Baseline ctDNA gene alterations as a biomarker of survival after panitumumab and chemotherapy in metastatic colorectal cancer.

Certain genetic alterations and right-sided primary tumor location are associated with resistance to anti-epidermal growth factor (EGFR) treatment in metastatic colorectal cancer (mCRC). The phase 3 PARADIGM trial (n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. This prespecified exploratory biomarker analysis of PARADIGM (n = 733) evaluated the association between circulating tumor DNA (ctDNA) gene alterations and efficacy outcomes, focusing on a broad panel of gene alterations associated with resistance to EGFR inhibition, including KRAS, NRAS, PTEN and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK, RET and NTRK1 fusions. Overall survival was prolonged with panitumumab plus modified FOLFOX6 versus bevacizumab plus modified FOLFOX6 in patients with ctDNA that lacked gene alterations in the panel (that is, negative hyperselected; median in the overall population: 40.7 versus 34.4 months; hazard ratio, 0.76; 95% confidence interval, 0.62-0.92) but was similar or inferior with panitumumab in patients with ctDNA that contained any gene alteration in the panel (19.2 versus 22.2 months; hazard ratio, 1.13; 95% confidence interval, 0.83-1.53), regardless of tumor sidedness. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795 .

Efficacy of second-line chemotherapy after treatment with gemcitabine plus nab-paclitaxel or FOLFIRINOX in patients with metastatic pancreatic cancer.

First-line chemotherapy for patients with metastatic pancreatic cancer (MPC) includes gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX). However, the efficacy of second-line chemotherapy and the role of combination chemotherapy in clinical practice is still unknown. Data was gathered from 14 hospitals in the Kyushu area of Japan from December 2013 to March 2017. The median overall survival (mOS) from second-line treatment was contrasted between patients who received second-line chemotherapy (CT group) and those who received the best supportive care (BSC group). Furthermore, the mOS of combination chemotherapy was compared to mono chemotherapy in the CT group. To control possible bias in the selection of treatment, we performed a propensity score-adjusted analysis. A total of 255 patients received GnP or FFX as first-line chemotherapy. There were 156 in the CT group and 77 in the BSC group of these. The CT group had a significantly longer mOS than the BSC group (5.2 vs. 2.6 months; adjusted hazard ratio (HR) 0.38; 95% CI 0.27-0.54). In the CT group, 89 patients received combination chemotherapy while 67 received mono chemotherapy. The mOS did not differ significantly between the combination and mono chemotherapy groups (5.5 vs. 4.8 months; adjusted HR 0.88; 95% CI 0.58-1.33). Among patients with MPC receiving second-line treatment, the CT group had a significantly longer mOS than the BSC group, but combination chemotherapy conferred no improvement in survival compared to mono chemotherapy.

Case Report: A case of complete response to entrectinib in NTRK fusion gene-positive parotid gland cancer.

Introduction: Expression of the NTRK gene is rare in solid tumors but is highly prevalent in salivary gland secretory carcinomas. Here, we report a case of a complete response to entrectinib in a patient with NTRK fusion gene-positive parotid carcinoma. Case description: The patient was a 44-year-old man who underwent total left parotidectomy and left cervical lymph node dissection for a left parotid tumor at 24 years of age. The histopathological diagnosis was mammary analog secretory carcinoma. Postoperatively, the patient received only radiation therapy. Sixteen years after the surgery, the patient became aware of a mass in the left parotid region. A close examination revealed local recurrence and multiple cervical lymph node metastases. S-1 monotherapy was started as chemotherapy but was discontinued 3 years later because of disease progression. As there was no standard treatment, a comprehensive genomic profiling test using a next-generation sequencer was performed, and the ETV6-NTRK3 fusion gene was identified. Entrectinib, an NTRK inhibitor, was immediately administered at a dose of 600 mg/day. The local recurrence rapidly shrank grossly from the beginning of treatment, and a complete response was observed 6 months later. However, creatinine levels exhibited an increase at week 68 of treatment; consequently, entrectinib dosage was lowered to 400 mg/day, leading to an immediate improvement in creatinine levels. Entrectinib was associated with additional side effects, including dysgeusia, fatigue, dizziness, and weight gain, all of which were also alleviated by the reduction in entrectinib dose. Thirty months after treatment initiation, the patient maintained a complete response and continued to receive entrectinib. Conclusion: The NTRK fusion gene should always be checked in the presence of salivary gland secretory carcinoma.

