Deep learning-based assessment of CT markers of sarcopenia and myosteatosis for outcome assessment in patients with advanced pancreatic cancer after high-intensity focused ultrasound treatment.

OBJECTIVES: To evaluate the prognostic value of CT-based markers of sarcopenia and myosteatosis in comparison to the Eastern Cooperative Oncology Group (ECOG) score for survival of patients with advanced pancreatic cancer treated with high-intensity focused ultrasound (HIFU). MATERIALS AND METHODS: For 142 retrospective patients, the skeletal muscle index (SMI), skeletal muscle radiodensity (SMRD), fatty muscle fraction (FMF), and intermuscular fat fraction (IMFF) were determined on superior mesenteric artery level in pre-interventional CT. Each marker was tested for associations with sex, age, body mass index (BMI), and ECOG. The prognostic value of the markers was examined in Kaplan-Meier analyses with the log-rank test and in uni- and multivariable Cox proportional hazards (CPH) models. RESULTS: The following significant associations were observed: Male patients had higher BMI and SMI. Patients with lower ECOG had lower BMI and SMI. Patients with BMI lower than 21.8 kg/m2 (median) also showed lower SMI and IMFF. Patients younger than 63.3 years (median) were found to have higher SMRD, lower FMF, and lower IMFF. In the Kaplan-Meier analysis, significantly lower survival times were observed in patients with higher ECOG or lower SMI. Increased patient risk was observed for higher ECOG, lower BMI, and lower SMI in univariable CPH analyses for 1-, 2-, and 3-year survival. Multivariable CPH analysis for 1-year survival revealed increased patient risk for higher ECOG, lower SMI, lower IMFF, and higher FMF. In multivariable analysis for 2- and 3-year survival, only ECOG and FMF remained significant. CONCLUSION: CT-based markers of sarcopenia and myosteatosis show a prognostic value for assessment of survival in advanced pancreatic cancer patients undergoing HIFU therapy. CLINICAL RELEVANCE STATEMENT: The results indicate a greater role of myosteatosis for additional risk assessment beyond clinical scores, as only FMF was associated with long-term survival in multivariable CPH analyses along ECOG and also showed independence to ECOG in group analysis. KEY POINTS: • This study investigates the prognostic value of CT-based markers of sarcopenia and myosteatosis for patients with pancreatic cancer treated with high-intensity focused ultrasound. • Markers for sarcopenia and myosteatosis showed a prognostic value besides clinical assessment of the physical status by the Eastern Cooperative Oncology Group score. In contrast to muscle size measurements, the myosteatosis marker fatty muscle fraction demonstrated independence to the clinical score. • The results indicate that myosteatosis might play a greater role for additional patient risk assessments beyond clinical assessments of physical status.

US-guided high-intensity focused ultrasound in pancreatic cancer treatment: a consensus initiative between Chinese and European HIFU centers.

Purpose: Ultrasound-guided high-intensity focused ultrasound (USgHIFU) represents a safe and effective non-invasive thermoablative technique for managing inoperable pancreatic cancer. This treatment method significantly alleviates disease-related symptoms and reduces pancreatic tumor volume. However, the current body of evidence is constrained by a lack of randomized controlled trials. The utilization of USgHIFU is primarily indicated for patients with unresectable, locally advanced, or metastatic pancreatic cancer, particularly those experiencing symptoms due to a locally advanced primary tumor.Methods: This collaborative consensus paper, involving European and Chinese HIFU centers treating pancreatic cancer, delineates criteria for patient selection, focusing on those most likely to benefit from USgHIFU treatment. Consideration is given to endpoints encompassing symptom alleviation, local response rates, other oncological outcomes, as well as overall and progression-free survival. Additionally, this paper defines relevant contraindications, side effects, and complications associated with USgHIFU. The publication also explores the feasibility and role of USgHIFU within the context of palliative care, including standard systemic chemotherapy.Results: The non-invasive local treatment of advanced pancreatic cancer using HIFU should be regarded as an adjunctive option alongside systemic chemotherapy or best supportive care for managing this aggressive disease. Based on the ability of USgHIFU therapy to mitigate pain and reduce primary tumor volume, it should be considered as a complementary therapy for symptomatic patients with inoperable pancreatic cancer and as a potential means of tumor debulking. The underutilized yet promising USgHIFU exhibits the potential to enhance patients' quality of life by alleviating cancer-related pain. Experts in the field should evaluate this treatment option be evaluated by experts in this field, with this consensus paper potentially serving as a guiding resource for the medical community.Conclusions: US-guided HIFU for advanced pancreatic cancer addresses treatment goals, available options, success rates, and limitations. As a non-invasive, effective local therapy, complementary to chemotherapy and best supportive care, it plays a pivotal role in pain relief, reducing of tumor volume, and potentially improving survival rates.

