A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins

The goal of resection of soft tissue sarcomas located in the extremity is to preserve limb function while completely excising the tumor with a margin of normal tissue. With surgery alone, one‐third of patients with soft tissue sarcoma of the extremity will have local recurrence due to microscopic residual disease in the tumor bed. Currently, a limited number of intraoperative pathology‐based techniques are used to assess margin status; however, few have been widely adopted due to sampling error and time constraints. To aid in intraoperative diagnosis, we developed a quantitative optical microscopy toolbox, which includes acriflavine staining, fluorescence microscopy, and analytic techniques called sparse component analysis and circle transform to yield quantitative diagnosis of tumor margins. A series of variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82 and 75%. The utility of this approach was tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78 and 82%. For comparison, if pathology was used to predict local recurrence in this data set, it would achieve a sensitivity of 29% and a specificity of 71%. These results indicate a robust approach for detecting microscopic residual disease, which is an effective predictor of local recurrence.     

Real-time intraoperative detection of breast cancer using near-infrared fluorescence imaging and Methylene Blue

Background

Despite recent developments in preoperative breast cancer imaging, intraoperative localization of tumor tissue can be challenging, resulting in tumor-positive resection margins during breast conserving surgery. Based on certain physicochemical similarities between Technetium(^99mTc)-sestamibi (MIBI), an SPECT radiodiagnostic with a sensitivity of 83–90% to detect breast cancer preoperatively, and the near-infrared (NIR) fluorophore Methylene Blue (MB), we hypothesized that MB might detect breast cancer intraoperatively using NIR fluorescence imaging.

Methods

Twenty-four patients with breast cancer, planned for surgical resection, were included. Patients were divided in 2 administration groups, which differed with respect to the timing of MB administration. N = 12 patients per group were administered 1.0 mg/kg MB intravenously either immediately or 3 h before surgery. The mini-FLARE imaging system was used to identify the NIR fluorescent signal during surgery and on post-resected specimens transferred to the pathology department. Results were confirmed by NIR fluorescence microscopy.

Results

20/24 (83%) of breast tumors (carcinoma in N = 21 and ductal carcinoma in situ in N = 3) were identified in the resected specimen using NIR fluorescence imaging. Patients with non-detectable tumors were significantly older. No significant relation to receptor status or tumor grade was seen. Overall tumor-to-background ratio (TBR) was 2.4 ± 0.8. There was no significant difference between TBR and background signal between administration groups. In 2/4 patients with positive resection margins, breast cancer tissue identified in the wound bed during surgery would have changed surgical management. Histology confirmed the concordance of fluorescence signal and tumor tissue.

Conclusions

This feasibility study demonstrated an overall breast cancer identification rate using MB of 83%, with real-time intraoperative guidance having the potential to alter patient management.     

Real-time detection of hepatic micrometastases from pancreatic cancer by intraoperative fluorescence imaging: preliminary results of a prospective study

BACKGROUND:

Recently, a highly sensitive fluorescent imaging technique was developed for the real‐time identification of hepatic tumors. The authors applied this procedure for the intraoperative detection of radiographically occult hepatic micrometastases from pancreatic cancer.

METHODS:

Forty‐nine consecutive patients with pancreatic cancer who underwent surgical intervention were examined. Preoperative clinical images had not revealed any hepatic metastases. On the day before surgery, indocyanine green was injected intravenously. During the operation, the liver was observed with a near‐infrared camera system, and abnormal fluorescent foci were examined by frozen‐section histology. The patients with hepatic micrometastases were judged to have unresectable disease and underwent only palliative surgery followed by systemic chemotherapy using gemcitabine.

RESULTS:

Abnormal hepatic fluorescence at least 1.5 mm in greatest dimension without any apparent tumor was observed in 13 patients. Among them, histologic examination confirmed micrometastases in 8 of 49 patients (16%). All patients with hepatic micrometastases had clinical T3 or T4 disease and high serum CA19‐9 levels (P = .042). On follow‐up computed tomography images that were obtained within 6 months after surgery, the patients with hepatic micrometastases manifested hepatic overt metastases (7 of 8 patients; 88%) more frequently than the patients without hepatic micrometastases (4 of 41 patients; 10%; P < .001). Regardless of histologic confirmation, the positive predictive value of abnormal fluorescence for the manifestation of hepatic relapse within 6 months was 77% (10 of 13 patients), and the negative predictive value was 97% (35 of 36 patients).

