Retroperitoneal approach for robot-assisted partial nephrectomy: technique and early outcomes

ABSTRACT Objectives The aim of our study is to present early outcomes of our series of retroperitoneal-RAPN (Robot Assisted Partial Nephrectomy). Materials and methods From September 2010 until December 2015, we performed 81 RAPN procedures (44 at left kidney and 37 at right). Average size was 3cm (1-9). Average PADUA score 7.1 (5-10). Average surgical time (overall and only robot time), ischemia time, blood loss, pathological stage, complications and hospital stay have been recorded. Results All of the cases were completed successfully without any operative complication or surgical conversion. Average surgical time was 177 minutes (75-340). Operative time was 145 minutes (80-300), overall blood loss was 142cc (60-310cc). In 30 cases the pedicle was late clamped with an average ischemia time of 4 minutes (2-7). None of the patient had positive surgical margins at definitive histology (49pT1a, 12pT1b, 3pT2a, 2pT3a). Hospital stay was 3 days (2-7). Conclusions The retroperitoneal robotic partial nephrectomy approach is safe and allows treatment of even quite complex tumors. It also combines the already well known advantages guaranteed by the da Vinci® robotic surgical system, with the advantages of the retroperitoneoscopic approach.

Retroperitoneal approach for robot-assisted partial nephrectomy: technique and early outcomes.

OBJECTIVES: The aim of our study is to present early outcomes of our series of retroperitoneal-RAPN (Robot Assisted Partial Nephrectomy). MATERIALS AND METHODS: From September 2010 until December 2015, we performed 81 RAPN procedures (44 at left kidney and 37 at right). Average size was 3cm (1-9). Average PADUA score 7.1 (5-10). Average surgical time (overall and only robot time), ischemia time, blood loss, pathological stage, complications and hospital stay have been recorded. RESULTS: All of the cases were completed successfully without any operative complication or surgical conversion. Average surgical time was 177 minutes (75-340). Operative time was 145 minutes (80-300), overall blood loss was 142cc (60-310cc). In 30 cases the pedicle was late clamped with an average ischemia time of 4 minutes (2-7). None of the patient had positive surgical margins at definitive histology (49pT1a, 12pT1b, 3pT2a, 2pT3a). Hospital stay was 3 days (2-7). CONCLUSIONS: The retroperitoneal robotic partial nephrectomy approach is safe and allows treatment of even quite complex tumors. It also combines the already well known advantages guaranteed by the da Vinci® robotic surgical system, with the advantages of the retroperitoneoscopic approach.

A preclinical evaluation of pemetrexed and irinotecan combination as second-line chemotherapy in pancreatic cancer.

Gemcitabine (GEM)-based chemotherapy is regarded as the standard treatment of pancreatic adenocarcinoma, but yields a very limited disease control. Very few studies have investigated salvage chemotherapy after failure of GEM or GEM-containing chemotherapy and preclinical studies attempting to widen the therapeutic armamentarium, not including GEM, are warranted. MIA PaCa2, CFPAC-1 and Capan-1 pancreatic cancer cell lines were treated with GEM, fluouracil (5-FU), docetaxel (DCT), oxaliplatin (OXP), irinotecan (CPT-11), pemetrexed (PMX) and raltitrexed (RTX) as single agent. Pemetrexed, inducing apoptosis with IC50s under the Cmax in the three lines tested, appeared the most effective drug as single agent. Based on these results, schedule- and concentration-dependent drug interactions (assessed using the combination index) of PMX/GEM, PMX/DCT and PMX-CPT-11 were evaluated. The combinatory study clearly indicated the PMX and CPT-11 combination as the most active against pancreatic cancer. To confirm the efficacy of PMX-CPT-11 combination, we extended the study to a panel of 10 pancreatic cancer cell lines using clinically relevant concentrations (PMX 10 microM; CPT-11 1 microm). In eight of 10 lines, the PMX-CPT-11 treatment significantly reduced cell recovery and increased both the subG1 and caspase 3/7 fraction. After a 5-day wash out period, an increased fraction of subG1 and caspase3/7 persisted in PMX-CPT-11-pretreated cell lines and a significant reduction in the clonogenicity capacity was evident. Finally, in vivo, the PMX/CPT-11 combination showed the ability to inhibit xenograft tumours growth as second-line therapy after GEM treatment. The PMX and CPT-11 combination displays a strong schedule-independent synergistic cytotoxic activity against pancreatic cancer, providing experimental basis for its clinical testing as salvage chemotherapy in pancreatic cancer patients.

