Imaged periductal infiltration: Diagnostic and prognostic role in intrahepatic mass-forming cholangiocarcinoma.

Purpose: This study examines periductal infiltration in intrahepatic mass-forming cholangiocarcinoma (IMCC), focusing on its importance for differentiating hepatic tumors and its influence on post-surgical survival in IMCC patients. Methods: Eighty-three consecutive patients with IMCC (n = 43) and liver cancer whose preoperative images showed intrahepatic bile duct dilatation adjacent to the tumor for differential diagnosis from hepatocellular carcinoma (HCC) [n = 21], metastatic liver cancer (MLC) [n = 16] and combined hepatocellular-cholangiocarcinoma (cHCC-CC) [n = 3] were enrolled. CT and MRI findings of simple bile duct compression, imaged periductal infiltration, and imaged intrabiliary growth adjacent to the main tumor were reviewed. Clinicopathological and imaging features were compared in each group. The sensitivity, specificity, and odds ratio were calculated for each imaging finding of IMCC versus the other tumor groups. Overall survival was compared between cases of IMCC with and without imaged periductal infiltration. Results: Simple bile duct compression and imaged intrabiliary growth were more frequently observed in HCC than in the others (p < 0.0001 and 0.040, respectively). Imaged periductal infiltration was observed more often in histopathologically confirmed large-duct type IMCC than in the small-duct type IMCC (p = 0.034). Multivariable analysis demonstrated that only imaged periductal infiltration (odds ratio, 50.67) was independently correlated with IMCC. Patients with IMCC who had imaged periductal infiltration experienced a poorer prognosis than those without imaged periductal infiltration (p = 0.0034). Conclusion: Imaged periductal infiltration may serve as a significant marker for differentiating IMCC from other liver cancers. It may also have the potential to predict post-surgical outcomes in patients with IMCC.

Impact of Conducting Adrenal Venous Sampling in the Morning Versus Afternoon in Primary Aldosteronism.

Context: Adrenal venous sampling (AVS) is the gold standard technique for subtype differentiation of primary aldosteronism (PA) and to obtain aldosterone and cortisol measurements; however, their secretion patterns show fluctuations during the day. Objective: We aimed to examine the effects of AVS timing on AVS results. Methods: This multicenter, retrospective, observational study included a total of 753 patients who were diagnosed with PA and underwent AVS in 4 centers in Japan. Among them, 504 and 249 patients underwent AVS in the morning (AM-AVS) and in the afternoon (PM-AVS), respectively. The outcome measures were the impact of AVS timing and hormone fluctuations in a day on AVS results. Results: There were no differences in the success rate of AVS, diagnostic rate of disease type, or frequency of discrepancy in PA subtypes between the AM-AVS and PM-AVS groups. Regarding patients with unilateral PA, aldosterone concentrations in adrenal venous blood did not differ between the 2 groups on the dominant or nondominant side. Conversely, regarding patients with bilateral PA, aldosterone concentrations in adrenal venous blood were significantly higher in the AM-AVS than in the PM-AVS group. Conclusions: The timing of AVS did not seem to have a significant impact on subtype diagnosis. The aldosterone levels in adrenal venous blood were significantly higher in patients with bilateral PA in the AM-AVS group, but there was no such difference between patients with unilateral PA in the AM-AVS and PM-AVS groups. Each subtype may have a different hormone secretion pattern in a day.

Dynamic CT and Gadoxetic Acid-enhanced MRI Characteristics of P53-mutated Hepatocellular Carcinoma.