CONCLUSIONS:

Indocyanine green‐fluorescent imaging can detect hepatic micrometastases of pancreatic cancer during surgery. The hepatic micrometastases seem to have an adverse clinical impact identical to that of evident distant metastases. Cancer 2011. © 2011 American Cancer Society.     

Near infrared thoracoscopy of tumoral protease activity for improved detection of peripheral lung cancer

Improvement in tumor detection using "smart" probes in combination with microcatheter fluorescence thoracoscopy was evaluated in a mouse model. These imaging probes increase in fluorescence intensity after protease activation; cathepsin B is a major activator of the probes used in this study. Lewis lung carcinoma cells were orthotopically implanted in the subpleural lung parenchyma. Two activatable near infrared (NIR) probes with different excitation and emission wavelength were administered intravenously to determine whether wavelength would modulate target to background ratio (TBR). Mice were selectively intubated and thoracoscopy performed. A 0.8 mm outer diameter imaging catheter was used to record simultaneous white-light (anatomic) and NIR (protease expression) images. At both wavelength pairs evaluated (680/700 and 750/780 nm excitation/emission), the intrinsic luminosity differences between tumors and normal lung in uninjected animals was low (p > 0.3 and p = 0.4, respectively and TBR near 1). In mice receiving protease probes IV, tumors were significantly more fluorescent than adjacent lung (p < 0.0005 for 680/700 and p < 0.006 for 750/780) and TBR increased to approximately 9-fold. Confirmatory fluorescence microscopy and immunohistochemistry were similar and revealed that normal lung had very low levels when compared to tumors of cathepsin B and probe fluorescence. In conclusion, protease sensitive imaging probes selective for cathepsin B, imaged with NIR microcatheters, significantly increase the TBR, making small peripheral lung tumors more readily apparent. Such an approach may be a useful adjunct in staging or restaging patients with lung cancer to find minimal disease in the pleural and subpleural space.     

Preclinical evaluation of near‐infrared (NIR) fluorescently labeled cetuximab as a potential tool for fluorescence‐guided surgery

The high rate of recurrence in patients with pancreatic ductal adenocarcinoma (PDAC) could be reduced by supporting the surgeons in discriminating healthy from diseased tissues with intraoperative fluorescence‐guidance. Here, we studied the suitability of Cetuximab, a therapeutic monoclonal antibody targeting the human epidermal growth factor receptor (EGFR), near‐infrared (NIR) fluorescently labeled as a new tool for fluorescence‐guided surgery. Distribution and binding of systemically injected Cetuximab Alexa Fluor 647 conjugate (Cetux‐Alexa‐647) and the co‐injected control human IgG Alexa Fluor 750 conjugate (hIgG‐Alexa‐750) was studied over 48 h by NIR fluorescence imaging in mice bearing human orthotopic AsPC‐1 and MIA PaCa‐2 PDAC tumors. Cetux‐Alexa‐647, but not the control hIgG‐Alexa‐750 fluorescence, was specifically detected in vivo in both primary pancreatic tumors with maximum fluorescence intensities at 24 h, and in metastases of AsPC‐1 tumors as small as 1 mm. Lifetime analysis and NIR fluorescence microscopy of tumor sections confirmed the binding specificity of Cetux‐Alexa‐647 to PDAC cells. Comparable results were obtained with Cetuximab conjugated to Alexa Fluor 750 dye (Cetux‐Alexa‐750). Fluorescence‐guided dissection, performed 24 h after injection of Cetuximab conjugated to IRDye 800CW (Cetux‐800CW), enabled a real‐time delineation of AsPC‐1 tumor margins, and small metastases. Odyssey scans revealed that only the vital part of the tumor, but not the necrotic part was stained with Cetux‐800CW. NIR fluorescently labeled Cetuximab may be a promising tool that can be applied for fluorescence‐guided surgery to visualize tumor margins and metastatic sites in order to allow a precise surgical resection.     

