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1.
J Endocrinol Invest ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38900373

ABSTRACT

PURPOSE: The contribution of endothelial-targeted autoantibodies against the angiotensin II type 1 receptor (anti-AT1R) and the anti-endothelin 1 type A receptor (anti-ETAR1) has been proposed in the development of cardiovascular diseases. However, no data have been reported yet in obesity. In this observational study we evaluated the relationship between anthropometric and metabolic parameters and anti-AT1R and anti-ETAR1 concentrations in a cohort of patients with severe obesity and associated comorbidities undergoing bariatric surgery. METHODS: Clinical evaluation and metabolic assessment were performed in 36 subjects referring to our Center for the Study and Integrated Treatment of Obesity at the University Hospital of Padova. Circulating inflammatory adipocytokines and the endothelial dysfunction marker asymmetric dimethylarginine (ADMA) were evaluated; plasma levels of anti-AT1R and anti-ETAR1 were also determined. 10 normal-weight subjects were considered as a control group. 29 patients out of 36 were re-evaluated after surgery. RESULTS: With respect to normal-weight controls patients showed significantly higher plasma levels of anti-AT1R (28 ± 20.4 vs 13.5 ± 2.8 U/mL, p < 0.005) and ADMA (0.8 ± 0.1 vs 0.54 ± 0.08 uM/L, p < 0.0001) but not anti-ETAR1 (14.2 ± 1.3 vs 13.3 ± 2 U/mL, p = 0.1). Anti-AT1R concentration showed an increasing trend with the worsening of glycemic status, while the presence of arterial hypertension among the patients did not affect autoantibodies levels. One year after surgery, a significant improvement in body weight and metabolic and inflammatory parameters was observed, along with a significant reduction of anti-AT1R (28.1 ± 20.4 U/mL vs 22.6 ± 16 U/mL, p < 0.05) and anti-ETAR1 (14.2 ± 1.3 U/L vs 13 ± 1.6 U/L, p < 0.01). CONCLUSIONS: Subjects with obesity present higher plasma levels of anti-AT1R which are more related to glycemic profile than blood pressure levels, and are reduced by bariatric surgery. Considering the detrimental effects of these autoantibodies on vascular health, they should be assessed as potential biomarkers in obesity and metabolic diseases.

2.
J Endocrinol Invest ; 46(10): 2147-2155, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36952215

ABSTRACT

PURPOSE: In mice, adipose tissue-derived stem cells (ASCs) reach the systemic circulation and establish ectopic adipose depots fostering insulin resistance, but whether this occurs in humans is unknown. We examined circulating ASCs in individuals with various combination of metabolic syndrome traits. METHODS: We enrolled patients attending a routine metabolic evaluation or scheduled for bariatric surgery. We quantified ASCs as CD34+CD45-CD31-(CD36+) cells in the stromal vascular fraction of subcutaneous and visceral adipose tissue samples and examined the presence and frequency of putative ASCs in peripheral blood. RESULTS: We included 111 patients (mean age 59 years, 55% males), 40 of whom were scheduled for bariatric surgery. The population of CD34+CD45-CD31- ASCs was significantly more frequent in visceral than subcutaneous adipose depots (10.4 vs 4.1% of the stromal vascular fraction; p < 0.001), but not correlated with BMI or metabolic syndrome traits. The same phenotype of ASCs was detectable in peripheral blood of 58.6% of patients. Those with detectable circulating ASCs had significantly higher BMI (37.8 vs 33.3 kg/m2; p = 0.003) and waist (111.2 vs 105.4 cm; p = 0.001), but no difference in other metabolic syndrome traits (p = 0.84). After bariatric surgery, patients with detectable circulating ASCs had greater BMI reductions at 6 months (- 10.4 vs - 7.8 kg/m2; p = 0.014). CONCLUSION: Presence of putative circulating ASCs, antigenically similar to those observed in the adipose tissue, is associated with greater adiposity and larger BMI reduction after surgery, but not with clinical signs of metabolic impairment. The role of circulating ASCs in adipose tissue biology and systemic metabolism deserves further investigation.