Significance of Desmoplastic Histopathological Growth Pattern for Colorectal Liver Metastases Treated With Preoperative Chemotherapy.

BACKGROUND/AIM: The aim of this study was to evaluate hepatectomy cases that underwent preoperative chemotherapy to examine the relationship between the development of desmoplastic histopathological growth pattern (dHGP) and prognosis and recurrence and determine whether it is useful for evaluating preoperative chemotherapy. PATIENTS AND METHODS: A total of 133 cases with hepatic metastasis for colorectal cancer that underwent surgical resection. RESULTS: Of the 102 cases that underwent preoperative chemotherapy, 34 (33%) were determined to be dHGP positive, which was statistically significantly higher than the 2 of 31 cases (6.5%) that had not undergone preoperative chemotherapy. Regarding the 5-year recurrence-free survival, the dHGP group had a value of 50.3%, whereas the non-dHGP group had a value of 7.1%. For the 5-year overall survival, the dHGP group had a better prognosis than the non-dHGP group (57.6% vs. 37.1%, respectively), with a statistically significant difference. Univariate analysis of recurrence-free survival showed that the number of tumours, the Response Evaluation Criteria in Solid Tumors, and the presence or absence of dHGP were prognostic factors, whereas multivariate analysis showed that the presence or absence of dHGP was an independent prognostic factor. Univariate analysis of the overall survival showed that the number of tumours, the Response Evaluation Criteria in Solid Tumors, and presence or absence of dHGP were prognostic factors. Multivariate analysis showed that the presence or absence of dHGP was an independent prognostic factor. CONCLUSION: dHGP is useful as a new evaluation method for evaluating the efficacy of preoperative chemotherapy.

Development of an Algorithm to Predict Recurrences After Resection of Liver Metastases in Patients With Metastatic Colorectal Cancer.

BACKGROUND/AIM: Hepatic recurrences after resection of metastatic lesions in advanced colorectal cancer (CRC) have an enormous impact on patient prognosis. Response evaluation criteria in solid tumor (RECIST) or morphologic response on computed tomography (CT) have been reported as surrogate prognostication markers. This study assessed a novel algorithm for the prognostication of liver metastasis treatment. PATIENTS AND METHODS: Forty-seven patients with liver metastases from CRC who underwent liver resection after systemic chemotherapy were included. The CT values examined before and after chemotherapy were collected. The velocity of CT values (CTvΔ) was calculated, and the subjects were divided into CTvΔ_high and _low groups. Clinicopathological variables, recurrence-free survival (RFS), and overall survival (OS) were statistically compared between the two groups. In addition, the effect of the combined evaluation of CTvΔ and carcinoembryonic antigen (CEA) was evaluated. RESULTS: In univariate analyses, the hazard ratio (HR) for a recurrence after liver resection was relatively higher in the RECIST_stable disease (SD) or _progressive disease (PD) and the CTvΔ_low groups. In multivariate analysis, the HR was significantly higher in the CEA_high, the RECIST_SD or PD, and the CTvΔ_low groups. The RFS was significantly longer in the CTvΔ_high group. Furthermore, the combination of CTvΔ and CEA predicted the RFS and OS. CONCLUSION: Our algorithm using CTvΔ could be a useful tool to select patients suitable for liver resection of hepatic CRC metastases.

Comparison of long-term quality of life based on surgical procedure in patients with rectal cancer.

Introduction: Reports on the long-term quality of life (QOL) over 3 years after surgery in patients who have undergone surgery for rectal cancer are limited. Therefore, we aimed to evaluate the long-term QOL of patients who underwent high anterior resection (HAR), low anterior resection (LAR), internal sphincter resection (ISR), or abdominoperineal resection (APR) for rectal cancer. Methods: A questionnaire regarding QOL was sent to 360 patients with rectal cancer who underwent curative resection by HAR, LAR, ISR, or APR between January 2005 and December 2015. QOL was assessed using the short-form 36 (SF-36) and modified fecal incontinence QOL (mFIQL) questionnaire. QOL between surgical procedures was analyzed using a multivariate model adjusted for age, sex, and postoperative time. Results: A total of 144 patients responded with a median follow-up period of 94 months (range 38-233 months). According to surgical procedure, HAR was performed in 26 patients, LAR in 80 patients, ISR in 32 patients, and APR in 6 patients. Patients who underwent HAR had significantly better mFIQL scores than those who underwent LAR and ISR (p=0.013 and p=0004, respectively) and significantly better role/social component summary scores on the SF-36 subscales (p=0.007). No difference was observed in the mFIQL scores between patients who underwent ISR and those who underwent APR (p=0.8423). In addition, postoperative anastomotic leakage sutures did not influence the mFIQL and SF-36 scores after surgery. Conclusion: The QOL of patients who underwent anus-preserving surgery was best in the HAR group, with the QOL of other groups similar to the APR group. These results suggest that anus- preserving surgery is acceptable from a QOL standpoint. However, a colostomy may be a more satisfactory procedure in some patients.

