Curative Laparoscopic Resection for Pancreatic Neoplasms: A Critical Analysis from a Single Institution

Laparoscopic pancreatic surgery (LPS) has seen significant development but much of the knowledge refers to small and benign pancreatic tumors. This study aims to evaluate the feasibility, safety, and long-term outcome of the laparoscopic approach in patients with benign, premalignant, and overt malignant lesions of the pancreas. This study, currently, is the largest single center experience worldwide. One hundred twenty-three consecutive patients underwent laparoscopic pancreatic surgery from April 1998 to April 2007, 20 patients with cysts or pseudocysts for acute and chronic pancreatitis, laparoscopic pancreatic drainage was performed, and were excluded from the analysis. The 103 patients were divided based on preoperative diagnosis: group I, inflammatory tumors for chronic pancreatitis (eight patients); group II, cystic pancreatic neoplasms (29 patients); group III, intraductal papillary mucinous neoplasms (10 patients); group IV, neuroendocrine pancreatic tumors (NETs) (43 patients); and group V ductal adenocarcinoma (13 patients). The median tumor size was 5.3 cm. Pathologic data include R ₀ or R ₁ resection (transection margins on the specimen were inked). Perioperative data, postoperative complications, and resection modalities were compared using statistical analysis. Long-term outcomes were analysed by tumor recurrence and patient survival. The overall conversion rate was 7%. Laparoscopic distal pancreatic resection was performed in 82 patients (79.6%). Laparoscopic spleen-preserving distal pancreatectomy (Lap SPDP) was performed in 52 patients (63.7%), but with splenic vessels preservation in 22% and without splenic vessels preservation in 41.5%. Laparoscopic en-bloc splenopancreatectomy (Lap SxDP) was performed in 30 patients (36.6%) and laparoscopic enucleation (Lap En) in 20 patients (19.4%). There was no mortality. The overall complication rate was 25.2, 16.7, and 40% after Lap SPDP, Lap SxDP, and Lap En, respectively. The overall morbidity rate was significantly higher (p > 0.05) in the group of Lap SPDP without splenic vessels preservation comparing with Lap SPDP with splenic vessels preservation because of the occurrence of splenic complications (20.6%). The overall pancreatic fistulas was 7.7, 10, and 35% after Lap SPDP, Lap SxDP, and Lap En, respectively; the severity of fistula was significantly higher in the Lap En group (p > 0.05). The mean hospital stay was within 1 week in all groups, except in the group of ductal adenocarcinoma, which is 8 days. In this series, 27 patients (26.2%) had malignant disease. R ₀ resection was achieved in 90% of ductal adenocarcinoma and 100% for other malignant tumors. The median survival for ductal adenocarcinoma patients was 14 months. This series demonstrates that LPS is feasible and safe in benign-appearing and malignant lesions of the pancreas.     

Transmission of HIV-1 infection between trophoblast placental cells and T-cells take place via an LFA-1-mediated cell to cell contact

HIV-1 vertical transmission is thought to mainly take place by virus crossing the placental barrier. However, the mechanism by which HIV-1-infects placental cells remains to be elucidated. We have found that purified cytotrophoblasts as well as trophoblastic cell lines are susceptible to infection by different HIV-1 isolates as detected by DNA-PCR and release of infectious virus, although with very low efficiency. Purified trophoblast or trophoblastic cell lines express low levels of chemokine receptors CCR-5 and CXCR-4 but not CD4 on the cell surface. To test if those molecules were used as receptors for HIV-1 infection, placental cells were pretreated with antibodies to CD4, CC-chemokines, C-X-C chemokines. None of those treatments inhibited HIV-1 infection. In contrast, we have found that HIV-1 infection of placental cells was increased in cocultures of infected T-cell blasts and placental cells. More interestingly, antibodies to beta(2) integrins and to LFA-1 were able to significantly block infection of placental cells. Cell surface expression of ICAM-1, an adhesion molecule involved in attachment of leukocytes to placenta, was upregulated in HIV-1-infected placental cells. Placental cells were able to transfer HIV-1 infection to T-cell blasts. This transmission required cell to cell contact and was also inhibited by anti-LFA-1 antibodies. In summary our results suggest that placental trophoblast could be infected by HIV-1 by a mechanism involving T cell to placental contact. Moreover, placental infection enhanced ICAM-1 expression and leukocyte adherence, an event which was required to transfer HIV-1 infection to T cells. This provides an explanation of the virus passing through the placental barrier during in utero HIV-1 vertical transmission.     