Management of acral myxoinflammatory fibroblastic sarcoma

BACKGROUND:

Acral myxoinflammatory fibroblastic sarcoma (AMFS) is a rare, low‐grade sarcoma that commonly affects the distal extremities. From the published cases, therapy for AMFS to date has been comprised of excision or amputation, with limited use of radiotherapy (RT) or chemotherapy. In this report, the outcome of 17 patients with AMFS treated at the study institution was reported.

METHODS:

A retrospective review of all cases of AMFS identified in the Sarcoma Database in the Department of Radiation Oncology at the study institution was conducted. Treatment records and data from follow‐up visits of patients were reviewed.

RESULTS:

Seventeen patients were identified. All the patients underwent surgical resection (15 excisions and 2 amputations). Positive surgical margins after excisions were noted in 5 patients and were widely positive in 1 patient. Of the 17 patients, 14 patients received some form of RT. The average total dose was 56.4 Gray (Gy). Eight patients received preoperative RT alone, 5 patients received preoperative RT and postoperative RT, and 1 patient received preoperative RT and intraoperative RT. Median follow‐up was 24.5 months. One patient presented with recurrent disease and was treated with resection, and both pre‐ and postoperative RT. He was free of disease 23 months after his last treatment. No local recurrence was noted in the remaining patients. Of the 14 patients undergoing preoperative RT, complete pathologic necrosis or no tumor was noted in 1 of the patients. No metastatic disease was observed in any of the patients. There was no significant radiation toxicity observed in any of the patients.

CONCLUSIONS:

Data were consistent with local control of distal extremity sarcomas with resection and RT, suggesting that limb‐sparing surgery with this treatment combination is an appropriate option in the limb‐sparing control of patients with AMFS, even those with positive surgical margins. Cancer 2010. © 2010 American Cancer Society.     

Computed tomography scan‐driven selection of treatment for retroperitoneal liposarcoma histologic subtypes

BACKGROUND:

Well differentiated (WD) and dedifferentiated (DD) retroperitoneal liposarcoma (RPLS) have distinct biologic behaviors. Consequently, the therapeutic approaches for these tumors differ and mandate an accurate preoperative diagnosis. The authors of this report evaluated whether computed tomography (CT) can be used to differentiate between WD and DD RPLS.

METHODS:

Imaging studies (CT, magnetic resonance imaging, and positron emission tomography‐CT) from 78 patients with RPLS who underwent surgery at the University of Texas M. D. Anderson Cancer Center (UTMDACC) between 2001 and 2007 were reviewed by a senior bone and soft tissue sarcoma radiologist who was blinded to the final histopathologic diagnosis. A focal nodular/water density area within an RPLS was interpreted as a marker suggestive of DD. Correlations between imaging diagnosis, histology, and clinical outcome were analyzed.

RESULTS:

The study radiologist identified 60 RPLS as DD and 17 RPLS as WD. A radiologic diagnosis of a WD was correlated with preoperative biopsy and postoperative histology in all patients (100%). Focal nodular/water density was a very sensitive marker of DD (97.8%); however, it had relatively low specificity (51.5%). Sixteen WD RPLS (48.5%) contained focal nodular/water density areas, leading to their misdiagnosis as DD; half of those tumors had hypercellular WD. Of 78 preoperative biopsies, 22 (28.2%) were performed at UTMDACC under CT guidance. Preoperative histologic diagnoses obtained from 12 biopsies derived from focal nodular/water density areas were confirmed as unchanged on final pathology; whereas, in 50% of biopsies that were not taken from a suspicious area, DD histology was misdiagnosed as WD.

CONCLUSIONS:

When CT features are suggestive of WD, no further diagnostic tests are needed for tumor characterization. Moreover, CT can accurately identify most DD, thereby rendering their under‐treatment unlikely; however, a CT‐guided biopsy is needed to differentiate between DD and WD RPLS that contain focal nodular/water density areas, thereby avoiding their over treatment. Cancer 2009. © 2009 American Cancer Society.     

