SciCombinator

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Concept: Lymph node

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Confocal laser endomicroscopy (pCLE) provides real-time histologic imaging of human tissues at a depth of 60-70 μm during endoscopy. pCLE of the extrahepatic bile duct after fluorescein injection demonstrated a reticular pattern within fluorescein-filled sinuses that had no known anatomical correlate. Freezing biopsy tissue before fixation preserved the anatomy of this structure, demonstrating that it is part of the submucosa and a previously unappreciated fluid-filled interstitial space, draining to lymph nodes and supported by a complex network of thick collagen bundles. These bundles are intermittently lined on one side by fibroblast-like cells that stain with endothelial markers and vimentin, although there is a highly unusual and extensive unlined interface between the matrix proteins of the bundles and the surrounding fluid. We observed similar structures in numerous tissues that are subject to intermittent or rhythmic compression, including the submucosae of the entire gastrointestinal tract and urinary bladder, the dermis, the peri-bronchial and peri-arterial soft tissues, and fascia. These anatomic structures may be important in cancer metastasis, edema, fibrosis, and mechanical functioning of many or all tissues and organs. In sum, we describe the anatomy and histology of a previously unrecognized, though widespread, macroscopic, fluid-filled space within and between tissues, a novel expansion and specification of the concept of the human interstitium.

Concepts: Lymph node, Liver, Human anatomy, Biology, Lymphatic system, Histology, Cancer, Anatomy

475

The increasing prevalence of tattoos provoked safety concerns with respect to particle distribution and effects inside the human body. We used skin and lymphatic tissues from human corpses to address local biokinetics by means of synchrotron X-ray fluorescence (XRF) techniques at both the micro (μ) and nano (ν) scale. Additional advanced mass spectrometry-based methodology enabled to demonstrate simultaneous transport of organic pigments, heavy metals and titanium dioxide from skin to regional lymph nodes. Among these compounds, organic pigments displayed the broadest size range with smallest species preferentially reaching the lymph nodes. Using synchrotron μ-FTIR analysis we were also able to detect ultrastructural changes of the tissue adjacent to tattoo particles through altered amide I α-helix to β-sheet protein ratios and elevated lipid contents. Altogether we report strong evidence for both migration and long-term deposition of toxic elements and tattoo pigments as well as for conformational alterations of biomolecules that likely contribute to cutaneous inflammation and other adversities upon tattooing.

Concepts: Heavy metal music, Tissue, Lymphatic system, Lymph node, Tattoo, Oxygen, Skin, Titanium dioxide

194

Subunit vaccines have been investigated in over 1000 clinical trials of cancer immunotherapy, but have shown limited efficacy. Nanovaccines may improve efficacy but have rarely been clinically translated. By conjugating molecular vaccines with Evans blue (EB) into albumin-binding vaccines (AlbiVax), here we develop clinically promising albumin/AlbiVax nanocomplexes that self-assemble in vivo from AlbiVax and endogenous albumin for efficient vaccine delivery and potent cancer immunotherapy. PET pharmacoimaging, super-resolution microscopies, and flow cytometry reveal almost 100-fold more efficient co-delivery of CpG and antigens (Ags) to lymph nodes (LNs) by albumin/AlbiVax than benchmark incomplete Freund’s adjuvant (IFA). Albumin/AlbiVax elicits ~10 times more frequent peripheral antigen-specific CD8+ cytotoxic T lymphocytes with immune memory than IFA-emulsifying vaccines. Albumin/AlbiVax specifically inhibits progression of established primary or metastatic EG7.OVA, B16F10, and MC38 tumors; combination with anti-PD-1 and/or Abraxane further potentiates immunotherapy and eradicates most MC38 tumors. Albumin/AlbiVax nanocomplexes are thus a robust platform for combination cancer immunotherapy.

Concepts: Antibody, Cytotoxic T cell, Cancer, Immunologic adjuvant, Lymph node, Vaccine, Immunology, Immune system

172

The aim of this study was to develop a new data-mining model to predict axillary lymph node (AxLN) metastasis in primary breast cancer. To achieve this, we used a decision tree-based prediction method-the alternating decision tree (ADTree).