Pregnancy with frozen-thawed and fresh testicular biopsy after motile and immotile sperm microinjection, using the mechanical touch technique to assess viability

BACKGROUND: There are few reports of pregnancy using immotile sperm, and none using a purely mechanical assessment of viability. METHODS: In this pilot study, we retrospectively analysed 66 cycles in 61 patients with determinant male factor, recording rates of fertilization, implantation, normal pregnancy and take-home babies achieved with ICSI. Sperm selection was based on morphologically normal appearance under the inverted microscope. Viability of immotile spermatozoa was assessed by the mechanical touch technique to observe tail flexibility and tail shape recovery. RESULTS: Of 17 ICSI cycles using frozen-thawed testicular sperm, six microinjected with immotile and 11 with motile sperm, we achieved fertilization rates of 65.7 and 74.3%, respectively, and five pregnancies (two and three, respectively). Of 49 ICSI cycles using fresh testicular sperm, 10 microinjected with immotile and 39 with motile sperm, we achieved fertilization rates of 73.4 and 64.4%, respectively, and 12 pregnancies (three and nine, respectively). CONCLUSIONS: Immotile (fresh and frozen-thawed) testicular sperm of normal morphological appearance can be used to achieve clinical pregnancy with ICSI. Our results strongly suggest that immotile sperm viability can be assessed by the mechanical touch technique.     

Characterization of an Agarophyton chilense Oleoresin Containing PPARγ Natural Ligands with Insulin-Sensitizing Effects in a C57Bl/6J Mouse Model of Diet-Induced Obesity and Antioxidant Activity in Caenorhabditis elegans

The biomedical potential of the edible red seaweed Agarophyton chilense (formerly Gracilaria chilensis) has not been explored. Red seaweeds are enriched in polyunsaturated fatty acids and eicosanoids, which are known natural ligands of the PPARγ nuclear receptor. PPARγ is the molecular target of thiazolidinediones (TZDs), drugs used as insulin sensitizers to treat type 2 diabetes mellitus. Medical use of TZDs is limited due to undesired side effects, a problem that has triggered the search for selective PPARγ modulators (SPPARMs) without the TZD side effects. We produced Agarophyton chilense oleoresin (Gracilex^®), which induces PPARγ activation without inducing adipocyte differentiation, similar to SPPARMs. In a diet-induced obesity model of male mice, we showed that treatment with Gracilex^® improves insulin sensitivity by normalizing altered glucose and insulin parameters. Gracilex^® is enriched in palmitic acid, arachidonic acid, oleic acid, and lipophilic antioxidants such as tocopherols and β-carotene. Accordingly, Gracilex^® possesses antioxidant activity in vitro and increased antioxidant capacity in vivo in Caenorhabditis elegans. These findings support the idea that Gracilex^® represents a good source of natural PPARγ ligands and antioxidants with the potential to mitigate metabolic disorders. Thus, its nutraceutical value in humans warrants further investigation.     

