Complexes of singly or doubly deprotonated indigo (H2Ind) with one or two Ru(pap)22+ fragments (pap = 2-phenylazopyridine) have been characterized experimentally molecular structure, voltammetry, ...electron paramagnetic resonance (EPR), and UV–vis–near-IR spectroelectrochemistry and by time-dependent density functional theory calculations. The compound Ru(pap)2(HInd–)ClO4 (1ClO4) was found to contain an intramolecular NH---O hydrogen bond, whereas {Ru(pap)2}2(μ-Ind2–)(ClO4)2 (2(ClO4)2), isolated as the meso diastereoisomer with near-IR absorptions at 1162 and 991 nm, contains two metals bridged at 6.354 Å distance by the bischelating indigo dianion. The spectroelectrochemical study of multiple reversible reduction and oxidation processes of 2 n (n = 4+, 3+, 2+, 1+, 0, 1–, 2–, 3–, 4−) reveals the stepwise addition of electrons to the terminal π-accepting pap ligands, whereas the oxidations occur predominantly at the anionic indigo ligand, producing an EPR-identified indigo radical intermediate and revealing the suitability of deprotonated indigo as a σ- and π-donating bischelating bridge.
This meta-analysis sought to evaluate the potential benefits and harms of laparoscopic gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer versus open surgery.
A comprehensive ...search for randomized controlled studies that compared laparoscopic versus open gastrectomy with D2 lymphadenectomy for locally advanced gastric cancer published until December 31, 2018, was conducted. Operative outcomes, early postoperative outcomes, and long-term results were analyzed using a random effects model.
Five randomized controlled trials containing a collective total of 2157 patients were included. In comparison with open surgery, laparoscopic gastrectomy for locally advanced gastric cancer showed similar risks of short-term mortality and serious adverse events within 30 days after surgery. Regarding intraoperative outcomes, operative time was increased for the laparoscopic approach, whereas the estimated intraoperative blood loss tended to be less. However, the amount of evidence was low for most outcomes. In addition, the results for the length of hospital stay and time to first flatus did not show statistically significant differences. The number of harvested lymph nodes and compliance with D2 lymphadenectomy did not significantly differ between the two groups, indicating oncological equivalence of both approaches. However, long-term oncological results could not be evaluated due to a lack of relevant data in four of the trials.
Laparoscopic gastrectomy with D2 lymphadenectomy can be performed with equivalent overall short-term morbidity and mortality versus the open approach for locally advanced gastric cancer. However, further well-designed randomized controlled trials are necessary to assess the possible advantages and risks of the laparoscopic approach as well as the long-term results.
Robotic surgery is increasingly gaining importance. While initial results suggest an advantage of the robotic over the minimally invasive approach in patients with gastric cancer, definitive proof of ...its superiority has yet to be provided. There are numerous approaches to recreate a gastric reservoir after a total gastrectomy. However, a major disadvantage of most conventional reconstructions are long term effects such as dumping syndrome, afferent loop syndrome and poor nutrition intake with severe impact on the patient quality of life. The jejunal pouch reconstruction is a beneficial reconstruction, which provides a larger reservoir capacity after gastrectomy and prevents anastomotic stenosis and dumping syndrome. The completely intercorporeal approach with a Pfannenstiel incision instead of an unfavorable midline incision can potentially decrease delayed complications such as incision hernias. With the increased deployment of robotic surgery, a complete intercorporeal reconstruction is now possible without major increase in operating time or further technical weak points. We provide for the first time a detailed technical explanation of the completely intercorporeal robotic jejunal pouch reconstruction after gastrectomy.
