Gabriele De Sena

Therapy with autologous adipose-derived regenerative cells for the care of chronic ulcer of lower limbs in patients with peripheral arterial disease.

BACKGROUND An ulcer is a trophic lesion with loss of tissue that often has a multifactorial genesis. It typically diverges from the physiologic processes of regeneration because it rarely tends to heal spontaneously. In this study, we used purified adipose-derived stem and regenerative cells (ADRCs) extracted from autologous fat, for the care of chronic ulcers of the lower limbs of arteriopathic patients. The primary objective of this study was complete re-epithelization of chronic ulcers; the secondary objective was a decrease in diameter and depth. METHODS From January 2010 to January 2012, 20 patients with peripheral arterial disease, with an ankle-brachial index between 0.30-0.40, in the age range 60-70 y (14 men and six women), with chronic ulcers of the lower limb, were involved in the study. Only 10 arteriopathic patients (seven men and three women) with chronic ulcers of the lower limb were surgically treated. Using the Celution system, we isolated a solution of ADRCs in about 150 min. The isolated cells were injected through a 10-mL syringe into the edges of the ulcer, taking care to spread it in all directions. Using a small amount of Celution extract, we performed cell characterization by flow cytometry analysis and cell viability assay. RESULTS We monitored patients treated with ADRC or untreated at 4, 10, 20, 60, and 90 d. In all cases treated with ADRC, we found a reduction in both diameter and depth of the ulcer, which led to a decrease in pain associated with the ulcer process. In six of 10 cases there was complete healing of the ulcer. Characterization of the cells by FACS clearly showed that the ADRC cells contained adipose-derived stem cells. Viability assays demonstrated that partial or total closure of the ulcer was attributable exclusively to ADRC cells present in the Celution extract, and not to growth factors extracted during the process of purification of the Celution and injected together with the cells. CONCLUSIONS For the first time, the Celution method has been applied for the care of chronic ulcers in the lower extremity of patients with peripheral arterial disease. Our results demonstrate that the technique is feasible for autologous cell application and is not associated with adverse events. Moreover, the transplantation of autologous stem cells extracted with Celution may represent a valuable method for the treatment of chronic ulcers in lower limbs of arteriopathic patients.

Modified versus standard D2 lymphadenectomy in total gastrectomy for nonjunctional gastric carcinoma with lymph node metastasis

BACKGROUND Although D2 lymphadenectomy has been shown to improve outcomes in gastric cancer, it may increase postoperative morbidity, mainly owing to splenopancreatic complications. In addition, the effects of nodal dissection along the proper hepatic artery have not been extensively elucidated. We hypothesized that modified D2 (ie, D1+) lymphadenectomy may decrease surgical risks without impairing oncologic adequacy. METHODS Patients with node-positive gastric cancer undergoing curative total gastrectomy were intraoperatively randomized to D1+ (group 1, 36 patients) or standard D2 lymphadenectomy (group 2, 37 patients), the latter including splenectomy and nodal group 12a. The index of estimated benefit was used to assess the efficacy of dissection of each nodal station. The primary endpoint for oncologic adequacy was the disease-free survival (DFS) rate. RESULTS Surgical complications were significantly more common in group 2, which also included 2 postoperative deaths. Overall, 35 patients (49%) experienced tumor recurrence. The primary site of tumor relapse and the 5-year DFS rate were not different between the 2 groups. Involvement of the second nodal level was associated with a worse DFS rate; however, patients undergoing more extensive lymphadenectomy did not show a better DFS rate. The incidence of involvement of nodal stations 10, 11d, and 12a was 5%, and the 5-year DFS rate was zero. Consequently, the benefit to dissect such lymph nodes was null. CONCLUSION These findings suggest that modified D2 lymphadenectomy confers the same oncologic adequacy as standard D2 lymphadenectomy, with a significant reduction of postoperative morbidity.

