Microwave ablation of hyperplastic parathyroid glands is a treatment option for end-stage renal disease patients ineligible for surgical resection

Background: Secondary hyperparathyroidism (SHPT) is a frequently encountered problem in patients with end-stage renal disease (ESRD). Some patients with severe SHPT could not be managed by medical treatment and are ineligible for surgical resection.

Purpose: Our objective was to evaluate the efficacy, safety of microwave ablation (MWA) on these patients.

Materials and Methods: Between 1 April 2015 and 28 February 2017, 35 patients (M/F 19/16, age 49.8?±?12.9?years) were enrolled. All patients were treated with MWA. Levels of intact parathyroid hormone (iPTH) and of serum calcium and phosphorus were compared pre- and post-ablation. Repeated-measures ANOVA was used to compare treatment outcomes pre- and post-ablation.

Results: Complete ablation was achieved in all 63 glands in the 35 patients with SHPT. The mean follow-up time was 15.9?±?2.2?months. The maximum gland diameter was 6–31?mm (mean, 14.9?±?5.5?mm). The trends of the changes in iPTH and calcium levels showed a curve: the level of iPTH and calcium at 6?months post-ablation were lower than those pre-ablation (both p?<?.0001); after then iPTH remained relatively stable and the end of follow up, with no rebound (p?<?.0001), while instead of calcium at the end of follow up was not significantly lower than pre-ablation (p?=?.462). The trend in the change in phosphate levels showed a straight line; the level of phosphate at 6?months post-ablation and at the end of follow up both were significantly lower than pre-MWA (p?<?.001). There was no major complication.

Conclusions: In this series, MWA was used successfully to treat SHPT patients who are ineligible for surgical resection.     

US-guided microwave ablation for secondary hyperparathyroidism in patients after renal transplantation: a pilot study

Objective: To assess the safety and efficacy of ultrasound-guided microwave ablation (MWA) in the treatment of patients who develop secondary hyperparathyroidism (SHPT) after renal transplantation (RT).

Methods: In total, nine patients, each with symptomatic SHPT caused by RT and at least one enlarged parathyroid gland, underwent MWA via hydrodissection. Intact parathyroid hormone (i-PTH), serum calcium, serum phosphorus, creatinine and blood urea nitrogen concentrations, before and after MWA, were assessed and compared.

Results: Complete ablation was achieved in all patients for a total of 14 ablated parathyroid glands. The mean follow-up time was 17.2?±?1.7?months post-operation. The mean maximum diameter of the parathyroid glands was 1.3?±?0.4?cm (range: 0.4–2.0?cm). The ablation power implemented was 30?W and the mean time for each parathyroid gland to achieve complete ablation was 287.5?±?83.4?s. The mean i-PTH, serum calcium and phosphorus concentrations at one day post-MWA (69.6?pg/mL, 2.23?±?0.29?mmol/L, 1.2 2?±?0.48?mmol/L, respectively) were significantly lower than those before MWA (780.0?pg/mL, 2.62?±?0.32?mmol/L, 1.39?±?0.61?mmol/L, respectively; p?<?.01), whereas the creatinine and blood urea nitrogen concentrations before and after MWA did not differ significantly from each other (p?>?.05). No significant differences were found between the biomarker concentrations observed at one day post-MWA and at the follow-ups (p?>?.05). No major operation-related complications occurred.

Conclusion: Ultrasound-guided MWA is a safe and effective technique for destroying parathyroid gland tissue in patients who develop SHPT after RT and its clinical effects are long-lasting.     

The impact of technical parameters on ablation volume during MR-guided focused ultrasound of desmoid tumors

Purpose: Desmoid tumors are benign, locally aggressive soft tissue tumors derived from fibroblasts. Magnetic resonance-guided focused ultrasound (MRgFUS) is a safe and effective treatment for desmoid tumors. The purpose of this study was to retrospectively review the MRgFUS treatments of desmoid tumors at our institution to determine which technical treatment parameters contributed most significantly to the accumulation of thermal dose.

Materials and methods: The study protocol was approved by the local IRB. We retrospectively reviewed data from MRgFUS treatments performed in histologically-confirmed desmoid tumors, over a period of 18?months. Sonication parameter means were compared with ANOVA. Mixed effects and linear regression models were used to evaluate the relative contribution of different parameters to thermal dose volume.