Subject(s)
Bariatric Surgery , Metabolic Syndrome , Male , Humans , Mice , Animals , Middle Aged , Female , Metabolic Syndrome/metabolism , Obesity/metabolism , Adipose Tissue/metabolism , Stem Cells/metabolism
3.
Ann Biomed Eng ; 48(10): 2466-2483, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32472365

ABSTRACT

Obesity is one of the main health concerns worldwide. Bariatric Surgery (BS) is the gold standard treatment for severe obesity. Nevertheless, unsatisfactory weight loss and complications can occur. The efficacy of BS is mainly defined on experiential bases; therefore, a more rational approach is required. The here reported activities aim to show the strength of experimental and computational biomechanics in evaluating stomach functionality depending on bariatric procedure. The experimental activities consisted in insufflation tests on samples of swine stomach to assess the pressure-volume behaviour both in pre- and post-surgical configurations. The investigation pertained to two main bariatric procedures: adjustable gastric banding (AGB) and laparoscopic sleeve gastrectomy (LSG). Subsequently, a computational model of the stomach was exploited to validate and to integrate results from experimental activities, as well as to broad the investigation to a wider scenario of surgical procedures and techniques. Furthermore, the computational approach allowed analysing stress and strain fields within stomach tissues because of food ingestion. Such fields elicit mechanical stimulation of gastric receptors, contributing to release satiety signals. Pressure-volume curves assessed stomach capacity and stiffness according to the surgical procedure. Both AGB and LSG proved to reduce stomach capacity and to increase stiffness, with markedly greater effect for LSG. At an internal pressure of 5 kPa, outcomes showed that in pre-surgical configuration the inflated volume was about 1000 mL, after AGB the inflated volume was slightly lower, while after LSG it fell significantly, reaching 100 mL. Computational modelling techniques showed the influence of bariatric intervention on mechanical stimulation of gastric receptors due to food ingestion. AGB markedly enhanced the mechanical stimulation within the fundus region, while LSG significantly reduced stress and strain intensities. Further computational investigations revealed the potentialities of hybrid endoscopic procedures to induce both reduction of stomach capacity and enhancement of gastric receptors mechanical stimulation. In conclusion, biomechanics proved to be useful for the investigation of BS effects. Future exploitations of the biomechanical methods may largely improve BS reliability, efficacy and penetration rate.


Subject(s)
Bariatric Surgery/instrumentation , Bariatric Surgery/methods , Models, Biological , Stomach/physiology , Animals , Biomechanical Phenomena , Biomedical Engineering , Eating , Equipment Design , Laparoscopy , Physical Stimulation , Swine
4.
5.
Br J Surg ; 107(2): e39-e55, 2020 01.
Article in English | MEDLINE | ID: mdl-31903602

ABSTRACT

BACKGROUND: Obesity has become an increasing problem worldwide during the past few decades. Hence, surgeons and anaesthetists will care for an increasing number of obese patients in the foreseeable future, and should be prepared to provide optimal management for these individuals. This review provides an update of recent evidence regarding perioperative strategies for obese patients. METHODS: A search for papers on the perioperative care of obese patients (English language only) was performed in July 2019 using the PubMed, Scopus, Web of Science and Cochrane Library electronic databases. The review focused on the results of RCTs, although observational studies, meta-analyses, reviews, guidelines and other reports discussing the perioperative care of obese patients were also considered. When data from obese patients were not available, relevant data from non-obese populations were used. RESULTS AND CONCLUSION: Obese patients require comprehensive preoperative evaluation. Experienced medical teams, appropriate equipment and monitoring, careful anaesthetic management, and an adequate perioperative ventilation strategy may improve postoperative outcomes. Additional perioperative precautions are necessary in patients with severe morbid obesity, metabolic syndrome, untreated or severe obstructive sleep apnoea syndrome, or obesity hypoventilation syndrome; patients receiving home ventilatory support or postoperative opioid therapy; and obese patients undergoing open operations, long procedures or revisional surgery.


ANTECEDENTES: La obesidad se ha convertido en un problema creciente en todo el mundo en las últimas décadas. Por lo tanto, cirujanos y anestesistas tratarán un número creciente de pacientes obesos en el futuro próximo y deberían estar preparados para proporcionar un tratamiento óptimo para estas personas. Esta revisión proporciona una actualización de la evidencia reciente respecto a las estrategias perioperatorias para pacientes obesos. MÉTODOS: Se llevó a cabo una búsqueda de los artículos sobre cuidados perioperatorios de pacientes obesos (lengua inglesa únicamente) en julio 2019 utilizando las bases de datos electrónicas PubMed, Google Scholar, Scopus, Web of Science y Cochrane Library. La revisión se centró en los resultados de ensayos aleatorizados y controlados, aunque se consideraron también estudios observacionales, metaanálisis, revisiones, guías clínicas, y otros artículos que discutían el cuidado perioperatorio de los pacientes obesos. Cuando los datos de los pacientes obesos no estaban disponibles, se utilizaron datos relevantes de las poblaciones no obesas. RESULTADOS Y CONCLUSIÓN: Los pacientes obesos requieren una evaluación preoperatoria integral. Los resultados postoperatorios se pueden mejorar mediante la presencia de equipos médicos con experiencia, equipamiento y monitorización apropiada, manejo anestésico cuidadoso, y una adecuada estrategia de ventilación perioperatoria. Son necesarias precauciones adicionales durante el periodo perioperatorio en pacientes con obesidad mórbida severa, síndrome metabólico, síndrome de apnea obstructiva del sueño severa o no tratada, síndrome de hipoventilación y obesidad, pacientes que reciben soporte ventilatorio domiciliario o tratamiento postoperatorio con opioides; y pacientes obesos sometidos a cirugía abierta, procedimientos largos o cirugía de revisión.