Safety of Early Bevacizumab Administration after Central Venous Port Placement for Patients with Colorectal Cancer.

Bevacizumab (BEV) requires an adequate withdrawal period to avoid BEV-related complications during major surgery. However, the safety of BEV administration immediately after surgical placement of the central venous (CV) port, a minor surgery, is still unclear. This study aimed to investigate whether BEV is safe when administered early after CV port placement. We retrospectively evaluated 184 patients with advanced colorectal cancer (CRC) treated with a BEV-containing regimen and divided them into two groups according to the interval between CV port implantation and chemotherapy initiation, with the early administration group being ≤7 days and late administration group being >7 days. Complications were then compared between the two groups. The early-administration group was significantly older and had a higher rate of colon cancer than the late-administration group. Overall, 24 (13%) patients developed CV port-related complications. Male sex was a risk factor for complications (odds ratio [OR], 3.154; 95% CI, 1.19-8.36). The two groups showed no significant difference in the frequency of complications (p = 0.84) or patient characteristics (after the inverse probability of treatment weighting, p = 0.537). In conclusion, the frequency of complications is not affected by the timing of BEV initiation after CV port implantation. Thus, early BEV administration after CV port placement is safe.

High intramuscular adipose tissue content was a favorable prognostic factor in patients with advanced gastric cancer treated with nivolumab monotherapy.

BACKGROUND: Nivolumab extends the overall survival (OS) of patients with advanced gastric cancer (AGC). Intramuscular adipose tissue (IMAT) is associated with the prognosis of patients with various cancers. We investigated the effect of IMAT on OS in patients with AGC treated with nivolumab. METHODS: We enrolled patients with AGC treated with nivolumab (n = 58, 67 years old, men/women 40/18). The subjects were classified into long-term or short-term survival groups according to the median value. The IMAT was evaluated using computed tomography scans at the umbilical level. The decision tree algorithm was employed to reveal the profile associated with prognosis. RESULTS: In decision tree analysis, immune-related adverse events (irAEs) were the first divergence variable, and prolonged survival was observed in 100% of patients with irAEs (profile 1). However, long survival was observed in 38% of patients with no irAEs. Among these patients, IMAT was identified as the second divergence variable, and long survival was observed in 63% of patients with high IMAT (profile 2). In patients with low IMAT, only 21% showed prolonged survival (profile 3). Median OS was 717 days (95% confidence interval [CI], 223 to not reached) in profile 1, 245 days (95% CI, 126 to 252) in profile 2, and 132 days (95% CI, 69 to 163) in profile 3. CONCLUSION: Immune-related adverse events and high IMAT were favorable factors for OS in patients with AGC treated with nivolumab. Thus, along with irAEs, skeletal muscle quality is important in managing patients with AGC treated with nivolumab.

Panitumumab vs Bevacizumab Added to Standard First-line Chemotherapy and Overall Survival Among Patients With RAS Wild-type, Left-Sided Metastatic Colorectal Cancer: A Randomized Clinical Trial.