Results: Nine-hundred thirty-six sonications were reviewed in 13 treatments. Accumulated dose per sonication was greatest for elongated sonications (0.96?cc?±?0.90) compared to short (0.88?±?0.93?cc) and nominal (0.55?±?0.70?cc) sonications, p?<?.001. 65.2% of short sonications resulted in high percentage ablations, compared to 46.0% of nominal and 35.1% of elongated sonications. Standardized beta coefficients (anticipated increased volume in cc per unit) for power, duration, energy and average temperature were 0.006, 0.057, 0.00035 and 0.03, p?<?.001. Regarding dose efficacy, dose area contributed the greatest to this variability – 50.7% (45.5–54.8%), followed by distance – 16.6% (12.9–20.0%).

Conclusions: A variety of sonication parameters significantly contributed to thermal ablation volume following MRgFUS of desmoid tumors, in reproducible patterns. This work can serve as the basis for future models working toward improved planning for MRgFUS treatments.     

Proteomic and bioinformatic analysis of condyloma acuminata: mild hyperthermia treatment reveals compromised HPV infectivity of keratinocytes via regulation of metabolism,differentiation and anti-viral responses

Background: Hyperthermia has proved successful in treating cutaneous human papillomavirus infectious diseases such as plantar wart and condyloma acuminata (CA). Moreover, this treatment provides improved therapeutic efficacy in these conditions as compared with conventional therapies.

Objectives: To investigate the global proteome changes in CA in response to hyperthermia and achieve a better understanding of the mechanisms of hyperthermia therapy against HPV-infectious diseases.

Methods: CA tissue was obtained from patients undergoing pathological examinations. Diagnosis was verified as based on results of both HE staining and HPV-DNA PCR assay. Hyperthermia was achieved with a 44?°C water bath. Differentially expressed proteins (DEPs) were identified by iTRAQ labeling, SCX chromatography and LC-MS/MS assay. Validation of proteomic results was performed using real-time qPCR and western blot, while bioinformatic analysis of DEPs was accomplished by R 3.4.1, STRING and Cytoscape softwares.

Results: In response to hyperthermia, a total of 102 DEPs were identified with 37 being upregulated and 65 downregulated. Among these DEPs, hyperthermia induced proteins involved with anti-viral processes such as OAS1, MX1, BANF1, CANX and AP1S1, whereas it inhibited proteins that participated in cellular metabolism, such as GALT, H6PD, EXOSC4 and EXOSC6; protein translation, such as RPS4Y1; as well as keratinocyte differentiation, such as KRT5, KRT27, KRT75, KRT76 and H2AFY2.

Conclusions: Hyperthermia inhibited enzymes and molecules responsible for metabolism modulation and keratinocyte differentiation in CA tissue, whereas it promoted factors involved in anti-viral responses. Such effects may, in part, contribute to the efficacy of local hyperthermia therapy against HPV infection.     

Efficacy and safety of high-intensity focused ultrasound ablation for hepatocellular carcinoma by changing the acoustic environment: microbubble contrast agent (SonoVue) and transcatheter arterial chemoembolization

Objective: To compare efficacy and safety of microbubble contrast agent (SonoVue) and transcatheter arterial chemoembolization (TACE) in combination with high-intensity focused ultrasound (HIFU) for treatment of patients with hepatocellular carcinoma (HCC).

Methods: According to our inclusion criteria, we retrospectively reviewed 52 patients with HCCs, and divided them into SonoVue group and TACE group. Tumors were examined by enhanced magnetic resonance imaging. Change of lesions, alpha-fetoprotein values, hepatic and renal function were measured pre- and postoperatively. Then, adverse events were observed and clinical follow-up was performed.