Background Imaging markers of hepatocellular carcinoma (HCC) on the basis of molecular classification are important for predicting malignancy grade and prognosis. P53-mutated HCC is a major aggressive subtype; however, its imaging characteristics have not been clarified. Purpose To clarify the imaging characteristics of P53-mutated HCC at dynamic CT and gadoxetic acid-enhanced MRI that are correlated with its clinical features, pathologic findings, and prognosis. Materials and Methods In this retrospective single-center study, patients with surgically resected HCC between January 2015 and May 2018 in a university hospital were evaluated. HCC was classified into P53-mutated HCC and non-P53-mutated HCC using immunostaining. Dynamic CT and gadoxetic acid-enhanced MRI findings, clinical features, pathologic findings, and prognosis were compared using Mann-Whitney test, χ2 test, multivariable regression analysis, receiver operating characteristic analysis, Kaplan-Meier method, and log-rank test. Immunohistochemical expression of P53, organic anion transporting polypeptide 1B3 (OATP1B3), and CD34 were evaluated, and the correlations were analyzed using the Pearson correlation test. Results In total, 149 patients (mean age, 67 years ± 9 [SD]; 103 men) with 173 HCCs were evaluated. P53-mutated HCC (n = 28) demonstrated higher serum α-fetoprotein (median, 127.5 ng/mL vs 5.5 ng/mL; P < .001), larger size (40.4 mm ± 29.7 vs 26.4 mm ± 20.5; P = .001), and higher rates of poorly differentiated HCC (22 of 28 [79%] vs 24 of 145 [17%]; P < .001). Dilated vasculature in the arterial phase of dynamic CT (odds ratio, 14; 95% CI: 3, 80; P = .002) and a lower relative enhancement ratio in the hepatobiliary phase (odds ratio, 0.05; 95% CI: 0.01, 0.34; cutoff value, 0.69; P = .002) independently predicted P53-mutated HCC. OATP1B3 expression and P53 expression were inversely correlated (P = .002; R = -0.24). Five-year overall survival was worse for P53-mutated HCC (50.0% vs 72.6%; P = .02). Conclusion Dilated vasculature at the arterial phase of dynamic CT and a lower relative enhancement ratio at the hepatobiliary phase of gadoxetic acid-enhanced MRI were useful markers for P53-mutated hepatocellular carcinoma with poor prognosis. © RSNA, 2022 Online supplemental material is available for this article.

Outcomes of embolization procedures for type II endoleaks following endovascular abdominal aortic repair.

OBJECTIVE: The objective of this study was to investigate the mid-term outcomes of embolization procedures for type II endoleak after endovascular abdominal aortic repair, and clarify the risk factors for aneurysm enlargement after embolization procedures. METHODS: This was a retrospective multicenter registry study enrolling patients who underwent embolization procedures for type II endoleaks after EVAR from January 2012 to December 2018 at 19 Japanese centers. The primary end point was the rate of freedom from aneurysm enlargement, more than 5 mm in the aortic maximum diameter, after an embolization procedure. Demographic, procedural, follow-up, and laboratory data were collected. Continuous variables were summarized descriptively, and Kaplan-Meier analyses and a Cox regression model were used for statistical analyses. RESULTS: A total of 315 patients (248 men and 67 women) were enrolled. The average duration from the initial embolization procedure to the last follow-up was 31.6 ± 24.6 months. The rates of freedom from aneurysm enlargement at 3 and 5 years were 55.4 ± 3.8% and 37.0 ± 5.2%, respectively. A multivariate analysis revealed that a larger aortic diameter at the initial embolization procedure and the presence of a Moyamoya endoleak, defined as heterogeneous contrast opacity with an indistinct faint border, were associated with aneurysm enlargement after embolization management. CONCLUSIONS: The embolization procedures were generally ineffective in preventing further expansion of abdominal aortic aneurysms in patients with type II endoleaks after EVAR, especially in patients with a large abdominal aortic aneurysm and/or a presence of a Moyamoya endoleak.

A low albumin level as a risk factor for transient severe motion artifact induced by gadoxetate disodium administration: A retrospective observational study with free-breathing dynamic MRI and an experimental study in rats.

OBJECTIVES: In the arterial phase of gadoxetate disodium administration for dynamic MRI, transient severe motion (TSM) sometimes occurs, making image evaluation difficult. This study was to identify risk factors for TSM in a clinical study, and confirm them and investigate the cause in an animal study. METHODS: A retrospective, single-center, observational study included patients who underwent dynamic MRI using gadoxetate disodium for the first time from April 2016 to September 2019 and free-breathing MRI was performed. Differences in clinical characteristics and laboratory tests between the presence and absence of TSM were examined. Animal experiments were conducted in 50 rats; gadoxetate disodium was injected into three sites (distal inferior vena cava (IVC), ascending aorta, and descending aorta) to identify the organ which triggers respiratory irregularities. Phosphate-buffered saline and gadopentetate dimeglumine were also injected into the distal IVC. In addition, to evaluate the effect of albumin, gadoxetate disodium was diluted with phosphate-buffered saline or 5% human serum albumin and injected into the ascending aorta. The time course of the respiratory rate was monitored and evaluated. RESULTS: 20 of 51 (39.2%) patients showed TSM. On multivariable analysis, a low albumin level was an independent risk factor (P = .035). Gadoxetate disodium administration caused significant tachypnea compared to gadopentetate dimeglumine or PBS (an elevation of 16.6 vs 3.0 or 4.3 breaths/min; both P < .001) in rats. The starting time of tachypnea was earlier with injection into the ascending aorta than into the descending aorta (10.3 vs 17.9 sec; P < .001) and the distal IVC (vs 15.6 sec; P < .001). With dilution with albumin instead of phosphate-buffered saline, tachypnea was delayed and suppressed (9.9 vs 13.0 sec; P < .001, 24.1 vs 17.0 breaths/min; P = .031). CONCLUSIONS: A low albumin level is a risk factor for TSM, which could be caused by the effect of gadoxetate disodium on the head and neck region.

