COLOR III: a multicentre randomised clinical trial comparing transanal TME versus laparoscopic TME for mid and low rectal cancer

Total mesorectal excision (TME) is an essential component of surgical management of rectal cancer. Both open and laparoscopic TME have been proven to be oncologically safe. However, it remains a challenge to achieve complete TME with clear circumferential resections margin (CRM) with the conventional transabdominal approach, particularly in mid and low rectal tumours. Transanal TME (TaTME) was developed to improve oncological and functional outcomes of patients with mid and low rectal cancer.An international, multicentre, superiority, randomised trial was designed to compare TaTME and conventional laparoscopic TME as the surgical treatment of mid and low rectal carcinomas. The primary endpoint is involved CRM. Secondary endpoints include completeness of mesorectum, residual mesorectum, morbidity and mortality, local recurrence, disease-free and overall survival, percentage of sphincter-saving procedures, functional outcome and quality of life. A Quality Assurance Protocol including centralised MRI review, histopathology re-evaluation, standardisation of surgical techniques, and monitoring and assessment of surgical quality will be conducted.The difference in involvement of CRM between the two treatment strategies is thought to be in favour of the TaTME. TaTME is therefore expected to be superior to laparoscopic TME in terms of oncological outcomes in case of mid and low rectal carcinomas

Holomorphic Factorization for a Quantum Tetrahedron

We provide a holomorphic description of the Hilbert space H(j_1,..,j_n) of SU(2)-invariant tensors (intertwiners) and establish a holomorphically factorized formula for the decomposition of identity in H(j_1,..,j_n). Interestingly, the integration kernel that appears in the decomposition formula turns out to be the n-point function of bulk/boundary dualities of string theory. Our results provide a new interpretation for this quantity as being, in the limit of large conformal dimensions, the exponential of the Kahler potential of the symplectic manifold whose quantization gives H(j_1,..,j_n). For the case n=4, the symplectic manifold in question has the interpretation of the space of "shapes" of a geometric tetrahedron with fixed face areas, and our results provide a description for the quantum tetrahedron in terms of holomorphic coherent states. We describe how the holomorphic intertwiners are related to the usual real ones by computing their overlap. The semi-classical analysis of these overlap coefficients in the case of large spins allows us to obtain an explicit relation between the real and holomorphic description of the space of shapes of the tetrahedron. Our results are of direct relevance for the subjects of loop quantum gravity and spin foams, but also add an interesting new twist to the story of the bulk/boundary correspondence.Comment: 45 pages; published versio

Local recurrence at the site of the Lone Star device through implantation of exfoliated cells during local excision for early rectal cancer:A case report

Introduction: Invasive procedures for colorectal cancer can cause iatrogenic tumor cell seeding. Implantation of these exfoliated cells in the surrounding tissue can result in locoregional cancer recurrence. This has been described in endoscopic procedures and major surgical resections, however recurrence in iatrogenic lesions of the anal canal during minimal invasive rectal surgery has not been shown in literature yet. This is the first reported case of recurrent rectal cancer that developed into an anal metastasis at the site where hooks of the Lone Star Retractor disrupted the epithelial lining of the anal canal during a local excision of early rectal cancer using TAMIS. Presentation of case: A 57 year old male was diagnosed with a high risk early stage rectal adenocarcinoma. He was treated with transanal minimally invasive surgery (TAMIS) with the use of a Lone Star retractor and he received subsequent chemo-radiotherapy. 23 months later the patient developed a bleeding mass bulging out of the anus. A true cut and incision biopsy was performed and the pathology report revealed localization of adenocarcinoma at the anal canal which was similar to the earlier diagnosed rectal carcinoma. The patient underwent an abdominal perineal resection and left-sided lymph node dissection. Discussion and conclusion: This shows that local recurrence through implantation of exfoliated tumor cells can occur in iatrogenic lesions of the anal canal not only in major but also in minimal invasive rectal surgery. Careful tissue handling and rectal washout may reduce the chance of this implantation metastasis.</p