Clinical impact of Mediterranean-enriched-protein diet on liver size, visceral fat, fat mass, and fat-free mass in patients undergoing sleeve gastrectomy

BACKGROUND Weight loss before laparoscopic sleeve gastrectomy (LSG) is desirable because it can reduce visceral fat and liver size thereby facilitating the surgical procedure. Preoperative very-low-energy diets have been demonstrated to decrease weight, visceral fat, and liver size. However, no studies have been conducted using the Mediterranean-protein-enriched diet (MPED) or on the amount of preoperative weight loss attributed to the loss of fat-free mass (FFM). OBJECTIVES To evaluate the effect of the MPED on weight, visceral fat, liver size, fat mass (FM), and FFM in obese patients undergoing LSG. SETTING University Hospital, Italy. MATERIALS AND METHODS Obese male patients (n = 37) with a mean body mass index (BMI) of 45.2 kg/m(2) scheduled for LSG underwent an 8-week preoperative MPED. Their weight, visceral fat, body composition, liver size, and biochemical and metabolic patterns were measured before and after the diet. Patient compliance was assessed by the presence of ketonuria and weight loss. Qualitative methods (5-point Likert questionnaire) were used to measure diet acceptability and side effects. RESULTS We observed highly significant decreases in weight, liver size, visceral fat, and FM; however, there was no significant reduction in FFM. All tested patients showed a high frequency of acceptability and compliance in following the diet, and no secondary effects were observed. CONCLUSION Based on our findings, we were able to support the hypothesis that MPED might be associated with significant reductions in weight loss, FM, and liver size without a significant loss of FFM.

Micronutrient Deficiencies in Patients Candidate for Bariatric Surgery: A Prospective, Preoperative Trial of Screening, Diagnosis, and Treatment

Bariatric surgery candidates often show preoperative micronutrient deficiency. Although it is documented that a comprehensive micronutrient assessment should be conducted preoperatively to correct the deficiencies before surgery, no previous studies have been effective in correcting deficiencies in sufficient time prior to surgery. Our aim was to identify micronutrient deficiencies preoperatively and correct them before surgery.

Fat mass, fat-free mass, and resting metabolic rate in weight-stable sleeve gastrectomy patients compared with weight-stable nonoperated patients

BACKGROUND There is evidence that body composition and resting metabolic rate (RMR) in weight-stable patients after Roux-en-Y gastric bypass and duodenal switch is similar to that of nonoperated individuals within the same body mass index (BMI) interval. Currently, data concerning fat mass (FM), fat-free mass (FFM), and RMR on weight-stable patients after sleeve gastrectomy (SG) are lacking. OBJECTIVES To assess FM, FFM, and RMR, in a selected and homogenous population of weight-stable SG patients (WSSG) and compare them with those obtained from healthy normal weight-stable nonoperated (WSNO) volunteers controls of similar sex, age, and BMI. SETTING University hospital, Italy. METHODS We assessed total weight, FM, and FFM by bioelectrical impedance assay, and RMR by indirect calorimetry, in 70 WSSG patients (47 females, 23 males) at a mean follow-up of 3.2 ± 2.1 years after SG and compared them with 70 healthy WSNO volunteers, as controls (47 females, 23 males). RESULTS There was no significant difference between WSSG and WSNO groups concerning total weight (males, 72 ± 2.66 versus 72.8 ± 1.99 kg, P = .0254; females 65.1 ± 2.53 versus 63.7 ± 2.87 kg, P = .0139), FM (males, 17.7 ± 1.53 versus 16.7 ± 1.57 kg, P = .0341; females 19.6 ± 0.50 versus 18.5 ± 2.85 kg, P = .0104), FFM (males, 54.3 ± 3.07 versus 56.1 ± 3.30 kg; P = .049; females 45.5 ± 2.29 versus 45.1 ± 1.13 kg, P = .287), and RMR (males, 1541 ± 121.3 versus 1463 ± 74.4 kcal/d; P = .0118; females 1214 ± 54.9 versus 1250 ± 90.1 kcal/d, P = .0215). CONCLUSION At a mean follow-up of 3.2 ± 2.1 years after SG, WSSG patients of both sexes have a FM, FFM, and RMR comparable to that of healthy WSNO individuals within the same age and BMI interval. These findings further support bariatric surgery-induced weight loss as a physiologic process and indicate that young patients, in the setting of an adequate preoperative and postoperative specific diet and moderate physical activity, do not suffer from excessive FFM depletion after SG in the mid-term.

Nonsurgical management of multiple splenic abscesses in an obese patient that underwent laparoscopic sleeve gastrectomy: case report and review of literature.

