Metastatic lymph nodes in the neck of patients with T1 and T2 squamous cell carcinoma of the lower lip detected with lymphoscintigraphy

Aims and backgroundThe aim of our research was to use lymphoscintigraphy as a main method to confirm and detect lymph nodes in the neck, in patients with squamos cell carcinoma of lower lip which were clinically T1, T2 and N0, and to justify the use of selective neck dissection in those patients. MethodsFrom April 2010 to January 2011, 31 patients with T1, T2 and N0 SCC of the lower lip were admitted to our center. To detect sentinel lymph nodes, we performed lymphoscintigraphy (LSG). LSG was performed on the day of surgery after intradermal injection of 37 Mbq of Tc99m-Sn-colloid/ml at four peritumoral sites. The sentinel lymph nodes were then extirpated and sent for biopsy. Results Among the 31 patients, three (9.7%) were female and 28 (90.3%) were male. LSG detected sentinel nodes in the neck in 21 (67.7%) of the patients. Of these, 10 (47.6%) had a positive sentinel node biopsy. Of all 31 patients enrolled in the study, occult metastases were found in 10 (32.3%).  Conclusions Our results indicate that, of the methods used to detect positive lymph nodes, the most accurate is LSG. The results also suggest that further study is needed to optimize the treatment protocol in patients with SCC of the lower lip, especially in those with T2 lesions.

Metabolic Response to Stress Differentiates Heterogeneous Cancer Cells with Varying Metastatic Potential

Intratumoral heterogeneity is ubiquitously present within primary tumors and contributes to intractable behaviors such as metastasis and mutability spatiotemporally. Mounting evidence has shown that heterogeneous cell populations can adversely affect cell metabolism and metastatic potential. The cell’s only fluorescent molecules within the electron transport chain, flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH), can allow the quantitation of cell metabolism. We demonstrate the use of the optical redox ratio (FAD/(NADH+FAD)) to determine the metabolic behaviors of a heterogeneous panel of cells with varying metastatic programs at normal conditions and following acute hypoxia. At normal conditions, we reveal an attenuation in the optical redox ratio as metastatic potential decreases, not including the non-metastatic cell line. We reveal that reoxygenating the clonogenic cells after hypoxia enabled further differences in the optical redox ratio for the highly metastatic (increased by 43 ± 9%), semi-metastatic (increased by 33 ± 4%), and non-metastatic (decreased by 14 ± 7%) cell lines. This work coalesces two potential strategies for cancer treatment: 1) the optical redox ratio to assess cell metabolic features and therapy-induced changes 2) the method of inducing a “stress” test to identify further differences in heterogeneous cell populations

Exosomes promote pre-metastatic niche formation in ovarian cancer.

Ovarian cancer is one of the most common gynecological malignancies. Upon initial diagnosis, the majority of patients present with widespread metastatic growth within the peritoneal cavity. This metastatic growth occurs in stages, with the formation of a pre-metastatic niche occurring prior to macroscopic tumor cell invasion. Exosomes released by the primary ovarian tumor are small extracellular vesicles which prepare the distant tumor microenvironment for accelerated metastatic invasion. They regulate intercellular communication between tumor cells and normal stroma, cancer-associated fibroblasts, and local immune cells within the tumor microenvironment. In this review, we highlight the emerging roles of ovarian cancer exosomes as coordinators of pre-metastatic niche formation, biomarkers amenable to liquid biopsy, and targets of chemotherapy

Fine needle aspiration cytology of hepatic metastases of neuroendocrine tumors: A 20‐year retrospective, single institutional study

Background Fine needle aspiration (FNA) is considered an excellent technique for documenting metastatic neuroendocrine tumors (NETs). This study aims to evaluate the accuracy of FNA in diagnosing metastatic NETs to the liver and determining the grade and origin of these metastases. Methods Our laboratory information system was searched from 1997 to 2016 to identify all cases of metastatic NETs to the liver that were sampled by FNA. The cytopathology and surgical pathology reports as well as the patients' electronic medical records were reviewed. The cytohistologic type and grade of the metastatic NETs, as well as the site of the patient's primary were recorded. Results High‐grade NETs, including small cell and poorly differentiated neuroendocrine carcinomas, constituted 62% (167/271) of the cases, while low‐grade NETs, including well differentiated NET (grade1 and grade 2), pheochromocytomas, paragangliomas, and carcinoid tumors of lung, constituted 38% (104/271) of cases. The most common diagnosis was metastatic small cell carcinoma accounting for 45% (122/271) of cases. The most common primary sites were lung (44%; 119/271) followed by pancreas (19%; 51/271). The FNA diagnosis was confirmed by histopathology in 121 cases that had a concurrent biopsies or resection specimens. Conclusions FNA is an accurate method for diagnosing metastatic NETs to the liver. There were significantly more high‐grade (62%) than low‐grade (38%) metastatic NETs to the liver. In our practice, lung (44%) and pancreas (19%) were the most common primary sites of metastatic NETs involving the liver. In 16% of the cases, a primary site could not be established