Local recurrence at the site of the Lone Star device through implantation of exfoliated cells during local excision for early rectal cancer:A case report

Introduction: Invasive procedures for colorectal cancer can cause iatrogenic tumor cell seeding. Implantation of these exfoliated cells in the surrounding tissue can result in locoregional cancer recurrence. This has been described in endoscopic procedures and major surgical resections, however recurrence in iatrogenic lesions of the anal canal during minimal invasive rectal surgery has not been shown in literature yet. This is the first reported case of recurrent rectal cancer that developed into an anal metastasis at the site where hooks of the Lone Star Retractor disrupted the epithelial lining of the anal canal during a local excision of early rectal cancer using TAMIS. Presentation of case: A 57 year old male was diagnosed with a high risk early stage rectal adenocarcinoma. He was treated with transanal minimally invasive surgery (TAMIS) with the use of a Lone Star retractor and he received subsequent chemo-radiotherapy. 23 months later the patient developed a bleeding mass bulging out of the anus. A true cut and incision biopsy was performed and the pathology report revealed localization of adenocarcinoma at the anal canal which was similar to the earlier diagnosed rectal carcinoma. The patient underwent an abdominal perineal resection and left-sided lymph node dissection. Discussion and conclusion: This shows that local recurrence through implantation of exfoliated tumor cells can occur in iatrogenic lesions of the anal canal not only in major but also in minimal invasive rectal surgery. Careful tissue handling and rectal washout may reduce the chance of this implantation metastasis.</p

Best Evidence for Each Surgical Step in Minimally Invasive Right Hemicolectomy:A Systematic Review

OBJECTIVE: The aim of this study was to systematically review the literature for each surgical step of the minimally invasive right hemicolectomy (MIRH) for non-locally advanced colon cancer, to define the most optimal procedure with the highest level of evidence.BACKGROUND: High variability exists in the way MIRH is performed between surgeons and hospitals, which could affect patients' postoperative and oncological outcomes.METHODS: A systematic search using PubMed was performed to first identify systematic reviews and meta-analyses, and if there were none then landmark papers and consensus statements were systematically searched for each key step of MIRH. Systematic reviews were assessed using the AMSTAR-2 tool, and selection was based on highest quality followed by year of publication.RESULTS: Low (less than 12 mmHg) intra-abdominal pressure (IAP) gives higher mean quality of recovery compared to standard IAP. Complete mesocolic excision (CME) is associated with lowest recurrence and highest 5-year overall survival rates, without worsening short-term outcomes. Routine D3 versus D2 lymphadenectomy showed higher LN yield, but more vascular injuries, and no difference in overall and disease-free survival. Intracorporeal anastomosis is associated with better intra- and postoperative outcomes. The Pfannenstiel incision gives the lowest chance of incisional hernias compared to all other extraction sites.CONCLUSION: According to the best available evidence, the most optimal MIRH for colon cancer without clinically involved D3 nodes entails at least low IAP, CME with D2 lymphadenectomy, an intracorporeal anastomosis and specimen extraction through a Pfannenstiel incision.</p

Best Evidence for Each Surgical Step in Minimally Invasive Right Hemicolectomy:A Systematic Review

OBJECTIVE: The aim of this study was to systematically review the literature for each surgical step of the minimally invasive right hemicolectomy (MIRH) for non-locally advanced colon cancer, to define the most optimal procedure with the highest level of evidence.BACKGROUND: High variability exists in the way MIRH is performed between surgeons and hospitals, which could affect patients' postoperative and oncological outcomes.METHODS: A systematic search using PubMed was performed to first identify systematic reviews and meta-analyses, and if there were none then landmark papers and consensus statements were systematically searched for each key step of MIRH. Systematic reviews were assessed using the AMSTAR-2 tool, and selection was based on highest quality followed by year of publication.RESULTS: Low (less than 12 mmHg) intra-abdominal pressure (IAP) gives higher mean quality of recovery compared to standard IAP. Complete mesocolic excision (CME) is associated with lowest recurrence and highest 5-year overall survival rates, without worsening short-term outcomes. Routine D3 versus D2 lymphadenectomy showed higher LN yield, but more vascular injuries, and no difference in overall and disease-free survival. Intracorporeal anastomosis is associated with better intra- and postoperative outcomes. The Pfannenstiel incision gives the lowest chance of incisional hernias compared to all other extraction sites.CONCLUSION: According to the best available evidence, the most optimal MIRH for colon cancer without clinically involved D3 nodes entails at least low IAP, CME with D2 lymphadenectomy, an intracorporeal anastomosis and specimen extraction through a Pfannenstiel incision.</p