Study Protocol of a Prospective, Monocentric, Single-Arm Study Investigating the Safety and Efficacy of Local Ablation of Symptomatic Uterine Fibroids with US-Guided High-Intensity Focused Ultrasound (HIFU).

Uterine fibroids are the most common benign tumors of the uterus. Approximately 20-50% of women with myomas experience a variety of symptoms such as vaginal bleeding, abdominal pain, pelvic pain and pressure, and urological problems, possibly interfering with fertility and pregnancy. Although surgery remains the standard treatment option for fibroids, non-invasive therapeutic options, such as high-intensity focused ultrasound (HIFU), have emerged over the last dec ade. During HIFU, ultrasound is focused on the target tissue causing coagulation necrosis. HIFU has, meanwhile, become an established method for treating uterine fibroids in many countries. Clinical data have shown that it effectively alleviates fibroid-related symptoms and reduces fibroid size with a very low rate of side effects. However, there is a lack of data on how this treatment affects laboratory parameters and structural features of uterine tissue. As our center is the only one in German-speaking countries where ultrasound-guided HIFU technology is currently established, the aim of this prospective, monocentric, single-arm trial is not only to evaluate the safety and efficacy of local US-guided HIFU in symptomatic uterine fibroid patients according to GCP standards but also to explore its effects on blood parameters and the structural integrity of uterine tissue using elastographic methods.

Comparison between regular additional endobiliary radiofrequency ablation and photodynamic therapy in patients with advanced extrahepatic cholangiocarcinoma under systemic chemotherapy.

Background and aims: Extrahepatic cholangiocarcinoma (eCCA) remains a malignancy with a dismal prognosis. The first-line standard of care includes systemic chemotherapy (SC) and biliary drainage through stenting. Endobiliary ablative techniques, such as photodynamic therapy (ePDT) and radio-frequency ablation (eRFA), have demonstrated feasibility and favorable survival data. This study aimed to compare the oncologic outcome in patients treated with SC and concomitant eRFA or ePDT. Method: All patients with eCCA were evaluated for study inclusion. Sixty-three patients receiving a combination of SC and at least one endobiliary treatment were retrospectively compared. Results: Patients were stratified into three groups: SC + ePDT (n = 22), SC + eRFA (n = 28), and SC + ePDT + eRFA (n = 13). The median overall survival (OS) of the whole cohort was 14.2 months with no statistically significant difference between the three therapy groups but a trend to better survival for the group receiving ePDT as well as eRFA, during SC (ePDT + SC, 12.7 months; eRFA + SC, 13.8 months; ePDT + eRFA + SC, 20.2 months; p = 0.112). The multivariate Cox regression and subgroup analysis highlighted the beneficial effect of eRFA on OS. Overall, combined therapy was well tolerated. Only cholangitis occurred more often in the SC + eRFA group. Conclusion: Additional endobiliary ablative therapies in combination with SC were feasible. Both modalities, eRFA and ePDT, showed a similar benefit in terms of survival. Interestingly, patients receiving both regimes showed the best OS indicating a possible synergism between both ablative therapeutic techniques.

Impaired immunogenicity after vaccination for SARS-CoV-2 in patients with gastrointestinal cancer: does tumor entity matter?

