Preservation Of Normal Tissue Research Articles

Two-color fluorescence-guided surgery for head and neck cancer resections.

Head and neck squamous cell carcinoma (HNSCC) has the sixth highest incidence worldwide, with cases annually. Surgery is the primary treatment option for HNSCC, during which surgeons balance two main goals: (1)complete cancer resection and (2)preservation of normal tissues to ensure post-surgical quality of life. Unfortunately, these goals are not synergistic, where complete cancer resection is often limited by efforts to preserve normal tissues, particularly nerves, and reduce life-altering comorbidities. Currently, no clinically validated technology exists to enhance intraoperative cancer and nerve recognition. Fluorescence-guided surgery (FGS) has successfully integrated into clinical medicine, providing surgeons with real-time visualization of important tissues and complex anatomy, where FGS imaging systems operate almost exclusively in the near-infrared (NIR, 650 to 900nm). Notably, this spectral range permits the detection of two NIR imaging channels for spectrally distinct detection. Herein, we evaluated the utility of spectrally distinct NIR nerve- and tumor-specific fluorophores for two-color FGS to guide HNSCC surgery. Using a human HNSCC xenograft murine model, we demonstrated that facial nerves and tumors could be readily differentiated using these nerve- and tumor-specific NIR fluorophores. The selected nerve-specific fluorophore showed no significant difference in nerve specificity and off-target tissue fluorescence in the presence of xenograft head and neck tumors. Co-administration of two NIR fluorophores demonstrated successful tissue-specific labeling of nerves and tumors in spectrally distinct NIR imaging channels. We demonstrate a comprehensive FGS tool for cancer resection and nerve sparing during HNSCC procedures for future clinical translation.

Improved ex vivo fluorescence imaging of human head and neck cancer using the peptide tracer TPP-IRDye800 targeting membrane-bound Hsp70 on tumor cells.

The primary goal of surgery in HNSCC is the complete resection of tumor cells with maximum preservation of normal tissue. The membrane Hsp70-targeting fluorescence labelled peptide TPP-IRDye800 represents a promising tool for real-time intraoperative tumor visualization, enabling the detection of true tumor margins, critical isles of high-grade dysplasia and LN metastases. Membrane Hsp70 (mHsp70) expression on HNSCC cell lines and primary HNSCC was determined by flow cytometry and fluorescence microscopy using FITC-conjugated mAb cmHsp70.1 and TPP. TPP-IRDye800 was sprayed on freshly resected tumor material of immunohistochemically confirmed HNSCC and LN metastases for tumor imaging. TBRs were compared using TPP-IRDye800 and Cetuximab-IRDye680, recognizing EGFR. mHsp70 expressing HNSCC cells specifically bind and internalize TPP in vitro. The TBR (2.56 ± 0.39) and AUC [0.98 CI, 0.95-1.00 vs. 0.91 CI, 0.85-0.97] of TPP-IRDye800 on primary HNSCC was significantly higher than Cetuximab-IRDye680 (1.61 ± 0.39) (p = 0.0068) and TPP-IRDye800 provided a superior tumor delineation. Fluorescence imaging showed higher AUC values than a visual inspection by surgeons [0.97 CI, 0.94-1.00 vs. 0.92 CI, 0.88-0.97] (p = 0.048). LN metastases could be visualized using TPP-IRDye800. Real-time tissue delineation was confirmed using the clinically applied KARL-STORZ imaging system. TPP-IRDye800 is a promising fluorescence imaging probe for HNSCC.

Minimizing Tissue Injury and Incisions in Multilevel Biportal Endoscopic Spine Surgery: Technical Note and Preliminary Results.