Percutaneous computed tomography‐guided lung biopsy and pleural dissemination

BACKGROUND:

Percutaneous computed tomography (CT)‐guided needle biopsy remains one of the most important diagnostic tools in the management of lung nodules; however, it carries a risk of intrapleural dissemination of cancer cells.

METHODS:

CT‐guided lung biopsy was performed before surgery in 171 (34.8%) of 491 patients. A coaxial biopsy system was used that comprised a 19‐gauge introducer needle and a 20‐gauge core biopsy needle. A total of 412 (83.9%) of the 491 patients underwent intraoperative pleural lavage cytology just after thoracotomy. Intraoperative pleural lavage cytology was performed immediately after opening the thorax, after the pleural cavity was gently washed with 50 mL of saline.

RESULTS:

No patients had implantation of cancer cells in the chest wall after a median follow‐up of 20.2 months. Intraoperative pleural lavage cytology results were positive for 5 (2.9%) of the 171 patients who underwent CT‐guided biopsy before surgery, in contrast to 13 (5.4%) of the 241 patients who did not undergo biopsy before surgery. The difference between the biopsy and nonbiopsy groups was not statistically significant. When the analysis was limited to patients with stage IA disease, intraoperative pleural lavage cytology results were positive for 1 (0.8%) of the 128 patients who underwent CT‐guided biopsy, in contrast to 3 (2.7%) of the 110 patients who did not undergo biopsy. This difference was also not statistically significant.

CONCLUSIONS:

No significant association was observed between percutaneous CT‐guided lung biopsy and intraoperative pleural lavage cytology results, even in patients with stage IA disease. Percutaneous CT‐guided lung biopsy with a coaxial needle does not seem to cause pleural dissemination. Cancer 2009. © 2009 American Cancer Society.     

Fluorescence-guided surgery in colorectal cancer; A review on clinical results and future perspectives

BackgroundColorectal cancer is the fourth most diagnosed malignancy worldwide and surgery is one of the cornerstones of the treatment strategy. Near-infrared (NIR) fluorescence imaging is a new and upcoming technique, which uses an NIR fluorescent agent combined with a specialised camera that can detect light in the NIR range. It aims for more precise surgery with improved oncological outcomes and a reduction in complications by improving discrimination between different structures.MethodsA systematic search was conducted in the Embase, Medline and Cochrane databases with search terms corresponding to ‘fluorescence-guided surgery’, ‘colorectal surgery’, and ‘colorectal cancer’ to identify all relevant trials.ResultsThe following clinical applications of fluorescence guided surgery for colorectal cancer were identified and discussed: (1) tumour imaging, (2) sentinel lymph node imaging, (3) imaging of distant metastases, (4) imaging of vital structures, (5) imaging of perfusion. Both experimental and FDA/EMA approved fluorescent agents are debated. Furthermore, promising future modalities are discussed.ConclusionFluorescence-guided surgery for colorectal cancer is a rapidly evolving field. The first studies show additional value of this technique regarding change in surgical management. Future trials should focus on patient related outcomes such as complication rates, disease free survival, and overall survival.     

Long-term outcome of the treatment of high-risk tenosynovial giant cell tumor/pigmented villonodular synovitis with radiotherapy and surgery

BACKGROUND:

The treatment of diffuse tenosynovial giant cell tumor (TGCT) requires extensive surgical resection of the hypertrophic synovium and multiple soft tissue masses yet still may result in high rates of local failure. The authors of this report examined their experience in treating patients with advanced/multiply recurrent TGCT with a combination of surgery and external‐beam radiotherapy.

METHODS:

Fifty patients who were treated for TGCT with radiotherapy and surgery from 1972 to 2006 were identified. Patient demographics, radiotherapy treatment parameters, surgical treatment, and oncologic and functional outcomes were evaluated. All patients had pathologic review at presentation and required at least 1 year follow‐up.