Transcatheter arterial embolization of iatrogenic massive arterioportal fistula in the liver.

BACKGROUND: Massive arterioportal fistula (APF) is naturally irreversible and can induce portal hypertension and portal vein thrombosis (PVT), worsening survival outcomes. PURPOSE: To evaluate the clinical course and details of transarterial embolization (TAE) procedures for massive APF. MATERIAL AND METHODS: This retrospective single-center observational study evaluated the time until embolization after puncture, imaging, embolization methods, and laboratory data of 10 consecutive patients who were diagnosed with massive APF after puncture and underwent TAE at our hospital from 1 April 2012 to 30 September 2019. RESULTS: Out of 10 cases, eight demonstrated a simple type and the other two cases a complex network type on the digital subtraction angiography pattern of massive APF. In two simple-type cases for which re-embolization was required, other subsegmental branches were embolized. The two cases showing a complex network type had been embolized via not only the subsegmental branch, but also the extrahepatic and multiple subsegmental branches. Child-Pugh scores were improved in eight of the ten cases. PVT was seen in six cases before embolization, but disappeared after embolization in all cases, despite the fact that three cases had not received anticoagulant therapy. Six cases had digestive varices before embolization, suggesting portal hypertension, and two of the six cases with esophageal varices and one with gastric varices decreased after embolization. CONCLUSION: TAE for massive APF contributed to the improvement of hepatic reserve, the disappearance of PVT, and the improvement of portal hypertension; however, embolization of multiple branches may still be required in some cases.

Predicting intestinal viability by consecutive photoacoustic monitoring of oxygenation recovery after reperfusion in acute mesenteric ischemia in rats.

The purpose was to assess whether consecutive monitoring of oxygenation by photoacoustic imaging (PAI) can objectively predict intestinal viability during surgery for acute mesenteric ischemia (AMI). PAI uses laser light to detect relative amounts of oxygenated and deoxygenated hemoglobin in intestinal tissue. In 30 rats, AMI was induced by clamping the mesenteric and marginal vessels of the ileum for 0 min in the control group, 30 min in the mild group, and 180 min in the severe group (10 rats per group). After 60 min of reperfusion, intestinal damage was evaluated pathologically. Oxygenation of the intestine was monitored throughout the procedure in real time by a commercially available PAI system and compared among the groups. All rats showed irreversible (i.e. transmucosal or transmural infarction) damage in the severe group. After reperfusion, the oxygenation in the mild group recovered immediately and was significantly higher than in the severe group at 1, 5, 10, 30, and 60 min (P = .011, 002, < .001, 001, and 001, respectively). Oxygenation showed a significant strong negative correlation with pathological severity (rs = - 0.7783, - 0.7806, - 0.7422, - 0.7728, and - 0.7704, respectively). In conclusion, PAI could objectively predict irreversible ischemic damage immediately after reperfusion, which potentially prevents inadequate surgery.

Pathophysiology and Imaging Findings of Bile Duct Necrosis: A Rare but Serious Complication of Transarterial Therapy for Liver Tumors.