Opinion statement
The surgical treatment of gastric carcinoma has progressed significantly in the past few decades. A major milestone was the establishment of multimodal therapies for locally ...advanced tumours. Improvements in the technique of endoscopic resection have supplanted surgery in the early stages of many cases of gastric cancer. In cases in which an endoscopic resection is not possible, surgical limited resection procedures for the early stages of carcinoma are an equal alternative to gastrectomy in the field of oncology. Proximal gastrectomy is extensively discussed in this context. Whether proximal gastrectomy leads to a better quality of life and better nutritional well-being than total gastrectomy depends on the reconstruction chosen. The outcome cannot be conclusively assessed at present. For locally advanced stages, total or subtotal gastrectomy with D2 lymphadenectomy is now the global standard. A subtotal gastrectomy requires sufficiently long tumour-free proximal resection margins. Recent data indicate that proximal margins of at least 3 cm for tumours with an expansive growth pattern and at least 5 cm for those with an infiltrative growth pattern are sufficient. The most frequently performed reconstruction worldwide following gastrectomy is the Roux-en-Y reconstruction. However, there is evidence that pouch reconstruction is superior in terms of quality of life and nutritional well-being. Oncological gastric surgery is increasingly being performed laparoscopically. The safety and oncological equivalency were first demonstrated for early carcinomas and then for locally advanced tumours, by cohort studies and RCTs. Some studies suggest that laparoscopic procedures may be advantageous in early postoperative recovery. Robotic gastrectomy is also increasing in use. Preliminary results suggest that robotic gastrectomy may have added value in lymphadenectomy and in the early postoperative course. However, further studies are needed to substantiate these results. There is an ongoing debate about the best treatment option for gastric cancer with oligometastatic disease. Preliminary results indicate that certain patient groups could benefit from resection of the primary tumour and metastases following chemotherapy. However, the exact conditions in which patients may benefit have yet to be confirmed by ongoing trials.
Immune checkpoint therapy (ICT) has shown promising potential in the treatment of multiple solid tumors. However, the role of ICT in pancreatic ductal adenocarcinoma (PDAC) remains limited. Patterns ...of immune checkpoints (ICs) in PDAC represent the basis for establishing a potent ICT. The aim of this study is to create a profile of IC expression and its prognostic relevance in cancer cells of PDAC. Therefore, tumor cells from peripheral and central tissue microarray (TMA) spots from histologically confirmed PDAC of 68 patients after tumor resection were investigated in terms of expressions of TIM3, IDO, B7H4, LAG3, VISTA, and PD-L1 using immunohistochemistry. The presence of the respective ICs was compared to overall survival (OS). The presence of VISTA and PD-L1 significantly correlates with shorter OS (median OS: 22 months vs. 7 months and 22 months vs. 11 months, respectively,
< 0.05). For the presence of TIM3, IDO, B7H4, and LAG3, no difference in OS was observed (
> 0.05). The analysis of OS of combined subgroups for VISTA and PD-L1 (VISTA and PD-L1 neg., VISTA pos. and PD-L1 neg., VISTA neg. and PD-L1 pos., and VISTA and PD-L1 pos.) yielded overall statistical significance difference (
= 0.02). These results suggest that the presence of VISTA and PD-L1 is of prognostic relevance and potentially qualifies them as targets for ICT.
Colorectal cancer is one of the most common malignancies worldwide. There is an urgent need for simple and fast methods to improve tumor detection in the diagnostic and intraoperative setting to ...avoid complications and provide objective information in distinguishing malignant and benign colorectal tissue. Optical spectroscopy methods have recently shown a great potential for this discrimination in different organs.
In this pilot study, fluorescence emission spectra (excitation: 473 nm) and diffuse reflectance spectra (DRS) of normal and tumor tissues from resected colorectal cancer specimen were measured using fiber optical probes in an ex vivo setting, and the data were subjected to multivariate analysis.
Substantial spectral differences were found in the fluorescence and DRS spectra of colorectal cancer tissue in comparison to benign tissue. The diagnostic potential of a multimode optical system combining both spectroscopic methods was investigated by mathematical combination. Compared with the individual techniques, a higher sensitivity of the joint DRS-fluorescence optical system in the discrimination between malignant and benign colorectal tissue could be observed.