Background and Objectives: Biportal endoscopic spine surgery (BESS) is a promising technique that can be applied for the treatment of various spinal diseases. However, traditional BESS procedures require multiple, separate incisions. We present, herein, various techniques to reduce the number of incisions in multi-level surgery and their clinical outcomes. Materials and Methods: Three different techniques were used to reduce the number of incisions for the preservation of normal tissue associated with BESS: the step-ladder technique, employing a common portal for the scope and instruments; the portal change technique employing a two-level procedure with two incisions; and the tilting technique, employing more than three levels. Pain (Visual Analog Scale), disability (Oswestry Disability Index), and patient satisfaction were evaluated before and 12 months after the procedure. Results: Among the 122 cases of multilevel spine surgery, 1.43 incisions per level were employed for multilevel BESS. Pain and disability showed significant improvement. Patient satisfaction showed favorable results. Conclusions: Combining multiple techniques during biportal surgery could decrease the number of incisions needed and preserve musculature with favorable clinical outcomes.

Multimodal Use of Contact Endoscopy in Neurosurgery: Case Series with Technical Note and Literature Review

BackgroundOriginally adopted for the cytological screening of cervical and uterine cancer, contact endoscopy (CE) is now widely used in several fields of oncological surgery. The CE method, with magnification power up to 150x, was designed to enhance visualization and identify microscopic changes indicative of pre-cancerous and cancerous lesions at early stages. In this pilot study, we evaluated the multimodal applications of CE during different endoscopic intracranial neurosurgical procedures. MethodsTwenty patients with skull base lesions underwent surgery using different minimally invasive endoscopic approaches (endonasal, transorbital, and supraorbital). CE was used to distinguish the pathology from the surrounding healthy tissue by positioning the endoscope either in proximity or directly onto the target tissue. Special attention was given to the visualization of the margins of the lesion to differentiate compression/displacement from infiltration of the normal surrounding tissue. ResultsWith its unprecedented range of magnification, CE could clearly identify the microvascular pattern and cytological architecture of a tissue not detectable by simple white light endoscopy, with no reported damage due to heat transmission or iatrogenic injuries. All the lesions diagnosed as “presumed neoplastic tissue” by CE were confirmed by histopathology. The most promising results were observed in surgeries for meningioma and pituitary adenoma, as these lesions exhibit distinctive microvascular networks. ConclusionCE represents a new and effective technique for the in vivo identification of pathological microvascular and tissue features, allowing preservation of normal tissue during different endoscopic approaches. The use of CE could improve diagnostic accuracy and assist in intraoperative decision-making, becoming a key tool in various applications in neurosurgical field.

Effective resection of dermatofibrosarcoma protuberans using the novel Saturn's rings technique.

Dermatofibrosarcoma protuberans (DFSP) is a rare, low-grade sarcoma with locally infiltrative characteristics. A wide excision is made with a 5 cm gross margin. However, recently, Mohs micrographic surgery has emerged as an alternative. In this study, we evaluate a novel method (Saturn's Rings technique) for removing tumors that combines the advantages of wide excision and Mohs micrographic surgery. Between September 2001 and March 2020, 29 patients with DFSP, excluding the head and neck, were treated using Saturn's rings technique. Frozen biopsies were performed at regular intervals under various conditions and depths. If the biopsy was positive, a negative margin was obtained through an additional session. The depth and breadth of excision, reconstruction method, and postoperative recurrence were analyzed. The breadth of excision was evaluated at 1 cm intervals. Only 1 session was required in 12 cases, 2 sessions were needed in 13 cases, and 3 or more sessions were performed in 4 cases. In 24 cases, the depth of excision was limited to above the superficial fascia, with a negative biopsy of the superficial fascia. Local flaps were the most common reconstruction method (n = 21, 72.4%). No cases of recurrence were observed at follow-up (average, 45.7 months). Saturn's rings technique for DFSP maximized the preservation of normal tissue with minimal resection, was advantageous for reconstruction, and yielded good results without recurrence.

Functioning Endocrine Outcome after Endoscopic Endonasal Transsellar Approach for Pituitary Neuroendocrine Tumors.

