Hyperthermia, the procedure of raising the temperature of tumour-loaded tissue to 40-43 degrees C, is applied as an adjunctive therapy with various established cancer treatments such as radiotherapy and chemotherapy. The potential to control power distributions in vivo has been significantly improved lately by the development of planning systems and other modelling tools. This increased understanding has led to the design of multiantenna applicators (including their transforming networks) and implementation of systems for monitoring of E-fields (eg, electro-optical sensors) and temperature (particularly, on-line magnetic resonance tomography). Several phase III trials comparing radiotherapy alone or with hyperthermia have shown a beneficial effect of hyperthermia (with existing standard equipment) in terms of local control (eg, recurrent breast cancer and malignant melanoma) and survival (eg, head and neck lymph-node metastases, glioblastoma, cervical carcinoma). Therefore, further development of existing technology and elucidation of molecular mechanisms are justified. In recent molecular and biological investigations there have been novel applications such as gene therapy or immunotherapy (vaccination) with temperature acting as an enhancer, to trigger or to switch mechanisms on and off. However, for every particular temperature-dependent interaction exploited for clinical purposes, sophisticated control of temperature, spatially as well as temporally, in deep body regions will further improve the potential.

https://www.thelancet.com/pdfs/journals/lanonc/PIIS1470-2045(02)00818-5.pdf

Hyperthermia in combined treatment of cancer

In oncology, the term 'hyperthermia' refers to the treatment of malignant diseases by administering heat in various ways. Hyperthermia is usually applied as an adjunct to an already established treatment modality (especially radiotherapy and chemotherapy), where tumor temperatures in the range of 40-43 degrees C are aspired. In several clinical phase-III trials, an improvement of both local control and survival rates have been demonstrated by adding local/regional hyperthermia to radiotherapy in patients with locally advanced or recurrent superficial and pelvic tumors. In addition, interstitial hyperthermia, hyperthermic chemoperfusion, and whole-body hyperthermia (WBH) are under clinical investigation, and some positive comparative trials have already been completed. In parallel to clinical research, several aspects of heat action have been examined in numerous pre-clinical studies since the 1970s. However, an unequivocal identification of the mechanisms leading to favorable clinical results of hyperthermia have not yet been identified for various reasons. This manuscript deals with discussions concerning the direct cytotoxic effect of heat, heat-induced alterations of the tumor microenvironment, synergism of heat in conjunction with radiation and drugs, as well as, the presumed cellular effects of hyperthermia including the expression of heat-shock proteins (HSP), induction and regulation of apoptosis, signal transduction, and modulation of drug resistance by hyperthermia.

The cellular and molecular basis of hyperthermia.

https://www.biophysik.physik.uni-muenchen.de/download/biopheinf/seminar_talks/16Hyperthermie.pdf

Magnetic fluid hyperthermia (MFH): Cancer treatment with AC magnetic field induced excitation of biocompatible superparamagnetic nanoparticles

Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as "optical biopsy," was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

In Vivo Endoscopic Optical Biopsy with Optical Coherence Tomography

Statistical Methods in Medical Research.

Ever since Kitai first performed fluorescent navigation of sentinel lymph nodes (SLNs) using indocyanine green (ICG) dye with a charge-couple device and light emitting diodes, the intraoperative use of near infrared fluorescence has served a critical role in increasing our understanding in various fields of surgical oncology. Here the authors review the emerging role of the ICG fluorophore in the development of our comprehension of the lymphatic system and its use in SLN mapping and biopsy in various cancers. In addition, they introduce the novel role of ICG-guided video angiography as a new intraoperative method of assessing microvascular circulation. The authors attempt to discuss the promising potential in addition to assessing several challenges and limitations in the context of specific surgical procedures and ICG as a whole. PubMed and Medline literature databases were searched for ICG use in clinical surgical settings. Despite ICG's significant impact in various fields of surgical oncology, ICG is still in its nascent stages, and more in-depth studies need to be carried out to fully evaluate its potential and limitations.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.26087

Current trends and emerging future of indocyanine green usage in surgery and oncology: a literature review.

Background: Sentinel lymph node (SLN) biopsy is a selective approach to axillary staging of breast cancer with reduced morbidity. Current detection methods including radioisotope and blue dye show good results but some drawbacks are remaining. Indocyanine green (ICG) fluorescence detection was evaluated as a new method for SLN biopsy in breast cancer allowing both transcutaneous visualization of lymphatic vessels and intraoperative identification of SLN. Methods: Forty-three women with clinically node negative breast cancer received subareolar injection of ICG for fluorescence detection of SLN. All patients underwent either planned axillary lymph node dissection (ALND) with SLN biopsy or selective SLN biopsy to determine need for ALND. Clinical feasibility, detection rate, sensitivity, and axillary recurrence after isolated SLN biopsy were analyzed. Results: Overall ICG fluorescence imaging identified 2.0 SLN in average in 42 of 43 patients (detection rate: 97.7%). Metastatic involvement of the SLN was found in 17 of 18 nodal positive patients by conventional histopathology (sensitivity: 94.4%). Immunohistochemistry revealed isolated tumor cells in five further cases. There was only one false-negative case in 43 patients (5.6%). In 17 of 23 overall nodal positive patients, the SLN was the only positive lymph node. After a median follow-up of 4.7 years none of the patients presented with axillary recurrence. Conclusion: ICG fluorescence imaging is a new method for SLN biopsy in breast cancer with acceptable sensitivity and specificity comparable to conventional methods. One advantage of this technique is that it allows transcutaneous visualization of lymphatic vessels and intraoperative lymph node detection without radioisotope.