Results: Clinical efficacy and the majority of treatment parameters were similar, except for time and energy required for the first massive grey-scale changes in SonoVue group, which were significantly lower than those in TACE group (p?<?.05). For adverse events, only rate of fever (3.85%) in SonoVue group was significantly lower than that in TACE group (50.00%, p?<?.05). The ‘diagnosis and treatment cycle’ in SonoVue group (11.5?±?2.9) was remarkably shorter than TACE group (22.7?±?6.3, p?<?.05). Energy efficiency factor was positively correlated with distance from the deepest layer of lesion to the hepatic capsule or to the abdominal wall in SonoVue group, while that was negatively correlated with iodized oil deposition in TACE group.

Conclusion: Using microbubble (SonoVue) in HIFU procedure has a similar therapeutic effect compared with TACE, and does not increase the risk of treatment. It might present a new strategy in clinical treatment, especially for patients with a smaller diameter of HCC.     

Intraperitoneal perfusion chemotherapy and whole abdominal hyperthermia using external radiofrequency following radical D2 resection for treatment of advanced gastric cancer

Background: The peritoneum is the most frequent site of disease recurrence in gastric cancer, and the prognosis remains poor. This study assessed the role of adjuvant intraperitoneal (IP) chemotherapy with whole abdominal hyperthermia using external radiofrequency in gastric cancer patients after D2 dissection.

Methods: Patients with gastric cancer who underwent gastrectomy with D2 regional lymph node dissection were enrolled in the study. Patients received IP chemotherapy with whole abdominal hyperthermia. Preheated normal saline containing 75?mg/m² of cisplatin was delivered into the abdominal cavity through a Tenckhoff catheter at McBurney’s point. Regional hyperthermia was performed using two sets of orthogonal radiofrequency waves immediately after all saline was irrigated into the abdominal cavity. For each patient, recurrent or metastatic sites and adverse events were evaluated.

Results: A total of 22 patients were finally included. All patients tolerated hyperthermia well. Only two patients experienced grade 1 superficial thermal injury. The most frequent grade 3/4 adverse events were myelosuppression, nausea/vomiting, trichomadesis and liver dysfunction. We also found IP chemotherapy with whole abdominal hyperthermia could reduce the total recurrent/metastatic rate, especially peritoneal metastasis (4.5%).

Conclusions: This hypothesis-generating study indicated that IP chemotherapy with whole abdominal hyperthermia might be feasible for gastric cancer patients after D2 resection.     

Real-time optoacoustic temperature determination on cell cultures during heat exposure: a feasibility study

Objective/Purpose: In order to study the effects of hyperthermia and other temperature-related effects on cells and tissues, determining the precise time/temperature course is crucial. Here we present a non-contact optoacoustic technique, which provides temperatures during heating of cultured cells with scalable temporal and spatial resolution.

Methods: A thulium laser (1.94?µm) with a maximum power of 15?W quickly and efficiently heats cells in a culture dish because of low penetration depth (1/e penetration depths of 78?µm) of the radiation in water. A repetitively Q-switched holmium laser (2.1?µm) is used simultaneously to probe temperatures at different locations in the dish by using the photoacoustic effect. Due to thermoelastic expansion of water, pressure waves are emitted and measured with an ultrasonic hydrophone at the side of the dish. The amplitudes of the waves are temperature dependent and can be used to calculate the temperature/time course at any location of probing.

Results: We measured temperatures of up to 55?°C with a heating power of 6?W after 10?s, and subsequent lateral temperature profiles over time. Within this profile, temperature fluctuations were found, likely owing to thermal convection and water circulation. By using cultured retinal pigment epithelial cells, it is shown that the probe laser pulses alone cause no biological damage, while immediate cell damage occurs when heating for 10?s at temperatures exceeding 45?°C.

Conclusions: This method shows great potential not only as a noninvasive, non-contact method to determine temperature/time responses of cells in culture, but also for complex tissue and other materials.     

Ultrasound-guided percutaneous laser ablation is safe and effective in the treatment of small renal tumors in patients at increased bleeding risk

Purpose: The aim of this retrospective study was to assess the safety and effectiveness of laser ablation (LA) in patients with small renal cell carcinomas (RCC) and increased risk of bleeding.

