 14 patients who had undergone orthotopic liver transplantation 2 weeks after the surgery and then once a month during the first year posttransplantation. The patients were divided into two groups on the basis of early (first 10 days) postoperative graft function: group I, 6 patients with severe ischemic damage; and II 8 patients with moderate-severe liver dysfunction.
The men retinol binding protein level at one year of follow-up was persistently higher in group I than in group II (83.1 +/- 33.4 vs 44.6 +/- 20.7 mg/L, p < 0.001). Interestingly, retinol binding protein levels remained higher in patients of group I event when the other biochemical parameter of liver function returned to normal. The increase in retinol binding protein serum levels was independent of variation in other parameters of liver and kidney function, but was correlated with an increase in transthyretin and retinol levels.
Our results show a close relationship between a permanent high retinol binding protein level and severe graft injury after liver transplantation. However, the mechanism underlying the increase remains to be defined.
Clinical Biochemistry 04/1998; 31(2):113-6. · 2.08 Impact Factor
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ABSTRACT: A series of 132 patients who underwent liver transplantation for primary liver cancer was collected from three different Italian hospitals and studied for recurrence of hepatocellular carcinoma after liver replacement. Twenty-one patients (15.9%) had a neoplastic recurrence after an average follow-up period of 7.8 months after transplantation (range, 1-25 months); 15 (71%) occurred within the first 18 months after transplant and only two recurred later than 2 years. The sites of recurrence were grafted liver (19%), lung (19%), bone (14%), and other (5%). Eight patients (38%) had multiple organ involvement at the onset. After 1, 2, 3, and 4 years the overall survival rates were 62%, 43%, 29%, and 23%, respectively. The tumor factors related to early cancer recurrence after transplantation were diameter of nodules more than 3 cm (P < 0.05), tumor stage not meeting the "Milan criteria" (P < 0.03), and presence of peri-tumoral capsule (P < 0.05); the number of nodules, TNM stage, presence of vascular invasion, alpha-fetoprotein level more than 150 UI/l, pre-transplant chemoembolization and resectability of cancer deposits did not seem to be related to early recurrence. The prognosis differed in the 7 patients with resectable recurrences (57% 4-year survival) and the 14 patients with unresectable disease (14% 4-year survival) (P < 0.02). Better patient selection and new combined medical strategies could reduce the incidence of and mortality from liver cancer recurrence after transplantation. The role of surgical resection of recurrence should be further investigated.
Journal of Hepato-Biliary-Pancreatic Surgery 01/1998; 5(1):29-34. · 1.60 Impact Factor