Subject(s)
Obesity/complications , Perioperative Care , Airway Management , Humans , Obesity/surgery , Patient Positioning , Perioperative Care/methods , Surgical Procedures, Operative
6.
Obes Surg ; 29(1): 292-296, 2019 01.
Article in English | MEDLINE | ID: mdl-30251088

ABSTRACT

BACKGROUND: Pre-operative diet may play an important role as far as patients' fitness for surgery, post-operative outcomes, and successful weight loss. Our aim was to compare surgical outcome and weight loss in two groups of patients who were offered two different pre-operative kinds of diet: very low calorie diet (VLCD) and very low calorie ketogenic diet (VLCKD). METHODS: Patients candidate for bariatric surgery (laparoscopic sleeve gastrectomy) were registered and assessed according to pre- and post-diet BMI, operative time, hospital stay, drainage output, and hemoglobin (Hb) levels. Patients' preference influenced the type of diet. RESULTS: From January to December 2016, 178 patients (139 F and 39 M) were enrolled in this study. The mean age was 43 years. In total, 72 patients were on VLCKD while 106 patients on VLCD. Pre-diet mean BMI was 46.3 ± 6.3 kg/m2 for VLCKD group and 43.1 ± 6.9 kg/m2 for VLCD group, while immediately pre-op BMI were 43.9 ± 5.9 kg/m2 and 41.9 ± 6.8 kg/m2, respectively. Drainage output and hemoglobin levels after surgery resulted significantly correlated with diet induced BMI reduction (141.2 ± 75.8 vs. 190.7 ± 183.6 ml, p = 0.032; 13.1 ± 1.2 vs. 12.7 ± 1.5 g/l, p = 0.04). The percentage of patients requiring a hospital stay longer than anticipated (> 3 days) was 2.8% in the VLCKD group and 10.4% in the VLCD group (p = 0.048). CONCLUSIONS: In our experience, VLCKD showed better results than VLCD on surgical outcome, influencing drainage output, post-operative hemoglobin levels, and hospital stay.


Subject(s)
Caloric Restriction/methods , Diet, Ketogenic/methods , Obesity, Morbid/diet therapy , Obesity, Morbid/surgery , Adult , Bariatric Surgery , Combined Modality Therapy , Female , Gastrectomy , Humans , Length of Stay , Male , Middle Aged , Operative Time , Preoperative Period , Treatment Outcome , Weight Loss
7.
Obes Surg ; 28(11): 3714-3716, 2018 11.
Article in English | MEDLINE | ID: mdl-30182333

ABSTRACT

Laparoscopic sleeve gastrectomy (LSG) is the most performed surgical procedure worldwide. Long-term outcomes report that up to 30% of patients require revisional surgery and re-sleeve gastrectomy (rLSG) is one of the revisional procedures available. The aim was to update the outcomes of a cohort of rLSG at 52 months. This study reports the 52-month follow-up of a cohort of 19 patients previously published after 24-month follow-up. Sixteen patients completed the follow-up. Nine patients complained of GERD symptoms after 36 months. Five patients were converted to laparoscopic RYGB. Two patients were converted to a laparoscopic BPD-DS for weight regain 4 patients are asymptomatic with stable weight. On the basis of our disappointing results, it can be said that rLSG is not currently offered as revisional procedure in both centers.