In vivo multi-parametric imaging of metastatic and non-metastatic breast cancer

A current issue in cancer therapy is the characterization of metastatic tumors, which can increase ease of treatment and patient trials. We present an in vivo study of metastatic (4T1) and non-metastatic (4T1-TWIST KO) breast tumor sister cell lines to understand their metabolic behavior, determine differences in two modes of imaging (reflection & transmission), and observe effect of breathing higher oxygen percentage on vascular hemoglobin oxygen saturation. After injection of 10,000 cells into mice dorsal window chambers, the glucose intake and hemoglobin oxygen saturation was measured using a fluorescent glucose analog (2-NBDG) and hyperspectral trans-illumination imaging from 520-620 nm at 10 nm intervals, respectively. The metastatic tumors exhibited increased oxygen saturation and decreased glucose metabolism than non-metastatic tumors. Reflection mode of imaging was unable to pick intricacies in tumor parameters, and increased inhalation of oxygen caused increase in hemoglobin oxygen saturation

Biopsy confirmation of metastatic sites in breast cancer patients:clinical impact and future perspectives

Determination of hormone receptor (estrogen receptor and progesterone receptor) and human epidermal growth factor receptor 2 status in the primary tumor is clinically relevant to define breast cancer subtypes, clinical outcome,and the choice of therapy. Retrospective and prospective studies suggest that there is substantial discordance in receptor status between primary and recurrent breast cancer. Despite this evidence and current recommendations,the acquisition of tissue from metastatic deposits is not routine practice. As a consequence, therapeutic decisions for treatment in the metastatic setting are based on the features of the primary tumor. Reasons for this attitude include the invasiveness of the procedure and the unreliable outcome of biopsy, in particular for biopsies of lesions at complex visceral sites. Improvements in interventional radiology techniques mean that most metastatic sites are now accessible by minimally invasive methods, including surgery. In our opinion, since biopsies are diagnostic and changes in biological features between the primary and secondary tumors can occur, the routine biopsy of metastatic disease needs to be performed. In this review, we discuss the rationale for biopsy of suspected breast cancer metastases, review issues and caveats surrounding discordance of biomarker status between primary and metastatic tumors, and provide insights for deciding when to perform biopsy of suspected metastases and which one (s) to biopsy. We also speculate on the future translational implications for biopsy of suspected metastatic lesions in the context of clinical trials and the establishment of bio-banks of biopsy material taken from metastatic sites. We believe that such bio-banks will be important for exploring mechanisms of metastasis. In the future,advances in targeted therapy will depend on the availability of metastatic tissue

Capecitabine as second-line treatment for metastatic cholangiocarcinoma: A report of two cases

Background: The management of recurrent, metastatic cholangiocarcinoma still remains a problem since this tumor entity is classified as chemotherapy-resistant. When advanced or metastatic disease is diagnosed, the therapeutic efforts are essentially directed toward palliation. Patients and Methods: We report on 2 patients suffering from metastatic cholangiocarcinoma. Both had received previous chemotherapy for metastatic disease, including hepatic artery infusion {[}5-fluorouracil (5-FU)/folinic acid (FA) and oxaliplatin] and a combination therapy consisting of 5-FU/FA and gemcitabine. Since a progression of the disease was diagnosed, both patients were started on oral capecitabine at a daily dose of 2,500 mg/m(2) in 2 divided doses for 2 weeks, followed by 1 week rest. Results: Capecitabine was tolerated well and severe side effects were not observed. A stop of progression, documented by imaging procedures and tumor marker kinetics, was achieved in both patients. Conclusion: Capecitabine could potentially be used for second-line treatment in patients with progressive metastatic cholangiocarcinoma