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Background: The role of stereotactic ablative radiation therapy (SABR) as local treatment option after chemotherapy for locally advanced pancreatic cancer (LAPC) is evolving. However adequate patient selection criteria for SABR in patients with LAPC are lacking. Methods: A prospective institutional database collected data of patients with LAPC treated with chemotherapy, mainly FOLFIRINOX, followed by SABR, which was delivered using magnetic resonance guided radiotherapy, 40 Gy in 5 fractions within two weeks. Primary endpoint was overall survival (OS). Cox regression analyses were performed to identify predictors for OS. Results: Overall, 74 patients were included, median age 66 years, 45.9% had a KPS score of ≥90. Median OS was 19.6 months from diagnosis and 12.1 months from start of SABR. Local control was 90% at one year. Multivariable Cox regression analyses identified KPS ≥90, age <70, and absence of pain prior to SABR as independent favorable predictors for OS. The rate of grade ≥3 fatigue and late gastro-intestinal toxicity was 2.7%. Conclusions: SABR is a well-tolerated treatment in patients with unresectable LAPC following chemotherapy, with better outcomes when applied in patients with higher performance score, age <70 years and absence of pain. Future randomized trials will have to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Significant comorbidities, advanced age, and a poor performance status prevent surgery and systemic treatment for many patients with localized (non-metastatic) pancreatic ductal adenocarcinoma (PDAC). These patients are currently treated with 'best supportive care'. Therefore, it is desirable to find a treatment option which could improve both disease control and quality of life in these patients. A brief course of high-dose high-precision radiotherapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible. Methods: A nationwide multicenter trial performed within a previously established large prospective cohort (the Dutch Pancreatic cancer project; PACAP) according to the 'Trial within cohorts' (TwiCs) design. Patients enrolled in the PACAP cohort routinely provide informed consent to answer quality of life questionnaires and to be randomized according to the TwiCs design when eligible for a study. Patients with localized PDAC who are unfit for chemotherapy and surgery or those who refrain from these treatments are eligible. Patients will be randomized between SABR (5 fractions of 8 Gy) with 'best supportive care' and 'best supportive care' only. The primary endpoint is overall survival from randomization. Secondary endpoints include preservation of quality of life (EORTC-QLQ-C30 and -PAN26), NRS pain score response and WHO performance scores at baseline, and, 3, 6 and 12 months. Acute and late toxicity will be scored using CTCAE criteria version 5.0: assessed at baseline, day of last fraction, at 3 and 6 weeks, and 3, 6 and 12 months following SABR. Discussion: The PANCOSAR trial studies the added value of SBRT as compared to 'best supportive care' in patients with localized PDAC who are medically unfit to receive chemotherapy and surgery, or refrain from these treatments. This study will assess whether SABR, in comparison to best supportive care, can relieve or delay tumor-related symptoms, enhance quality of life, and extend survival in these patients. Trial registration: Clinical trials, NCT05265663, Registered March 3 2022, Retrospectively registered. [ABSTRACT FROM AUTHOR]

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Thermal ablation, including MWA, is gaining popularity as a treatment modality for colorectal liver metastases [[1]]. During follow-up, two liver metastases (segment 7 and segment 4, both 28 mm) were treated with chemotherapy, as primary resection was not deemed feasible, followed by open partial hepatectomy of the metastasis in segment 7 only (pathology: no viable remnant tumor) since no remnant metastasis was found during perioperative ultrasound in segment 4. [Extracted from the article]