In the pilot study presented herein, a quick and reliable method to differentiate malignant and benign colorectal tissue ex vivo with different spectroscopic techniques using spectral fiber probes could be established. Joint fluorescence and near-infrared spectroscopy had a higher sensitivity in tissue discrimination and showed to be a promising combination of two spectroscopic methods. Further studies using the synergic effect of fluorescence and DRS spectroscopy are needed to transfer these findings into the in vivo situation.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. TRAIL has historically been distinct from the Fas ligand and TNFα in terms of selective ...apoptosis induction in tumor cells and has a nearly non-existent systemic toxicity. Consequently, in the search for an ideal drug for tumor therapy, TRAIL rapidly drew interest, promising effective tumor control with minimal side effects. However, euphoria gave way to disillusionment as it turned out that carcinoma cells possess or can acquire resistance to TRAIL-induced apoptosis. Additionally, studies on models of inflammation and autoimmunity revealed that TRAIL can influence immune cells in many different ways. While TRAIL was initially found to be an important player in tumor defense by natural killer cells or cytotoxic T cells, additional effects of TRAIL on regulatory T cells and effector T cells, as well as on neutrophilic granulocytes and antigen-presenting cells, became focuses of interest. The tumor-promoting effects of these interactions become particularly important for consideration in cases where tumors are resistant to TRAIL-induced apoptosis. Consequently, murine models have shown that TRAIL can impair the tumor microenvironment toward a more immunosuppressive type, thereby promoting tumor growth. This review summarizes the current state of knowledge on TRAIL's interactions with the immune system in the context of cancer.
Lymph node staging of ductal adenocarcinoma of the pancreatic head (PDAC) by cross-sectional imaging is limited. The aim of this study was to determine the diagnostic accuracy of expanded criteria in ...nodal staging in PDAC patients.
Sixty-six patients with histologically confirmed PDAC that underwent primary surgery were included in this retrospective IRB-approved study. Cross-sectional imaging studies (CT and/or MRI) were evaluated by a radiologist blinded to histopathology. Number and size of lymph nodes were measured (short-axis diameter) and characterized in terms of expanded morphological criteria of border contour (spiculated, lobulated, and indistinct) and texture (homogeneous or inhomogeneous). Sensitivities and specificities were calculated with histopathology as a reference standard.
Forty-eight of 66 patients (80%) had histologically confirmed lymph node metastases (pN+). Sensitivity, specificity, and Youden's Index for the criterion "size" were 44.2%, 82.4%, and 0.27; for "inhomogeneous signal intensity" 25.6%, 94.1%, and 0.20; and for "border contour" 62.7%, 52.9%, and 0.16, respectively. There was a significant association between the number of visible lymph nodes on preoperative CT and lymph node involvement (pN+, p = 0.031).
Lymph node staging in PDAC is mainly limited due to low sensitivity for detection of metastatic disease. Using expanded morphological criteria instead of size did not improve regional nodal staging due to sensitivity remaining low. Combining specific criteria yields improved sensitivity with specificity and PPV remaining high.
Crohn's disease (CD) is associated with changes in the microbiome. The role of these changes and their precise association with disease course and activity remain ambiguous. In this prospective ...single-center study, the mucosal microbiome of surgical CD and non-CD patients was compared at the time of surgery. Microbial analyses were individually performed for ileal and colonic tissue samples obtained during surgery using 16S-rRNA-gene amplicon sequencing. Three groups out of the 46 included patients were formed: 1) a study group of CD of patients who received ileocecal resection due to CD involvement (CD study, n=10); 2) a control group of non-CD of patients who received intestinal resection due to indications other than CD (non-CD control, n=27); and 3) a second control group of CD who underwent resection of the intestine not affected by CD (CD non-affected control, n=9). Species richness and Shannon diversity were not different between all formed groups and regions analyzed (p>0.05). Several significant taxonomic differences were seen at the phylum-, order-, and genus-levels between the formed groups, such as a decrease of
(phylum-level) and an increase of
and
(genus-level) in CD study - colon vs. the non-CD control - colon (p ≤ 0.05). The CD non-affected control presented the largest amount of differentially abundant taxa in comparison to the other groups. These results underline that CD is accompanied by changes in affected and non-affected intestinal regions compared to non-CD controls. This study contributes the mucosal microbiome of a well-defined subset of surgical CD patients without confounding aspects of the fecal microbiome or regional microbial differences to the existing literature.
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