Background: SARS-CoV-2 immunogenicity in patients with gastrointestinal cancer (GI cancer) following second and third vaccination was analyzed. Methods: A total of 125 patients under active anticancer therapy or in follow-up care were included in this prospective study. Seroprevalence of SARS-CoV-2 anti-spike and surrogate neutralization antibodies (NABs) was measured. Results: Four weeks after second vaccination, adequate titers of SARS-CoV-2 anti-spike immunoglobulin G (IgG) [≥282.0 binding antibody units (BAU)/mL] were found in 62.2% of patients under treatment versus 96.3% of patients in follow-up care (P<0.01). Sufficient titers of SARS-CoV-2 surrogate NAB (≥85.0%) were found in 32.7% of patients under treatment versus 70.6% in follow-up care (P<0.01). Titers of SARS-CoV-2 anti-spike IgG were especially low in patients with colorectal cancer (CRC). For SARS-CoV-2 surrogate NAB, patients with hepatocellular carcinoma (HCC) and with pancreaticobiliary cancer showed the lowest titers (P<0.01). SARS-CoV-2 anti-spike IgG and SARS-CoV-2 surrogate NAB were associated with a correlation coefficient of 0.93. Reaching a titer of SARS-CoV-2 anti-spike IgG ≥482.0 BAU/mL, protective levels of SARS-CoV-2 surrogate NAB (≥85.0%) could be assumed. Following booster vaccination, all patients reached effective antibody titers. Conclusions: Patients with active GI cancer showed impaired immunogenicity after second SARS-CoV-2 vaccination which was overcome by booster vaccination. Our findings were tumor-related and pronounced in patients with CRC and HCC. Waning immunity over time and antibody escape phenomena by variant of concern Omicron must be considered in these especially vulnerable patients.

Leaving the hospital on time: hospital bed utilization and reasons for discharge delay in the Netherlands.

Inappropriate bed occupancy due to delayed hospital discharge affects both physical and psychological well-being in patients and can disrupt patient flow. The Dutch healthcare system is facing ongoing pressure, especially during the current coronavirus disease pandemic, intensifying the need for optimal use of hospital beds. The aim of this study was to quantify inappropriate patient stays and describe the underlying reasons for the delays in discharge. The Day of Care Survey (DoCS) is a validated tool used to gain information about appropriate and inappropriate bed occupancy in hospitals. Between February 2019 and January 2021, the DoCS was performed five times in three different hospitals within the region of Amsterdam, the Netherlands. All inpatients were screened, using standardized criteria, for their need for in-hospital care at the time of survey and reasons for discharge delay. A total of 782 inpatients were surveyed. Of these patients, 94 (12%) were planned for definite discharge that day. Of all other patients, 145 (21%, ranging from 14% to 35%) were without the need for acute in-hospital care. In 74% (107/145) of patients, the reason for discharge delay was due to issues outside the hospital; most frequently due to a shortage of available places in care homes (26%, 37/145). The most frequent reason for discharge delay inside the hospital was patients awaiting a decision or review by the treating physician (14%, 20/145). Patients who did not meet the criteria for hospital stay were, in general, older [median 75, interquartile range (IQR) 65-84 years, and 67, IQR 55-75 years, respectively, P < .001] and had spent more days in hospital (7, IQR 5-14 days, and 3, IQR 1-8 days respectively, P < .001). Approximately one in five admitted patients occupying hospital beds did not meet the criteria for acute in-hospital stay or care at the time of the survey. Most delays were related to issues outside the immediate control of the hospital. Improvement programmes working with stakeholders focusing on the transfer from hospital to outside areas of care need to be further developed and may offer potential for the greatest gain. The DoCS can be a tool to periodically monitor changes and improvements in patient flow.

Second-line and third-line therapy with nanoliposomal irinotecan (nal-IRI) in pancreatic cancer: a single-center experience and review of literature.

Background: Prognosis of patients with pancreatic cancer is still extremely poor. First-line palliative therapies with FOLFIRINOX or gemcitabine/nab-paclitaxel have been established in the last decade. In the second-line, 5-FU/LV in combination with nanoliposomal irinotecan (nal-IRI) after gemcitabine has been shown to be effective. However, the use of nal-IRI as third-line therapy after FOLFIRINOX and gemcitabine-based chemotherapies is still controversial. In this study, we report about the use of 5-FU/LV + nal-IRI in a daily practice and analyze whether nal-IRI is an option as third-line therapy after FOLFIRINOX and gemcitabine/nab-paclitaxel. Methods: This is a single center retrospective analysis of patients with irresectable pancreatic cancer who were treated with 5-FU/LV and nal-IRI from 2017 to 2021 as second- or third-line palliative treatment. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed, and multivariate analysis was used to identify independent prognostic factors. Results: Twenty-nine patients receiving 5-FU/LV and nal-IRI were included in the analysis. The majority of patients (n=19) received 5-FU/nal-IRI as third-line therapy after pre-exposition to FOLFIRINOX and gemcitabine/nab-paclitaxel. Median OS and PFS were 9.33 months (95% CI: 3.37, 15.30) and 2.90 months (95% CI: 1.64, 4.16), respectively. Furthermore, patients receiving nal-IRI + 5-FU/LV as third-line treatment also showed some benefits, with no OS difference compared to second-line patients (9.33 vs. 10.27 months; HR: 1.85; 95% CI: 0.64, 5.41; P=0.253). Adverse effects were similar to reported trials. Conclusions: In our study, the use of 5-FU/nal-IRI in unselected patients with advanced pancreatic cancer showed similar OS, PFS and tolerance as randomized prospective phase II/III trials. Interestingly, the use of 5-FU/nal-IRI seemed to be beneficial in third-line therapy, despite a pre-exposure to non-liposomal irinotecan.