The endoscopic endonasal approach (EEA) is a well-established technique for the treatment of pituitary neuroendocrine tumor Preservation of normal gland tissue is crucial to retain effective neuroendocrine pituitary function. The aim of this paper is to analyze pituitary endocrine secretion after EEA for pituitary neuroendocrine tumor to identify potential predictors of functioning gland recovery. Patients who underwent an exclusive EEA for pituitary neuroendocrine tumors between October 2014 and November 2019 were reviewed. Patients were divided into groups according to postoperative pituitary function (Group 1, unchanged; group 2, recovering; group 3, worsening). Among the 45 patients enrolled, 15 presented a silent tumor and showed no hormonal impairment, and 30 patients presented pituitary dysfunction. A total of 19 patients (42.2%) were included in group 1, 12 (26.7%) patients showed pituitary function recovery after surgery (group 2), and 14 patients (31.1%) exhibited the onset of new pituitary deficiency postoperatively (group 3). Younger patients and those with functioning tumor were more likely to have complete pituitary hormonal recovery (p = 0.0297 and p = 0.007, respectively). No predictors of functional gland worsening were identified. EEA for pituitary neuroendocrine tumor is a reliable and safe technique regarding postoperative hormonal function. Preserving pituitary function after tumor resection should be a primary goal in a minimally invasive approach.

Effects of Microbeam Irradiation on Rodent Esophageal Smooth Muscle Contraction.

High-dose-rate radiotherapy has shown promising results with respect to normal tissue preservation. We developed an ex vivo model to study the physiological effects of experimental radiotherapy in the rodent esophageal smooth muscle. We assessed the physiological parameters of the esophageal function in ex vivo preparations of the proximal, middle, and distal segments in the organ bath. High-dose-rate synchrotron irradiation was conducted using both the microbeam irradiation (MBI) technique with peak doses greater than 200 Gy and broadbeam irradiation (BBI) with doses ranging between 3.5-4 Gy. Neither MBI nor BBI affected the function of the contractile apparatus. While peak latency and maximal force change were not affected in the BBI group, and no changes were seen in the proximal esophagus segments after MBI, a significant increase in peak latency and a decrease in maximal force change was observed in the middle and distal esophageal segments. No severe changes in physiological parameters of esophageal contraction were determined after high-dose-rate radiotherapy in our model, but our results indicate a delayed esophageal function. From the clinical perspective, the observed increase in peak latency and decreased maximal force change may indicate delayed esophageal transit.

Can Proton Linear Accelerator Beams and Minibeams Achieve Superior Plan Quality over Cyclotron-Generated Proton Beams and Photons in the Treatment of Multiple Brain Metastases?

<h3>Purpose/Objective(s)</h3> To compare plan quality and delivery timing among photon Volumetric Arc Therapy (VMAT), Intensity-Modulated Proton Therapy using cyclotron-generated proton beams (CPB), linear accelerator proton beams (LPB), and linear accelerator proton minibeams (LPMB). <h3>Materials/Methods</h3> Thirty-five brain lesions from twenty patients were planned using CPBs and compared against LPBs and LPMBs and VMAT. All proton plans were optimized with multi-field optimization technique using the Monte Carlo algorithm. Benchmarked on the photon plans, dose coverage to each lesion for each proton plan was set to 99% of the GTV receiving the prescription (Rx) dose for all plans. Conformity index (CI), gradient index (GI), V_12Gy, V_4.5Gy and mean dose of the brain were compared. To achieve similar PTV dose coverage to photons, ±2 mm setup uncertainty and ±2% range uncertainty were included in robust evaluation using V_100%Rx > 95% of the GTV for proton plans. Additionally, the plan delivery timing was assessed based on the proton modalities' energy switching and spot scanning times. <h3>Results</h3> All metrics of CI, GI, V_12Gy, V_4.5Gy, and mean brain dose for VMAT photon and three different proton plans are listed in Table 1. When compared to CPB generated plans, CI and GI were significantly better for the LPB and LPMB plans with a mean CI of 1.7 ± 0.5, 1.57 ± 0.4, and 1.4 ± 0.6 and a mean GI of 4.64 ± 1.48, 3.7 ± 1.1 and 2.8 ± 0.7, respectively. In comparison, mean CI and GI from photon VMAT plans were 2 ± 1.2, 4.7 ± 1.4. All proton plans achieved better V_4.5Gy than photon VMAT plans. LPBs reduced the mean brain dose by 17% compared to the CPB plans, and LPMB plans reduced the mean brain dose by 44%. While all plans had V_100%Rx of the GTV > 99% in the nominal scenario, in the voxel-wise worst scenario, 97.1%, 92.8% and 84.2% of the lesions had V_100%Rx > 95% for CPB, LPB, and LPMB, respectively, and in the worst-case scenario, 97.1%, 94.3% and 78.6% of the plans showed V_100%Rx > 95% among all lesions. The LPB energy switching time (5 ms) enables a rapid beam delivery, 58% faster on average than for CPB plans. LPMB beam delivery time can be further reduced by spot reduction planning (SRP) with equal plan quality. <h3>Conclusion</h3> We successfully quantified plan quality and evaluated robustness for CPBs, LPBs and LPMBs for brain metastases. The LPB and LPMB stand as an excellent alternative to CPB therapy and can significantly increase the preservation of normal tissue while ensuring fast delivery time.