Material and methods: From 2013 to 2017, nine patients (six males, three females, aged 68.5?±?12.2 years) at high risk of bleeding underwent ultrasonography-guided LA for an RCC. Patients were considered at increased risk of bleeding because of impairment of coagulation parameters, concomitant antiplatelet therapy, or at-risk location of the tumor (one, five, and three patients, respectively). RCC diameter ranged from 11 to 23?mm. According to tumor size, two or three laser fibers were introduced through 21-gauge needles and 1800 J per fiber were delivered in 6?min with a fixed power of 5 W. Major and minor complications, technical success, and primary and secondary technical effectiveness and tumor recurrence were recorded.

Results: Just one Grade 1 complication was observed: a small asymptomatic hematoma that spontaneously resolved. Technical success was 100%, 1 month technical efficacy was 88.9% (8/9 patients). One patient with residual tumor was successfully retreated 1 month later, and secondary efficacy rate was 100%. No local tumor recurrence occurred during a median follow-up of 26 months (range 11–49 months).

Conclusions: LA is safe and effective in the treatment of small RCC and might represent a valid option in patients with increased risk of bleeding.     

An assessment of the survival impact of multimodal anesthesia/analgesia technique in adults undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy: a propensity score matched analysis

Background: Studies suggest volatile anesthetics and opioids may enhance the malignant potential of cancer cells. The objective of this single institution retrospective study was to evaluate the survival impact of a multimodal opioid-sparing nonvolatile anesthetic technique (MA) in a group of patients who had undergone cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for appendiceal carcinomatosis.

Methods: Propensity score matching (PSM) and Cox proportional hazard models were used to compare the survivals of patients who received MA (MA group), to those who received volatile-opioid anesthesia (volatile-opioid group).

Results: Of the 373 patients, 110 (29%) were in the MA group and 263 (71%) in the volatile-opioid group. The MA group was older (mean?±?standard deviation (SD): 55?±?11 versus 53?±?10?years, p?=?.035) and had more patients with ASA scores 3 or 4 (90% versus 81%, p?=?.032), and those with high grade tumors (18% versus 12%, p?=?.009). Intraoperative opioid consumption was lower in the MA group (mean morphine equivalents?±?SD: 13?±?10 versus 194?±?789, p?<?.0001). After PSM, 107 patients remained in each group. In the adjusted Cox proportional hazards model after PSM, MA was not associated with improved progression free survival (PFS) (HR 1.45, 95% CI [0.94–2.22], p?=?.093) or overall survival (OS) (HR 1.66, 95% CI [0.86–3.20], p?=?.128), when compared to volatile-opioid anesthesia.

Conclusions: In this retrospective study, a multimodal opioid-sparing nonvolatile anesthetic approach was not associated with improved survival.

Precis’ statement: In this study of patients undergoing major cancer surgery, the use of multimodal anesthetic and analgesic agents, while avoiding volatile anesthetics and minimizing opioid use was not associated with improved survival.     

Local tumor progression after ultrasound-guided percutaneous microwave ablation of stage T1a renal cell carcinoma: risk factors analysis of 171 tumors

Purpose: To retrospectively review long-term oncologic outcomes after ultrasound (US)-guided percutaneous microwave ablation (MWA) of T1a renal cell carcinoma (RCC) and to identify the incidence and risk factors that predict local tumor progression (LTP) after MWA of RCC.

Materials and methods: The present study was approved by the institutional review board. A total of 162 patients with 171 RCC nodules (mean size, 2.6?±?0.8?cm; range, 0.6–4.0?cm) were treated by MWA between April 2006 and January 2017. The influence of eight factors (age; sex; longest tumor diameter; tumor number, location and pathology type; ablation power and time) affecting the risk of LTP was assessed. Univariate Kaplan–Meier and Cox proportional hazard models were used for statistical analysis.

Results: LTP occurred in five patients (5 tumors) after US-guided percutaneous MWA of stage T1a RCC. The overall occurrence of LTP was 2.9% per tumor and 3.0% per patient with a median follow-up of 45.5?months. Among the 162 patients, there were no instances of LTP-related deaths; however, 20 patients died of other diseases. All patients with LTP survived through follow-up. The survival rate of LTP-free patients at 1, 3 and 5?years were 98.7%, 89.5% and 82.1%, respectively (p?=?.38). Univariate and multivariate analysis identified tumor location to be the only independent predictor of LTP.