Subject(s)
Bariatric Surgery/methods , Gastrectomy/adverse effects , Obesity, Morbid/surgery , Reoperation/methods , Bariatric Surgery/adverse effects , Follow-Up Studies , Gastroesophageal Reflux/etiology , Humans , Laparoscopy , Reoperation/adverse effects , Retrospective Studies , Treatment Failure , Weight Loss
9.
Nutr Metab Cardiovasc Dis ; 24(4): 447-53, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24548662

ABSTRACT

BACKGROUND AND AIMS: Obesity, systemic inflammation and changes in the heart functions are associated with increased cardiovascular risk. This study aimed to investigate coronary microvascular dysfunction as an early marker of atherosclerosis in obese patients without any evidence of cardiovascular disease. METHODS AND RESULTS: 86 obese subjects (aged 44 ± 12 years, body mass index (BMI) 41 ± 8 kg m(-2)), without evidence of heart disease, and 48 lean controls were studied using transthoracic Doppler echocardiography for detecting coronary flow reserve (CFR). A value of CFR ≤ 2.5 was considered abnormal. We measured interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and adiponectin in all patients. Patients with abnormal CFR underwent coronary multislice computed tomography (MSCT) in order to exclude an epicardial stenosis. CFR in obese subjects was lower than in lean subjects (3.2 ± 0.8 vs. 3.7 ± 0.7, p = 0.02) and was abnormal in 27 (31%) obese patients and in one (2%) control (p < 0.0001). All subjects with abnormal CFR showed no coronary stenosis at MSCT. At multivariable analysis, IL-6 and TNF-α were the only determinants of CFR (p < 0.02 and p < 0.02, respectively). At multivariable logistic regression analysis, IL-6 and TNF-α were the only determinants of CFR ≤ 2.5 (p < 0.03 and p < 0.03, respectively). CONCLUSIONS: CFR is often reduced in obese subjects without clinical evidence of heart disease, suggesting a coronary microvascular impairment. This microvascular dysfunction seems to be related to a chronic inflammation mediated by adipocytokines. Our findings may explain the increased cardiovascular risk in obesity, independently of BMI.


Subject(s)
Coronary Artery Disease/etiology , Coronary Vessels/physiopathology , Inflammation/complications , Microvessels/physiopathology , Obesity/complications , Adiponectin/blood , Adult , Biomarkers/blood , Body Mass Index , Case-Control Studies , Chi-Square Distribution , Coronary Angiography/methods , Coronary Artery Disease/diagnosis , Coronary Artery Disease/physiopathology , Coronary Vessels/diagnostic imaging , Cross-Sectional Studies , Echocardiography, Doppler , Female , Fractional Flow Reserve, Myocardial , Humans , Inflammation/blood , Inflammation/diagnosis , Inflammation Mediators/blood , Interleukin-6/blood , Logistic Models , Male , Microcirculation , Microvessels/diagnostic imaging , Middle Aged , Multidetector Computed Tomography , Multivariate Analysis , Obesity/blood , Obesity/diagnosis , Predictive Value of Tests , Risk Factors , Severity of Illness Index , Tumor Necrosis Factor-alpha/blood
10.
Dis Markers ; 34(4): 269-78, 2013.
Article in English | MEDLINE | ID: mdl-23396294

ABSTRACT

BACKGROUND: Obesity is currently epidemic in many countries worldwide and is strongly related to diabetes and cardiovascular disease. Mass spectrometry, in particular matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) is currently used for detecting different pattern of expressed protein. This study investigated the differences in low molecular weight (LMW) peptide profiles between obese and normal-weight subjects in combination with multivariate statistical analysis. MATERIALS: Serum samples of 60 obese patients and 10 healthy subjects were treated by cut-off membrane (30000 Da) to remove the most abundant proteins. The filtrates containing the LMW protein/peptides were analyzed by MALDI-TOF mass spectrometry. Dataset was elaborated to align and normalize the spectra. We performed cluster analysis and principal component analysis to detect some ionic species that could characterize and classify the subject groups. RESULTS: We observed a down-expression of ionic species at m/z 655.94 and an over-expression of species at m/z 1518.78, 1536.77, 1537.78 and 1537.81 in obese patients. Furthermore we found some ionic species that can distinguish obese patients with diabetes from those with normal glucose level. CONCLUSION: Serum peptide profile of LMW associate with multivariate statistical approach was revealed as a promising tool to discriminate and characterize obese patients and it was able to stratify them in relation to comorbidity that usually are associated with this disease. Further research involving a larger sample will be required to validate these findings.


