Combined approach of perioperative 18F-FDG PET/CT imaging and intraoperative 18F-FDG handheld gamma probe detection for tumor localization and verification of complete tumor resection in breast cancer

<p>Abstract</p> <p>Background</p> <p>¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) has become an established method for detecting hypermetabolic sites of known and occult disease and is widely used in oncology surgical planning. Intraoperatively, it is often difficult to localize tumors and verify complete resection of tumors that have been previously detected on diagnostic PET/CT at the time of the original evaluation of the cancer patient. Therefore, we propose an innovative approach for intraoperative tumor localization and verification of complete tumor resection utilizing ¹⁸F-FDG for perioperative PET/CT imaging and intraoperative gamma probe detection.</p> <p>Methods</p> <p>Two breast cancer patients were evaluated. ¹⁸F-FDG was administered and PET/CT was acquired immediately prior to surgery. Intraoperatively, tumors were localized and resected with the assistance of a handheld gamma probe. Resected tumors were scanned with specimen PET/CT prior to pathologic processing. Shortly after the surgical procedure, patients were re-imaged with PET/CT utilizing the same preoperatively administered ¹⁸F-FDG dose.</p> <p>Results</p> <p>One patient had primary carcinoma of breast and a metastatic axillary lymph node. The second patient had a solitary metastatic liver lesion. In both cases, preoperative PET/CT verified these findings and demonstrated no additional suspicious hypermetabolic lesions. Furthermore, intraoperative gamma probe detection, specimen PET/CT, and postoperative PET/CT verified complete resection of the hypermetabolic lesions.</p> <p>Conclusion</p> <p>Immediate preoperative and postoperative PET/CT imaging, utilizing the same ¹⁸F-FDG injection dose, is feasible and image quality is acceptable. Such perioperative PET/CT imaging, along with intraoperative gamma probe detection and specimen PET/CT, can be used to verify complete tumor resection. This innovative approach demonstrates promise for assisting the oncologic surgeon in localizing and verifying resection of ¹⁸F-FDG positive tumors and may ultimately positively impact upon long-term patient outcomes.</p

Gamma probes and their use in tumor detection in colorectal cancer

The purpose of this article is to summarize the role of gamma probes in intraoperative tumor detection in patients with colorectal cancer (CRC), as well as provide basic information about the physical and practical characteristics of the gamma probes, and the radiopharmaceuticals used in gamma probe tumor detection. In a significant portion of these studies, radiolabeled monoclonal antibodies (Mabs), particularly 125I labeled B72.3 Mab that binds to the TAG-72 antigen, have been used to target tumor. Studies have reported that intraoperative gamma probe radioimmunodetection helps surgeons to localize primary tumor, clearly delineate its resection margins and provide immediate intraoperative staging. Studies also have emphasized the value of intraoperative gamma probe radioimmunodetection in defining the extent of tumor recurrence and finding sub-clinical occult tumors which would assure the surgeons that they have completely removed the tumor burden. However, intraoperative gamma probe radioimmunodetection has not been widely adapted among surgeons because of some constraints associated with this technique. The main difficulty with this technique is the long period of waiting time between Mab injection and surgery. The technique is also laborious and costly. In recent years, Fluorine-18-2-fluoro-2-deoxy-D-glucose (18F-FDG) use in gamma probe tumor detection surgery has renewed interest among surgeons. Preliminary studies during surgery have demonstrated that use of FDG in gamma probe tumor detection during surgery is feasible and useful

DAX-1 expression in human breast cancer: comparison with estrogen receptors ER-α, ER-β and androgen receptor status

BACKGROUND: So far there have been no reports on the expression pattern of DAX-1 (dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1) in human breast cells and its relationship to the estrogen receptors, ER-α and ER-β, and the androgen receptor (AR). METHODS: In this study we evaluated, by immunohistochemistry and Western blot analysis, the presence and distribution of DAX-1 in benign breast disease (BBD), in situ carcinoma (CIS), and ductal and lobular breast carcinomas. RESULTS: In BBD and breast carcinomas, DAX-1 was present in both the nuclei and the cytoplasm of epithelial cells, although in infiltrative carcinomas the percentage of nuclear immunoreaction was higher than in CIS. An important relation was observed between DAX-1 and AR expression and between this orphan receptor and nodal status. CONCLUSION: DAX-1 might modify the AR and ER-β intracellular location, and because a direct positive relation between the expression of these three receptors was found it could be assumed that the presence of DAX-1 in neoplastic cells might indicate a possible failure of endocrine therapies