Conclusions: US-guided percutaneous MWA for T1a RCC achieved a relatively low LTP incidence rate. Tumors adjacent to the renal pelvis or bowel increased the potential of LTP occurrence.     

Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia

Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.     

Mental health comorbidities and cost/utilization outcomes in head and neck cancer patients

Purpose: Examine the relationship between mental health comorbidities and health services outcomes in non-elderly adults with head and neck cancer (HNC).

Design: Retrospective, cross-sectional.

Sample: Non-elderly adults with a primary diagnosis of HNC in U.S. Department of Defense (TRICARE) administrative claims data for fiscal years (FY) 2007–2014.

Methods: Linear regression and generalized linear models were used to examine predictors of reimbursed cost and healthcare utilization, respectively.

Findings: On average, there were 2944 HNC patients each year, the majority age 55–64, male, military retirees or family members of retirees, cared for in civilian facilities, and residing in the U.S. southern region. Between FY2007 and FY2014, there were slight increases in prevalence rates for diagnosed depression (12.4%–13.1%), anxiety (8.2%–11.9%), adjustment disorders (3.7%–5.8%), and drug use disorders (10.3%–19.4%), and a slight decrease in alcohol use disorders (12.3%–11.4%). In the cost regression model, depression and anxiety were the seventh and eighth strongest predictors (p?<?.001), behind hospice use, treatment modalities, chronic physical conditions, and tobacco use. In the utilization regression models, depression, adjustment disorder, and anxiety ranked seventh, ninth, and eleventh as the strongest predictors for the number of ambulatory visits; anxiety, depression and substance use disorder ranked fifth, sixth, and eighth in the model examining predictors of the number of annual hospitalizations; and anxiety and depression ranked fifth and sixth in the model examining predictors of the annual number of bed days.

Conclusions: We found strong evidence that mental health comorbidities impact cost and utilization among HNC patients, independent of other factors.

Implications for Psychosocial Providers or Policy: Addressing mental health comorbidities among HNC patients may reduce cost and improve resource efficiency.     

Three-dimensional contrast-enhanced ultrasound fusion imaging predicts local tumor progression by evaluating ablative margin of radiofrequency ablation for hepatocellular carcinoma: a preliminary report

Purpose: To investigate the feasibility of three-dimensional contrast-enhanced ultrasound (3DCEUS) fusion in evaluating ablative margin (AM) after radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) and compare with those of computed tomography (CT) fusion.

Patients and methods: In total, 55 patients (47 men, 8 women; mean age, 56.0?±?10.6?years) with 55 HCCs were included. Pre- and post-RFA 3DCEUS images were fused to assess AM immediately after RFA. The AM measured on fusion imaging was categorized into two groups: (A) AM <5?mm, and (B) AM ≥5?mm. The agreement of AM evaluation was compared between 3DCEUS and CT fusion. The influence of AMs evaluated by 3DCEUS fusion on the risk of local tumor progression (LTP) was assessed.

Results: For 3DCEUS fusion, registration success rate was 96.4% (53/55). AM evaluation resulted in 28 tumors in group A and 25 tumors in group B. For CT fusion, AM evaluation resulted in 31 tumors with AM <5?mm and 23 tumors with AM ≥5?mm. AM was successful evaluated by both technique in 53 (96.4%) tumors. The agreement between 3DCEUS and CT fusion was excellent (kappa coefficient?=?0.924, p?<?.001). LTP was identified in 5 tumors (9.4%, 5/53). LTPs all occurred in the area where unachieved 5?mm AM was evaluated by 3DCEUS fusion. Cumulative rate of LTP was significantly higher in group A than in group B (28% versus 0%; p?=?.033, log-rank test).

Conclusions: 3DCEUS fusion enables AM evaluation for HCC immediately after RFA with comparable accuracy to CT fusion. AM <5?mm evaluated by 3DCEUS fusion has high predictive value for LTP.     

Prostate cancer: the influence of stigma on quality of life and relationship satisfaction for survivors and their partners

Objectives: Prostate cancer (PCa) stigma and its relationship to quality of life (QoL) is a relatively new finding. As the experiences of couples facing PCa are shared, the study examined the relationship between of PCa stigma, QoL, and relationship satisfaction of PCa survivors and their spouses.