Recent Progress in Second Near-Infrared (NIR-II) Fluorescence Imaging in Cancer.

Cancer continues to be one of the leading causes of death worldwide, and its incidence is on the rise. Although cancer diagnosis and therapy have advanced significantly in recent decades, it is still a challenge to achieve the accurate identification and localization of cancer and to complete tumor elimination with a maximum preservation of normal tissue. Recently, second near-infrared region (NIR-II, 1000–1700 nm) fluorescence has shown great application potential in cancer theranostics due to its inherent advantages, such as great penetration capacity, minimal tissue absorption and scattering, and low autofluorescence. With the development of fluorescence imaging systems and fluorescent probes, tumor detection, margin definition, and individualized therapy can be achieved quickly, enabling an increasingly accurate diagnosis and treatment of cancer. Herein, this review introduces the role of NIR-II fluorescence imaging in cancer diagnosis and summarizes the representative applications of NIR-II image-guided treatment in cancer therapy. Ultimately, we discuss the present challenges and future perspectives on fluorescence imaging in the field of cancer theranostics and put forward our opinions on how to improve the accuracy and efficiency of cancer diagnosis and therapeutics.

Function-preserving surgery via single transverse cervical incision for Warthin's tumor in the parotid gland.

This study evaluated functional and disease control outcomes after gland-preserving surgery via a single transverse cervical incision for Warthin's tumor of the parotid gland. One-hundred eleven patients with Warthin's tumor underwent the preservation of most normal parotid tissues and the facial nerve combined with the en-bloc resection of tumors. Postoperative complications, subjective satisfaction, salivary function, and metachronous tumor were assessed in each patient. No patients had an extension to modified Blair or periauricular incision with the median operation time of 32 min. Temporary and permanent paralysis of the facial nerve was 5 (4.0%) and none of 125 tumor resection sides, respectively. Postoperative complications were minimal. The secretory functions between the affected and unaffected glands did not differ. One patient had metachronous tumor for a median follow-up of 72 months. Functional gland-preserving surgery via single transverse cervical incision can safely treat Warthin's tumor in the parotid gland.

Laparoscopy-endoscopy Cooperative Surgery for the Treatment of Gastric Gastrointestinal Stromal Tumors.