Importance: For patients with RAS wild-type metastatic colorectal cancer, adding anti-epidermal growth factor receptor (anti-EGFR) or anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined. Objective: To evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) vs bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic colorectal cancer. Design, Setting, and Participants: Randomized, open-label, phase 3 clinical trial at 197 sites in Japan in May 2015-January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic colorectal cancer (final follow-up, January 14, 2022). Interventions: Panitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days. Main Outcomes and Measures: The primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resection rate. Results: In the as-treated population (n = 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had left-sided tumors. Median follow-up was 61 months. Median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio [HR] for death, 0.82; 95.798% CI, 0.68-0.99; P = .03) and 36.2 vs 31.3 months, respectively, in the overall population (HR, 0.84; 95% CI, 0.72-0.98; P = .03). Median progression-free survival for panitumumab vs bevacizumab was 13.1 vs 11.9 months, respectively, for those with left-sided tumors (HR, 1.00; 95% CI, 0.83-1.20) and 12.2 vs 11.4 months overall (HR, 1.05; 95% CI, 0.90-1.24). Response rates with panitumumab vs bevacizumab were 80.2% vs 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI, 4.4%-17.9%) and 74.9% vs 67.3% overall (difference, 7.7%; 95% CI, 1.5%-13.8%). Median duration of response with panitumumab vs bevacizumab was 13.1 vs 11.2 months for left-sided tumors (HR, 0.86; 95% CI, 0.70-1.10) and 11.9 vs 10.7 months overall (HR, 0.89; 95% CI, 0.74-1.06). Curative resection rates with panitumumab vs bevacizumab were 18.3% vs 11.6% for left-sided tumors; (difference, 6.6%; 95% CI, 1.0%-12.3%) and 16.5% vs 10.9% overall (difference, 5.6%; 95% CI, 1.0%-10.3%). Common treatment-emergent adverse events were acneiform rash (panitumumab: 74.8%; bevacizumab: 3.2%), peripheral sensory neuropathy (panitumumab: 70.8%; bevacizumab: 73.7%), and stomatitis (panitumumab: 61.6%; bevacizumab: 40.5%). Conclusions and Relevance: Among patients with RAS wild-type metastatic colorectal cancer, adding panitumumab, compared with bevacizumab, to standard first-line chemotherapy significantly improved overall survival in those with left-sided tumors and in the overall population. Trial Registration: ClinicalTrials.gov Identifier: NCT02394795.

Efficacy and Safety of Balloon Pulmonary Angioplasty for Patients With Chronic Thromboembolic Pulmonary Hypertension and Comorbid Chronic Obstructive Pulmonary Disease.

Background Balloon pulmonary angioplasty (BPA) is a promising treatment modality for nonoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, BPA for atypical CTEPH with concurrent chronic obstructive pulmonary disease (COPD) remains controversial owing to the risk of exacerbation of ventilation-perfusion mismatch. We aimed to evaluate the efficacy and safety of BPA for CTEPH with moderate or severe COPD. Methods and Results Data from 149 patients with CTEPH, who underwent BPA from March 2011 to June 2021, were retrospectively analyzed. Patients were divided based on COPD comorbidity: the COPD group (n=32, defined as forced expiratory volume in 1 second/forced vital capacity <70% and forced expiratory volume in 1 second <80% predicted) and the non-COPD group (n=101); patients with mild COPD (n=16) were excluded. Hemodynamic and respiratory parameters were compared between the groups. Hemodynamics improved similarly in both groups (reduction in pulmonary vascular resistance): -55.6±29.0% (COPD group) and -58.9±21.4% (non-COPD group); P=nonsignificant. Respiratory function and oxygenation improved in the COPD group (forced expiratory volume in 1 second/forced vital capacity [61.8±7.0% to 66.5±10.2%, P=0.02] and arterial oxygen partial pressure [60.9±10.6 mm Hg to 69.3±13.6 mm Hg, P<0.01]). Higher vital capacity (P=0.024) and higher diffusing capacity for lung carbon monoxide (P=0.028) at baseline were associated with greater improvement in oxygenation in the multivariable linear analysis. Lung injury per BPA session was 1.6% in the COPD group. Conclusions The efficacy and safety of BPA for nonoperable CTEPH in patients with comorbid COPD were similar to those in patients without COPD. Oxygenation and forced expiratory volume in 1 second/forced vital capacity improved in patients with COPD. BPA should be considered in patients with CTEPH with concurrent COPD.

Case report: A case of fulminant type 1 diabetes mellitus after COVID-19 vaccination during treatment of advanced gastric cancer: pitfall in managing immune-related adverse events.