Allogeneic NK cells induce the <i>in vitro</i> activation of monocyte-derived and conventional type-2 dendritic cells and trigger an inflammatory response under cancer-associated conditions

Natural killer (NK) cells are innate lymphocytes capable to recognize and kill virus-infected and cancer cells. In the past years, the use of allogeneic NK cells as anti-cancer therapy gained interest due to their ability to induce graft-versus-cancer responses without causing graft-versus-host disease and multiple protocols have been developed to produce high numbers of activated NK cells. While the ability of these cells to mediate tumor kill has been extensively studied, less is known about their capacity to influence the activity of other immune cells that may contribute to a concerted anti-tumor response in the tumor microenvironment (TME). In this study, we analyzed how an allogeneic off-the-shelf cord blood stem cell-derived NK-cell product influenced the activation of dendritic cells (DC). Crosstalk between NK cells and healthy donor monocyte-derived DC (MoDC) resulted in the release of IFNγ and TNF, MoDC activation, and the release of the T-cell-recruiting chemokines CXCL9 and CXCL10. Moreover, in the presence of prostaglandin-E2, NK cell/MoDC crosstalk antagonized the detrimental effect of IL-10 on MoDC maturation leading to higher expression of multiple (co-)stimulatory markers. The NK cells also induced activation of conventional DC2 (cDC2) and CD8 + T cells, and the release of TNF, GM-CSF, and CXCL9/10 in peripheral blood mononuclear cells of patients with metastatic colorectal cancer. The activated phenotype of MoDC/cDC2 and the increased release of pro-inflammatory cytokines and T-cell-recruiting chemokines resulting from NK cell/DC crosstalk should contribute to a more inflamed TME and may thus enhance the efficacy of T-cell-based therapies.</p

Supercoherent States, Super K\"ahler Geometry and Geometric Quantization

Generalized coherent states provide a means of connecting square integrable representations of a semi-simple Lie group with the symplectic geometry of some of its homogeneous spaces. In the first part of the present work this point of view is extended to the supersymmetric context, through the study of the OSp(2/2) coherent states. These are explicitly constructed starting from the known abstract typical and atypical representations of osp(2/2). Their underlying geometries turn out to be those of supersymplectic OSp(2/2) homogeneous spaces. Moment maps identifying the latter with coadjoint orbits of OSp(2/2) are exhibited via Berezin's symbols. When considered within Rothstein's general paradigm, these results lead to a natural general definition of a super K\"ahler supermanifold, the supergeometry of which is determined in terms of the usual geometry of holomorphic Hermitian vector bundles over K\"ahler manifolds. In particular, the supergeometry of the above orbits is interpreted in terms of the geometry of Einstein-Hermitian vector bundles. In the second part, an extension of the full geometric quantization procedure is applied to the same coadjoint orbits. Thanks to the super K\"ahler character of the latter, this procedure leads to explicit super unitary irreducible representations of OSp(2/2) in super Hilbert spaces of $L^2$ superholomorphic sections of prequantum bundles of the Kostant type. This work lays the foundations of a program aimed at classifying Lie supergroups' coadjoint orbits and their associated irreducible representations, ultimately leading to harmonic superanalysis. For this purpose a set of consistent conventions is exhibited.Comment: 53 pages, AMS-LaTeX (or LaTeX+AMSfonts