Does previous surgery influence the asymmetric distribution of endometriotic lesions?

Our objective was to investigate the role of previous abdominal-pelvic surgery in the asymmetric distribution of pelvic endometriosic lesions. This was a retrospective study carried out at the Clinic of Obstetrics and Gynecology, University of Ancona, Italy, and included 238 patients with histological confirmation of endometriosis. The interventions were surgical treatment, at laparoscopy or laparotomy, for pelvic pain and endometriosis. The main outcome measure(s) were endometriotic lesions and adhesions in the pelvis found during surgery and the dinical records of the patients. We found unilateral lesions in 149 patients (62.6%): the right side of the pelvis affected in 55 patients (36.9%) and the left side in 94 patients (63.1%) (p < 0.01). In the group of patients who had undergone previous abdominal surgery, we found lesions on the right side in 26 cases (32.5%), and on the left in 54 cases (67.5%) (p < 0.01). We found that the patients who had undergone previous abdominal surgery had significantly more adhesions than those with no previous surgery (80/116 vs. 73/122, p = 0. 002). As a new finding, we have demonstrated that the left side of asymmetric distribution of intrapelvic macroscopic lesions is preserved and more evident in patients with previous abdominal surgery, including previous appendectomy. These data seem to be in agreement with our previous supposition of a possible interaction between previous abdominal surgery and the mechanisms of endometriosis development.     

Personalized therapeutic strategies in HER2-driven gastric cancer

Gastric Cancer - Trastuzumab is the only approved targeted therapy in patients with HER2-amplified metastatic gastric cancer (GC). Regrettably, in clinical practice, only a fraction of them...     

Apolipoprotein C-II deficiency syndrome. Clinical features, lipoprotein characterization, lipase activity, and correction of hypertriglyceridemia after apolipoprotein C-II administration in two affected patients.

Two patients (brother and sister, 41 and 39 yr of age, respectively) have been shown to have marked elevation of plasma triglycerides and chylomicrons, decreased low density lipoproteins (LDL) and high density lipoproteins (HDL), a type I lipoprotein phenotype, and a deficiency of plasma apolipoprotein C-II (apo C-II). The male patient had a history of recurrent bouts of abdominal pain often accompanied by eruptive xanthomas. The female subject, identified by family screening, was asymptomatic. Hepatosplenomegaly was present in both subjects. Analytical and zonal ultracentrifugation revealed a marked increase in triglyceride-rich lipoproteins including chylomicrons and very low density lipoproteins, a reduction in LDL, and the presence of virtually only the HDL3 subfraction. LDL were heterogeneous with the major subfraction of a higher hydrated density than that observed in plasma lipoproteins of normal subjects. Apo C-II levels, quantitated by radioimmunoassay, were 0.13 mg/dl and 0.12 mg/dl, in the male and female proband, respectively. A variant of apo C-II (apo C-IIPadova) with lower apparent molecular weight and more acidic isoelectric point was identified in both probands by two-dimensional gel electrophoresis. The marked hypertriglyceridemia and elevation of triglyceride-rich lipoproteins were corrected by the infusion of normal plasma or the injection of a biologically active synthesized 44-79 amino acid residue peptide fragment of apo C-II. The reduction in plasma triglycerides after the injection of the synthetic apo C-II peptide persisted for 13-20 d. These results definitively established that the dyslipoproteinemia in this syndrome is due to a deficiency of normal apo C-II. A possible therapeutic role for replacement therapy of apo C-II by synthetic or recombinant apo C-II in those patients with severe hypertriglyceridemia and recurrent pancreatitis may be possible in the future.     

Preoperative Nutritional Interventions in Morbid Obesity: Impact on Body Weight, Energy Intake, and Eating Quality

Background

Although the benefits of preoperative weight loss and adequacy of dietary patterns in bariatric surgery is well-recognized, the nutritional strategies in the preoperative period have been scarcely investigated. We aimed to evaluate the impact of intensive and standard nutritional interventions on body weight, energy intake, and eating quality.

Methods

This is a retrospective study in which 32 patients undergoing intensive nutritional intervention, with low-calorie diet (10?kcal/kg) and biweekly visits, were pair-matched by age, sex, and body mass index with 32 patients under a standard nutritional intervention, based on a general dietary counseling. Twenty-four-hour food recall was used to assess energy intake and to derive healthy eating index (HEI). The follow-up preoperative period varied from 8 to 16?weeks.

Results

Weight loss was observed in 72?% of the patients from the intensive intervention group and 75?% of the patients from the standard intervention group. According to the mixed model analysis, time effect on weight loss in both groups was significant (P?=?0.0002); however, no difference was found between the intervention groups (P?=?0.71). The time effect was significant in both groups for energy intake reduction as well (P?<?0.0001), but no difference was found between the intervention groups (P?=?0.25). Improvement of eating quality was expressed by the nutrient score of the HEI that increased significantly overtime (P?=?0.02), also without distinction between the groups (P?=?0.61).

Conclusion

Both intensive and standard nutritional interventions promoted weight loss, energy intake reduction, and improvement of eating quality in morbidly obese patients during preoperative period.     

