Single-access transumbilical laparoscopic splenectomy using curved reusable instruments

Background The authors report a single-access transumbilical laparoscopic splenectomy (SATLS) performed with curved reusable instruments. Methods A 23-year-old female consulted for steroidresistant idiopathic thrombocytopenic purpura and clinical evidence of secondary Cushing syndrome. Preoperative workup showed a normal-sized spleen and thrombocytopenia. The umbilicus was incised and a purse-string suture was applied. A reusable 11-mm trocar was inserted for a 10-mm, 30° angled scope. Curved reusable instruments (Karl Storz-Endoskope, Tuttlingen, Germany) were advanced without trocars transumbilically. After opening the splenocolic and gastrosplenic ligaments, the main splenic artery and vein were dissected off at the level of the hilum, clipped with 5-mm clips introduced transumbilically, and sectioned. Posterior splenic attachments were freed at the hilum cranially and caudally. The spleen was finally retrieved transumbilically in a plastic bag. Results Addition of supplementary trocars or incisions was not necessary. Operative time was 180 min and final umbilical scar 16 mm. The patient was discharged on postoperative day 3, and after 6 months she was doing well. Conclusions SATLS was feasible and safe to be performed using curved reusable instruments. The curves of the instruments permitted the surgeon to work in an ergonomic position, without the instruments clashing thanks to the obtained triangulation. Since only reusable instruments were used, the cost of SATLS remained similar to that of standard laparoscopy. © Springer Science+Business Media, LLC 2011.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Low molecular weight heparin (LMWH) enhances immunotherapy (I) activity in pancreatic cancer cells.

50 Background: The aim is to investigate the effect of LMWH in combination with chemotherapy (C) and I in PC. Methods: BxPC-3, PANC-1, MIA PACA-2 cell lines were exposed in Tinzaparin (T) (0.5, 0.7, 0.9 μΜ) and/or 1 μΜ Nab-Paclitaxel (A) and/or 1 μΜ Gemcitabine (G) and/or 1 μΜ Nivolumab (NI), 1 μΜ, Pembrolizumab (PE) and 1 μΜ ipilimumab (IPI). Protein levels of VEGFR2, p-ERK1/2, p-AKT detected by Western blotting. Cells viability was measured through MTT assay. Results: Increasing protein levels of VEGFR2 was observed in all PC cell lines exposed to a constant dose of T and/or A,G. NI and PE +/- with IPI increased VEGFR2. In NI/PE+IPI+T scheme VEGFR2 levels were decreased (0.1-0.7 folds) in a dose dependent way in mtKRAS cells (PANC1, MIAPACA2). C (G or A) + I decreased VEGFR2 protein levels in mtKRAS cells PANC1 (0.1-0.4 folds), MIAPACA2 (0.1-0.6 folds) in double scheme. T+G/A+NI/PE+IPI scheme increased VEGFR2 in all PC cells. PANC-1 cells were decreased 40% in 0,7T+IPI+(NI or PE) after 48hours. The effect of these schemes on signaling pathways (MEK/EKR, AKT/mTOR) and apoptosis was identified through pERK1/2, pAKT, PARP, cl. caspase-3. Conclusions: These results identify the different effect of I alone or in combination with T and C in PC cells bearing mutant or wild type KRAS. Double or triple combination reduced VEGFR2 protein levels in mtKRAS and not in wtKRAS PC cells. The 0,7T+IPI+(NI or PE) combination decreases cell viability of PC cells through apoptosis. Testing of the combinatorial scheme T+chemo+IPI+(NI or PE) with PANC-1 PC in scid mice is ongoing and will be presented. NC:not changed, -:&lt;20% protein vs control, +:&gt;20% protein vs control, ++:&gt;40% protein vs control. [Table: see text] </jats:p

Combinatorial Treatment of Tinzaparin and Chemotherapy can Induce a Significant Antitumor Effectin Pancreatic Cancer

Abstract Background: Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor, with over 20% of patients suffering from venous thromboembolism during the disease. Thus, low-molecular-weight heparin (LMWH) such as Tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approach to treating highly malignant and refractory cancers such as PC, we hypothesized that Tinzaparin can augment the effectiveness of traditional chemotheurapeutic drugs and induce efficient antitumor activity.Methods: PANC-1 and MIAPaCa-2 were incubated alone or in combination with Tinzaparin, Nab-paclitaxel and gemcitabine. In vivo evaluation of these compounds was performed at NOD/SCID mouse using a model injected with PANC-1.Results: Tinzaparin enhances the anti-tumor effect of Nab-paclitaxel and gemcitabine in mtKRAS PC cell lines via apoptosis at in vitro experiments. The triple combination acts through induction of apoptosis, reduction of the proliferative potential and angiogenesis hence contributing to a decrease in tumor volume observed in vivo. Tumor reduction observed in mice receiving the triple combinational chemotherapy, was 74.5% compared to the control. The triple regime provided an extra 8.2% and 24.3% tumor reduction compared to the control and the double combination (gemcitambine plus Nab-paclitaxel) respectively.Conclusions: Combinatorial strategy can create novel therapeutic approaches for the treatment of patients with Pancreatic Cancer, achieving a better clinical outcome and prolonged survival. Further prospective randomized research is recommended and the investigation of various concentrations of Tinzaparin above of 150 UI/Kg, would potentially provide a valuable synergistic effect to the conventional therapeutic compounds.</jats:p

Combinatorial Treatment of Tinzaparin and Chemotherapy Can Induce a Significant Antitumor Effect in Pancreatic Cancer

Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor; thus, low-molecular-weight heparin (LMWH) such as tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approaches to treat highly malignant and refractory cancers such as PC, we hypothesized that tinzaparin can augment the effectiveness of traditional chemotherapeutic drugs and induce efficient antitumor activity. PANC-1 and MIAPaCa-2 were incubated alone or in combination with tinzaparin, nab-paclitaxel and gemcitabine. In vivo evaluation of these compounds was performed in a NOD/SCID mouse using a model injected with PANC-1. Tinzaparin enhances the anti-tumor effects of nab-paclitaxel and gemcitabine in mtKRAS PC cell lines via apoptosis in in vitro experiments. The triple combination power acts through the induction of apoptosis, reduction of the proliferative potential and angiogenesis; hence, contributing to a decrease in tumor volume observed in vivo. The triple regimen provided an extra 24.3% tumor reduction compared to the double combination (gemcitabine plus nab-paclitaxel). Combinatorial strategies can create novel therapeutic approaches for the treatment of patients with PC, achieving a better clinical outcome and prolonged survival. Further prospective randomized research is needed and the investigation of various concentrations of tinzaparin above 150 UI/Kg, would potentially provide a valuable synergistic effect to the conventional therapeutic compounds.</jats:p

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide. Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters. Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 per cent of patients (2901 of 4223). Major complication rates (Clavien–Dindo grade at least IIIa) were 24, 18, and 27 per cent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 per cent; however, it was 41 per cent in low-to-middle- compared with 19 per cent in very high-HDI countries. Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)