Design: A correlational design with dyadic data was used.

Sample: Participants (N?=?80 dyads) were PCa survivors and their spouses sampled from an oncology center and PCa support groups.

Methods: Structural equation modeling was used to assess how stigma related to the QoL and relationship satisfaction of participants.

Findings: Stigma had a negative association with QoL, but not relationship satisfaction. There were no significant demographic differences in regards to stigma.

Conclusion: Overall, stigma has a relationship with the experience of couples, but not with every aspect of their experience.

Implications for psychosocial providers: Implications for clinicians in regards to addressing PCa stigma with clients and areas for future research are discussed.     

Benefits,challenges, and needs of people living with cancer and their companion dogs: An exploratory study

Purpose/Objectives: The study examined whether the bond with a companion dog is associated with well-being among people with cancer, and described the perceived benefits, challenges, and needs accompanying the relationship with the dog.

Design: The design was cross-sectional.

Sample: Participants were 140 people recently diagnosed with cancer with at least one dog in their household.

Methods: The online survey included measures of the human–pet bond, depressive symptoms, positive affect, and health-related quality of life, as well as open-ended questions about the experience of having a dog since being diagnosed with cancer.

Findings: Although the bond with a companion dog was not directly linked with well-being, the association between the human–pet bond and depressive symptoms depended in part on treatment status.

Conclusions: Companion dogs may play an important role in the lives of people recently diagnosed with cancer.

Implications for psychosocial providers: Health care providers can help to support the bond with a companion dog.     

Feasibility study of metabolically supported chemotherapy with weekly carboplatin/paclitaxel combined with ketogenic diet,hyperthermia and hyperbaric oxygen therapy in metastatic non-small cell lung cancer

Background: Previous evidence suggests that metabolically supported chemotherapy (MSCT), ketogenic diet, hyperthermia and hyperbaric oxygen therapy (HBOT) could all target vulnerabilities of cancer cells. This study aimed to evaluate the efficacy and the tolerability of this combination therapy in the treatment of stage IV non-small cell lung cancer (NSCLC).

Methods: Forty-four NSCLC patients with distant metastasis that received MSCT (administration of chemotherapy regimen following induced hypoglycemia) plus ketogenic diet, hyperthermia and HBOT combination were included in this retrospective study. Survival and treatment response rates as well as toxicities were evaluated.

Results: Overall response rate (ORR, complete response plus partial response) was 61.4%; whereas, 15.9% and 22.7% of patients had stable disease (SD) and progressive disease (PD), respectively. Mean overall survival (OS) and progression-free survival (PFS) was 42.9?months (95% CI: 34.0–51.8) and 41.0?months (95% CI: 31.1–50.9), respectively. A higher Eastern Cooperative Oncology Group (ECOG) performance status (ECOG ≥2) was associated with worse OS and PFS. Patients received chemotherapy cycles with acceptable toxicity and adverse events. No problems were encountered due to fasting, hypoglycemia, ketogenic diet, hyperthermia or hyperbaric oxygen therapy.

Conclusions: Findings of this study suggest that MSCT combined with other modalities targeting multiple pathways and cellular vulnerabilities may bring about remarkable improvements in survival outcomes and treatment response rates in metastatic NSCLC, without additional safety concerns. Large comparative studies are warranted to draw robust conclusions.     

Clinical analysis of high-intensity focussed ultrasound ablation for abdominal wall endometriosis: a 4-year experience at a specialty gynecological institution

Objective: To evaluate the long-term clinical effect of high-intensity focussed ultrasound (HIFU) as a non-invasive modality for ablation of abdominal wall endometriosis (AWE) foci.

Methods: All women who were diagnosed with cutaneous endometriosis and underwent HIFU ablation and 4-year follow-up were included. Patient symptoms, imaging performed, HIFU ablation, recurrence, lesion location, size and number were collected and analyzed.