Searching for Indicators of Malignancy in Pancreatic Intraductal Papillary Mucinous Neoplasms: The Value of 18FDG–PET Confirmed

Background

Malignancy in intraductal papillary mucinous neoplasms (IPMN) of the pancreas may be predicted on the basis of a number of clinical and radiologic features, which have raised sensitivity but result in a specificity as low as 20?C50%. We sought to confirm the additional value of ¹⁸F-18-fluorodeoxyglucose?Cpositron emission tomography (¹⁸FDG?CPET) in diagnostic accuracy of imaging-based IPMN malignancy assessment.

Methods

This prospective uncontrolled case series contained 44 patients with IPMN undergoing comprehensive diagnostic evaluation, including magnetic resonance cholangiopancreatography and ¹⁸FDG?CPET. Average follow-up time was 39.3?months (range 3?C97?months). Diagnostic performance regarding the diagnosis of malignancy was evaluated for the classic preoperative assessment, including clinical signs, CA 19-9, imaging (computed tomography and magnetic resonance cholangiopancreatography), and International Consensus Guidelines criteria, as well as ¹⁸FDG?CPET scan.

Results

Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 100, 22, 32, 100, and 43%, and 83, 100, 100, 94, and 96%, respectively, for comprehensive assessment without and with ¹⁸FDG?CPET [maximum standardized uptake value (SUV_max) cutoff of 2.5?MBq]. Elevated CA 19-9 values and positive PET scan were the only independent prognostic factors for malignancy (odds ratio 2.11, 95% confidence interval 1.15?C2.74 and 5.49, 95% confidence interval 3.98?C21.44, respectively).

Conclusions

¹⁸FDG?CPET is useful for detection of malignancy in IPMN, improving the differential diagnosis with benign cases by functional data. The choice of SUV_max cutoff should maximize specificity.     

Antiproliferative effects of somatostatin and the somatostatin analog SMS 201-995 on three human breast cancer cell lines

Summary The antiproliferative effect of somatostatin and the somatostatin analog SMS 201-995 on three human breast cancer cell lines (CG5, T 47 D, and ZR 75-1 is reported. Both peptides markedly inhibited CG5 cell growth with a maximal inhibition of about 40% as compared with control cells. The antiproliferative effect of somatostatin on T 47 D and ZE 75-1 cells was much less evident. These results suggest that somatostatin is a peptide inhibitory factor for human breast cancer cells. Possible therapeutic implications of these findings are still to be investigated.     

Isolation and characterization of CD146+ multipotent mesenchymal stromal cells

Mesenchymal stromal cells (MSCs) represent a bone marrow (BM) population, classically defined by five functional properties: extensive proliferation, ability to differentiate into osteoblasts, chondrocytes, adipocytes, and stromal cells-supporting hematopoiesis. However, research progress in this area has been hampered by lack of suitable markers and standardized procedures for MSC isolation. We have isolated a CD146(+) multipotent MSC population from 20 human BM donors displaying the phenotype of self-renewing osteoprogenitors; an extensive 12-week proliferation; and the ability to differentiate in osteoblasts, chondrocytes, adipocytes, and stromal cells supporting hematopoiesis. Furthermore, the CD146(+) MSCs secrete a complex combination of growth factors (GFs) controlling hematopoietic stem cells (HSCs) function, while providing a >2-log increase in the long-term culture (LTC) colony output in 8-week LTC over conventional assays. The hematopoietic stromal function exhibited by the MSCs was further characterized by manipulating LTCs with the chemical inhibitors Imatinib or SU-5416, targeting two GF receptors (GFRs), KIT or VEGFR2/1, respectively. Both treatments similarly impaired LTC colony output, indicating key roles for these two GF/GFR interactions to support LTC-initiating cell activity. CD146(+) MSCs may thus represent a tool to explore the MSC-HSC cross-talk in an in vitro surrogate model for HSC "niches," and for regenerative therapy studies. In addition, the MSC microRNA (miRNA) expression profile was analyzed by microarrays in both basic conditions and chondrogenic differentiation. Our analysis revealed that several miRNAs are modulated during chondrogenesis, and many of their putative targets are genes involved in chondrogenic differentiation.     

Durable hematologic complete response and suppression of HTLV-1 viral load following alemtuzumab in zidovudine/IFN-{alpha}-refractory adult T-cell leukemia

Adult T-cell leukemia (ATL) is a highly chemoresistant and usually fatal T-cell malignancy due to the human T-cell lymphotropic virus-1 (HTLV-1). After chemotherapy failure, antiretrovirals and interferon-alpha (IFN-alpha) produce brief responses followed by progression and death. More effective agents and new approaches to detect and treat minimal residual disease are needed. ATL cells express CD52, the target of the antibody alemtuzumab, which is active in a preclinical model of ATL and is cytotoxic for p53-deficient cells. A patient with refractory chronic ATL in transformation achieved longer than a 1-year complete hematologic response following 12 weeks of outpatient subcutaneous alemtuzumab. Persistent suppression of HTLV-1 viral load, even at recovery of T cells, after alemtuzumab and efficient in vitro complement-mediated cytotoxicity of primary ATL cells with mutated TP53 were observed. The unprecedented response and the profound suppression of HTLV-1 viral load observed in this patient suggest that further clinical investigation of alemtuzumab in ATL is warranted.