The Role of P16, P53, KI-67 and PD-L1 Immunostaining in Primary Vaginal Cancer.

BACKGROUND: To analyze clinical, pathological and immunohistochemical correlates of survival in vaginal cancer patients. METHODS: Retrospective analysis of primary vaginal cancer patients, treated at the Department of Gynecology and Gynecological Oncology of the University Hospital Bonn between 2007 and 2021. RESULTS: The study cohort comprised 22 patients. The median age was 63 years (range: 32-87 years). Squamous cell histology was present in 20 patients. Five-year OS in Stage I, II, III and IV was 100%, 56.25%, 0% and 41.67%, respectively (p = 0.147). Five-year DFS was 100%, 50%, 0% and 20.83%, respectively (p = 0.223). The 5-year OS was significantly reduced in the presence of nodal metastasis (p = 0.004), lymphangiosis (p = 0.009), hemangiosis (p = 0.002) and an age above 64 years (p = 0.029). Positive p 16 staining was associated with significantly improved OS (p = 0.010). Tumoral and immune cell PD-L1 staining was positive in 19 and in 16 patients, respectively, without significant impact on OS; 2 patients with metastastic disease are long-term survivors treated with either bevacizumab or pembrolizumab. CONCLUSION: P16 expression, absence of lymph- or hemangiosis, nodal negative disease and an age below 64 years show improved survival rates in PVC. Tumoral PD-L1 expression as well as PD-L1 expression on immune cells is frequent in PVC, without impacting survival. Within our study cohort, long-term survivors with recurrent PVC are treated with anti-VEGF and immunotherapy.

Deep learning enables automated MRI-based estimation of uterine volume also in patients with uterine fibroids undergoing high-intensity focused ultrasound therapy.

BACKGROUND: High-intensity focused ultrasound (HIFU) is used for the treatment of symptomatic leiomyomas. We aim to automate uterine volumetry for tracking changes after therapy with a 3D deep learning approach. METHODS: A 3D nnU-Net model in the default setting and in a modified version including convolutional block attention modules (CBAMs) was developed on 3D T2-weighted MRI scans. Uterine segmentation was performed in 44 patients with routine pelvic MRI (standard group) and 56 patients with uterine fibroids undergoing ultrasound-guided HIFU therapy (HIFU group). Here, preHIFU scans (n = 56), postHIFU imaging maximum one day after HIFU (n = 54), and the last available follow-up examination (n = 53, days after HIFU: 420 ± 377) were included. The training was performed on 80% of the data with fivefold cross-validation. The remaining data were used as a hold-out test set. Ground truth was generated by a board-certified radiologist and a radiology resident. For the assessment of inter-reader agreement, all preHIFU examinations were segmented independently by both. RESULTS: High segmentation performance was already observed for the default 3D nnU-Net (mean Dice score = 0.95 ± 0.05) on the validation sets. Since the CBAM nnU-Net showed no significant benefit, the less complex default model was applied to the hold-out test set, which resulted in accurate uterus segmentation (Dice scores: standard group 0.92 ± 0.07; HIFU group 0.96 ± 0.02), which was comparable to the agreement between the two readers. CONCLUSIONS: This study presents a method for automatic uterus segmentation which allows a fast and consistent assessment of uterine volume. Therefore, this method could be used in the clinical setting for objective assessment of therapeutic response to HIFU therapy.

Improvement of fibroid-associated symptoms and quality of life after US-guided high-intensity focused ultrasound (HIFU) of uterine fibroids.

