Four-arm robotic lobectomy for the treatment of early-stage lung cancer

We investigated the feasibility and safety of four-arm robotic lung lobectomy in patients with lung cancer and described the robotic lobectomy technique with mediastinal lymph node dissection.

Readaptation of the peritoneum following extended pelvic lymphadenectomy and cystectomy has a significant beneficial impact on early postoperative recovery and complications: results of a prospective randomized trial

Prolonged postoperative pain and delayed intestinal transit are frequent problems following extended pelvic lymph-node dissection (PLND) and cystectomy.

Potential influence of the anesthetic technique used during open radical prostatectomy on prostate cancer-related outcome: a retrospective study

Recently published studies suggest that the anesthetic technique used during oncologic surgery affects cancer recurrence. To evaluate the effect of anesthetic technique on disease progression and long-term survival, we compared patients receiving general anesthesia plus intraoperative and postoperative thoracic epidural analgesia with patients receiving general anesthesia alone undergoing open retropubic radical prostatectomy with extended pelvic lymph node dissection.

DW-MRI of the urogenital tract: applications in oncology

Diffusion-weighted magnetic resonance imaging (DW-MRI) appears to hold promise as a non-invasive imaging modality in the detection of early microstructural and functional changes of different organs. DW-MRI is an imaging technique with a high sensitivity for the detection of a large variety of diseases in the urogenital tract. In kidneys, DW-MRI has shown promise for the characterization of solid lesions. Also in focal T1 hyperintense lesions DW-MRI was able to differentiate hemorrhagic cysts from tumours according to the lower apparent diffusion coefficient (ADC) values reported for renal cell carcinomas. Promising results were also published for the detection of prostate cancer. DW-MRI applied in addition to conventional T2-weighted imaging has been found to improve tumour detection. On a 3 T magnetic resonance unit ADC values were reported to be lower for tumours compared with the normal-appearing peripheral zone. The combined approach of T2-weighted imaging and DW-MRI also showed promising results for the detection of recurrent tumour in patients after radiation therapy. DW-MRI may improve the performance of conventional T2-weighted and contrast-enhanced MRI in the preoperative work-up of bladder cancer, as it may help in distinguishing superficial from muscle invasive bladder cancer, which is critical for patient management. Another challenging application of DW-MRI in the urogenital tract is the detection of pelvic lymph node metastases. As the ADC is generally reduced in malignant tumours and increased under inflammatory conditions, reduced ADC values were expected in patients with lymph node metastases.

Diffusion-weighted MRI in head and neck radiology: applications in oncology

Extracranial application of diffusion-weighted magnetic resonance imaging (MRI) has gained increasing importance in recent years. As a result of technical advances, this new non-invasive functional technique has also been applied in head and neck radiology for several clinical indications. In cancer imaging, diffusion-weighted MRI can be performed for tumour detection and characterization, monitoring of treatment response as well as the differentiation of recurrence and post-therapeutic changes after radiotherapy. Even for lymph node staging promising results have been reported recently. This review article provides overview of potential applications of diffusion-weighted MRI in head and neck with the main focus on its applications in oncology.

Differential efficacy of three cycles of CMF followed by tamoxifen in patients with ER-positive and ER-negative tumors: long-term follow up on IBCSG Trial IX

The benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)-positive lymph node-negative breast cancer is being reassessed.

Diffusion-weighted magnetic resonance imaging detects local recurrence after radical prostatectomy: initial experience

Current conventional cross-sectional imaging techniques, such as contrast-enhanced computed tomography and magnetic resonance imaging (MRI), are largely inaccurate in detecting local recurrence after radical prostatectomy. We report on five patients with biochemical recurrence after radical retropubic prostatectomy and pelvic lymph node dissection for whom local recurrence could only be detected with diffusion-weighted (DW) MRI. Prior to DW-MRI, all patients had negative digital rectal examinations, negative or equivocal conventional cross-sectional imaging, and negative bone scans. All suspicious lesions on DW-MRI imaging were histologically proved to be local recurrences of prostate cancer after either transrectal ultrasound-guided or transurethral biopsy. These results should encourage other centres to test our findings.

Lymphadenectomy for bladder cancer: indications and controversies

Pelvic lymph node dissection (PLND) at the time of cystectomy remains the most accurate method of staging and can have a positive impact on cancer control, and there is general agreement as to its necessity at the time of surgery. There is, however, a lack of consensus regarding the terminology of PLND and controversy concerning the optimal extent of lymph node dissection, especially because recent investigations have suggested a survival benefit with extended PLND.