The occurrence of fulminant type 1 diabetes mellitus as an adverse event during cancer immunotherapy has been previously reported. However, little is known about the causal relationship between the coronavirus disease 2019 (COVID-19) vaccination and fulminant type 1 diabetes mellitus. A 60-year-old man with advanced gastric cancer, receiving S-1 + oxaliplatin and nivolumab therapy, followed by nab-paclitaxel + ramucirumab as a second-line treatment, with steroid supplementation for complications of hypopituitarism-induced hypoadrenocorticism, was administered a COVID-19 vaccine after three cycles of nab-paclitaxel + ramucirumab. Two days later, he developed severe malaise and anorexia, which required emergency admission to our hospital for suspected adrenal insufficiency. Despite increasing steroids, his general condition changed suddenly after 12 hours leading to his death. Histopathological analysis of autopsy samples revealed loss of the islets of Langerhans, indicating fulminant type 1 diabetes mellitus. We failed to recognize the onset of fulminant type 1 diabetes mellitus because its symptoms were similar to those of adrenal insufficiency. The number of reports on the onset of fulminant type 1 diabetes mellitus after COVID-19 vaccination has been increasing, and in this case, the onset occurred on the second day after COVID-19 vaccination, suggesting an association between vaccination and fulminant type 1 diabetes mellitus. Clinicians should be aware of the risk of fulminant type 1 diabetes mellitus, although rare, after COVID-19 vaccination.

Case report: Changes in serum bevacizumab concentration in a hemodialysis patient with unresectable colorectal cancer treated with FOLFIRI plus bevacizumab.

The global incidence of colorectal cancer (CRC) in patients receiving hemodialysis is steadily rising. However, current information on the clinical use of chemotherapy for patients undergoing hemodialysis with CRC is limited. Herein, we describe a clinical course of a 74-year-old patient undergoing hemodialysis with unresectable CRC treated with folinic acid, 5-fluorouracil (5FU), and irinotecan (FOLFIRI) plus bevacizumab whose changes in serum bevacizumab concentration were analyzed. Treatment was initiated with a standard dosage of 5-FU and 80% of the standard dose of irinotecan to avoid any adverse events. However, neutropenia (grade 4) was observed after five treatment cycles, which prompted a dose reduction of 5-FU and irinotecan, after which treatment was safely completed. Progression-free survival of the patient was 7.5 months. Changes in serum bevacizumab concentration were similar to those documented in patients with normal renal function. In addition, no bevacizumab-related adverse events occurred. It was inferred that FOLFIRI plus bevacizumab therapy could be implemented as a safe and efficient treatment for patients undergoing hemodialysis with unresectable CRC. To the best of our knowledge, this is the first report of the analysis of serum bevacizumab concentrations in a patient undergoing hemodialysis with unresectable CRC.

Hyperlipidemia as a risk factor for Trousseau syndrome-related cerebral infarction in patients with advanced gastrointestinal cancer.

Trousseau syndrome-related cerebral infarction rarely occurs during chemotherapy in patients with gastrointestinal (GI) cancer, and its clinical features remain unclear. The present study aimed to examine the clinical features of Trousseau syndrome-related cerebral infarction developed during chemotherapy for GI cancer. The present retrospective cohort study consecutively enrolled 878 patients with unresectable GI cancer who received chemotherapy at the Multidisciplinary Treatment Cancer Center, Kurume University Hospital (Kurume, Japan) between April 2014 and March 2020. Patients with colorectal cancer (n=308) were the most common, followed by those with pancreatic (n=242), gastric (n=222) and biliary tract (n=59) cancer, neuroendocrine tumors (n=34) and duodenal cancer (n=11). Among the 878 patients, Trousseau syndrome-related cerebral infarction occurred in 8 (0.9%) patients with a median age of 70.5 years (range, 58-75 years), and 50% of the patients were male (4/8). In total, 3 patients had gastric cancer, 3 had pancreatic cancer and 2 had biliary tract cancer. A greater percentage of patients with Trousseau syndrome-related cerebral infarction had hyperlipidemia (38.0%) than those without (8.2%; P=0.005). Hyperlipidemia was a risk factor for occurrence of Trousseau syndrome-related cerebral infarction with an odds ratio of 7.009 (95% confidence interval, 1.785-27.513). Trousseau syndrome-related cerebral infarction developed during GI chemotherapy was rare and hyperlipidemia may predict its onset.

Microvasculopathy Evaluated by Dual-Energy Computed Tomography in Patients with Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension.