Subject(s)
Obesity, Morbid/blood , Peptides/blood , Case-Control Studies , Humans , Multivariate Analysis , Software , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
11.
Nucl Med Commun ; 25(1): 61-6, 2004 Jan.
Article in English | MEDLINE | ID: mdl-15061266

ABSTRACT

Isolated limb perfusion (ILP) therapy using a combination of tumour necrosis factor alpha (TNF) and cytostatic agents in hyperthermic conditions has proven to be effective in treating cancers limited to limbs or to a single organ such as the liver. A critical step for ILP is the accurate and real-time monitoring of that TNF toxic effects become relevant when overcoming the 10% limit of the 'effective' therapeutic dose administered during ILP. The most diffuse procedure for systemic leakage monitoring is based on the utilization of human soluble serum albumin (HSA) labelled with 131I and an external scintillation detector. In order to overcome some drawbacks connected with the properties of 131I, we developed a new procedure based on the utilization of HSA labelled with 99mTc in combination with a hand held gamma probe used as a detector. Our procedure consists of the following steps: (1) a 99mTc-HSA dose standardized as 0.5 MBq x kg(-1) body weight is injected into the ILP circuit before TNF administration; (2) a hand held gamma probe is placed over the pre-cordial area in a zone pre-marked on the patient's skin during a simulation test; (3) 48-72 h before ILP, a simulation test is obtained using a 99mTc-HSA dose corresponding to 10% of the dose calculated for ILP (i.e., 0.05 MBq x kg(-1) body weight); (4) during the simulation test the maximum count-rate zone detected on the pre-cordial area is marked on patient's skin; (5) a 60 min time-activity curve corresponding to the circulating 99mTc-HSA radioactivity effective decay is calculated and fitted; and (6) this time-activity curve is used to compensate for the leakage systemic counting observed during ILP. In order to compare the external, probe counting with the circulating radioactivity, in the first 10 patients from a total series of 43 treated patients, the results of external, probe monitoring were compared with the results of patient blood and perfusion circuit samples taken simultaneously every 5 min and measured by a laboratory gamma counter placed in the operating theatre. A good correlation was found between the two methods (R2 = 0.965, P < 0.01). It is concluded that the proposed procedure, based on the combination of 99mTc-HSA as the radiotracer and a hand held gamma probe as the detector, appears to be technically simple and accurate enough in the real-time monitoring of perfusion leakage in ILP cancer therapy. Moreover, using 99mTc-HSA as the radiotracer, the risk of radioactive contamination is significantly lower in comparison with 131I-HSA.


Subject(s)
Chemotherapy, Cancer, Regional Perfusion/methods , Drug Therapy, Computer-Assisted/methods , Extravasation of Diagnostic and Therapeutic Materials/diagnostic imaging , Melanoma/diagnostic imaging , Sarcoma/diagnostic imaging , Technetium Tc 99m Aggregated Albumin , Tumor Necrosis Factor-alpha/administration & dosage , Antineoplastic Agents/therapeutic use , Chemotherapy, Cancer, Regional Perfusion/adverse effects , Extravasation of Diagnostic and Therapeutic Materials/etiology , Extravasation of Diagnostic and Therapeutic Materials/metabolism , Extravasation of Diagnostic and Therapeutic Materials/prevention & control , Extremities , Gamma Cameras , Humans , Melanoma/drug therapy , Melanoma/metabolism , Radioisotope Dilution Technique , Radionuclide Imaging , Radiopharmaceuticals/pharmacokinetics , Sarcoma/drug therapy , Sarcoma/metabolism , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/drug therapy , Skin Neoplasms/metabolism , Technetium Tc 99m Aggregated Albumin/pharmacokinetics , Treatment Outcome , Tumor Necrosis Factor-alpha/adverse effects
12.
J Chemother ; 16 Suppl 5: 44-7, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15675477

ABSTRACT

Stop-flow perfusion (SFP) is a recently implemented locoregional treatment based on the vascular isolation of the tumor bearing body district through a radiointerventistic technique. SFP is currently under investigation as a palliative therapeutic option for patients with locally advanced tumors. This paper reports on the results of our prospective study of limb and pelvic SFP. Thirty-seven patients were treated with SFP. No postoperative deaths occurred. Locoregional and systemic toxicity were observed after 22 and 31 treatments, respectively; complete and partial response after 3 (6%) and 24 (51%) SFPs, respectively. The pharmacokinetic study showed that pelvic SFP was associated with a leakage rate higher than femoral SFP (38% vs 28%). In conclusion, SFP is a feasible procedure. Toxicity and tumor response rates strictly depend upon drug leakage control.


