Evidence for disseminated tumor cells in lymphatic vessels afferent to sentinel lymph nodes in patients diagnosed with cervical cancer.

BACKGROUND: In patients diagnosed with cervical cancer, the purpose of lymphadenectomy is the removal of lymph nodes for diagnosis and potential treatment of metastasized tumor cells. It is unclear if afferent lymphatic vessels harbor tumor cells and, thus, may pose additional risk for recurrence or progression if not removed. AIM: In this feasibility study, we analyzed the lymphatic vessels afferent to sentinel lymph node (SLN) using a highly sensitive and specific molecular marker for cervical cancer cells. METHODS AND RESULTS: Twenty patients diagnosed with cervical cancer of FIGO stage IA1 to IIB2 underwent laparoscopic SLN removal. Labeling was done using patent blue and the afferent lymphatic vessels were harvested from the parametric tissue and frozen at -80°C. HPV DNA type was evaluated in the primary tumor. Lymphatic vessels afferent to the sentinel lymph nodes were analyzed for the presence of viral oncogene transcripts of the respective HPV type. In one of 18 patients, all with tumor stage ≤IBI and pN0 by conventional histopathology, HPV mRNA could be detected in two of four lymphatic vessels, whereas at least one of the lymphatic vessel biopsies of both patients with tumors ˃4 cm and pN1 status was HPV mRNA positive. No clinical correlation with recurrence after a median follow-up of 9 years was noticed. CONCLUSION: HPV mRNA indicative of disseminated tumor cells could be detected in lymphatic vessels. The relevance of harvesting lymphatic vessels afferent to SLN in order to increase oncologic safety will have to be investigated in a future prospective study.

Limits of and Complications after Embolization of the Hepatic Artery and Portal Vein to Induce Segmental Hypertrophy of the Liver: A Large Mini-Pig Study.

BACKGROUND: The aim of this study was to compare arterial embolization (AE) with portal vein embolization (PVE) for the induction of segmental hypertrophy regarding procedural efficacy, safety and outcome. METHODS: A total of 29 mini pigs were subjected to PVE, AE or assigned to the sham (SO) group. Correspondingly, 75% of the hepatic artery or portal vein branches were embolized. Growth and atrophy of the liver lobes, calculating the liver-to-body weight index (LBWI), laboratory data, arteriography, portography, Doppler ultrasound (US) and histopathology were analyzed. RESULTS: After PVE, 2 animals had to be excluded due to technical problems. After AE, 4 animals had to be excluded because of technical problems and early sacrifice. Postprocedural US demonstrated effective AE and PVE of the respective lobes. Four weeks after PVE, portography showed a slow refilling of the embolized lobe by collateral portal venous vessels. Four weeks after AE, arteriography revealed a slight revascularization of the embolized lobes by arterial neovascularization. Segmental AE led to extensive necrotic and inflammatory alterations in the liver and bile duct parenchyma. Significant hypertrophy of the non-embolized lobe was only noted in the PVE group (LBWI: 0.91 ± 0.28%; p = 0.001). There was no increase in the non-embolized lobe in the AE (LBWI: 0.45 ± 0.087%) and SO group (LBWI: 0.45 ± 0.13%). CONCLUSION: PVE is safe and effective to induce segmental hypertrophy. Portal reperfusion by collateral vessels may limit hypertrophy. AE did not increase the segmental hepatic volume but carries the risk of extensive necrotic inflammatory damage.

Effects of hydroxyethyl starch and cell-free hemoglobin on microcirculation, tissue oxygenation, and survival in severe acute porcine pancreatitis: results of a randomized experimental trial.

OBJECTIVE: Severe acute pancreatitis is a life-threatening disease with a high mortality; so far, no causal treatment is known. The aim of this study was to evaluate the therapeutic potential of hydroxyethyl starch (HES) and cell-free hemoglobin in an experimental model. METHODS: Thirty-nine pigs were randomly assigned into 3 groups. Severe acute pancreatitis was induced by intraductal injection of glycodeoxycholic acid in combination with intravenous administration of cerulein. All animals were kept in isovolemic conditions by application of Ringer solution, 10% HES, or cell-free hemoglobin. The pancreatic microcirculation was evaluated over 8 hours. Thereafter, the animals were observed for 6 days followed by killing of the animals and histopathologic examination. RESULTS: The administration of HES and cell-free hemoglobin led to improved microcirculation and tissue oxygenation compared with the Ringer's group. Consequently, the histopathologic damage was reduced (5.5 [3-8.5] vs 9.5 [7.5-11]; P < 0.001). In addition, the mean survival was significantly longer at 121 hours (95% confidence interval, 102-139) versus the Ringer group's 57 hours (95% confidence interval, 32-82; P < 0.001). CONCLUSIONS: The administration of HES and cell-free hemoglobin can improve microcirculation in severe acute porcine pancreatitis, with consequent reduction in histopathologic damage and mortality. Therefore, this might represent an interesting therapeutic option in the treatment of severe acute pancreatitis.