Background: Poor subpleural perfusion (PSP) on dual-energy computed tomography (DE-CT) suggests microvasculopathy in chronic thromboembolic pulmonary hypertension (CTEPH). However, whether the microvasculopathy findings are equivalent to those in pulmonary arterial hypertension (PAH) remains unclear. The aim of this study was to elucidate the characteristics of microvasculopathy in CTEPH compared to those of that in PAH. Methods: We retrospectively reviewed subpleural perfusion on DE-CT and the hemodynamics of 23 patients with PAH and 113 with inoperable CTEPH. Subpleural perfusion on DE-CT was classified as poor (subpleural spaces in all segments with little or no perfusion) or normal. Results: PSP was observed in 51% of patients with CTEPH and in 4% of those with PAH (p < 0.01). CTEPH patients with PSP had poorer baseline hemodynamics and lower diffusing capacity for carbon monoxide divided by the alveolar volume (DLCO/VA) than those with CTEPH with normal perfusion (pulmonary vascular resistance [PVR]: 768 ± 445 dynes-sec/cm5 vs. 463 ± 284 dynes-sec/cm5, p < 0.01; DLCO/VA, 60.4 ± 16.8% vs. 75.9 ± 15.7%, p < 0.001). Despite the existence of PSP, hemodynamics improved to nearly normal in both groups after balloon pulmonary angioplasty. Conclusions: PSP on DE-CT, which is one of the specific imaging findings in CTEPH, might suggest a different mechanism of microvasculopathy from that in PAH.

Efficacy of myocardial washout of 99mTc-MIBI/Tetrofosmin for the evaluation of inflammation in patients with cardiac sarcoidosis: comparison with 18F-fluorodeoxyglucose positron emission tomography findings.

OBJECTIVE: Both myocardial perfusion scintigraphy and 18F-fluorodeoxyglucose positron emission tomography (FDG PET) are useful for the diagnosis of cardiac sarcoidosis (CS). However, the association between the washout of 99mTc-labeled tracer and FDG PET has not been established. This study aimed to evaluate the association between the washout of 99mTc-labeled tracer and FDG PET findings in patients with CS. METHODS: We retrospectively analyzed 64 patients (65.0 ± 11.2 years, 53% male) with suspected CS who underwent myocardial single-photon emission computed tomography (SPECT) with 99mTc-labeled tracer and FDG PET. The SPECT images were acquired at 15 min (early images) and 3 h (delayed images) after injection and scored visually using a 17-segment model with a 5-point scoring system. The washout score was defined as the difference between the early and delayed total defect scores. FDG positivity was considered as focal or focal on diffuse patterns on visual assessment, and FDG uptake was quantified by measuring the standardized uptake value (SUV) of each of the 17 segments. RESULTS: The washout score was significantly higher for the CS group than for the non-CS group (3.0 [-1.0-5.0] vs. 0.0 [-0.5-1.0], p = 0.010). Receiver operating characteristic analysis showed that a washout score of ≥ 2 had the best accuracy for detecting CS (88% sensitivity and 56% specificity) and FDG positivity (71% sensitivity and 89% specificity). In the segment-based analysis of 833 segments from 49 patients, excluding 15 patients with diffuse FDG uptake, the median SUVs for FDG uptake for the washout scores of ≤ 0, 1, and 2 were 2.3 (1.8-3.6), 4.2 (2.9-7.8), and 8.3 (6.5-9.4), respectively (p < 0.001). CONCLUSIONS: The washout of 99mTc-labeled tracer can be a useful marker for the evaluation of FDG PET findings in patients with CS.

The impact of computed tomography-derived aortic atheroma volume on prognosis after transcatheter aortic valve replacement.

BACKGROUND: The impact of the extent of aortic atheroma on patients' prognosis after transcatheter aortic valve replacement (TAVR) has not been completely evaluated. This study aimed to evaluate the prognostic value of the aortic atheroma volume (AAV) derived from computed tomography, and the effect of its differences among the segments of the aorta, in patients undergoing TAVR. METHODS: In total, 143 patients with symptomatic severe aortic stenosis who underwent pre-procedural computed tomography before TAVR procedure indication were evaluated. AAV was calculated by measuring the aortic lumen and vessel volume using every 1-mm axial image and was further divided into thoracic (TAAV) and abdominal segments (AbAAV). RESULTS: During a median follow-up of 651 days, 24 all-cause and 14 cardiac deaths occurred. In the Kaplan-Meier analysis, the high AAV group had significantly higher all-cause and cardiac mortalities than the low AAV group (p = 0.016 and 0.023, respectively). Regarding segmental AAV, all-cause and cardiac mortalities did not have significant differences between the high and low TAAV groups. Moreover, all-cause and cardiac mortalities were significantly higher in the high AbAAV group than in the low AbAAV group (p = 0.0043 and 0.023, respectively). The multivariable analysis showed that only AbAAV was an independent predictor for all-cause mortality (hazard ratio: 1.06, p = 0.046). CONCLUSION: AAV was significantly associated with the mortality after TAVR. The current study suggests the pre-procedural assessment of AAV is valuable in predicting prognosis after TAVR. However, further investigation with a larger sample size is needed to validate our findings.