Objective: To describe the initial experience with irreversible electroporation (IRE) to treat pelvic tumor recurrences.Methods: A retrospective single-center analysis was performed. Adverse events were recorded using Common Terminology Criteria of Adverse Events (CTCAE) 4.0. Clinical outcome was determined using pain- and general- symptom assessment, including Seddon's peripheral nerve injury (PNI) types. Radiological outcome was evaluated by comparing baseline with three-month 18F-FDG PET-CT follow-up.Results: Eight patients (nine tumors [recurrences of primary rectal (n = 4), anal (n = 1), sigmoid (n = 1), cervical (n = 1), and renal cell carcinoma (n = 1)]) underwent percutaneous IRE as salvage therapy. Median longest tumor diameter was 3.7 cm (range 1.2-7.0). One CTCAE grade III adverse event (hemorrhage) and eight CTCAE grade II complications occurred in 6/8 patients: vagino-tumoral fistula (n = 1), lower limb motor loss (n = 3; PNI type II) with partial recovery in one patient, hypotonic bladder (n = 2; PNI types I and II) with complete recovery in one patient, and upper limb motor loss (n = 2; PNI type II) with partial recovery in both patients. No residual tumor tissue was observed at 3-month follow-up. After a median follow-up of 12 months, local progression was observed in 5/9 lesions (4/5 were >3 cm pre-IRE); one lesion was successfully retreated. Debilitating preprocedural pain (n = 3) remained unchanged (n = 1) or improved (n = 2).Conclusion: IRE may represent a suitable technique to treat pelvic tumor recurrences, although permanent neural function loss can occur. Complete ablation seems realistic for smaller lesions; for larger lesions symptom control should be the focus. [ABSTRACT FROM AUTHOR]

Background and Aim. To provide a comprehensive quantitative assessment of nutritional status, digestion and absorption, and quality of life (QoL) in patients with locally advanced pancreatic cancer (LAPC). Methods. Sixteen patients with LAPC were prospectively assessed for weight loss (WL), body mass index (BMI), fat-free mass index (FFMI), handgrip strength (HGS), dietary macronutrient intake, serum vitamin levels, resting and total energy expenditure (REE and TEE, indirect calorimetry), intestinal absorption capacity and fecal losses (bomb calorimetry), exocrine pancreatic function (fecal elastase-1 (FE1)), and gastrointestinal quality of life (GIQLI). Results. Two patients had a low BMI, 10 patients had WL > 10%/6 months, 8 patients had a FFMI < P10, and 8 patients had a HGS < P10. Measured REE was 33% higher (P=0.002) than predicted REE. TEE was significantly higher than daily energy intake (P=0.047). Malabsorption (<85%) of energy, fat, protein, and carbohydrates was observed in, respectively, 9, 8, 12, and 10 patients. FE1 levels were low (<200 μg/g) in 13 patients. Total QoL scored 71% (ample satisfactory). Conclusion. Patients with LAPC have a severely impaired nutritional status, most likely as a result of an increased REE and malabsorption due to exocrine pancreatic insufficiency. The trial is registered with PANFIRE clinicaltrials.gov NCT01939665. [ABSTRACT FROM AUTHOR]

B Correction: BMC Cancer 22, 1363 (2022) b B https://doi.org/10.1186/s12885-022-10419-4 b Following publication of the original article [[1]], the authors reported an error in the author group. Stereotactic ablative radiotherapy or best supportive care in patients with localized pancreatic cancer not receiving chemotherapy and surgery (PANCOSAR): a nationwide multicenter randomized controlled trial according to a TwiCs design. [Extracted from the article]

Introduction: Irreversible electroporation (IRE) is a novel ablation technique in the treatment of unresectable cancer. The non-thermal mechanism is thought to cause mostly apoptosis compared to necrosis in thermal techniques. Both in experimental and clinical studies, a waiting time between ablation and tissue or imaging analysis to allow for cell death through apoptosis, is often reported. However, the dynamics of the IRE effect over time remain unknown. Therefore, this study aims to summarize these effects in relation to the time between treatment and evaluation. Methods: A systematic search was performed in Pubmed, Embase and the Cochrane Library for original articles using IRE on pancreas, liver or surrounding structures in animal or human studies. Data on pathology and time between IRE and evaluation were extracted. Results: Of 2602 screened studies, 36 could be included, regarding IRE in liver (n = 24), pancreas (n = 4), blood vessels (n = 4) and nerves (n = 4) in over 440 animals (pig, rat, goat and rabbit). No eligible human studies were found. In liver and pancreas, the first signs of apoptosis and haemorrhage were observed 1–2 hours after treatment, and remained visible until 24 hours in liver and 7 days in pancreas after which the damaged tissue was replaced by fibrosis. In solitary blood vessels, the tunica media, intima and lumen remained unchanged for 24 hours. After 7 days, inflammation, fibrosis and loss of smooth muscle cells were demonstrated, which persisted until 35 days. In nerves, the median time until demonstrable histological changes was 7 days. Conclusions: Tissue damage after IRE is a dynamic process with remarkable time differences between tissues in animals. Whereas pancreas and liver showed the first damages after 1–2 hours, this took 24 hours in blood vessels and 7 days in nerves. [ABSTRACT FROM AUTHOR]