In vivo analysis of uropod function during physiological T cell trafficking

Migrating lymphocytes acquire a polarized phenotype with a leading and a trailing edge, or uropod. Although in vitro experiments in cell lines or activated primary cell cultures have established that Rho-p160 coiled-coil kinase (ROCK)-myosin II-mediated uropod contractility is required for integrin de-adhesion on two-dimensional surfaces and nuclear propulsion through narrow pores in three-dimensional matrices, less is known about the role of these two events during the recirculation of primary, nonactivated lymphocytes. Using pharmacological antagonists of ROCK and myosin II, we report that inhibition of uropod contractility blocked integrin-independent mouse T cell migration through narrow, but not large, pores in vitro. T cell crawling on chemokine-coated endothelial cells under shear was severely impaired by ROCK inhibition, whereas transendothelial migration was only reduced through endothelial cells with high, but not low, barrier properties. Using three-dimensional thick-tissue imaging and dynamic two-photon microscopy of T cell motility in lymphoid tissue, we demonstrated a significant role for uropod contractility in intraluminal crawling and transendothelial migration through lymph node, but not bone marrow, endothelial cells. Finally, we demonstrated that ICAM-1, but not anatomical constraints or integrin-independent interactions, reduced parenchymal motility of inhibitor-treated T cells within the dense lymphoid microenvironment, thus assigning context-dependent roles for uropod contraction during lymphocyte recirculation.

Characterization of antibodies specific for canine TLR4, 5 and 9 by ELISA, Western blotting and immunohistochemistry

Toll-like receptors recognize pathogen-associated molecular patterns of microbial origin, and ligand recognition results in the production of different immune mediators such as pro-inflammatory cytokines, interferon, reactive oxygen and nitrogen intermediates, and upregulation of costimmulatory molecules. As these receptors have a critical role in linking pathogen recognition to induction of inflammation and innate as well as adaptive immunity, there is tremendous interest in understanding how the tissue and cell-type expression of TLRs is regulated and its influence on the local innate immune response. While TLRs are well studied in humans and rodents, to date little is known about them in dogs. The purpose of this study was to develop canine specific antibodies against TLR2, 4, 5 and 9 that were used to measure relative expression of these TLRs in healthy and reactive canine mesenteric lymph nodes. All 8 rabbit sera (2 each for TLR2, 4, 5 and 9) were strongly positive in ELISA against the respective 2 peptides per TLR used for immunization. The purified antibodies selected specifically detected a protein band with an apparent size of approximately 70 kDa in lysates of canine PBMCs by Western blotting. Immunostaining was observed with purified antibodies against TLR4, 5 and 9, whereas for canine TLR2, staining was only observed with the unpurified antibodies. In the mesenteric lymph node of healthy dogs, the overall staining pattern was very similar for TLR4 and 5 with positive cells predominantly found in the internodular areas and lower part of the cortex. Compared to the TLR4 and 5, more cells stained positive for TLR9 especially in the lymphoid nodules. The reactive lymph nodes contained more TLR4 and 9 positive cells. Moreover, a shift of TLR-9 positive cells from the lymphoid follicles to the deep cortex and medullary cords was observed. Whereas TLR9 co-localized with CD79-positive areas, TLR4 and 5 antibodies stained cells primarily in the CD3-positive areas. All three TLR antibodies stained cells within the area that co-localized with lysozyme-positive cells. In conclusion, this study demonstrates that the antibodies generated against canine TLR 4, 5 and 9 identify the expression of these TLRs in formalin-fixed canine lymph nodes and demonstrate increased expression in reactive canine mesenteric lymph nodes.

[Juvenile sterile granulomatous dermatitis and lymphadenitis in the dog]

Juvenile sterile granulomatous dermatitis and lymphadenitis is a rare immune-mediated skin disease in young dogs. History, signalment, diagnostics, treatment, and outcome in 10 dogs are described. The age ranged from 8 - 36 weeks. The lymph nodes were enlarged in all dogs, especially the mandibular and prescapular lymph nodes. Systemic signs including fever were present in 8 dogs. Seven dogs suffered from blepharitis and painful edema of the muzzle with hemorrhagic discharge, pustules and papules. Cytology of pustules and lymph node aspirates revealed a pyogranulomatous inflammation. In 7 cases the diagnosis of juvenile sterile granulomatous dermatitis and lymphadenitis was confirmed by histology. Nine dogs were treated with prednisolone (0.5 - 1.25 mg/kg BID), H2-receptor antagonists and analgetics; all dogs were treated with antibiotics. Four dogs were treated with eye ointment containing antibiotics and glucocorticoids. The prednisolone dosage was tapered over 3 - 8 weeks. One dog had a relapse.