In view of the shortcomings of endoscopic or laparoscopic surgeries alone in the treatment of gastric gastrointestinal stromal tumors (G-GISTs), this approach makes an innovative improvement in the treatment of G-GISTs that are less than 5 cm in size. Laparoscopy-endoscopy cooperative surgery (LECS) is used to combine endoscopic and laparoscopic surgeries, fully realizing their respective advantages and avoiding their drawbacks. The main steps are as follows. First, gastroscopy and laparoscopy are combined to confirm the location and boundary of the tumor. Tumor resection is carried out laparoscopically, guided by a gastroscope. The specimen is removed orally and the gastric wound closed laparoscopically. Then, gastroscopy and laparoscopy are combined to determine whether there is wound bleeding, if the suture is satisfactory, and if the gastric cavity is deformed. LECS has natural advantages in the treatment of G-GISTs that are less than 5 cm in size. The accurate estimation of tumor location and boundary greatly improves the complete resection rate of tumors. The risk of tumor rupture is substantially reduced, and the long-term prognosis of patients is significantly improved. The process allows for accurate resection of the tumor, maximum preservation of normal gastric tissue and organ function, and avoids postoperative gastric deformation. The patient's postoperative rehabilitation is greatly accelerated, and oral feeding can resume on the day of the operation. The specimen is taken out through the mouth to avoid the need for an extended abdominal incision. This greatly reduces the patient's postoperative pain and scarring. The method greatly shortens the postoperative hospital stay (i.e., discharge is possible on the day after the operation), increasing the turnover of hospital beds.

Laparoscopy-endoscopy Cooperative Surgery for the Treatment of Gastric Gastrointestinal Stromal Tumors

In view of the shortcomings of endoscopic or laparoscopic surgeries alone in the treatment of gastric gastrointestinal stromal tumors (G-GISTs), this approach makes an innovative improvement in the treatment of G-GISTs that are less than 5 cm in size. Laparoscopy-endoscopy cooperative surgery (LECS) is used to combine endoscopic and laparoscopic surgeries, fully realizing their respective advantages and avoiding their drawbacks. The main steps are as follows. First, gastroscopy and laparoscopy are combined to confirm the location and boundary of the tumor. Tumor resection is carried out laparoscopically, guided by a gastroscope. The specimen is removed orally and the gastric wound closed laparoscopically. Then, gastroscopy and laparoscopy are combined to determine whether there is wound bleeding, if the suture is satisfactory, and if the gastric cavity is deformed. LECS has natural advantages in the treatment of G-GISTs that are less than 5 cm in size. The accurate estimation of tumor location and boundary greatly improves the complete resection rate of tumors. The risk of tumor rupture is substantially reduced, and the long-term prognosis of patients is significantly improved. The process allows for accurate resection of the tumor, maximum preservation of normal gastric tissue and organ function, and avoids postoperative gastric deformation. The patient's postoperative rehabilitation is greatly accelerated, and oral feeding can resume on the day of the operation. The specimen is taken out through the mouth to avoid the need for an extended abdominal incision. This greatly reduces the patient's postoperative pain and scarring. The method greatly shortens the postoperative hospital stay (i.e., discharge is possible on the day after the operation), increasing the turnover of hospital beds.

Is Real-Time Inverse Planning Optimizing Dose to the Normal Brain? A Prospective Comparative Trial in a Series of Brain Metastases Treated by Stereotactic Radiosurgery

Background: Radiosurgery has demonstrated good safety and efficacy in the treatment of multiple brain metastases (BMs). However, multi-target dose planning can be challenging and time-consuming. A recently developed real-time inverse treatment planning (IP) by convex optimization has been demonstrated to produce high-quality treatment plans with good conformity and selectivity in single-target plans. We intended to test the capacity of this IP to rapidly generate efficient plans while optimizing the preservation of normal tissue in multiple BM. Methods: Seventy-nine patients (mean age 62.4, age range 22–85) with a total of 272 BMs were treated by Gamma Knife Radiosurgery. All subjects were treated using a forward planning (FP) technique by an expert neurosurgeon. The new Intuitive Plan was applied and able to automatically generate an alternative plan for each patient. All planning variables were collected from the IP to be compared with the corresponding measurements obtained from the FP. A paired sample t test was applied to compare the 2 plans for the following variables: brain volumes receiving 10 Gy (V10) (primary endpoint), and 12 Gy (V12), planning indices (selectivity, coverage, gradient, and Paddick Conformity Index [PCI]), beam-on time (BOT), and integral doses. Additionally, the noninferiority margin for each item was calculated, and the 2 plans were compared for noninferiority using a paired t test. Results: The mean age of patients was 62.4 years old (age range 22–85), with a sex ratio of 1.02. The average number of lesions per patient was 3.4 (range 1–12). The mean prescription dose was 21.46 Gy (range 14–24 Gy). Noninferiority of the IP was concluded for V10, V12, prescription isodose volume, BOT, PCI, and selectivity. The V10 (and V12) was significantly lower with the IP (p < 0.001). These volumes were 8.69 cm³ ± 11.39 and 5.47 cm³ ± 7.03, respectively, for the FP and 7.57 cm³ ± 9.44 and 4.78 cm³ ± 5.86 for the IP. Only the coverage was significantly lower with the IP (−2.3%, p < 0.001), but both selectivity (+17%) and PCI (+15%) were significantly higher with the IP than FP (p < 0.001). Conclusion: This IP demonstrated its capacity to generate multi-target plans rapidly, with a dose to the brain (V10) and BOT noninferior to the one of a human expert planner. These results would benefit from confirmation in a larger prospective series.

Augmented Reality Assisted Endoscopic Transforaminal Lumbar Interbody Fusion: 2-Dimensional Operative Video.

Augmented reality (AR) is a novel technology for spine navigation. This tracking camera-integrated head-mounted display (HMD) represents a novel stereotactic computer navigation modality that has demonstrated excellent precision and accuracy with spinal instrumentation.1 Standard computer-assisted spine navigation systems have two major shortcomings: attention shift and line-of-sight limitations. The HMD allows visualization of the surgical field and navigation data concurrently in the same field of view.2,3 However, the use of AR in spine surgery has been limited to use for instrumentation, not for endoscopy. Fully endoscopic transforaminal interbody fusion under conscious sedation is an effective treatment option for degenerative spondylolisthesis and spinal stenosis. Although this technique has a steep learning curve, the advantages are vast, including preservation of normal tissue, smaller incisional requirement, and reduced postoperative pain, all enabling rapid recovery after surgery. As with other endoscopic spine surgeries, this procedure has a steep learning curve and requires a robust understanding of foraminal anatomy in order to safely access the disc space.4,5 However, with the introduction of AR, the safety and precision of this procedure could be greatly improved upon. In this video, we present a case of a 60-yr-old female who presented with a grade 1 spondylolisthesis and severe spinal stenosis and was treated with an L4-L5 interbody fusion. All instrumentation steps and localization for the endoscopic portion of the case were performed with assistance from the AR-HMD system. Informed written consent was obtained from the patient. The participant and any identifiable individuals consented to the publication of his/her image.

Anti-Tumor Immune Response and Long-Term Immunological Memory Induced by Minibeam Radiation Therapy: A Pilot Study

<h3>Purpose/Objective(s)</h3> Minibeam radiation therapy (MBRT) is a novel therapeutic approach that uses narrow beams (0.5 to 1 mm) to create a distinct spatial modulation of the dose, featuring alternating regions of high dose (peaks) and low dose (valleys). MBRT with both x-rays and protons was shown to provide a remarkable normal (skin and brain) tissue preservation in preclinical experiments, including sparing of cognitive, emotional, and motor processes. Equivalent or superior (glioma) tumor control compared to conventional radiation therapy was observed, and that even with highly heterogeneous dose distributions in small animal experiments. The underlying biological mechanisms under MBRT efficiency remain elusive. The aim of this work was to investigate the possible participation of the immune system in the anti-tumor response of MBRT. We also hypothesized the possible establishment of a long-term anti-tumor immunity. <h3>Materials/Methods</h3> We collected original <b>in vivo</b> radiopathological data in rats, thanks to the implementation of MBRT on a small animal radiation system. Firstly, we compared the response to MBRT of RG2-bearing nude (athymic) rats versus immunocompetent (Fischer) rats. The dose prescription was 30 Gy (average) in one fraction, with approximately one half of the tumor volume receiving (valley) doses of 6 Gy. Secondly, RG2-bearing rats having survived to the first part of the study were reinjected with the same tumor cell line and tumor development was monitored by MRI and bioluminescence imaging. <h3>Results</h3> While a significant increase of lifespan was observed in the irradiated immunocompetent rats with respect to non-irradiated controls, the irradiated nude rats showed no response to the treatment, pointing out a determinant role of T-cells in MBRT efficiency. Quantification of immune cells is ongoing. Additionally, the irradiated and cured immunocompetent RG2-bearing rats were rechallenged with RG2 tumor cells (3 to 6 months after irradiation). While naïve controls developed tumor normally, this was not the case for any of the previously irradiated animals. <h3>Conclusion</h3> These results suggest that T cells play a central role in tumor cell killing in MBRT. Moreover, MBRT seems to act as an anti-tumor vaccine. The remarkable reduction in neurotoxicity along with the potential activation of the immune system makes MBRT an ideal candidate to achieve an effective radio-immunotherapy in very infiltrative and immunosuppressive brain tumors, such as high-grade gliomas (GBM).

Functional gland-preserving surgery via periauricular incision for pleomorphic adenoma of the parotid gland

IntroductionGland-preserving surgery is often used for benign tumours in the parotid gland. Partial superficial parotidectomy via a periauricular incision may bring satisfactory cosmetic outcomes but the disease control outcome remains unrevealed. This study evaluated functional and disease control outcomes after gland-preserving surgery via periauricular incision for pleomorphic adenoma of the parotid gland. MethodsThis longitudinal study included 248 consecutive patients with parotid pleomorphic adenoma who underwent the preservation of most normal parotid tissues and the facial nerve combined with the en-bloc resection of tumours via periauricular incision. Postoperative complications, subjective satisfaction, salivary function, and tumour recurrence were assessed in each patient. The secretory function of the salivary gland was measured using salivary scintigraphy at 6 months after surgery, and ultrasonography was regularly followed. ResultsMedian tumour size was 2.5 cm (range, 0.8–5.2 cm) and median operation time was 55 min (range, 39–88 min). All tumours were safely removed by gland-preserving surgery via periauricular incision without extension to Blair or hairline incision and tumour spillage. Temporary and permanent paralysis of the facial nerve was 14 (5.6%) and none of the study patients, respectively. Postoperative complications were minor and Frey's syndrome was found in 6 (2.4%) patients. The Secretary function of the affected gland was equal to that of the unaffected gland. No patients had a recurrence for a median follow-up of 78 months (range, 24–126 months). ConclusionsFunctional gland-preserving surgery via periauricular incision can treat pleomorphic adenoma in the parotid gland with satisfactory functional, cosmetic, and disease control outcomes.

Curcumin-Microsphere/IR820 Hybrid Bifunctional Hydrogels for In Situ Osteosarcoma Chemo-co-Thermal Therapy and Bone Reconstruction.

Conventional biomaterial-mediated osteosarcoma therapy mainly focuses on its antitumor effect yet often fails to overcome the problem of post-treatment bone tissue defect repair. Simultaneously, minimally invasive drug delivery methods are becoming spotlights for normal tissue preservation. Herein, an injectable curcumin-microsphere/IR820 coloaded hybrid methylcellulose hydrogel (Cur-MP/IR820 gel) platform was designed for osteosarcoma therapy and bone regeneration. In vitro, the K7M2wt osteosarcoma cells were eradicated by hyperthermia and curcumin. Later, the sustained release of curcumin promoted alkaline phosphatase expression and calcium deposition of bone mesenchymal stem cells. In vivo, this hybrid hydrogel could reach tumor site via injection and turned into hydrogel due to heat sensitivity. Under the irradiation of an 808 nm laser, localized hyperthermia (∼51 °C) generated in 5 min to ablate the tumor. Meanwhile, the thermal-accelerated curcumin release and thermal-increased cell membrane permeability led to tumor cell apoptosis. Tumors in photothermal-co-chemotherapy group were successfully restrained from day 2 after treatment. After that, bone reconstruction was promoted because of sustained released curcumin. The chemo-co-thermal efficacy and osteogenic capacity of Cur-MP/IR820 hydrogel suggest a promising approach to the treatment of osteosarcoma and provide provoking inspiration for treating bone tumors and repairing bone tissue.