Uterine fibroids are the most common benign uterine tumors and can cause various severe symptoms as abnormal menstrual bleeding or pelvic pain. Therefore, the primary objective in the treatment of uterine fibroids is a sufficient symptom relief. Ultrasound (US)-guided High-intensity focused ultrasound (HIFU) is an effective non-invasive treatment strategy for ablation of uterine fibroids that can achieve a significant tumor volume reduction. The aim of the study is to evaluate if US-guided HIFU treatment can reduce fibroid-associated symptoms leading to an improvement of health-related quality of life. Fifty-five women with symptomatic uterine fibroids underwent US-guided HIFU ablation. Clinical evaluation was performed on the basis of the Uterine Fibroid Symptom and Health-Related Quality of Life Questionnaire (UFS-QOL) at baseline, 6 weeks, 3, 6, 9 and 12 months after HIFU. Imaging follow-up included contrast-enhanced ultrasound (CEUS) and contrast-enhanced MRI. A significant reduction of the Symptom Severity Scale (SSS) was observed between 6 weeks and 12 months after HIFU (49.9 ± 19.4 at baseline vs. 42.2 ± 20.1 at 6 weeks and 23.6 ± 12.7 at 12 months after treatment, p < 0.001) correlating with a significant improvement (p < 0.001) of Health-related Quality of Life (HRQL) (52.5 ± 22.7 at baseline vs. 59.8 ± 22 at 6 weeks and 77.9 ± 17.3 at 12 months after treatment). Significant postinterventional improvement was observed in every subscale of HRQL. In the majority of patients, only minor, short-lasting and self-limiting side effects were observed, e.g. soft tissue edema of the anterior lower abdominal wall in the acoustic pathway or transient moderate lower abdominal pain as during menstruation. One patient with a very large fibroid experienced strong short-lasting pain after the procedure; two patients experienced post-procedurally a transient sciatic nerve irritation. US-guided HIFU of uterine fibroids reduces disease-related symptoms and improves health-related quality of life.

Postoperative Femoral Nerve Palsy and Meralgia Paresthetica after Gynecologic Oncologic Surgery.

Femoral nerve palsy and meralgia paresthetica following gynecologic cancer surgery are rare, but severe and long lasting. Here, we aimed to study their incidence, severity, possible risk factors and its time to remission. Between January 2008 and December 2017 976 gynecologic cancer patients were identified in our institutional database receiving surgery. Complete patient charts were reviewed retrospectively. Possible risk factors were analyzed by Fisher's exact test. 441 (45.18%) out 976 were treated for Ovarian cancer. In total 23 patients were identified with a postoperative neurological leg disorder. A femoral nerve palsy was present in 15 patients (1.5%) and a meralgia paresthetica in 8 patients (0.82%). Three patients showed both disorders. Duration of surgery (p = 0.0000), positioning during surgery (p = 0.0040), femoral artery catheter (p = 0.0051), prior chemotherapy (p = 0.0007), nicotine abuse (p = 0.00456) and prior polyneuropathy (p = 0.0181) showed a significant association with a postoperative femoral nerve palsy. Nicotine abuse (p = 0.0335) and prior chemotherapy (p = 0.0151) were significant for the development of a meralgia paresthetica. Long lasting surgery, patient positioning and femoral arterial catheter placement are risk factors for a postoperative femoral nerve palsy in gynecologic cancer surgery. Polyneuropathy, nicotine abuse, and prior chemotherapy are predisposing risk factors for a femoral nerve palsy and a meralgia paresthetica. A resolution of symptoms is the rule for both disorders within different time schedules.

Tumor Load Matters - the Peritoneal Cancer Index in Patients With High-grade Serous Ovarian Cancer.

BACKGROUND/AIM: The aim of this study was to analyze the predictive and prognostic value of the peritoneal cancer index (PCI) with regard to complete cytoreduction and clinical outcomes in patients with high-grade serous ovarian cancer. PATIENTS AND METHODS: In a cohort comprising 188 patients with high-grade serous ovarian cancer, the PCI was retrospectively assessed. Clinical factors and perioperative complications were analyzed according to different PCI groups. Five-year disease-free survival (DFS) and overall survival (OS) were calculated based on the Kaplan-Meier Log rank analysis. Receiver operating characteristic (ROC) analysis was applied to detect associations of PCI and complete cytoreduction. Multivariate survival analysis was performed by Cox proportional hazards model. RESULTS: In our study, the PCI was predictive of complete cytoreduction (ROC analysis; AUC 0.8227). In patients with optimal cytoreduction, higher PCI scores were associated with poorer 5-year OS (p<0.001) and 5-year DFS (p<0.001). Complications (G1-G5) were significantly more frequent in patients with PCI scores >9 (p=0.0023). Five-year OS was reduced in patients with severe complications compared to patients with none or mild complications (30.88% versus 51.01%; p=0.001). There were significant OS (p<0.001) and DFS (p<0.001) differences between patients with none or mild versus severe complications following complete cytoreduction within the PCI subgroups (PCI: 9-11, PCI: 12-18, PCI >18). CONCLUSION: The PCI score showed high predictability for complete cytoreduction and was associated with clinical outcomes. In presence of severe complications, higher PCI scores were associated with poorer survival. Hence, in patients with high tumor load, the prevention of severe perioperative complications is of utmost importance in all cases where complete cytoreduction is deemed to be feasible.

Postoperative paralytic ileus following debulking surgery in ovarian cancer patients.

Aim: This study aims to evaluate the incidence of postoperative ileus (POI) following cytoreductive surgery in epithelial ovarian cancer (EOC) patients and its impact on anastomotic leakage occurrence and postoperative complications. Methods: A total of 357 surgeries were performed on 346 ovarian cancer patients between 1/2010 and 12/2020 at our institution. The postoperative course regarding paralytic ileus, anastomotic leakage, and postoperative complications was analyzed by Fisher's exact test and through ordinal logistic regression. Results: A total of 233 patients (65.3%) returned to normal gastrointestinal functions within 3 days after surgery. A total of 123 patients (34.5%) developed POI. There were 199 anastomoses in 165 patients and 24 leakages (12.1%). Postoperative antibiotics (p 0.001), stoma creation (p 0.0001), and early start of laxatives (p 0.0048) significantly decreased POI, while anastomoses in general (p 0.0465) and especially low anastomoses (p 0.0143) showed increased POI rates. Intraoperative positive fluid excess >5,000 cc was associated with a higher risk for POI (p 0.0063), anastomotic leakage (p 0.0254), and severe complications (p 0.0012). Conclusion: Postoperative antibiotics, an early start with laxatives, and stoma creation were associated with reduced POI rates. Patients with anastomoses showed an increased risk for POI. Severe complications, anastomotic leakages, and POI were more common in the case of intraoperative fluid balance exceeding 5,000 cc.

Predicting incomplete cytoreduction in patients with advanced ovarian cancer.

Purpose: The most important prognostic factor for survival in ovarian cancer patients is complete cytoreduction. The preoperative prediction of suboptimal cytoreduction, considered as any residual disease at the end of surgery, could prevent futile surgery and morbidity. Here, we aimed to identify markers in the preoperative abdominal CT scans of an unselected cohort of patients with ovarian cancer that are predictive of incomplete cytoreduction. Methods: This is a single-institution retrospective analysis of 105 epithelial ovarian cancer (EOC) patients treated with surgical cytoreduction between 2010 and 2020. Twenty-two variables on preoperative abdominal CT scans were compared to the intraoperative macroscopic findings by Fisher's exact test. Parameters with a significant correlation between intraoperative findings and imaging were analyzed by multivariate binary logistic regression analysis regarding the surgical outcome of complete versus incomplete cytoreduction. Results: Complete cytoreduction (CC), indicated by the absence of macroscopic residual disease, was achieved in 79 (75.2%) of 105 patients and 46 (63.9%) of 72 International Federation of Gynecology and Obstetrics (FIGO) stage III and IV patients. Twenty patients (19%) were incompletely cytoreduced due to miliary carcinomatosis of the small bowel, and six patients (5.7%) had various locations of residual disease. Thirteen variables showed a significant correlation between imaging and surgical findings. Large-volume ascites, absence of numerically increased small lymph nodes at the mesenteric root, and carcinomatosis of the transverse colon in FIGO stage III and IV patients decreased the rate of CC to 26.7% in the multivariate analysis. Conclusion: Large-volume ascites, the absence of numerically increased small lymph nodes at the mesenteric root, and carcinomatosis of the transverse colon are markers in preoperative CT scans predicting a low chance for complete cytoreduction in unselected ovarian cancer patients in a real-world setting.

First Line and Second Line Chemotherapy in Advanced Cholangiocarcinoma and Impact of Dose Reduction of Chemotherapy: A Retrospective Analysis.

OBJECTIVE: Prognosis of patients with irresectable cholangiocarcinoma is still poor. The ABC-02 trial established the current first line (1L) standard systemic chemotherapy (CT) with gemcitabine/platinum derivate for advanced cholangiocarcinoma. However, the majority of patients needed therapy adaptions. Thus, the aim of this study was to evaluate 1L and second line (2L) therapy regimens and the impact of therapy adaptions in an unselected real-life cohort of patients with advanced cholangiocarcinoma. MATERIALS AND METHODS: This is a single institution retrospective analysis of patients with irresectable cholangiocarcinoma who were treated with gemcitabine/platinum derivate from 2010 to 2018. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed for all patients, especially with regard to CT de-escalation. RESULTS: Fifty-eight patients receiving gemcitabine/platinum derivate were included in the analysis. Median OS and PFS were 12.2 and 6.9 months. Interestingly, 41 patients (71%) needed therapy de-escalation. However, despite reduced CT exposition, there was no-significant difference in OS (10.8 months vs. 15.6 months, p = 0.127), and patients suffered from less adverse events during CT. 21 (36%) patients reached 2L CT, most often with FOLFIRI (57%). Survival beyond the end of 1L CT was 7.1 months with 2L CT vs. 2.9 months with BSC. CONCLUSION: In our study, the combination of gemcitabine/platinum derivate showed similar OS and PFS as randomized prospective phase II/III trials. Therapy regimen adaptions were needed in the majority of patients. However, individualized modifications of the therapy regimen allowed better tolerance as well as continuation of therapy and did not significantly influence median OS. Furthermore, our study revealed a potential survival benefit with 2L CT for selected patients.

Equality and diversity in health governance systems: are we getting it right and are there lessons from COVID-19?

The COVID-19 pandemic highlighted major challenges in governance and inequalities particularly among those from Black, Asian and minority ethnic (BAME) groups. This paper focuses on the BAME community and explores this through a governance lens, with particular reference to the representation and functioning of boards involved in healthcare and building a transparent culture. To illustrate this, the paper utilises a series of structured reflective questions with model answers termed Right Question, Right Answer and links to the Centre for Quality in Governance (CQG) Maturity Matrix. This article highlights the need to improve diversity and accountability of health and care organisations to their staff and local population. For governance to be effective, it must be aligned and comply with healthcare system regulations to ensure improvement of legislative acts and standards. The paper aims to inform government policy by moving from rhetoric, or merely describing challenges, to action and change by increasing accountability.

Multidisciplinary management to optimize outcome of ultrasound-guided high-intensity focused ultrasound (HIFU) in patients with uterine fibroids.

Little is known about the specific anaesthesiological and multidisciplinary management of high-intensity focused ultrasound (HIFU) in uterine fibroids. This observational single-center study is the first reporting on an interdisciplinary approach to optimize outcome following ultrasound (US)-guided HIFU in German-speaking countries. A sample of forty patients with symptomatic uterine fibroids was treated by HIFU. Relevant treatment parameters such as total treatment time for intervention, anaesthesia, and sonication time as well as total energy, body temperature, peri-interventional medication and complications were analyzed. Interventional variables did not correlate significantly either with opioid dose or with body temperature. The average fibroid volume reduction rate was 37.8% ± 23.5%, 48.5% ± 22.0% and 70.2% ± 25.5% after 3, 6 and 12 months, respectively. No major anaesthesiological complications occurred apart from an epileptic seizure prior to HIFU treatment in one patient. Peri-procedural hyperthermia (> 37.5 °C) occurred in two patients. Post-procedural two patients experienced a sciatic nerve irritation up to one year; one patient with very large treated fibroid experienced strong short-lasting post-procedural pain. There were two complication-free pregnancies of HIFU-treated patients. Multidisciplinary management is crucial to optimize safety and outcome of US-guided HIFU for uterine fibroids. Peri-procedural pain and temperature management are critical points where an adequate collaboration between anesthesiologist and interventionalist is mandatory.

Acute medical units during the first wave of the COVID-19 pandemic: a cross-national exploratory study of impact and responses.

BACKGROUND: The COVID-19 pandemic represents one of the greatest ever challenges for healthcare. In the UK and beyond, acute medical units (AMUs) are the first point of assessment and care for the majority of medical inpatients. By their design and systems, they inevitably played an important role in the COVID-19 response but to date little has been published on how the COVID-19 pandemic has affected how AMUs have reorganised their resources, processes and structure. METHODS: This retrospective study in August 2020 of 10 AMUs across Europe and Australasia used a standardised questionnaire to investigate existing practice and structure of AMUs, the national context of local hospital experience, changes to practice during the COVID-19 pandemic and views regarding future practice. RESULTS: Changes to AMU structure, process and organisation are described in two contexts: preventing and controlling the spread of COVID-19 and adding value to the patient's acute care journey in the local context. We describe novel practices that have arisen and highlight areas of concern. CONCLUSIONS: The AMUs were able to adapt to meet the demands of acute care delivery during the first wave of the COVID-19 pandemic. Operational planning and prioritisation of resources must be optimised to ensure sustainability of these services for future waves.

US-guided high-intensity focused ultrasound (HIFU) of abdominal tumors: outcome, early ablation-related laboratory changes and inflammatory reaction. A single-center experience from Germany.

INTRODUCTION: High-intensity focused ultrasound (HIFU) is an innovative noninvasive procedure for local ablation of different benign and malignant tumors. Preliminary data of animal studies suggest an ablation-associated immune response after HIFU that is induced by cell necrosis and release of intracellular components. The aim of this study is to evaluate if a HIFU-induced early sterile inflammatory reaction is initiated after ablation of uterine fibroids (UF) and pancreatic carcinoma (PaC) which might contribute to the therapeutic effect. MATERIAL AND METHODS: A hundred patients with PaC and 30 patients with UF underwent US-guided HIFU treatment. Serum markers of inflammation (leukocytes, CRP, IL-6) and LDH in both collectives as well as tumor markers CA 19-9, CEA and CYFRA in PaC patients were determined in sub-cohorts before and directly after HIFU (0, 2, 5 and 20 h post-ablation) as well as at 3, 6, 9 and 12 months follow-up. Peri-/post interventional imaging included contrast-enhanced MRI of both cohorts and an additional CT scan of PaC patients. RESULTS: An early post-ablation inflammatory response was observed in both groups with a significant increase of leukocytes, CRP and LDH within the first 20 h after HIFU. Interestingly, IL-6 was increased at 20 h after HIFU in PaC patients. A significant reduction of tumor volumes was observed during one year follow-up (p < .001) for both tumor entities demonstrating effective treatment outcome. CONCLUSION: Tumor ablation with HIFU induces an early sterile inflammation that might serve as a precondition for long-term tumor immunity and a sustainable therapeutic effect.

Efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for uterine fibroids: an observational single-center study.

INTRODUCTION: To evaluate treatment response of uterine fibroids after ultrasound guided high-intensity focused ultrasound (USgHIFU) with a special focus on fibroid size and characterization based on Funaki classification scheme, as well as clinical response to treatment of leading fibroid-associated symptoms. MATERIALS AND METHODS: Uterine fibroids treated by USgHIFU were assigned to Funaki type 1-3 based on T2-w-MRI. Differences in size, non-perfused volume ratio (NPVR) and volume reduction over time were determined using T1-/T2-w MRI sequences and contrast-enhanced sonography. Treatment effects on three leading fibroid-associated symptoms were also evaluated. Measurements were compared by mixed model, Bland-Altman's plot and Spearman's correlation. RESULTS: In this prospective single-center study, 35 patients with 44 symptomatic uterine fibroids were treated by USgHIFU (n = 22, n = 12 and n = 10 assigned to Funaki type 1, 2 and 3, respectively). NPVRs of Funaki type 1 and 2 fibroids were significantly higher compared to type 3 (p = .0023). A significant fibroid shrinkage was observed independent of Funaki type compared to baseline: 38.8 ± 26.9%, 46.7 ± 30.3% and 54.5 ± 29.3% at 3, 6 and 12 months, respectively (each p < .05). Moreover, patients experienced a significant improvement of fibroid-associated hypermenorrhea (3.9 ± 1.3 vs. 2.3 ± 1.3), pressure in the pelvic area (3.5 ± 1.3 vs. 2.1 ± 0.9) and frequent urination (2.8 ± 1.5 vs. 1.9 ± 0.8) one year post-procedure (each p < .05), regardless of fibroid Funaki type. CONCLUSION: Following USgHIFU, a significant shrinkage of uterine fibroids and improvement of leading fibroid-associated symptoms were demonstrated regardless of the Funaki type.