Application of triple immunohistochemistry to characterize amyloid plaque-associated inflammation in brains with Alzheimer's disease.

Inflammation, characterized by the presence of activated microglia and reactive astrocytes (gliosis), has been described in Alzheimer's disease (AD). We used our routine single immunohistochemical (IHC) labeling protocol to label amyloid plaques, an AD neuropathological hallmark, activated microglia, and reactive astrocytes in serial sections of AD hippocampus and entorhinal cortex of brain. Although most amyloid plaques were associated with inflammation throughout the serial sections, the extent of microglial and astrocytic activation varied among the amyloid plaques. We also observed a population of amyloid plaques that did not appear to coincide with immunolabeled microglia and astrocytes in serial sections, leading us to speculate that some amyloid plaques are not associated with inflammation. Because serial sectioning limited our ability to confirm these findings, we developed a triple IHC protocol to investigate the association of activated microglia and reactive astrocytes simultaneously with amyloid plaques in sections of AD brain entorhinal cortex and hippocampus. Unlike the potential errors of extrapolating descriptive information from routine IHC or histochemical staining methods on sectioned tissues, triple IHC allowed direct characterization of three differently colored antigens in situ. The success of the protocol depended on selection of distinguishable color schemes and resolution of other critical technical elements including the compatibility of the reagents and the sensitivity and sequence of the detection systems. The results of the triple IHC protocol clarified the spatial relation of microglia and astrocytes with amyloid plaques and provoked novel interpretations about the roles of inflammation in AD brain tissues. We categorized three distinct populations of amyloid plaques related to of inflammation: 1) Abeta42 immunoreactive (a marker of amyloid plaques) amyloid plaques without activated microglia or reactive astrocytes, 2) Abeta42-positive amyloid plaques with HLA-DR (a marker of microglia)-positive microglia and no astrocytes, 3) Abeta42-positive amyloid plaques among HLA-DR and GFAP (a marker of astrocytes) immunoreactive astrocytes. Most amyloid plaques had varying degrees of activated microglia and reactive astrocytes. Some of the amyloid plaques were not associated with inflammation while others were associated only with activated microglia. These findings suggest that amyloid plaques without associated inflammation may represent recently formed plaques and that the presence of amyloid plaques in AD brains may activate microglia prior to gliosis. Furthermore, the shape of the amyloid plaques may be altered subsequently from its typical spherical to an aspherical shape by the inflammatory cells.

Increased expression of serine palmitoyltransferase (SPT) in balloon-injured rat carotid artery.

The response to vascular injury is a complex wound healing response involving cell proliferation, migration, remodeling and inflammation. In the present studies we employed a rat balloon angioplasty model of vascular injury to investigate the potential role of sphingolipid signaling in the response to vascular injury. The enzyme serine palmitoyltransferase (SPT) catalyzes the first committed step in de novo sphingolipid biosynthesis. We observed marked upregulation of expression of both SPT subunits in actively proliferating cells in injured vessels. This enhanced SPT expression occurs in de-differentiated fibroblasts and proliferating vascular smooth muscle cells. The upregulation is particularly apparent in the proliferating luminal edge of the neointima and the adventitial de-differentiated fibroblasts and may serve as a hallmark of this process. The possible functional consequences of this enzyme upregulation and its role in the response to vascular injury are suggested but remain to be determined.