RESULTS:

Forty‐nine patients had diffuse TGCT with both intra‐articular and extra‐articular disease (1 had malignant TGCT). Twenty‐eight patients (56%) were referred after at least 1 local recurrence. Thirty patients (60%) underwent at least 2 operations before radiotherapy. The mean dose of radiation delivered was 39.8 gray. At a mean follow‐up of 94 months (range, 19‐330 months), 47 patients (94%) had not developed a recurrence or had stable disease/signal characteristics on serial cross‐sectional imaging (for those patients who had gross residual disease at the time of radiotherapy). Two patients required subsequent total hip arthroplasty because of progressive osteoarthritis, and there were 4 cases of avascular necrosis (only 1 post‐treatment). Forty‐one patients had good/excellent function.

CONCLUSIONS:

For patients with extensive or multiple local relapses or when surgery alone would result in a large burden of residual disease or major functional loss, the addition of moderate‐dose adjuvant radiotherapy provided excellent local control while maintaining good function with low treatment‐related morbidity. Cancer 2012. © 2012 American Cancer Society.     

Influence of compartmental involvement on the patterns of morbidity in soft tissue sarcoma of the thigh

BACKGROUD:

The authors sought to determine whether differences existed in patterns of outcome and morbidity between the 3 thigh compartments after limb‐sparing surgery and postoperative radiation therapy (RT).

METHODS:

A total of 255 patients with primary soft tissue sarcoma (STS) of the thigh were identified in our sarcoma database (1982–2002). More than 80% of tumors were >5 cm, high grade, and deep; 33% had close or positive microscopic resection margins. Adjuvant RT consisted of brachytherapy alone (BRT; 63%), external beam RT alone (EBRT; 31%), or a combination of brachytherapy and EBRT (6%). There were 125 anterior, 58 medial, and 72 posterior lesions. The 3 compartments were balanced as to tumor grade, size, depth, margin status, and RT type.

RESULTS:

Overall local control (LC) was 89%, distant metastases‐free survival (DMFS) was 61%, and overall survival (OS) was 66% at 5 years (median follow‐up, 71 months). Overall rates for complications at 5 years were wound reoperation (10%), edema (13%), joint stiffness (12%), nerve damage (8%), and bone fractures (7%). Wound reoperation and edema were significantly higher for medial‐compartment tumors (P = .01 and .005, respectively), whereas nerve damage occurred more frequently in posterior‐compartment tumors (P < .001). There were no differences among bone fracture, joint stiffness, DMFS, or OS rates between compartments.

CONCLUSIONS:

Although tumor control was similar for all 3 compartments, more wound reoperation and edema were observed in the medial compartment, and more nerve damage was noted in the posterior compartment. These results may help guide decisions concerning current patients and improve the design of future treatments tailored to compartments. Cancer 2009. © 2008 American Cancer Society.     

18F‐Fluorodeoxyglucose positron emission tomography/computed tomography for the detection of recurrent bone and soft tissue sarcoma

BACKGROUND:

The clinical utility of modern hybrid imaging modalities for detecting recurrent bone or soft tissue sarcoma remains to be determined. In this report, the authors present a clinical study on the diagnostic accuracy and incremental value of integrated ¹⁸F‐fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F‐FDG PET/CT) in patients with a history of sarcoma who have clinically suspected disease recurrence.

METHODS:

Forty‐three patients who had a history of bone or soft tissue sarcoma and had documented complete remission underwent ¹⁸F‐FDG PET/CT. Image analysis was performed independently for ¹⁸F‐FDG PET (n = 43) and for contrast‐enhanced spiral CT (CE‐CT) (n = 30) by 2 separate readers, whereas combined ¹⁸F‐FDG PET/CT (n = 43) images were analyzed in consensus by both readers. Imaging findings were rated on a 5‐point scale and finally were reported as malignant, benign, or equivocal. Imaging findings were validated either by histopathology (n = 24) or by clinical follow‐up (n = 19).