Comparative analysis of four lipoproteins from Mycoplasma mycoides subsp. mycoides Small Colony identifies LppA as a major T-cell antigen

Control of contagious bovine pleuropneumonia (CBPP), caused by Mycoplasma mycoides subsp. mycoides Small Colony (MmmSC), remains an important goal in Africa. Subunit vaccines triggering B and T-cell responses could represent a promising approach. To this aim, the T-cell immunogenicity of four MmmSC lipoproteins (LppA, LppB, LppC and LppQ), present in African strains and able to elicit humoral response, was evaluated. In vitro assays revealed that only LppA was recognized by lymph node lymphocytes taken from three cattle, 3 weeks after MmmSC exposure. Maintenance of the LppA-specific response, relying on CD4 T-cells and IFN gamma production, was then demonstrated 1 year after infection. LppA is thus an important target for the CD4 T-cells generated early after MmmSC infection and persisting in the lymph nodes of recovered cattle. Its role as a protective antigen and ability to in vivo trigger both arms of the host immune response remain to be evaluated.

Human epidermal growth factor receptor-2 gene amplification in gastric cancer using tissue microarray technology

To assess human epidermal growth factor receptor-2 (HER2)-status in gastric cancer and matched lymph node metastases by immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH).

Factors predicting prognosis and recurrence in patients with esophago-gastric adenocarcinoma and histopathological response with less than 10 % residual tumor

PURPOSE: Neoadjuvant treatment is an accepted standard approach for treating locally advanced esophago-gastric adenocarcinomas. Despite a response of the primary tumor, a significant percentage dies from tumor recurrence. The aim of this retrospective exploratory study from two academic centers was to identify predictors of survival and recurrence in histopathologically responding patients. METHODS: Two hundred thirty one patients with adenocarcinomas (esophagus: n = 185, stomach: n = 46, cT3/4, cN0/+, cM0) treated with preoperative chemotherapy (n = 212) or chemoradiotherapy (n = 19) followed by resection achieved a histopathological response (regression 1a: no residual tumor (n = 58), and regression 1b < 10 % residual tumor (n = 173)). RESULTS: The estimated median overall survival was 92.4 months (5-year survival, 56.6 %) for all patients. For patients with regression 1a, median survival is not reached (5-year survival, 71.6 %) compared to patients with regression 1b with 75.3 months median (5-year survival, 52.2 %) (p = 0.031). Patients with a regression 1a had lymph node metastases in 19.0 versus 33.7 % in regression 1b. The ypT-category (p < 0.001), the M-category (p = 0.005), and the type of treatment (p = 0.04) were found to be independent prognostic factors in R0-resected patients. The recurrence rate was 31.7 % (n = 66) (local, 39.4 %; peritoneal carcinomatosis, 25.7 %; distant metastases, 50 %). Recurrence was predicted by female gender (p = 0.013), ypT-category (p = 0.007), and M-category (p = 0.003) in multivariate analysis. CONCLUSION: Response of the primary tumor does not guarantee recurrence-free long-term survival, but histopathological complete responders have better prognosis compared to partial responders. Established prognostic factors strongly influence the outcome, which could, in the future, be used for stratification of adjuvant treatment approaches. Increasing the rate of histopathological complete responders is a valid endpoint for future clinical trials investigating new drugs.

MALDI imaging mass spectrometry reveals COX7A2, TAGLN2 and S100-A10 as novel prognostic markers in Barrett's adenocarcinoma

To characterize proteomic changes found in Barrett's adenocarcinoma and its premalignant stages, the proteomic profiles of histologically defined precursor and invasive carcinoma lesions were analyzed by MALDI imaging MS. For a primary proteomic screening, a discovery cohort of 38 fresh frozen Barrett's adenocarcinoma patient tissue samples was used. The goal was to find proteins that might be used as markers for monitoring cancer development as well as for predicting regional lymph node metastasis and disease outcome. Using mass spectrometry for protein identification and validating the results by immunohistochemistry on an independent validation set, we could identify two of 60 differentially expressed m/z species between Barrett's adenocarcinoma and the precursor lesion: COX7A2 and S100-A10. Furthermore, among 22 m/z species that are differentially expressed in Barrett's adenocarcinoma cases with and without regional lymph node metastasis, one was identified as TAGLN2. In the validation set, we found a correlation of the expression levels of COX7A2 and TAGLN2 with a poor prognosis while S100-A10 was confirmed by multivariate analysis as a novel independent prognostic factor in Barrett's adenocarcinoma. Our results underscore the high potential of MALDI imaging for revealing new biologically significant molecular details from cancer tissues which might have potential for clinical application. This article is part of a Special Issue entitled: Translational Proteomics.