The anisotropic nature of the human vocal fold: an ex vivo study.

The purpose of this study was to measure the relationship between the shear elastic properties of vocal fold with respect to the direction of applied stress. There is extensive published material that quantifies the shear viscoelastic properties of the vocal fold, but as much of these data were obtained using rotating parallel plate rheometers, which are unable to resolve out difference of the shear elastic behaviour with respect to direction, there is very little data that indicates anisotropic behaviour. To overcome this gap in knowledge, the team devised an apparatus that is capable of applying a shear stress in a known direction. A series of measurements were taken at the mid-membranous position, in the transverse and longitudinal directions. Point-specific measurements were performed using fourteen human cadaver excised larynges, which were hemi-sectioned to expose the vocal fold. An extremely low sinusoidal shear force of 1 g was applied tangentially to the membrane surface in both the longitudinal and transverse direction, and the resultant shear strain was measured. With the probe applied to the intact vocal fold, the average ratio of the elasticity in the transverse with respect to the longitudinal direction was 0.55. Further investigation using histological staining of collagens in the lamina propria indicates that there is a visible difference in the general alignment of collagen fibres when comparing the coronal and the sagittal sections. Our conclusion is that there is a quantifiable difference between the shear elastic response of the lamina propria in the longitudinal and transverse directions, and that this could be explained by the difference in alignment of collagen fibres within the lamina propria.

Heterogeneity of ERBB2 amplification in adenocarcinoma, squamous cell carcinoma and large cell undifferentiated carcinoma of the lung.

The HER2 protein, encoded by the ERBB2 gene, is a molecular target for the treatment of breast and gastric cancer by monoclonal antibodies or tyrosine kinase inhibitors. While intratumoral heterogeneity of ERBB2 amplification is rare in breast cancer it is reported to be frequent in bladder and colorectal cancer. To address the potential heterogeneity of the HER2 status in adenocarcinomas, squamous cell carcinomas and large cell undifferentiated carcinomas of the lung, 590 tumors were analyzed for HER2 overexpression and ERBB2 amplification using FDA-approved reagents for immunohistochemistry and fluorescence in-situ hybridization (FISH). Moderate and strong immunostaining (2+, 3+) was seen in 10% of the tumors. ERBB2 amplification was found in 17 (3%) lung cancer patients including 10 cases (2%) with high-level amplification forming gene clusters. ERBB2 amplification was significantly related to histologic subtype and tumor grade, resulting in 12% ERBB2 amplified tumors in the subgroup of high-grade adenocarcinomas. Heterogeneity was analyzed in all highly amplified tumors. For this purpose, all available tumor tissue blocks from these patients were evaluated. Heterogeneity of ERBB2 amplification was found in 4 of 10 tumors as assessed by FISH. These included two tumors with a mixture of low-level and high-level amplification and two tumors with non-amplified tumor areas next to regions with high-level ERBB2 amplification. High-level ERBB2 amplification occurs in a small fraction of lung cancers with a strong propensity to high-grade adenocarcinomas. Heterogeneity of amplification may limit the utility of anti-HER2 therapy in some of these tumors. Further attempts to assess the utility of HER2-targeting therapy in homogeneously amplified lung cancers appear to be justified.

Interactive real-time mapping and catheter ablation of the cavotricuspid isthmus guided by magnetic resonance imaging in a porcine model.

AIMS: We investigated the feasibility of real-time magnetic resonance imaging (RTMRI) guided ablation of the cavotricuspid isthmus (CTI) by using a MRI-compatible ablation catheter. METHODS AND RESULTS: Cavotricuspid isthmus ablation was performed in an interventional RTMRI suite by using a novel 7 French, steerable, non-ferromagnetic ablation catheter in a porcine in vivo model (n = 20). The catheter was introduced and navigated by RTMRI visualization only. Catheter position and movement during manipulation were continuously visualized during the entire intervention. Two porcine prematurely died due to VT/VF. Anatomical completion of the CTI ablation line could be achieved after a mean of 6.3+/-3 RF pulses (RF energy: 1807+/-1016.4 Ws/RF pulse, temperature: 55.9+/-5.9 degrees C) in n = 18 animals. In 15 of 18 procedures (83.3%) a complete CTI block was proven by conventional mapping in the electrophysiological (EP) lab. CONCLUSION: Completely non-fluoroscopic ablation guided by RTMRI using a steerable and non-ferromagnetic catheter is a promising novel technology in interventional electrophysiology.