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1.
J Visc Surg ; 157(2): 79-86, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31837942

ABSTRACT

INTRODUCTION: Cytoreductive surgery of locally advanced ovarian cancer has evolved in the last few years from surgery to remove macroscopic residual disease (<1cm; R2b) to macroscopic complete cytoreductive surgery with no gross residual disease (R1). The aim of this study was to evaluate the impact of the adoption of a maximalist surgical approach on postoperative complications, disease recurrence and survival. MATERIALS AND METHODS: This was a retrospective study using prospectively collected data on patients who received either conservative approach (CA) or radical approach (RA) surgical treatment for primary ovarian cancer stage IIIc/IVa/IVb between June 2006 and June 2013. RESULTS: Data for 114 patients were included, 33 patients in the CA group and 68 patients in the RA group were consequently analysed. In the RA group, operative time was longer, in relation to more complex surgical procedures; with more blood losses and a higher rate of compete macroscopic resection. Totally, 77% of the patients had postoperative complications, with more grade I/II complications in the RA group but the same rates of grade III/IV complications in the both groups (P=0.14). For all patient study population, the overall and disease-free survivals were improved in case of no macroscopic residual disease. Overall survival was improved in the RA group (P=0.05), with no difference in terms of disease-free survival (P=0.29) CONCLUSION: A radical approach in advanced ovarian cancer allows a higher rate of complete cytoreductive surgery impacting overall survival. However, a non-significant trend for increased mild complications (grade I/II) rate is observed in this group.


Subject(s)
Carcinoma/surgery , Cytoreduction Surgical Procedures/methods , Ovarian Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma/mortality , Carcinoma/pathology , Carcinoma/secondary , Conservative Treatment , Female , Humans , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Neoplasm, Residual , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/secondary , Peritoneal Neoplasms/surgery , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Retrospective Studies , Survival Analysis , Treatment Outcome
2.
Diabetologia ; 56(7): 1605-14, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23620058

ABSTRACT

AIMS/HYPOTHESIS: Alginate-encapsulated human islet cell grafts have not been able to correct diabetes in humans, whereas free grafts have. This study examined in immunodeficient mice whether alginate-encapsulated graft function was inferior to that of free grafts of the same size and composition. METHODS: Cultured human islet cells were equally distributed over free and alginate-encapsulated grafts before implantation in, respectively, the kidney capsule and the peritoneal cavity of non-obese diabetic mice with severe combined immunodeficiency and alloxan-induced diabetes. Implants were followed for in vivo function and retrieved for analysis of cellular composition (all) and insulin secretory responsiveness (capsules). RESULTS: Free implants with low beta cell purity (19 ± 1%) were non-functional and underwent 90% beta cell loss. At medium purity (50 ± 1%), they were functional at post-transplant week 1, evolving to normoglycaemia (4/8) or to C-peptide negativity (4/8) depending on the degree of beta cell-specific losses. Encapsulated implants immediately and sustainably corrected diabetes, irrespective of beta cell purity (16/16). Most capsules were retrievable as single units, enriched in endocrine cells that exhibited rapid secretory responses to glucose and glucagon. Single capsules with similar properties were also retrieved from a type 1 diabetic recipient at post-transplant month 3. However, the vast majority were clustered and contained debris, explaining the poor rise in plasma C-peptide. CONCLUSIONS/INTERPRETATION: In immunodeficient mice, i.p. implanted alginate-encapsulated human islet cells exhibited a better outcome than free implants under the kidney capsule. They did not show primary non-function at low beta cell purity and avoided beta cell-specific losses by rapidly establishing normoglycaemia. Retrieved capsules presented secretory responses to glucose, which was also observed in a type 1 diabetic recipient.