Bile duct necrosis (BDN) with biloma formation is a type of ischemic bile duct injury that is one of the serious complications associated with transarterial therapies, such as transcatheter chemoembolization therapy (TACE), and radioembolization for hepatocellular carcinoma (HCC) and hepatic arterial infusion chemotherapy (HAIC) for metastatic liver cancer from colorectal carcinoma. In terms of the occurrence of BDN and subsequent biloma formation, ischemic injury to the peribiliary vascular plexus (PBP), the supporting vessel of bile duct epithelium, is thought to be intimately associated. In this paper, we first describe the anatomy, blood supply, and function of the intrahepatic bile duct, and then illustrate the pathophysiology of BDN, and finally present the imaging findings of BDN. Under the process of BDN formation, ischemia of the PBP induces the disruption of the bile duct epithelial protection mechanism that causes coagulation and fibrinoid necrosis of the surrounding tissue by the detergent action of exuded bile acids, and eventually a biloma forms. Once BDN occurs, persistent tissue damage to the surrounding bile duct is induced by imbibed bile acids, and portal vein thrombosis may also be observed. On pre-contrast and contrast-enhanced computed tomography (CT), BDN shows similar findings to intrahepatic bile duct dilatation, and, therefore, it is sometimes misdiagnosed. Differentiation of imaging findings on CT and ultrasound (US)/magnetic resonance (MR) imaging/MR cholangiopancreatography (MRCP) is important for correct diagnosis of BDN.

Coil-assisted retrograde transvenous obliteration (CARTO) for the treatment of gastric varices via a single access route using steerable microcatheter: a case report.

BACKGROUND: Coil-assisted retrograde transvenous obliteration (CARTO) is a modified balloon-occluded retrograde transvenous obliteration (BRTO) technique using coils instead of an indwelling balloon. A method involving two microcatheter systems forming a double access route has been reported. We report a case of CARTO using a steerable microcatheter to successfully treat gastric varices (GV). CASE PRESENTATION: A 79-year-old man was admitted for treatment of intractable GV due to liver cirrhosis. The GV were drained mainly into the left inferior phrenic vein, not the usual gastrorenal shunt. Introducing the balloon catheter to the left inferior phrenic vein was difficult due to mild stenosis between the inferior vena cava and inferior phrenic vein and the shunt angle. A CARTO technique was performed with 5% ethanolamine oleate with iopamidol from a single access route by inverting the steerable microcatheter distal to the coil placement site. CONCLUSION: CARTO has advantages in cases where performing BRTO is difficult. Using a steerable microcatheter simplifies the procedure by reducing the required access routes in CARTO.

Gadoxetic acid-enhanced MR imaging for hepatocellular carcinoma: molecular and genetic background.

Gadoxetic acid-enhanced magnetic resonance imaging (MRI) plays important roles in diagnosis of hepatic lesions because of its superiority in the detectability of small lesions, its differentiation ability, and its utility for the early diagnosis of hepatocellular carcinoma (HCC). In HCC, expression of organic anion transporting polypeptide (OATP) 1B3 correlates with the enhancement ratio in the hepatobiliary phase. Gadoxetic acid-enhanced MRI, an indirect molecular imaging method, reflects OATP1B3 expression in HCC. OATP1B3 expression gradually decreases from the dysplastic nodule stage to advanced HCC. Decreased expression is a sensitive marker of multistep hepatocarcinogenesis, especially in the early stages. Hypervascular HCCs commonly show hypointensity in the hepatobiliary phase corresponding to a decrease in OATP1B3; however, approximately 10% of HCCs show hyperintensity due to OATP1B3 overexpression. This hyperintense HCC shows less aggressive biological features and has a better prognosis than hypointense HCC. Hyperintense HCC can be classified into a genetic subtype of HCC with a mature hepatocyte-like molecular expression. OATP1B3 expression and the less aggressive nature of hyperintense HCC are regulated by the molecular interaction of ß-catenin signaling and hepatocyte nuclear factor 4α, a tumor suppressor factor. Gadoxetic acid-enhanced MR imaging has the potential to be an imaging biomarker for HCC. KEY POINTS: • The hepatobiliary phase is a sensitive indirect indicator of organic anion transporting polypeptide1B3 (OATP1B3) expression in hepatocellular carcinoma (HCC). • The OATP1B3 expression, namely, enhancement in the hepatobiliary phase, decreases from the very early stage of hepatocarcinogenesis, contributing to early diagnosis of HCC. • HCC showing hyperintensity on the hepatobiliary phase is a peculiar genetic subtype of HCC with OATP1B3 overexpression, a less aggressive nature, and mature hepatocyte-like molecular/genetic features.

Relationship between the degree of abdominal wall movement and the image quality of contrast-enhanced MRI: semi-quantitative study especially focused on the occurrence of transient severe motion artifact.