Concepts: Chemotherapy, Cancer staging, Decision trees, Decision tree learning, Breast cancer, Lymph node, Metastasis, Cancer

169

BackgroundIpilimumab is a recently approved immunotherapy that has demonstrated an improvement in the overall survival (OS) of patients with metastatic melanoma. We report a single-institution experience in patients treated in a compassionate-use program.Patients and methodsIn this prospective study, patients were treated between June 2010 and September 2011. Inclusion criteria were a diagnosis of unresectable stage III or IV melanoma, at least one previous line of chemotherapy, and survival 12 weeks after the first perfusion. Four courses of ipilimumab were administered at a dose of 3 mg/kg every 3 weeks.ResultsSeventy-three patients were included. Median OS was 9.1 months (95% CI 6.4-11.3) from the start of ipilimumab. Immune-related adverse events were observed in 45 patients (62%), including 19 grade 3-4 events (26%). No drug-related death occurred. A lymphocyte count >1000/mm(3) at the start of the second course and an increase in the eosinophil count >100/mm(3) between the first and second infusions were correlated with an improved OS.ConclusionIpilimumab toxic effect is manageable in real life. Biological data such as lymphocyte and eosinophil counts at the time of the second ipilimumab infusion appear to be early markers associated with better OS.

Concepts: Improve, Lymph node, Chemotherapy, White blood cell, Better, Cytotoxicity, Immune system, Melanoma

169

The administration of interleukin 33 and deletion of IL-33 receptor, ST2 molecule, affects the induction of autoimmunity in different experimental models of human autoimmune diseases. The aim of this study was to analyze the effect of ST2 deletion on the induction of experimental autoimmune encephalomyelitis (EAE) in resistant BALB/c mice. Mice were immunized with MOG(35-55) peptide or disease was induced by passive transfer of encephalitogenic singenic cells and EAE was clinically and histologically evaluated. Expression of intracellular inflammatory cytokines, markers of activation and chemokine receptors on lymphoid tissue and CNS infiltrating mononuclear cells was analyzed by flow cytometry. We report here that deletion of ST2(-/-) molecule abrogates resistance of BALB/c mice to EAE induction based on clinical and histopathological findings. Brain and spinal cord infiltrates of ST2(-/-) mice had significantly higher number of CD4(+) T lymphocytes containing inflammatory cytokines compared to BALB/c WT mice. Adoptive transfer of ST2(-/-) primed lymphocytes induced clinical signs of the disease in ST2(-/-) as well as in WT mice. MOG(35-55) restimulated ST2(-/-) CD4(+) cells as well as ex vivo analyzed lymph node cells had higher expression of T-bet and IL-17, IFN-γ, TNF-α and GM-CSF in comparison with WT CD4(+) cells. ST2(-/-) mice had higher percentages of CD4(+) cells expressing chemokine receptors important for migration to CNS in comparison with WT CD4(+) cells. Draining lymph nodes of ST2(-/-) mice contained higher percentage of CD11c(+)CD11b(+)CD8(-) cells containing inflammatory cytokines IL-6 and IL-12 with higher expression of activation markers. Transfer of ST2(-/-) but not WT dendritic cells induced EAE in MOG(35-55) immunized WT mice. Our results indicate that ST2 deficiency attenuates inherent resistance of BALB/c mice to EAE induction by enhancing differentiation of proinflammatory antigen presenting cells and consecutive differentiation of encephalitogenic T cells in the draining lymph node rather than affecting their action in the target tissue.

Concepts: Lymph, Lymph vessel, Interleukin, Inflammation, Dendritic cell, Lymphatic system, Immune system, Lymph node

168

Intussusception is uncommon in adults. To our knowledge, synchronous colocolic intussusceptions have never been reported in the literature. Here we described the case of a 59-year-old female of synchronous colocolic intussusceptions presenting as acute abdomen that was diagnosed by CT preoperatively. Laparotomy with radical right hemicolectomy and sigmoidectomy was undertaken without reduction of the invagination due to a significant risk of associated malignancy. The final diagnosis was synchronous adenocarcinoma of proximal transverse colon and sigmoid colon without lymph nodes or distant metastasis. The patient had an uneventful recovery. The case also emphasizes the importance of thorough exploration during surgery for bowel invagination since synchronous events may occur.