Adult pancreatic tissue fate after pancreatic fragment autotransplantation into the spleen of the pancreatectomized dog

As far as we know, after adult enzyme-digested pancreatic fragment autotransplantation, the fate of the inoculated pancreatic tissue has never been reported and the hypothetic engrafted islet mass growth by mitotic division or by a true islet neogenesis from ductular precursor cells has never been demonstrated. In dogs with total or near-total (90%) pancreatectomy that preserves the duodenum and the common bile duct, morphologic study of the pancreatic tissue inoculated into the spleen has demonstrated an exuberant ductular-acinar-islet regenerative process, with progressive cystic degeneration of the newly formed ductular-acinar structures occurring simultaneously with the selective survival and growing predominance of extraductal tissue scattered as distinct islets, clusters of islet cells, or single islet cells. In addition to the B, A₂, and D cell types of the normal adult dog islet, we have also seen a peculiar ultrastructural pleomorphism of the insular B cells, frequently combined with their ductular or glandular arrangement in maturing islets. Rare or never before reported islet cell types in the adult dog's islets (G cells, mixed endocrine cells of the A₂-D, D-B, and A₂-B types, and mixed acinar-islet cells of the D-acinar type) were also putatively identified. Using light microscopy we have identified many mitotic figures on ductular and centroacinar cells in ductules and ductular-acinar structures. Moreover, we have ultrastructurally characterized a pluriendocrine nesidioblastic process identified in the most common islet cell types (B, A₂, D) and in G cells and mixed acinar islet cells of the B-ac, A₂-ac, D-ac, F-ac, and G-ac types as well as intermediary or transitional cells of incipient ductular-acinar, ductular-islet, and ductular-acinar-islet differentiation. The characteristics of the extraductal islet tissue and the exuberant nesidioblastic process have demonstrated neogenesis of islets and islet cells from precursor ductular cells at several points after the autotransplant, and we suggest that this mechanism may be of fundamental importance for the engrafted islet mass growth—keeping in mind the age of the pancreatic tissue donors and the life-span of the juvenile diabetic recipient receiving the transplant. This evolution has taken place simultaneously with the progressive rarefaction of the regenerated ductular-acinar structures definitively deprived of an intestinal drainage route by virtue of their heterotopic location.

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Resumen Hasta donde sabemos, después del autotrasplante de fragmentos pancreáticos enzimáticamente digeridos, no se ha reportado la evolución final del tejido pancreático inoculado; y el crecimiento de la hipotética masa del tejido insular trasplantado, por división mitótica a por verdadera neogénesis de islotes a partir de células ductales precursoras, nunca ha sido demostrado.En el perro sometido a pancreatectomía total o casi total (90%) con preservación del duodeno y del colédoco, el estudio morfológico del tejido pancreático inoculado en el bazo ha demostrado un exuberante proceso regenerativo de células dactulares-acinares-insulares-, con progresiva degeneración quística de las neoformadas estructuras ductulares-acinares simultánea con la sobrevida selectiva y el crecimiento predominante del tejido insular a partir de ductos, y de células insulares aisladas o en grupos. Además de los tipos B, A2 y D de las células insulares del perro, también hemos podido identificar un peculiar pleomorfismo ultraestructural de las células insulares B, con frecuencia combinado con su ordenación ductular o glandular en los islotes en vía de maduración. También fueron putativamente identificados tipos celulares muy raros o nunca reportados en los islotes caninos (células G, células endocrinas mixtas de los tipos A2/D, D/B, Y A2/B, y células mixtas acinares e insulares del tipo D-acinar). En las estructuras ductulares y ductular-acinares hemos podido reconocer muchas figuras mitóticas en células ductulares y centroacinares mediante microscopia de luz y un proceso pluriendocrino nesidio-blástico con la identificación netraestructural de los tipos más comunes de células insulares (B, A2, D), pero también células G y células mixtas acinar-insulares de los tipos B-ac, A2-ac, D-ac, F-ac y G-ac, así como células intermedias o transicionales de la incipiente diferenciación ductular-acinar, ductular-insular, y ductular-acinar-insular. Las caracteristicas del tejido insular originado en ductos y el exuberante proceso nesidioblástico han demostrado la neogénesis de células insulares y de islotes a partir de células precursoras en diferentes períodos después del autotrasplante; nosotros sugerimos que este mecanismo puede ser de importancia fundamental para el crecimiento de la masa insular trasplantada, teniendo en cuenta la edad de los donantes de tejido pancreático y la duración de la vida de los recipientes diabéticos y juveniles. Esta evolución ha cursado con una progresiva rarefacción de las estructuras ductulares-acinares, definitivamente desprovista de una vía de drenaje intestinal debido a su ubicación heterotópica.