Sleeve gastrectomy (SG) is a surgical weight‐loss procedure. Splenic abscess is a rare complication of SG. Four cases of splenic abscess after SG have been reported, all managed by surgical intervention. We report the first documented case of multiple splenic abscesses following SG managed conservatively by an integrated medical treatment.

Preservation of Fat-Free Mass After Bariatric Surgery: Our Point of View

Obesity is a well-recognized global health problem, and bariatric surgery (BS)-induced weight reduction has been demonstrated to improve survival and obesity-related conditions [1]. Indeed, contrary to lifestyle modifications and dietary programs, BS is becoming an increasingly accepted treatment for severe obesity [2] because it results in massive and sustained weight loss with consequent improvements in health and disease outcomes [3, 4]. It is universally accepted that an important goal during weight loss is to maximize fat mass (FM) loss while preserving metabolically active fat-free mass (FFM) [5]. Maintaining adequate FFM is an important point when making dietary intake recommendations for weight loss because muscles play a central role in whole-body protein metabolism [6]. Additionally, a significant decrease in FFM may negatively affect the resting metabolic rate (RMR) [7], slow the rate of weight loss, and predispose to weight regain [8]. However, it is important to underline that RMR, defined as the minimal amount of energy that the body expends in order to maintain vital processes, does not depend exclusively on the amount of FFM [5] but depends also on other factors such as age, gender, physical activity, lifestyle, and hormones [9]. However, in the nutritionist’s community, concerns have been raised that BS yields a catabolic state, with significant nutritional risks, such as a greater and rapid weight loss that may be accompanied by significant loss of FFM. For this reason, one of the key nutritional issues in patients scheduled for BS should be to measure body composition before and after surgery to quantify changes in FM and FFM [10]. Furthermore, protein and general diet composition should be adjusted to manage the risk of FFM depletion after surgery. Interestingly, available data regarding the preservation of FFM after BS are controversial. In fact, there are studies suggesting that the loss of FFM is minimized with restrictive procedures, such as sleeve gastrectomy (SG), when compared with procedures including an intestinal bypass such as Roux-en-Y gastric bypass (RYGB) and duodenal switch (BPD/DS), whereas other studies show that RYGB helps preserve overall FFM in comparison with SG [11]. Moreover, we recently

New Treatment of Medullary and Papillary Human Thyroid Cancer

The aim of this paper is based on the use of a hyaluronic acid hydrogel of Quercetin tested alone and in combination to an inhibitor of Aurora Kinase type A and B (SNS‐314) on human medullary and papillary thyroid cancer cells. Biological investigations were focused on the cellular uptake of the hydrogel, cell viability, antioxidant, and cytokines secretion studies. Quercetin delivered from hydrogel show a time and CD44 dependent interaction with both cell lines with significant anti‐inflammatory effects. Combination of Quercetin and SNS‐314 leads to a synergistic cytotoxic effect on medullary TT and papillary BCPAP cell lines with a significant reduction of the IC50 value. These results, highlights the importance of synergistic effect of the hyaluronic acid hydrogel of Quercetin with SNS‐314 in the regulation of human thyroid cancer cell proliferation and emphasize the anti‐tumor activity of these molecules. J. Cell. Physiol. 231: 1784–1795, 2016.

New Treatment of Medullary and Papillary Human Thyroid Cancer: Biological Effects of Hyaluronic Acid Hydrogel Loaded With Quercetin Alone or in Combination to an Inhibitor of Aurora Kinase: NEW TREATMENT OF HUMAN THYROID CANCER

The aim of this paper is based on the use of a hyaluronic acid hydrogel of Quercetin tested alone and in combination to an inhibitor of Aurora Kinase type A and B (SNS‐314) on human medullary and papillary thyroid cancer cells. Biological investigations were focused on the cellular uptake of the hydrogel, cell viability, antioxidant, and cytokines secretion studies. Quercetin delivered from hydrogel show a time and CD44 dependent interaction with both cell lines with significant anti‐inflammatory effects. Combination of Quercetin and SNS‐314 leads to a synergistic cytotoxic effect on medullary TT and papillary BCPAP cell lines with a significant reduction of the IC50 value. These results, highlights the importance of synergistic effect of the hyaluronic acid hydrogel of Quercetin with SNS‐314 in the regulation of human thyroid cancer cell proliferation and emphasize the anti‐tumor activity of these molecules. J. Cell. Physiol. 231: 1784–1795, 2016.