Concepts: Large intestine, Sigmoid colon, Lymph node, Colectomy, Ascending colon, Peritoneum, Cancer, Medical terms

168

The current study sought to assess the role of paraaortic lymphadenectomy (LNE) in females with endometrial cancer. A retrospective analysis of patients diagnosed with endometrial cancer of stage IA to II preoperatively, between 2009 and 2011 was conducted. Patients were included who had suffered from endometrial cancer without preoperative adjuvant therapy and who underwent hysterectomy plus systematic pelvic LNE and paraaortic LNE by laparoscopy or laparotomy. A total of 54 patients who underwent surgery for preoperative endometrial cancer were selected. All patients underwent LNE. The incidences of pelvic and paraaortic lymph node metastases were 11.1% (6/54) and 7.4% (4/54), with a total positive lymph node rate of 14.8% (8/54). In addition, among the 8 positive cases, 5 patients underwent laparotomy and 3 underwent laparoscopy; 3 cases were classified as stage I and 5 as stage II preoperatively. Of these, 7 patients were identified with pathology-related risk factors, including low differentiation or clear cell adenocarcinoma postoperatively. Discordance of pathological differentiation between the pre- and postoperative stages reached 57.1% (4/7). The results revealed the high occurrence of positive lymph nodes in endometrial cancer which demonstrate the importance of systematic LNE. Additonally, no severe complications were caused by LNE besides lymph cysts. In summary, it is neccesary to perform LNE, particularly the removal of the paraaortic lymph node, in patients with endometrial cancers in order to improve postoperative therapy. Laparoscopy has similar surgical effects as laparotomy, but has a number of advantages.

Concepts: Paraaortic lymph node, Lung cancer, Surgery, Endometrial cancer, Metastasis, Lymph node, Cancer, Cancer staging

168

The aim of this study was to determine the impact of prognostic factors in primary fallopian tube carcinoma (PFTC). All cases of PFTC diagnosed between 1990 and 2010 were retrieved from the files of 6 academic centers. The cases were staged according to a modification of the International Federation of Obstetrics and Gynecology staging system proposed by Alvarado-Cabrero et al (Gynecol Oncol 1999; 72: 367-379). One hundred twenty-seven PFTC cases were identified. The mean age of the patients was 64.2 years. Stage distribution was as follows: 72 (57%), stage I; 19 (15%), stage II; 28 (22%), stage III; and 8 (6.2%), stage IV. Depth of infiltration of the tubal wall was an independent prognostic factor in stage I cases (P < .001). Carcinomas located in the fimbriated end even without invasion had a worse prognosis than did carcinomas involving the tubal portion of the organ. The presence of vascular space invasion correlated with the depth of tubal wall invasion (P = .001) and the presence of lymph node metastases (P = .003). Tumor grade significantly correlated with survival (P < .0001), but histologic type was of marginal significance and only if it was grouped as nonserous/non-clear cell vs serous/clear cell (P = .04). The depth of invasion of the tubal wall and the presence of carcinoma in the fimbriated end even without invasion are important prognostic indicators. The modified International Federation of Obstetrics and Gynecology staging system should be used on a routine basis in all carcinomas of the fallopian tube.

Concepts: Gynecology, Obstetrics and gynaecology, Fallopian tube cancer, Prognosis, Lymph node, Cancer staging, Lung cancer, Cancer

167

The cellular retinoic acid-binding protein II (CRABPII) and epidermal fatty acid-binding protein (E-FABP) both serving as the transport protein of retinoic acid (RA), through RA signal transduction pathway, commit the cell to opposite fate, apoptosis or survival. The aim of this study is to investigate the expression of CRABPII and E-FABP and significance in non-small cell lung cancer (NSCLC) and their lymph node metastases with tissue microarray technique.

Concepts: Signal transduction, Lymph node, Hormone, Protein, Metastasis, Non-small cell lung carcinoma, Lung cancer, Cancer