Subject(s)
Antineoplastic Agents/administration & dosage , Chemotherapy, Cancer, Regional Perfusion/methods , Melphalan/pharmacokinetics , Neoplasms/drug therapy , Adult , Aged , Antineoplastic Agents/pharmacokinetics , Female , Humans , Male , Middle Aged , Neoplasms/mortality , Prospective Studies
13.
J Chemother ; 16 Suppl 5: 58-61, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15675481

ABSTRACT

We report here the results of 27 patients who underwent hyperthermic isolated limb perfusion with low-dose TNFalpha (1 mg) and doxorubicin (8.5 mg/l of limb volume) for locally advanced soft tissue sarcomas. A tumor response was observed in 85% of cases. After a median follow-up of 30 months, limb salvage and local disease control were achieved in 82 and 85% of patients, respectively. Locoregional toxicity was low or mild in 14 patients, while 2 patients had severe limb toxicity. Systemic side effects were negligible. The perfusate/plasma area under the curve (AUC) ratio for TNFalpha was 56. HILP with low-dose TNFalpha and DXR proved to be an active neoadjuvant drug regimen against limb-threatening STS.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Chemotherapy, Cancer, Regional Perfusion/methods , Doxorubicin/administration & dosage , Hyperthermia, Induced , Sarcoma/drug therapy , Tumor Necrosis Factor-alpha/administration & dosage , Adult , Aged , Extremities , Female , Humans , Male , Middle Aged , Sarcoma/mortality , Tumor Necrosis Factor-alpha/pharmacokinetics
14.
Melanoma Res ; 13(3): 293-7, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12777985

ABSTRACT

Isolation limb perfusion (ILP) is the treatment of choice for locally advanced limb melanoma. With melphalan, the referral drug, complete response (CR) is achieved in about 50% of patients, but significant local toxicity occurs in up to 30%. The aim of the present phase I-II study was to challenge fotemustine (F) in ILP after systemic chemosensitization with dacarbazine (DTIC), given its lower toxicity and greater efficacy, as reported in a previous pilot study. Eleven patients with locally advanced limb melanoma were subdivided into triplets, and given F ILP at escalating doses (starting from 25 mg/l) after intravenous administration of 500 mg/m2 DTIC. Acute and chronic locoregional and systemic toxicity, tumour response and clinical outcome were evaluated. Two patients in the first triplet had G3-G4 local toxicity, so that the scheduled F dosage was halved. At drug levels of 12.5, 15.6 and 18.2 mg/l, local toxicity decreased, but only one of eight patients showed CR. The trial was then interrupted due to the low tolerability and poor efficacy of this perfusion regimen. At present, F ILP after DTIC chemosensitization should not be recommended for the treatment of locally advanced limb melanoma.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemotherapy, Cancer, Regional Perfusion , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Dacarbazine/administration & dosage , Extremities , Female , Humans , Male , Middle Aged , Nitrosourea Compounds/administration & dosage , Organophosphorus Compounds/administration & dosage , Treatment Outcome
15.
J Exp Clin Cancer Res ; 22(4 Suppl): 103-7, 2003 Dec.
Article in English | MEDLINE | ID: mdl-16767915

ABSTRACT

Isolated limb perfusion (ILP) is currently considered the standard treatment for melanoma patients with extensive in-transit disease, and L-PAM, combined or not with TNF, represents the most active drug. We here report on our clinical experience with TNF-based limb perfusion. Thirty-seven stage III patients underwent TNF-based limb perfusion, 22 with bulky disease, 15 with recurrences after perfusion with L-PAM. Ten patients were enrolled in a phase I-II study and treated with escalating doses of TNF (0.5-3 mg). The impact of disease burden, temperature, perfusion duration was assessed on tumor response. No postoperative death was observed. No significant systemic toxicity was recorded. Locoregional toxicity was G5 in one patient, G3 in 2, G2 in 9 and G1 in 25. Twenty-four (66%) patients had complete response, 11 (31%) partial and 1 (3%) no change. After a median follow-up of 20 months 14 (38%) patients are NED, 10 (27%) are AWD and 13 (35%) DOD. No significant statistical difference for tumor response were seen for disease burden, ILP temperatures and duration. Our results showed that it is possible to modify the perfusion schedule, without compromising the response rate but with lower cost and toxicity.


Subject(s)
Chemotherapy, Cancer, Regional Perfusion , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Tumor Necrosis Factor-alpha/administration & dosage , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Alkylating/therapeutic use , Dose-Response Relationship, Drug , Extremities/pathology , Female , Humans , Hyperthermia, Induced , Male , Melphalan/therapeutic use , Middle Aged , Neoplasm Recurrence, Local/drug therapy , Time Factors , Treatment Outcome
16.
Tumori ; 88(3): S61-3, 2002.
Article in English | MEDLINE | ID: mdl-12369560