Prognostic Impact of Myocardial Extracellular Volume Fraction Assessment Using Dual-Energy Computed Tomography in Patients Treated With Aortic Valve Replacement for Severe Aortic Stenosis.

Background Myocardial extracellular volume fraction (ECV), measured by cardiac magnetic resonance imaging, is a useful prognostic marker for patients who have undergone aortic valve replacement (AVR) for aortic stenosis. However, the prognostic significance of ECV measurements based on computed tomography (CT) is unclear. This study evaluated the association between ECV measured with dual-energy CT and clinical outcomes in patients with aortic stenosis who underwent transcatheter or surgical AVR. Methods and Results We retrospectively enrolled 95 consecutive patients (age, 84.0±5.0 years; 75% women) with severe aortic stenosis who underwent preprocedural CT for transcatheter AVR planning. ECV was measured using iodine density images obtained by delayed enhancement dual-energy CT. The primary end point was a composite outcome of all-cause death and hospitalization for heart failure after AVR. The mean ECV measured with CT was 28.1±3.8%. During a median follow-up of 2.6 years, 22 composite outcomes were observed, including 15 all-cause deaths and 11 hospitalizations for heart failure. In Kaplan-Meier analysis, the high ECV group (≥27.8% [median value]) had significantly higher rates of composite outcomes than the low ECV group (<27.8%) (log-rank test, P=0.012). ECV was the only independent predictor of adverse outcomes on multivariable Cox regression analysis (hazards ratio, 1.25; 95% CI, 1.10‒1.41; P<0.001). Conclusions Myocardial ECV measured with dual-energy CT in patients who underwent aortic valve intervention was an independent predictor of adverse outcomes after AVR.

Rescue balloon pulmonary angioplasty for life-threatening acute pulmonary embolism on chronic thromboembolic pulmonary hypertension patients.

We report the cases of two patients with life-threatening acute pulmonary embolism (PE) on chronic thromboembolic pulmonary hypertension (CTEPH) who were treated with rescue balloon pulmonary angioplasty (BPA). These cases highlight the effect of rescue BPA on acute PE on CTEPH, which requires veno-arterial extracorporeal membrane oxygenation.

"Pericardial flare" associated with immunoglobulin G4-related disease: A case report - rapid transition from cardiac tamponade to effusive constrictive pericarditis.

Immunoglobulin G4-related disease (IgG4-RD) has recently been recognized as a systemic fibroinflammatory disease characterized by IgG4-positive lymphoplasmacytic infiltration. Despite the increased awareness of this disease category, cardiovascular involvement has rarely been reported. An 83-year-old man was admitted because of a moderate amount of pericardial effusion concomitant with bilateral pleural effusion. Despite aggressive heart failure therapy, pericardial effusion increased. He underwent pericardial drainage, and heart failure symptoms significantly improved. After only 1 month, right-sided heart failure with re-accumulation of pericardial fluid recurred, although the results of cardiac catheter examination were not indicative of constrictive pericarditis. Despite the aggressive medication, he developed weight gain and pleural effusion 6 months after pericardial drainage. Based on multimodal hemodynamic and morphological evaluations, he was finally diagnosed with effusive constrictive pericarditis and underwent total pericardiectomy. Based on histopathological findings, the final diagnosis was established as IgG4-RD associated constrictive pericarditis. We report an extremely rare case of IgG4-RD associated pericardial involvement, in which rapid transition from cardiac tamponade to effusive constrictive pericarditis was confirmed. Diagnostic work-up for constrictive pericarditis requires a high index of suspicion. Increased recognition of IgG4-RD associated pericardial involvement could potentially mitigate morbidity and might contribute to improved patient outcomes. .