Objectives: Irreversible electroporation (IRE) is a new ablation technique that relies on high-voltage electrical pulses. This clinical study evaluates the pathological response of colorectal liver metastases (CRLM) treated with IRE and the clinical safety and feasibility. Methods: Ten patients with resectable CRLM were included. During laparotomy, the metastases were treated with IRE and resected 60 min later. Safety and feasibility were assessed based on adverse events, laboratory values, technical success and intra-operative ultrasound findings. Tissue response was assessed using triphenyl tetrazolium chloride (TTC) vitality staining and (immuno)histochemical stainings (HE, complement-3d and caspase-3). Results: Ten lesions with a mean diameter of 2.4 cm were successfully electroporated and resected, on average, 84 min later (range 51-153 min). One minor transient cardiac arrhythmia occurred during IRE. Ultrasound showed a sharply demarcated hypoechoic ablation zone around the tumour. TTC showed avitality of all lesions, covering the complete tumour in 8/10 lesions. Although immunohistochemistry proved heterogeneous and difficult to interpret within the tumours, it confirmed irreversible cell damage in the tumour-free margin of all specimens. Conclusions: This ablate-and-resect study demonstrated avitality caused by IRE of CRLM in humans. Further characterisation of tissue- and tumour-specific electrical properties is warranted to improve ablation protocols for maximised tissue ablation. Key Points: • Irreversible electroporation induces cell death in colorectal liver metastases within 1 h. • The ablation zone shows a sharp demarcation between avital and vital tissue. • Apoptosis is involved in cell death of colorectal liver metastases after IRE. • Effects of IRE can be monitored real-time using intraoperative ultrasound. • Local electrical heterogeneities of tumour tissue may require tumour-specific ablation protocols. [ABSTRACT FROM AUTHOR]

Intraoperative ultrasonography (IOUS) has been the standard in surgical decision making in oncologic liver surgery. Preoperative imaging techniques have improved substantially in resent years; therefore, the importance of IOUS might change. The current results of IOUS were compared with preoperative high-resolution helical CT scanning and the impact of IOUS on surgical decision making was evaluated. A total of 100 consecutive patients who underwent open surgery for colorectal liver metastases within 4 weeks after preoperative imaging, performed with high-speed helical CT scanners, were included for this study. During surgery, IOUS was performed by a liver specialized radiologist. The findings on preoperative and intraoperative imaging and surgical exploration were compared regarding number, site, and size of the hepatic lesions. The preoperative surgical plan was compared with the final surgical treatment. One hundred patients with CRLM underwent 117 surgical treatments. In 38 patients IOUS differed from preoperative data. In 23 cases IOUS identified more metastatic lesions. In five patients, intraoperative findings identified smaller or less hepatic lesions. Additional information on the localization of the hepatic lesions was gathered by IOUS and changed the surgical treatment in ten cases. IOUS alone altered the surgical strategy 35 times during 117 procedures. In nearly all cases, discrepancy between the preoperative CT scan and IOUS resulted in a change of surgical treatment. Despite improvement in preoperative imaging technology, the intraoperative use of ultrasonography remains of crucial importance. The detection of preoperatively unknown lesions remains high with great consequence on surgical therapy. [ABSTRACT FROM AUTHOR]