ABSTRACT

AIMS: Isolated limb perfusion (ILP) with high doses of an alkylating agent alone or in combination with tumor necrosis factor (TNF) in hyperthermic conditions (HAP) has been proposed for the treatment of locoregional tumors. A critical step in ILP/HAP is accurate monitoring of systemic leakage to prevent the toxic effects of chemotherapy, and in particular of TNF. Ten percent systemic leakage from the perfusion circuit is considered the maximum acceptable leakage. In this study we report our experience of a new leakage monitoring system. MATERIALS AND METHODS: Ths new simplified procedure is based on the use of 99mTc-labeled soluble human serum albumin (HSA) and a hand-held gamma probe as detector. The procedure consists of the following steps: 1) A standardized 99mTc-HSA dose of 0.5 MBq/kg body weight is injected into the perfusion circuit before chemotherapy/TNF perfusion and a hand-held gamma probe (IGP) is placed over the precordial area in a zone that was marked on the skin during a simulation test; 2) 48-72 hours before ILP/HAP a complete simulation test is performed with a 99mTc-HSA dose corresponding to 10% of the total dose calculated for the patient's body weight; 3) during the simulation test the maximum count-rate zone on the precordial area is detected by IGP and marked on the patient's skin; 4) a 60-min curve of effective 99mTc-HSA radioactivity decay (physical and biological) is calculated and fitted; 5) to compare external counting with the effective circulating radioactivity, patient blood samples and circuit blood samples are taken every five minutes during ILP/HAP and measured by a laboratory gamma counter and very convenient thanks to the favorable characteristics of IGP. The placed in the operating room. RESULTS: External counting with a hand-held gamma probe was easy to perform time/activity curves obtained during simulation tests showed a regular and constant effective decay with a mean decay rate of 30% at 60 minutes compared to baseline values. The external measurements obtained by IGP proved to be well correlated with blood samples measured in vitro by a laboratory gamma counter. The results of this procedure, in particular the data of the simulation test for each patient, allowed us to correct the limit of 10% maximum leakage during ILP/HAP in accordance with the time/activity curve. CONCLUSIONS: Although 99mTc-HSA has some unfavorable characteristics, it offers many advantages over 131I-HSA. The procedure proposed by us, which was based on the use of an IGP and 99mTc-HAS at a standardized dose of 0.5 MBq/kg body weight and on an individual simulation test for each patient performed 48 hours before ILP/HAP, proved to be simple and accurate in monitoring systemic leakage during ILP/HAP anti-cancer therapy.


Subject(s)
Chemotherapy, Cancer, Regional Perfusion/methods , Monitoring, Intraoperative/methods , Humans , Hyperthermia, Induced , Radionuclide Imaging , Radiopharmaceuticals , Serum Albumin, Radio-Iodinated , Technetium Tc 99m Aggregated Albumin
17.
Eur J Surg Oncol ; 28(5): 544-53, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12217309

ABSTRACT

AIMS: The therapeutic approach for primary or recurrent advanced solid tumours, particularly when unresectable, is still one of the main medical challenges in the management of cancer patients. The stop-flow (SF) technique has been recently proposed as a semi-invasive drug delivery system based on the blood supply blockage of the tumour-bearing area. Here, we discuss the principles underlying the SF technique as well as the worldwide experience published so far. We also report on the results of our pilot study on pelvic and limb SF perfusion. METHODS: We reviewed the worldwide experience on SF as reported by the literature published on PubMed from 1990 through 2001. In our series, we treated 20 patients affected with locally advanced melanoma, soft tissue sarcoma or colorectal cancer. RESULTS: This therapeutic modality - at least for some tumours - can achieve encouraging results in terms of clinical response even after conventional therapies have failed. Moreover, as a safe and relatively simple procedure, SF can be applied to patients for whom traditional treatments (i.e. surgery, systemic chemotherapy) are contraindicated because of poor general conditions. CONCLUSIONS: At present, the SF technique should be considered an investigational approach to locally advanced cancers. The encouraging results obtained with this procedure should be validated by large phase III trials.


Subject(s)
Antineoplastic Agents/therapeutic use , Drug Delivery Systems/methods , Drug Delivery Systems/trends , Humans , Neoplasms/drug therapy , Pilot Projects
18.
Obes Surg ; 12(3): 385-90, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12082893