GP88 (PC-Cell Derived Growth Factor, progranulin) stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Aromatase inhibitors (AI) that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER⁺) breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88), also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER⁺breast cancer cells</p> <p>Methods</p> <p>We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined.</p> <p>Results</p> <p>GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole.</p> <p>Conclusion</p> <p>Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER⁺breast cancer.</p

Empirical studies on informal patient payments for health care services: a systematic and critical review of research methods and instruments

<p>Abstract</p> <p>Background</p> <p>Empirical evidence demonstrates that informal patient payments are an important feature of many health care systems. However, the study of these payments is a challenging task because of their potentially illegal and sensitive nature. The aim of this paper is to provide a systematic review and analysis of key methodological difficulties in measuring informal patient payments.</p> <p>Methods</p> <p>The systematic review was based on the following eligibility criteria: English language publications that reported on empirical studies measuring informal patient payments. There were no limitations with regard to the year of publication. The content of the publications was analysed qualitatively and the results were organised in the form of tables. Data sources were Econlit, Econpapers, Medline, PubMed, ScienceDirect, SocINDEX.</p> <p>Results</p> <p>Informal payments for health care services are most often investigated in studies involving patients or the general public, but providers and officials are also sample units in some studies. The majority of the studies apply a single mode of data collection that involves either face-to-face interviews or group discussions.</p> <p>One of the main methodological difficulties reported in the publication concerns the inability of some respondents to distinguish between official and unofficial payments. Another complication is associated with the refusal of some respondents to answer questions on informal patient payments.</p> <p>We do not exclude the possibility that we have missed studies that reported in non-English language journals as well as very recent studies that are not yet published.</p> <p>Conclusions</p> <p>Given the recent evidence from research on survey methods, a self-administrated questionnaire during a face-to-face interview could be a suitable mode of collecting sensitive data, such as data on informal patient payments.</p

Axillary lymph node dissection for breast cancer utilizing Harmonic Focus®

<p>Abstract</p> <p>Background</p> <p>For patients with axillary lymph node metastases from breast cancer, performance of a complete axillary lymph node dissection (ALND) is the standard approach. Due to the rich lymphatic network in the axilla, it is necessary to carefully dissect and identify all lymphatic channels. Traditionally, these lymphatics are sealed with titanium clips or individually sutured. Recently, the Harmonic Focus^®, a hand-held ultrasonic dissector, allows lymphatics to be sealed without the utilization of clips or ties. We hypothesize that ALND performed with the Harmonic Focus^®will decrease operative time and reduce post-operative complications.</p> <p>Methods</p> <p>Retrospective review identified all patients who underwent ALND at a teaching hospital between January of 2005 and December of 2009. Patient demographics, presenting pathology, treatment course, operative time, days to drain removal, and surgical complications were recorded. Comparisons were made to a selected control group of patients who underwent similar surgical procedures along with an ALND performed utilizing hemostatic clips and electrocautery. A total of 41 patients were included in this study.</p> <p>Results</p> <p>Operative time was not improved with the use of ultrasonic dissection, however, there was a decrease in the total number of days that closed suction drainage was required, although this was not statistically significant. Complication rates were similar between the two groups.</p> <p>Conclusion</p> <p>In this case-matched retrospective review, there were fewer required days of closed suction drainage when ALND was performed with ultrasonic dissection versus clips and electrocautery.</p

Epithelial atypia in biopsies performed for microcalcifications. Practical considerations about 2,833 serially sectioned surgical biopsies with a long follow-up

This study analyzes the occurrence of epithelial atypia in 2,833 serially sectioned surgical breast biopsies (SB) performed for microcalcifications (median number of blocks per SB:26) and the occurrence of subsequent cancer after an initial diagnosis of epithelial atypia (median follow-up 160 months). Epithelial atypia (flat epithelial atypia, atypical ductal hyperplasia, and lobular neoplasia) were found in 971 SB, with and without a concomitant cancer in 301 (31%) and 670 (69%) SB, respectively. Thus, isolated epithelial atypia were found in 670 out of the 2,833 SB (23%). Concomitant cancers corresponded to ductal carcinomas in situ and micro-invasive (77%), invasive ductal carcinomas not otherwise specified (15%), invasive lobular carcinomas (4%), and tubular carcinomas (4%). Fifteen out of the 443 patients with isolated epithelial atypia developed a subsequent ipsilateral (n = 14) and contralateral (n = 1) invasive cancer. The high slide rating might explain the high percentages of epithelial atypia and concomitant cancers and the low percentage of subsequent cancer after a diagnosis of epithelial atypia as a single lesion. Epithelial atypia could be more a risk marker of concomitant than subsequent cancer

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology