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Purpose There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed. Methods Narrative review and presentation of PBM parameters are based on current evidence and expert opinion. Results PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows: wavelength , typically between 633 and 685 nm or 780–830 nm; energy density , laser or light-emitting diode (LED) output between 10 and 150 mW; dose , 2–3 J (J/cm 2 ), and no more than 6 J/cm 2 on the tissue surface treated; treatment schedule , two to three times a week up to daily; emission type , pulsed (<100 Hz); and route of delivery , intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations. Conclusion PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.

Purpose There is a large body of evidence supporting the efficacy of low level laser therapy (LLLT), more recently termed photobiomodulation (PBM), for the management of oral mucositis (OM) in patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved, may expand the applications for PBM in the management of other complications associated with HNC treatment. This article (part 1) describes PBM mechanisms of action, dosimetry, and safety aspects and, in doing so, provides a basis for a companion paper (part 2) which describes the potential breadth of potential applications of PBM in the management of side-effects of (chemo)radiation therapy in patients being treated for HNC and proposes PBM parameters. Methods This study is a narrative non-systematic review. Results We review PBM mechanisms of action and dosimetric considerations. Virtually, all conditions modulated by PBM (e.g., ulceration, inflammation, lymphedema, pain, fibrosis, neurological and muscular injury) are thought to be involved in the pathogenesis of (chemo)radiation therapy-induced complications in patients treated for HNC. The impact of PBM on tumor behavior and tumor response to treatment has been insufficiently studied. In vitro studies assessing the effect of PBM on tumor cells report conflicting results, perhaps attributable to inconsistencies of PBM power and dose. Nonetheless, the biological bases for the broad clinical activities ascribed to PBM have also been noted to be similar to those activities and pathways associated with negative tumor behaviors and impeded response to treatment. While there are no anecdotal descriptions of poor tumor outcomes in patients treated with PBM, confirming its neutrality with respect to cancer responsiveness is a critical priority. Conclusion Based on its therapeutic effects, PBM may have utility in a broad range of oral, oropharyngeal, facial, and neck complications of HNC treatment. Although evidence suggests that PBM using LLLT is safe in HNC patients, more research is imperative and vigilance remains warranted to detect any potential adverse effects of PBM on cancer treatment outcomes and survival.

Aim Patients treated with allogeneic hematopoietic stem cell transplantation (HSCT) may experience oral complications associated with chronic graft-versus-host disease (cGVHD). These complications may significantly affect quality of life, even many years post-HSCT. Current treatment options for oral cGVHD are limited and often include steroid or other immunomodulatory medications, which may not adequately control the oral condition. A non-immunosuppressive intervention for symptomatic relief in oral cGVHD would thus be a welcome addition to the treatment paradigm. Materials and methods We report seven cases of oral cGVHD that were treated with photobiomodulation therapy (PBM), previously known as low-level laser therapy (LLLT). Patients underwent at least two PBM treatments per week in addition to local treatment with steroids, and if on systemic therapies, these were either unchanged or dosage was reduced during the period of PBM therapy. Follow-up data is presented for 4 weeks of treatment. Results Oral pain, sensitivity, and dry mouth improved in most patients. These findings suggest PBM therapy may represent an additional approach for management of oral cGVHD, and suggest that controlled studies should be conducted to confirm the efficacy and safety of PBM therapy in oral cGVHD and to determine optimal PBM therapy protocols.

Purpose To test the hypothesis that the sensitivity of near-infrared spectroscopy (NIRS) in reflecting the degree of (compensated) hypovolemia would be affected by the application site and probing depth. We simultaneously applied multi-site (thenar and forearm) and multi-depth (15–2.5 and 25–2.5 mm probe distance) NIRS in a model of simulated hypovolemia: lower body negative pressure (LBNP). Methods The study group comprised 24 healthy male volunteers who were subjected to an LBNP protocol in which a baseline period of 30 min was followed by a step-wise manipulation of negative pressure in the following steps: 0, −20, −40, −60, −80 and −100 mmHg. Stroke volume and heart rate were measured using volume-clamp finger plethysmography. Two multi-depth NIRS devices were used to measure tissue oxygen saturation (StO2) and tissue hemoglobin index (THI) continuously in the thenar and the forearm. To monitor the shift of blood volume towards the lower extremities, calf THI was measured by single-depth NIRS. Results The main findings were that the application of LBNP resulted in a significant reduction in stroke volume which was accompanied by a reduction in forearm StO2 and THI. Conclusions NIRS can be used to detect changes in StO2 and THI consequent upon central hypovolemia. Forearm NIRS measurements reflect hypovolemia more sensitively than thenar NIRS measurements. The sensitivity of these NIRS measurements does not depend on NIRS probing depth. The LBNP-induced shift in blood volume is reflected by a decreased THI in the forearm and an increased THI in the calf.

Background Little is known about the effects of carbon dioxide (CO 2 ) insufflation on cerebral oxygenation during thoracoscopy in neonates. Near-infrared spectroscopy can measure perioperative brain oxygenation [regional cerebral oxygen saturation (rScO 2 )]. Aims To evaluate the effects of CO 2 insufflation on rScO 2 during thoracoscopic esophageal atresia (EA) repair. Methods This is an observational study during thoracoscopic EA repair with 5 mmHg CO 2 insufflation pressure. Mean arterial blood pressure (MABP), arterial oxygen saturation (SaO 2 ), partial pressure of arterial carbon dioxide (paCO 2 ), pH, and rScO 2 were monitored in 15 neonates at seven time points: baseline (T0), after anesthesia induction (T1), after CO 2 -insufflation (T2), before CO 2 -exsufflation (T3), and postoperatively at 6 (T4), 12 (T5), and 24 h (T6). Results MABP remained stable. SaO 2 decreased from T0 to T2 [97 ± 3–90 ± 6 % ( p  < 0.01)]. PaCO 2 increased from T0 to T2 [41 ± 6–54 ± 15 mmHg ( p  < 0.01)]. pH decreased from T0 to T2 [7.33 ± 0.04–7.25 ± 0.11 ( p  < 0.05)]. All parameters recovered during the surgical course. Mean rScO 2 was significantly higher at T1 compared to T2 [77 ± 10–73 ± 7 % ( p  < 0.05)]. Mean rScO 2 levels never dropped below a safety threshold of 55 %. Conclusion The impact of neonatal thoracoscopic repair of EA with insufflation of CO 2 at 5 mmHg was studied. Intrathoracic CO 2 insufflation caused a reversible decrease in SaO 2 and pH and an increase in paCO 2 . The rScO 2 was higher at anesthesia induction but remained stable and within normal limits during and after the CO 2 pneumothorax, which suggest no hampering of cerebral oxygenation by the thoracoscopic intervention. Future studies will focus on the long-term effects of this surgery on the developing brain.

The sublingual mucosa is a commonly used intraoral location for identifying microcirculatory alterations using handheld vital microscopes (HVMs). The anatomic description of the sublingual cave and its related training have not been adequately introduced. The aim of this study was to introduce anatomy guided sublingual microcirculatory assessment. Measurements were acquired from the floor of the mouth using incident dark-field (IDF) imaging before (T0) and after (T1) sublingual cave anatomy instructed training. Instructions consists of examining a specific region of interested identified through observable anatomical structures adjacent and bilaterally to the lingual frenulum which is next to the sublingual papilla. The anatomical location called the sublingual triangle, was identified as stationed between the lingual frenulum, the sublingual fold and ventrally to the tongue. Small, large, and total vessel density datasets (SVD, LVD and TVD respectively) obtained by non-instructed and instructed measurements (NIN (T0) and IM (T1) respectively) were compared. Microvascular structures were analyzed, and the presence of salivary duct-related microcirculation was identified. A total of 72 video clips were used for analysis in which TVD, but not LVD and SVD, was higher in IM compared to NIM (NIM vs. IM, 25 ± 2 vs. 27 ± 3 mm/mm2 (p = 0.044), LVD NIM vs. IM: 7 ± 1 vs. 8 ± 1mm/mm2 (p = 0.092), SVD NIM vs. IM: 18 ± 2 vs. 20 ± 3 mm/mm2 (p = 0.103)). IM resulted in microcirculatory assessments which included morphological properties such as capillaries, venules and arterioles, without salivary duct-associated microcirculation. The sublingual triangle identified in this study showed consistent network-based microcirculation, without interference from microcirculation associated with specialized anatomic structures. These findings suggest that the sublingual triangle, an anatomy guided location, yielded sublingual based measurements that conforms with international guidelines. IM showed higher TVD values, and future studies are needed with larger sample sizes to prove differences in microcirculatory parameters.

Purpose A high incidence of oral complications is associated with chemotherapy (CT) treatment in cancer patients; however, while knowledge into molecular mechanisms of their pathobiology continue to evolve, the direct physiological effects of CT on oral tissue perfusion remain unexplored. The aim of this investigation was to assess the acute effects of CT on gingival microcirculation perfusion by measuring gingival capillary density. Methods Twenty female specific-pathogen free New Zealand White rabbits were randomly divided into four groups receiving four different intravenous dose levels of cyclophosphamide, methotrexate, and fluorouracil (CMF). Noninvasive measurements of gingival capillary density were performed using sidestream dark-field (SDF) imaging prior to and 30 min after CT treatment. Four rabbits receiving saline solution were used as control animals. Results Baseline gingival capillary density was 58 ± 11 cpll/mm², no significant differences in baseline capillary densities between the groups were found. From low to high dose CT, capillary density 30 min after CMF treatment increased in each group by 1 ± 7, 5 ± 7, 13 ± 18 and 20 ± 13 cpll/mm², respectively. Capillary density increase was significant in the high-dose group. No change in gingival capillary density was found in the control group. Conclusions Periodontal microcirculation perfusion had increased 30 min after CT treatment as indicated by a rise in gingival capillary density. Our results support the idea that CT-induced microcirculatory response not only diligently delivers but also saturates peripheral oral tissues with antineoplastic agents by increasing surface area exposure. This functional response of the microcirculation to CT drugs may play a role in contribution to oral complications and the treatment of oral tumors.

Postoperative stroke and encephalopathy are potentially serious complications associated with coronary artery bypass grafting. In this case report a 78-year-old male patient receiving routine elective cardiac surgery presented with microaggregations in the sublingual microcirculation while on cardiopulmonary bypass that was undetected by routine intraoperative anticoagulation assessment. Microaggregates identified using video microscopy on his sublingual microcirculation during the procedure preceded a stroke postoperatively. Postoperative cerebral and carotid artery examination with computed tomography scanning revealed a left watershed cerebral infarct with carotid stenosis. This report presents intraoperative microcirculation-based evidence suggesting that observations of microaggregations, otherwise undetected by conventional anticoagulation assessment techniques, could serve as an early warning in elderly patients at high risk for postoperative cerebrovascular events.

Background/Aims: This study describes the peritoneal microcirculation, compares quantitative parameters and angioarchitecture to the standard of sublingual microcirculatory assessment, and determines the practical feasibility of this method. Methods: Incident dark field imaging was performed of the peritoneum and sublingually to determine angioarchitecture, total and perfused vessel density (TVD and PVD), the proportion of perfused vessels (PPV), the microvascular flow index (MFI) and image acquisition time. Results: Peritoneal angioarchitecture was characterized by a quadrangular network of longitudinally oriented capillaries, often flanked by fat cells. Differences between peritoneal and sublingual microcirculation were observed with regard to TVD (peritoneum 12 mm/mm 2 [95% CI 10–14] vs. sublingual 23 mm/mm 2 [95% CI 21–25]; p < 0.0001), PVD (peritoneum 11 mm/mm 2 [95% CI 9–13] vs. sublingual 23 mm/mm 2 [95% CI 21–25]; p < 0.0001), PPV (peritoneum 88% [95% CI 79–97] vs. sublingual 99% [95% CI 99–100]; p = 0.014), and MFI (peritoneum 3 [IQR 2.3–3.0] vs. sublingual 3 [IQR 3.0–3.0]; p = 0.012). There was no difference in image acquisition time (peritoneum 2: 34 min [95% CI 1: 49–3: 19] vs. sublingual 2: 38 [95% CI 1: 37–3: 32]; p = 0.916). Conclusion: The peritoneal microcirculation was characterized by a low capillary density and a distinctive angioarchitecture. The possibility of peri­toneal microcirculatory assessment offers promise for the study of peritoneal (patho-)physiology and (monitoring or detection of) associated diseases.

Background Little is known about the direct effect of pneumoperitoneum (PP) on microcirculation and its influence on the quality of tissue perfusion. This study aimed to investigate the intraoperative effects of carbon dioxide (CO 2 ) gas PP on microcirculation density and perfusion in neonates receiving laparoscopic surgery for hypertrophic pyloric stenosis. Methods In a single-center observational study, the oral microcirculation in 12 neonates receiving laparoscopic pyloromyotomy was investigated. Intraoperative hemodynamic parameters, intermittent buccal mucosa capillary density measurements (pre- and postoperative), and continuous intraoperative sublingual microcirculation measurements (i.e., vessels with a diameter <25 μm) of total vessel density, perfused vessel density, proportion of perfused blood vessels, blood vessel diameters (BVd), and microvascular flow index were obtained before (at baseline), during, and after PP insufflation for all patients using sidestream dark-field imaging for the duration of the complete surgical procedure. Results With the exception of a significantly elevated end-tidal CO 2 (34 ± 4–40 ± 8 mmHg; p  < 0.05 vs before [baseline], one-way analysis of variance [ANOVA]) during intraoperative insufflation, no significant differences were found between time points for the intraoperative hemodynamic parameters. Pre- and postoperative buccal capillary density showed no significant changes in mucosal perfusion. Analysis of continuous intraoperative sublingual microcirculation parameters exhibited a statistically significant increase in BVd during insufflation (8.8 ± 2.4–9.3 ± 2.5 μm; p  < 0.05, one-way ANOVA) and a significant decrease after exsufflation (8.2 ± 2.3 μm; p  < 0.01 vs during insufflation and p  < 0.05 vs baseline, one-way ANOVA, respectively). No other significant differences were found between time points for the remaining microcirculatory parameters. Conclusion The installation of CO 2 gas PP during laparoscopic pyloromyotomy procedures regulates microcirculatory perfusion by inducing changes in microvascular diameters but does not alter microcirculation density in neonates.