RESULTS:

¹⁸F‐FDG PET/CT had greater sensitivity and specificity compared with CE‐CT alone (94% and 92% vs 78% and 67%, respectively), resulting in significantly greater accuracy (93% vs 73%; P = .03). ¹⁸F‐FDG PET/CT was particularly superior regarding detection of local recurrence or soft tissue lesions (sensitivity and specificity: 83% and 100% vs 50% and 100%, respectively) or bone metastases (100% and 100% vs 85% and 88%, respectively).

CONCLUSIONS:

¹⁸F‐FDG PET/CT had greater diagnostic accuracy in the detection of recurrent bone or soft tissue sarcoma compared with CE‐CT alone. The detection of local recurrence was the most evident advantage of ¹⁸F‐FDG PET/CT over CE‐CT. Cancer 2013. © 2012 American Cancer Society.     

Clinical outcomes for patients with soft tissue sarcoma of the hand

BACKGROUND:

In an earlier report from the current study center regarding surgical treatment for patients with soft tissue sarcoma (STS) of the hand, it was concluded that repeat resection or amputation improves outcomes. Since then, the authors have aggressively sought to achieve negative resection margins, using standard or modified amputations when needed, and performing repeat resections to negative surgical margins when they were not achieved at the time of initial surgery. The current review was conducted to determine whether this approach resulted in better outcomes.

METHODS:

A retrospective review of 53 patients with STS of the hand who were treated between 1996 and 2005 was performed. Recurrence‐free survival (RFS) and functional outcome of hand‐preserving procedures were assessed according to the Musculoskeletal Tumor Society (MSTS) system.

RESULTS:

The median RFS was not reached at the time of last follow‐up. Of 53 patients, 6 (11%) had positive microscopic resection margins. Three patients underwent repeat resection to negative surgical margins, whereas another 3 patients did not. All 3 patients with positive microscopic surgical margins that were not re‐excised developed local disease recurrence; 2 patients also developed distant metastases. Two of the 50 patients with negative resection margins developed distant metastases. All 5 patients who developed local and/or distant disease recurrence had deep tumors. The median MSTS score was 29 (interquartile range, 27‐30). Patients who underwent more extensive resections, such as double ray amputations, had lower MSTS scores.

CONCLUSIONS:

Suboptimal biopsies and positive resection margins are associated with local and distant disease recurrence in patients with STS. The results of the current study suggest that aggressive surgical treatment can result in better clinical outcomes, and underscore that care must be taken when planning biopsies of hand tumors. Cancer 2011. © 2010 American Cancer Society.     

Age-related disparities in the use of radiotherapy for treatment of localized soft tissue sarcoma

BACKGROUND:

Many elderly patients with cancer experience increased cancer‐related morbidity and mortality compared with younger patients. In soft tissue sarcoma, adjuvant radiotherapy is an integral part of definitive therapy for limb preservation. The authors of this report hypothesized that age‐related disparities exist in the use of radiation.

METHODS:

Surveillance, Epidemiology, and End Results (SEER) data were used to conduct a retrospective cohort study among patients aged ≥25 years who were diagnosed from 1998 to 2004 with nonmetastatic, biopsy‐proven, high‐grade soft tissue sarcoma of the extremities and underwent a limb‐sparing procedure. Patients were stratified according to age (ages <50 years, 50‐70 years, and >70 years). Logistic regression was used to determine the association between age and the receipt of radiotherapy adjusting for histology, tumor location, tumor size, surgery, sex, race, and marital status. A Cox proportional hazards model was used to compare disease‐specific and all‐cause mortality.

RESULTS:

Among 1354 eligible patients; 37.1% were aged >70 years, 44.3% were women, and 84.4% were Caucasian. Although 73.8% of the cohort received radiotherapy, receipt decreased from 78.2% among patients aged <50 years to 69.6% among patients aged >70 years (test for trend; P = .006). After adjusting for demographic and tumor factors, older patients remained less likely to receive radiotherapy (odds ratio, 0.66; 95% confidence interval, 0.47‐0.92) and more likely to experience disease‐specific death (hazard ratio, 2.4; 95% confidence interval, 1.4‐4.1) compared with the youngest group.