     

Effect of reminder cards on compliance with antihypertensive medication

Objective Poor compliance to antihypertensive medications has been identified as a primary cause of uncontrolled blood pressure (BP), with consequent increases in hypertension‐related morbidity and mortality. Therefore, any measure known to improve compliance should be encouraged. This study assessed the impact of reminder cards on compliance to antihypertensive therapy. Method A field trial was undertaken in pharmacies located in the districts of Lisbon and Porto. Eligible participants comprised those aged 30–74 years, prescribed an angiotensin‐converting enzyme inhibitor (ACEI) in monotherapy, and taken on a once‐daily regimen. Patients were allocated to control group (CG) or intervention group (IG), the latter being provided with a reminder card, an alarm‐type device due to remind the patient of the time to take his medication. Patients were monitored monthly during 3 months for compliance and blood pressure control. Key findings Seventy‐one patients participated in the study (intervention: 35; control group: 36). Compliance was similar between the groups in the first 2 months of follow‐up (97.1% IG vs 94.9% CG at first follow‐up and 97.5% IG vs 94.2% CG at second follow‐up) and higher in the intervention group at the end of the study (97.3% IG vs 87.3% CG; P = 0.011). There were no mean blood pressure differences between compliant and non‐compliant subjects at the end of the study (P value for differences in systolic BP (P_syst) = 0.580; and P value for differences in diastolic BP (P_dlast) = 0.175). Conclusion This small‐scale study indicates a possible positive impact on patients' compliance resulting from the use of reminder cards. However, this needs confirming in larger scale studies with longer monitoring periods.     

Colorectal cancer mortality and industrial pollution in Spain

ABSTRACT: BACKGROUND: Records kept as a result of the implementation of Integrated Pollution Prevention and Control (IPPC) and the European Pollutant Release and Transfer Register (E-PRTR) constitute a public inventory of industries, created by the European Commission, which is a valuable resource for monitoring industrial pollution. Our objective is to ascertain whether there might be excess colorectal cancer mortality among populations residing in the vicinity of Spanish industrial installations that are governed by the IPPC Directive and E-PRTR Regulation and report their emissions to air. METHODS: An ecological study was designed to examine colorectal cancer mortality at a municipal level (8098 Spanish towns), over the period 1997-2006. We conducted an exploratory "near vs. far" analysis to estimate the relative risks (RR) of towns situated at a distance of less than 2 km from industrial installations. The analysis was repeated for each of the 24 industrial groups. RR and their 95 % credible/confidence intervals (95%CI) were estimated on the basis of Poisson regression models, using two types of modelling: a) the conditional autoregressive Bayesian model proposed by Besag, York and Mollie, with explanatory variables; and b) a mixed regression model. Integrated nested Laplace approximations were used as a Bayesian inference tool. RESULTS: Statistically significant RRs were detected in the vicinity of mining industry (RR 1.258; 95%CI 1.082 - 1.463), paper and wood production (RR 1.071; 95%CI 1.007 - 1.140), food and beverage sector (RR 1.069; 95%CI 1.029 - 1.111), metal production and processing installations (RR 1.065; 95 % CI 1.011 - 1.123) and ceramics (RR 1.050 ; 95%CI 1.004 - 1.099). CONCLUSIONS: Given the exploratory nature of this study, it would seem advisable to check in other countries or with other designs, if the proximity of industries that emit pollutants into the air could be an added risk factor for colorectal cancer mortality. Nevertheless, some of the differences between men and women observed in the analyses of the industrial groups suggest that there may be a component of occupational exposure, little-studied in the case of cancers of the digestive system.