Background: Because sunitinib can induce extensive necrosis in metastatic renal cell cancer (mRCC), we examined whether criteria defined by Choi might be valuable to predict early sunitinib efficacy.Methods: Computed tomography was used for measurement of tumour lesions in mm and lesion attenuation in Hounsfield units (HUs). According to Choi criteria partial response (PR) was defined as > or =10% decrease in size or > or =15% decrease in attenuation.Results: A total of 55 mRCC patients treated with sunitinib were included. At first evaluation, according to the Response Evaluation Criteria in Solid Tumours (RECIST) 7 patients had PR, 38 stable disease (SD), and 10 progressive disease (PD), whereas according to Choi criteria 36 patients had PR, 6 SD and 13 PD. Median tumour attenuation decreased from 66 to 47 HUs (P< or =0.001). In patients with PR, Choi criteria had a significantly better predictive value for progression-free survival and overall survival (both Ps<0.001) than RECIST (P=0.685 and 0.191 respectively). The predictive value for RECIST increased (P=0.001 and <0.001 respectively), when best response during treatment was taken into account.Conclusion: Choi criteria could be helpful to define early mRCC patients who benefit from sunitinib, but the use of these criteria will not change the management of these patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the feasibility of functional MR imaging (fMRI) at 1.5 T, exploiting blood oxygenation level-dependent (BOLD) contrast, for detecting changes in whole-tumour oxygenation induced by carbogen (5% CO2+95% O2) inhalation of the host. Adult WAG/Rij rats with rhabdomyosarcomas growing subcutaneously in the lower flank were imaged when tumours reached sizes between 1 and 11 cm3 (n=12). Air and carbogen were alternatively supplied at 2 l/min using a snout mask. Imaging was done on a 1.5-T MR scanner using a T2*-weighted gradient-echo, echo-planar imaging (GE-EPI) sequence. Analysis of the whole-tumour EPI images was based on statistical parametric maps. Voxels with and without signal intensity changes (SIC) were recorded. Significance thresholds were set at p<0.05, corrected for multiple comparisons. In continuous air breathing condition, 3 of 12 tumours showed significant negative SIC and 1 tumour had a clear-cut positive SIC. The remaining tumours showed very little or no change. When switching to carbogen breathing, the SIC were significantly positive in 10 of 12 tumours. Negative SIC were present in 4 tumours, of which three were simultaneously characterised by positive SIC. The overall analysis indicated that 6 of the 12 tumours could be considered as strong positive responders to carbogen. Our research demonstrates the applicability of fMRI GE-EPI at 1.5 T to study whole-tumour oxygenation non-invasively. The observed negative SIC during air condition may reflect the presence of transient hypoxia during these measurements. Selection of tumours on the basis of their individual response to carbogen is possible, indicating a role of such non-invasive measurements for using tailor-made treatments. [ABSTRACT FROM AUTHOR]

Electronic noses are a new class of analytical instruments anticipated to have an impact in many areas. They are based around an array of sensors each having a partial specificity and thus producing an odour fingerprint that can be identified by a pattern recognition system. In this review the technologies involved are discussed, giving particular emphasis to the sensors since these form the heart of the systems. The major sensor technologies are described, indicating both their strengths and their weaknesses. Finally, after a brief discussion of data processing technologies, the review ends with an assessment of the current state of the art and possible future directions. [ABSTRACT FROM AUTHOR]

The thermoregulatory effects of dopamine (DA, 400 μg), injected intracerebroventricularly (i.c.v.) in rabbits, were investigated at different ambient temperatures ( T). The effects at 20° C T were compared with those of 5-hydroxytryptamine (5-HT, 200 μg) and noradrenaline (NA, 200 μg). At 20° C T DA induced a dilatation of the ear vessels but did not change rectal temperature ( T). I.c.v. injection of 5-HT induced panting and fall in T while after NA a rise in T and constriction of the ear vessels were observed. At 32° C T no change in T was observed after DA. At 5° C T DA caused a short-lasting decrease in T. After treatment with the DA antagonist haloperidol (400 μg, i.c.v.) a hypothermia was observed after DA at 20° C T. Haloperidol did not influence the response after 5-HT or NA. The 5-HT antagonist methysergide (500 μg, i.c.v.) blocked panting and the hypothermia normally caused by i.c.v. 5-HT at 20° C T; instead of decreasing, T tended to increase after 5-HT. After pretreatment with methysergide T rose immediately after i.c.v. injection of DA. These results suggest that the hypothermia after i.c.v. DA in the rabbit is secondarily mediated by serotonergic structures in the pathway between heat sensors and heat loss effectors. The hyperthermic effect of i.c.v. DA, which showed after pretreatment with methysergide and was apparently blocked by haloperidol, is probably the result of an activation of DA receptors in the pathway from cold sensors to heat production effectors. The hyperthermia after i.c.v. NA could be due to an inhibition of the heat loss pathway. [ABSTRACT FROM AUTHOR]