CONCLUSIONS:

Older adults appeared to be less likely to receive definitive therapy for soft tissue sarcoma of the extremities. In the absence of clinical trials and treatment guidelines tailored to this population, under treatment may disadvantage elderly patients, who have increased cancer‐related morbidity and mortality. Cancer 2011;. © 2011 American Cancer Society.     

Serous cystadenoma of the pancreas

BACKGROUND

Expectant management of serous cystadenoma (SCA) of the pancreas requires an accurate preoperative diagnosis. Previously published cytologic diagnostic sensitivities have ranged widely, from 10% to 100%. In the current study, the authors evaluated the diagnostic sensitivity of endoscopic ultrasound (EUS)‐guided fine‐needle aspiration biopsy (FNAB) and cross‐sectional imaging for SCA.

METHODS

Group I consisted of 21 histologically confirmed SCAs. Group II (n = 7 lesions) lacked histologic confirmation and was defined by EUS findings that were consistent with SCA and a cyst fluid carcinoembryonic antigen (CEA) level <5 ng/mL. Group III was comprised of 2 nonserous and potentially malignant cysts of the pancreas for which a preoperative diagnosis of SCA was considered. Cross‐sectional imaging data were recorded. The smears were evaluated for the presence of serous lining epithelium, gastrointestinal‐contaminating epithelium, and inflammatory cells including hemosiderin‐laden macrophages. The authors also evaluated the presence of hemosiderin‐laden macrophages in a series of 110 FNA specimens from histologically confirmed neoplastic mucinous cysts of the pancreas and 45 pseudocysts of the pancreas.

RESULTS

Prospectively among Group I lesions, the appearance on computed tomography (CT) was considered definitive for SCA in 3 of 12 cases (25%). The histologically confirmed SCA cases had CEA levels of <5 ng/mL, except for 1 case for which the CEA level was 176.5 ng/mL. A cytologic diagnosis of SCA was made prospectively in only 1 CT‐guided case. Retrospectively, 3 intraoperative FNAs and 1 additional CT‐guided aspirate contained rare epithelial cells of a SCA. None of the EUS‐guided aspirates demonstrated serous epithelium. Among Group II aspiration specimens, only 1 contained serous epithelial cells. Approximately 52% of the EUS‐guided aspirates demonstrated gastrointestinal contamination. This glandular epithelium was categorized as atypical in 2 cases. Hemosiderin‐laden macrophages were identified in 43% of the SCAs. Conversely, only 2% of neoplastic mucinous cysts and 9% of pseudocysts produced hemosiderin‐laden macrophages in aspirate fluid.

CONCLUSIONS

In the current study, serous epithelial cells were identified in <20% of cases. Gastrointestinal‐contaminating epithelium, often observed in EUS‐guided aspirates, further contributes to difficulties in interpretation. The presence of hemosiderin‐laden macrophages as a surrogate marker for SCA requires further study. A preoperative diagnosis of SCA remains a challenge, and an EUS‐guided FNAB is unlikely to provide the high level of diagnostic accuracy necessary to permit a nonoperative approach. Cancer (Cancer Cytopathol) 2008. © 2008 American Cancer Society.     

Near-infrared fluorescence (NIRF) imaging in breast-conserving surgery: Assessing intraoperative techniques in tissue-simulating breast phantoms

Purpose

Breast-conserving surgery (BCS) results in tumour-positive surgical margins in up to 40% of the patients. Therefore, new imaging techniques are needed that support the surgeon with real-time feedback on tumour location and margin status. In this study, the potential of near-infrared fluorescence (NIRF) imaging in BCS for pre- and intraoperative tumour localization, margin status assessment and detection of residual disease was assessed in tissue-simulating breast phantoms.

Methods

Breast-shaped phantoms were produced with optical properties that closely match those of normal breast tissue. Fluorescent tumour-like inclusions containing indocyanine green (ICG) were positioned at predefined locations in the phantoms to allow for simulation of (i) preoperative tumour localization, (ii) real-time NIRF-guided tumour resection, and (iii) intraoperative margin assessment. Optical imaging was performed using a custom-made clinical prototype NIRF intraoperative camera.