ABSTRACT

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) with the Lap-Band has been our first choice operation for morbid obesity since September 1993. Results in terms of complications and weight loss are analyzed. METHODS: 830 consecutive patients (F 77.9%) underwent LAGB. Initial body weight was 127.9 +/- SD 23.9 kg, and body mass index (BMI) was 46.4 +/- 7.2 kg/m2. Mean age was 37.9 (15-65). Steps in LAGB were: 1) establishment of reference points for dissection (equator of the balloon inflated with 25 cc air and left crus); 2) creation of a retrogastric tunnel above the bursa omentalis; 3) creation of "virtual" pouch; 4) embedding the band. RESULTS: Mortality was 0, conversion 2.7%, and follow-up 97%. Major complications requiring reoperation developed in 3.9% (36 patients). Early complications were 1 gastric perforation (requiring band removal) and 1 gastric slippage (requiring repositioning). Late complications included 17 stomach slippages (treated by band repositioning in 12 and band removal in 5), 9 malpositions (all treated by band repositioning), 4 gastric erosions by the band (all treated by band removal), 3 psychological intolerance (requiring band removal), and 1 HIV positive (band removed). A minor complication requiring reoperation in 91 patients (11%) was reservoir leakage. 20% of patients who had % excess weight loss < 30 had lost compliance to dietetic, psychological and surgical advice. BMI declined significantly from the initial 46.4 +/- 7.2 to 37.3 +/- 6.8 at 1 year, 36.4 +/- 6.9 at 2 years, 36.8 +/- 7.0 at 3 years, and 36.4 +/- 7.8 at 5 years. CONCLUSION: LAGB is a relatively safe and effective procedure.


Subject(s)
Bandages/adverse effects , Gastroplasty/adverse effects , Laparoscopy/adverse effects , Obesity, Morbid/surgery , Patient Selection , Postoperative Complications , Adolescent , Adult , Aged , Body Mass Index , Female , Follow-Up Studies , Humans , Male , Middle Aged , Obesity, Morbid/physiopathology , Time Factors , Weight Loss/physiology
19.
Eur J Surg Oncol ; 27(2): 125-34, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11289746

ABSTRACT

Peritoneal carcinomatosis and sarcomatosis (PCS) are short-term fatal conditions amenable only to palliative treatment. They are generally considered as a systemic disease at clinical presentation, and are resistant to standard treatments. However, there may be in the natural history a phase of loco-regional tumour spread during which the tumour may still be curable. Surgical treatment alone, or in combination with systemic chemotherapy, has yielded poor results in terms of survival and quality of life. One approach is cytoreductive surgery (CS) combined with the intraperitoneal administration of antiblastic agents. This may diminish any residual tumour following macroscopic excision and may overcome the pharmacokinetic limits of systemic chemotherapy. A further improvement in this multimodal approach may be achieved by the use of hyperthermic intraperitoneal intraoperative chemotherapy (HIIC). Results so far have been encouraging. However, series reported in the literature are relatively small and heterogeneous, and clinical and technical factors which include the selection of patients, optimal drugs dosage and temperature, evaluation of outcome and costs are still under discussion.


Subject(s)
Carcinoma/therapy , Peritoneal Neoplasms/therapy , Sarcoma/therapy , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Carcinoma/diagnostic imaging , Carcinoma/mortality , Humans , Hyperthermia, Induced , Neoadjuvant Therapy , Peritoneal Neoplasms/diagnostic imaging , Peritoneal Neoplasms/mortality , Quality of Life , Radiography , Sarcoma/diagnostic imaging , Sarcoma/mortality , Survival Rate
20.
Tumori ; 86(4): 339-40, 2000.
Article in English | MEDLINE | ID: mdl-11016722

ABSTRACT

The role of the patent blue dye (PBD) technique and intraoperative probe-guided lymphoscintigraphy (LS) in detecting the sentinel node (SN) was investigated in a group of 130 consecutive stage I cutaneous melanoma patients. The preoperative workup included high-resolution US scanning and LS performed 15-18 hours before surgery. On the basis of preoperative LS, in the group of examined patients a total of 143 lymphatic drainage basins were identified and surgically explored: 41.6% in the axilla, 52.8% in the groin, and 5.6% in the head/neck. A total of 228 SNs were intraoperatively detected and removed; 110 lymphatic basins contained histologically negative SNs, while 33 basins had metastatic SNs. The sensitivity for SN detection using PBD alone was 93%, while it was 100% when PBD was combined with intraoperative LS. Preoperative and intraoperative LS appears to be a highly sensitive technique for SN detection in cutaneous melanoma patients. Furthermore, in view of the limited skin incision when radioguided surgery is performed, SN biopsy could be feasible under local anesthesia.


Subject(s)
Lymph Nodes/pathology , Lymph Nodes/surgery , Melanoma/pathology , Melanoma/surgery , Sentinel Lymph Node Biopsy/methods , Skin Neoplasms/pathology , Skin Neoplasms/surgery , Adolescent , Adult , Aged , Coloring Agents , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Rosaniline Dyes , Sensitivity and Specificity
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