A narrative review of near-infrared fluorescence imaging in hepatectomy for hepatocellular carcinoma.

Hepatectomy is a main therapeutic strategy for hepatocellular carcinoma (HCC), which requires removal of primary and disseminated tumors and maximum preservation of normal liver tissue. However, in a clinical operation, it is difficult to recognize the tumor tissue and its boundary with the naked eye and palpation, which often leads to insufficient or excessive resection. Near-infrared fluorescence (NIRF) imaging, a non-invasive, real-time, low-cost, and highly sensitive imaging technique has been extensively studied in surgical navigation. With the development of fluorescence imaging system and fluorescent probe, intraoperative tumor detection and margin definition can be achieved, making the operation more accurate. Advances in fluorescence imaging of HCC in the NIR region have focused on the traditional first NIR window (NIR-I, 700–900 nm), and have recently been extended to the second NIR window (NIR-II, 1,000–1,700 nm). Compared with NIR-I imaging, fluorescence imaging in the NIR-II exhibits great advantages, including higher spatial resolution, deeper penetration depth, and lower optical absorption and scattering from biological substrates with minimal tissue autofluorescence. There is no doubt that developing novel NIRF probes for in vivo imaging of HCC has high significance and direct impact on the field of liver surgery. In this article, the development of various NIRF probes for fluorescence image guided HCC hepatectomy is reviewed, and current challenges and potential opportunities of these imaging probes are discussed.

P-304 Effectiveness and safety of thermal ablation of pulmonary metastases in patients with colorectal cancer

Pulmonary oligometastatic disease in colorectal cancer can be managed with either resection or ablation. Radiologically guided thermal ablation procedures have the benefit of disease control, preservation of adjacent normal tissue and improved quality of life, based on a short hospital admission and recovery time. We sought to report the effectiveness and safety of radiofrequency and microwave ablation for pulmonary metastases in patients with colorectal cancer.

Verification of a Monte Carlo dose calculation engine in proton minibeam radiotherapy in a passive scattering beamline for preclinical trials.

Proton minibeam radiation therapy (pMBRT) is a novel therapeutic strategy that combines the benefits of proton therapy with the remarkable normal tissue preservation observed with the use of submillimetric spatially fractionated beams. This promising technique has been implemented at the Institut Curie-Proton therapy centre (ICPO) using a first prototype of a multislit collimator. The purpose of this work was to develop a Monte Carlo-based dose calculation engine to reliably guide preclinical studies at ICPO. The whole "Y1"-passive beamline at the ICPO, including pMBRT implementation, was modelled using the Monte Carlo GATE v. 7.0 code. A clinically relevant proton energy (100 MeV) was used as starting point. Minibeam generation by means of the brass collimator used in the first experiments was modelled. A virtual source was modelled at the exit of the beamline nozzle and outcomes were compared with dosimetric measurements performed with EBT3 gafchromic films and a diamond detector in water. Dose distributions were recorded in a water phantom and in rat CT images (7-week-old male Fischer rats). The dose calculation engine was benchmarked against experimental data and was then used to assess dose distributions in CT images of a rat, resulting from different irradiation configurations used in several experiments. It reduced computational time by an order of magnitude. This allows us to speed up simulations for in vivo trials, where we obtained peak-to-valley dose ratios of 1.20 ± 0.05 and 6.1 ± 0.2 for proton minibeam irradiations targeting the tumour and crossing the rat head. Tumour eradication was observed in the 67 and 22% of the animals treated respectively. A Monte Carlo dose calculation engine for pMBRT implementation with mechanical collimation has been developed. This tool can be used to guide and interpret the results of in vivo trials. This is the first Monte Carlo dose engine for pMBRT that is being used to guide preclinical trials in a clinical proton therapy centre.