Results

Tumour-like inclusions in breast phantoms could be detected up to a depth of 21 mm using a NIRF intraoperative camera system. Real-time NIRF-guided resection of tumour-like inclusions proved feasible. Moreover, intraoperative NIRF imaging reliably detected residual disease in case of inadequate resection.

Conclusion

We evaluated the potential of NIRF imaging applications for BCS. The clinical setting was simulated by exploiting tissue-like breast phantoms with fluorescent tumour-like agarose inclusions. From this evaluation, we conclude that intraoperative NIRF imaging is feasible and may improve BCS by providing the surgeon with imaging information on tumour location, margin status, and presence of residual disease in real-time. Clinical studies are needed to further validate these results.     

Malignant sarcoma of the pelvic bones: treatment outcomes and prognostic factors vary by histopathology

BACKGROUND:

Treatment of malignant sarcomas of the pelvis poses a challenge for local disease control and oncologic outcome. Many reports have described the dismal outcomes. Most studies are retrospective series coming out of single centers, thus biased toward patient selection and are of limited statistical power.

METHODS:

The authors used the Surveillance, Epidemiology, and End Results database to analyze 1185 pelvic sarcoma cases from 1987 to 2006. Kaplan‐Meier and Cox regression were used to analyze the significance of prognostic factors. The analysis was repeated for different histopathological subtypes to determine specific prognostic factors in each case.

RESULTS:

Incidence of pelvic sarcoma in 2006 was 89 per 100,000 persons; it has significantly increased since 1973 (P < .05). The overall 5‐year survival for all the patients with pelvic sarcoma was 47%, with osteosarcoma having the worst 5‐year survival at 19% and patients with chordoma having the best 5‐year survival at 60%. Independent prognostic factors included age, stage, grade, size of primary lesion, histopathology, and treatment‐related factors. Comparing the patients only with high‐grade lesions, patients with Ewing sarcoma have the best prognosis.

CONCLUSIONS:

This is an analysis of patients with pelvic sarcomas derived from a population‐based registry. Survival and prognostics vary with histopathological diagnoses. Although surgical resection was associated with superior outcomes for osteosarcoma and chondrosarcoma, there was no significant difference in outcomes of patients with Ewing sarcoma treated with surgery and/or radiotherapy. Cancer 2011. © 2010 American Cancer Society.     

Intraoperative near-infrared fluorescence imaging of colorectal metastases targeting integrin αvβ3 expression in a syngeneic rat model

Aim

Near-infrared (NIR) fluorescence optical imaging is a promising technique to assess the extent of colorectal metastases during curative-intended surgery. However, NIR fluorescence imaging of liver metastases is highly challenging due to hepatic uptake and clearance of many fluorescent dyes. In the current study, the biodistribution and the ability to demarcate liver and peritoneal metastases were assessed during surgery in a syngeneic rat model of colorectal cancer using an integrin α_vβ₃-directed NIR fluorescence probe.

Methods

Liver tumors and peritoneal metastases were induced in 7 male WAG/Rij rats by subcapsular inoculation of 0.5 × 10⁶ CC531 colorectal cancer rat cells into three distinct liver lobes. Intraoperative and ex vivo fluorescence measurements were performed 24 (N = 3 rats, 7 tumors) and 48 h (N = 4 rats, 9 tumors) after intravenous administration of the integrin α_vβ₃-directed NIR fluorescence probe.

Results

Colorectal metastases had a minimal two-fold higher NIR fluorescence signal than healthy liver tissue and other abdominal organs (p < 0.001). The tumor-to-background ratio was independent of time of imaging (24 h vs. 48 h post-injection; p = 0.31), which facilitates flexible operation planning in future clinical applications. Total fluorescence intensity was significantly correlated with the size of metastases (R² = 0.92 for the 24 h group, R² = 0.96 for the 48 h group).

Conclusion

These results demonstrate that colorectal intra-abdominal metastases can be clearly demarcated during surgery using an integrin α_vβ₃ targeting NIR fluorescence probe. Translating these findings to the clinic will have an excellent potential to substantially improve the quality of cancer surgery.