Subject(s)
Alginates/chemistry , Diabetes Mellitus, Type 1/surgery , Islets of Langerhans Transplantation/methods , Islets of Langerhans/cytology , Peritoneal Cavity/cytology , Animals , Blood Glucose/metabolism , C-Peptide/blood , Cells, Cultured , Female , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Humans , Mice , Middle Aged
3.
Diabetologia ; 53(11): 2380-8, 2010 Nov.
Article in English | MEDLINE | ID: mdl-20645074

ABSTRACT

AIMS/HYPOTHESIS: Neogenesis of beta cells and their clustering to small aggregates is a key process in prenatal development of beta cell mass. We investigated the contribution of postnatally formed small aggregates to functional beta cell mass in adult rats. METHODS: Conditions were defined for (1) counting total beta cell number in pancreases with relative error of <10% and (2) determining their distribution over aggregates of different size and over functionally different subpopulations. RESULTS: Pancreases of 10-week-old male Wistar rats contained 2.8 ± 0.2 × 106 beta cells, of which >90% was generated postnatally, involving: (1) neo-formation of 30,000 aggregates with diameter <50 µm including single cells; and (2) growth of 5,500 aggregates to larger sizes, accounting for 90% of the increase in cell number, with number of growing aggregates in the tail 50% greater than elsewhere. At 10 weeks, 86% of aggregates were <50 µm; compared with aggregates >200 µm, their beta cells exhibited a higher basal insulin content that was also resistant to glibenclamide-induced degranulation. The pool of Ki67-positive beta cells was sixfold larger than at birth and distributed over all aggregate sizes. CONCLUSIONS/INTERPRETATION: We describe a method for in situ counting of beta cell numbers and subpopulations with low relative error. In adult rats, >90% of beta cells and beta cell aggregates are formed after birth. Aggregates <50 µm are more than 100-fold more abundant than aggregates >200 µm, which are selected for isolated islet studies. Their topographic and functional properties contribute to the functional heterogeneity of the beta cell population; their growth to larger aggregates with characteristic beta cell functions may serve future metabolic needs.


Subject(s)
Insulin-Secreting Cells/cytology , Pancreas/cytology , Animals , Animals, Newborn , In Vitro Techniques , Insulin-Secreting Cells/metabolism , Male , Pancreas/growth & development , Pancreas/metabolism , Rats , Rats, Wistar
4.
Diabetes Obes Metab ; 10 Suppl 4: 54-62, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18834433

ABSTRACT

Type 1 and type 2 diabetes have often been presented as disease forms that profoundly differ in the presence and pathogenic significance of a reduced beta-cell mass. We review evidence indicating that the beta-cell mass in type 1 diabetes is usually not decreased by at least 90% at clinical onset, and remains often detectable for years after diagnosis at age above 15 years. Clinical and experimental evidence also exists for a reduced beta-cell mass in type 2 diabetes where it can be the cause for and/or the consequence of dysregulated beta-cell functions. With beta-cell mass defined as number of beta-cells, these views face the limitation of insufficient data and methods for human organs. Because beta-cells can occur under different phenotypes that vary with age and with environmental conditions, we propose to use the term functional beta-cell mass as an assessment of a beta-cell population by the number of beta-cells and their phenotype or functional state. Assays exist to measure functional beta-cell mass in isolated preparations. We selected a glucose-clamp test to evaluate functional beta-cell mass in type 1 patients at clinical onset and in type 1 recipients following intraportal islet cell transplantation. Comparison of the data with those in non-diabetic controls helps targeting and monitoring of therapeutic interventions.


Subject(s)
Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/metabolism , Insulin-Secreting Cells/physiology , Islets of Langerhans Transplantation/physiology , Islets of Langerhans/metabolism , Adolescent , Adult , Blood Glucose/metabolism , Child , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 1/surgery , Diabetes Mellitus, Type 2/physiopathology , Female , Glucose Clamp Technique/methods , Humans , Insulin/therapeutic use , Islets of Langerhans/physiopathology , Male , Regeneration/drug effects , Treatment Outcome
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