Results: A total of 51 women with 57 painful abdominal wall masses with a median volume of 4.00?cm³ and a mean age of 30.5±2.12 years were treated with HIFU. The main symptoms were a palpable painful abdominal mass (93%), protrusion of the skin (28.1%, 16) or lack of protrusion of the skin (71.9%, 41). Ultrasound was initially performed in 100% (51) of women, whereas 6% (3) required MRI examinations to distinguish the features and range of the masses. Ablation was performed with a median 300?s of sonication time, 40?min treatment time, 150?W of power and 41800?J of total energy to treat lesions that were a median volume of 3.83?cm³. No severe complications occurred, except in one patient with a first-degree skin burn, during the 48-month follow-up period. The pooled recurrence of cutaneous endometriosis occurred in 3.9% (2) of women.

Conclusion: The diagnosis of AWE should be confirmed with imaging of the lesion number, location, size and features before HIFU ablation. HIFU should be the first choice for the treatment of AWE as it is a non-invasive method, with high efficiency and safety and rapid postoperative recovery.     

Decision-making,knowledge, and psychosocial outcomes in pediatric siblings identified to donate hematopoietic stem cells

Purpose: To (a) describe the decision-making experience and psychosocial outcome of sibling hematopoietic stem cell (HSC) donors, and (b) to determine the feasibility of completing a prospective and longitudinal assessment of HSC sibling donors at a single institution.

Design: A mixed-methods approach was utilized.

Sample and methods: 12 potential siblings HSC donors aged 10–21?years completed various psychological measures and participated in semi-structured interviews at three time points in the donation experience: pre-donation, within 1?week after the harvest procedure, and six months post-donation. Caregivers also completed parent-proxy measures.

Findings: Qualitative analysis indicated donors want to make their own decision about donation but may not be given the option or may feel that there is no choice given their limited awareness of alternative options. Donors felt well prepared for the donation procedure but demonstrated a poor understanding of possible recipient outcomes. A minority of donors endorsed emotional distress prior to and after donation; however, this was not linked to recipient health. Forty percent of donors felt that they had inadequate support following their donation. Small sample size restricted quantitative data analysis.

Conclusions and implications: Utilizing a donor advocate offers opportunity to work with donors to encourage decision-making tied to ideals rather obligation, increase education about possible recipient outcomes, and offer support at key times, such as when a recipient dies. Future research should include prospective multi-site studies.     

‘Relationship between thermal dose and cell death for “rapid” ablative and “slow” hyperthermic heating’

Aim: Thermal isoeffective dose (TID) has not been convincingly validated for application to predict biological effects from rapid thermal ablation (e.g., using >55?°C). This study compares the classical method of quantifying TID (derived from hyperthermia data) with a temperature-adjusted method based on the Arrhenius model for predicting cell survival in vitro, after either ‘rapid’ ablative or ‘slow’ hyperthermic exposures.

Methods: MTT assay viability data was obtained from two human colon cancer cell lines, (HCT116, HT29), subjected to a range of TIDs (120–720 CEM₄₃) using a thermal cycler for hyperthermic (>2?minutes, <50?°C) treatments, or a novel pre-heated water bath based technique for ablative exposures (<10?seconds, >55?°C). TID was initially estimated using a constant R_CEM>43°_C=0.5, and subsequently using R_CEM(T), derived from temperature dependent cell survival (injury rate) Arrhenius analysis.

Results: ‘Slow’ and ‘rapid’ exposures resulted in cell survival and significant regrowth (both cell lines) 10?days post-treatment for 240 CEM₄₃ (R_CEM>43°_C=0.5), while 340-550 CEM₄₃ (R_CEM>43°_C =0.5) delivered using ‘rapid’ exposures showed 12?±?6% viability and ‘slow’ exposures resulted in undetectable viability. Arrhenius analysis of experimental data (activation energy ΔE?=?5.78?±?0.04?×?10⁵ J mole^?1, frequency factor A?=?3.27?±?11?×?10⁹¹?sec^?1) yielded R_CEM=0.42?*?e^0.0041*T which better-predicted cell survival than using R _CEM> 43°_C=0.5.

Conclusions: TID calculated using an R_CEM(T) informed by Arrhenius kinetic parameters provided a more consistent, heating strategy independent, predictor of cell viability, improving dosimetry of ablative thermal exposures. Cell viability was only undetectable above 305?±?10 CEM₄₃ using this revised measure.