/pdf/icg-fluorescence-guided-sentinel-node-biopsy-for-axillary-169ybru2ln.pdf

ICG fluorescence-guided sentinel node biopsy for axillary nodal staging in breast cancer

The aim of this study was to compare CT, MRI and FDG-PET in the prediction of outcome of neoadjuvant radiochemotherapy in patients with locally advanced primary rectal cancer. A total of 23 patients with T3/4 rectal cancer underwent a preoperative radiochemotherapy combined with regional hyperthermia. Staging was performed using four-slice CT (n=23), 1.5-T MRI (n=10), and (18)F-FDG-PET (n=23) before and 2-4 weeks after completion of neoadjuvant treatment. Response criteria were a change in T category and tumour volume for CT and MRI and a change in glucose uptake (standard uptake value) within the tumour for FDG-PET. Imaging results were compared with those of pretherapy endorectal ultrasound and histopathological findings. Histopathology showed a response to neoadjuvant therapy in 13 patients whereas 10 patients were classified as nonresponders. The mean SUV reduction in responders (60+/-14%) was significantly higher than in nonresponders (37+/-31%; P=0.030). The sensitivity and specificity of FDG-PET in identifying response was 100% (CT 54%, MRI 71%) and 60% (CT 80%, MRT 67%). Positive and negative predictive values were 77% (CT 78%, MRI 83%) and 100% (CT 57%, MRI 50%) (PET P=0.002, CT P=0.197, MRI P=0.500). These results suggest that FDG-PET is superior to CT and MRI in predicting response to preoperative multimodal treatment of locally advanced primary rectal cancer.

Comparison of CT, MRI and FDG-PET in response prediction of patients with locally advanced rectal cancer after multimodal preoperative therapy: Is there a benefit in using functional imaging?

Background:

Sentinel lymph node (SLN) biopsy with radioisotope and blue dye has been used successfully for axillary staging in breast cancer. This study evaluated the feasibility of fluorescence detection of SLNs with indocyanine green (ICG) for lymphatic mapping and SLN biopsy.



Methods:

Thirty women with breast cancer had a periareolar injection of ICG for fluorescence detection of SLN using a near-infrared camera. Twenty also received 99mTc-labelled sulphur radiocolloid for SLN scintigraphy. All patients underwent axillary lymph node dissection. Detection rate and sensitivity of both methods were the study endpoints.



Results:

Visualization of lymphatic vessels by fluorescence detection depended on the dose of ICG. ICG imaging identified SLNs in 29 of 30 women (detection rate 97 per cent). Nineteen of 21 patients had metastatic SLN involvement (sensitivity 90 per cent) with false-negative results in two. Among the 20 patients who had both methods, ICG fluorescence and radiocolloid identified SLNs in 20 and 17 patients respectively. Metastatic lymph nodes were diagnosed in 12 and ten of 13 patients (sensitivity 92 and 77 per cent). False-negative rates were 8 and 23 per cent respectively.



Conclusion:

ICG fluorescence allowed transcutaneous imaging of lymphatic vessels and SLN detection, thus combining the advantages of radioisotope and blue dye methods. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

Sentinel lymph node biopsy in breast cancer guided by indocyanine green fluorescence.

Despite advances in the various treatment modalities, surgery continues to be the mainstay of treatment of patients with resectable esophageal cancer. Five-year survival rates as high as 40% to 50% have been achieved after curative resection in specialized centers.1,2 Esophagectomy remains a challenging operation that can be associated with considerable postoperative morbidity and mortality.3,4 The most frequently reported major complications include respiratory failure and anastomotic leaks. Cervical anastomoses have been associated with leakage rates of 10% to 20%, but leak-related mortality is low.5,6 Leaks from thoracic anastomoses occur in 5% to 10% of the cases and carry mortality rates as high as 30% to 60%.7–9 The most efficient treatment of such leaks remains controversial. Aggressive surgical treatment has been recommended by some authors, whereas others advocate a more conservative approach using perianastomotic drainage, total parenteral nutrition, nasogastric decompression, and broad-spectrum antibiotics.10,11

The aim of this study was to prospectively evaluate the efficacy of self-expanding plastic stents in the treatment of thoracic anastomotic leaks after esophagectomy and to compare the results with conventional treatment.

Michael Hünerbein

Papers

Current trends and emerging future of indocyanine green usage in surgery and oncology: a literature review.

ICG fluorescence-guided sentinel node biopsy for axillary nodal staging in breast cancer

Comparison of CT, MRI and FDG-PET in response prediction of patients with locally advanced rectal cancer after multimodal preoperative therapy: Is there a benefit in using functional imaging?

Sentinel lymph node biopsy in breast cancer guided by indocyanine green fluorescence.

Treatment of thoracic anastomotic leaks after esophagectomy with self-expanding plastic stents.