PURPOSE: To reveal the relationship between abdominal movement and artifact, and to reveal if the transient artifact in arterial phase is caused by transient abdominal movement (TAM) in contrast-enhanced (CE) MRI. MATERIALS AND METHODS: 325 CE-MRI series (206 with EOB and 119 with EGCM) were included. The abdominal movement was classified into three groups by respiratory bellows waveform (= bellows grade, BG 1-3), and MR image quality (= artifact score, AS) was graded 1-5 for the precontrast, arterial and portal venous phase, respectively. The relationship between the BG and AS was evaluated. The occurrence of transient artifact in arterial phase was compared to the degree of TAM. RESULTS: In the acquisitions with BG3, all images showed AS of > 2, while no images had AS of > 4 in the acquisitions with BG1. Numbers of transient artifact in the arterial phase with no-abdominal movement (NAM), mild-TAM, severe-TAM were 0 of 120, 4 of 27, 7 of 8 in EOB and 0 of 91, 1 of 4, 0 of 0 in EGCM, respectively. CONCLUSION: Image quality is highly correlated with abdominal movement. Moreover, artifact in arterial phase was not observed in NAM, which indicated abdominal movement is the direct cause of artifact.

A prospective phase II study of carboplatin and nab-paclitaxel in patients with advanced non-small cell lung cancer and concomitant interstitial lung disease (HOT1302).

OBJECTIVES: Patients with concomitant advanced non-small cell lung cancer (NSCLC) and interstitial lung disease (ILD) are excluded from most clinical chemotherapy trials because of the high risk of exacerbating the latter condition. This study prospectively investigated the efficacy and safety of albumin-bound paclitaxel (nab-paclitaxel) in combination with carboplatin in patients with both advanced NSCLC and ILD. PATIENTS AND METHODS: The enrolled patients had treatment-naïve, advanced NSCLC with ILD. Patients received 100 mg/m2nab-paclitaxel weekly and carboplatin at an area under the concentration-time curve of 6 once every 3 weeks for 4-6 cycles. The primary endpoint was the overall response rate (ORR); secondary endpoints included toxicity, progression-free survival (PFS), and overall survival (OS). RESULTS: Thirty-six patients were enrolled between April 2014 and September 2017. Sixteen patients (44.4%) had adenocarcinoma, 15 (41.7%) had squamous cell carcinoma (Sq), and 5 (13.9%) had non-small cell carcinoma. The median number of cycles administered were 4 (range: 1-6). The ORR was 55.6% (95% confidence interval [CI]: 39.6-70.5). The median PFS and OS were 5.3 months (95% CI: 3.9-8.2) and 15.4 months (95% CI: 9.4-18.7), respectively. A greater proportion of patients with Sq experienced improvements than did those with non-Sq: ORRs, 66.7% (95% CI: 41.7-84.8) vs. 47.6% (95% CI: 28.3-67.6) (P = 0.254); median PFS, 8.2 months (95% CI: 4.0-10.2) vs. 4.1 months (95% CI: 3.3-5.4) (HR, 0.60 [95% CI, 0.30-1.20]; P = 0.15); and median OS, 16.8 months (95% CI: 9.8-not reached) vs. 11.9 months (95% CI: 7.3-17.4) (HR, 0.56 [95% CI, 0.24-1.28]; P = 0.17). Two patients (5.6%) experienced grade ≥2 pneumonitis and 1 patient (2.8%) died. CONCLUSION: Weekly nab-paclitaxel combined with carboplatin showed favorable efficacy with acceptable toxicity in patients with both advanced NSCLC and ILD.

Doughnut-like hyperintense nodules on hepatobiliary phase without arterial-phase hyperenhancement in cirrhotic liver: imaging and clinicopathological features.

OBJECTIVES: To determine the imaging and clinicopathological features of MRI doughnut-like nodules (HBP-doughnut nodules), hyperintense at the hepatobiliary phase (HBP) after injection of gadoxetic acid (EOB) and without arterial-phase hyperenhancement (APHE) in cirrhotic liver. METHODS: The Institutional Review Board approved this retrospective study and informed consent was waived. We enrolled 309 consecutive patients with liver cirrhosis who were examined by EOB-MRI, dynamic CT, and angiography-assisted CT between 2008 and 2012 and searched for HBP-doughnut nodules. We evaluated imaging characteristics including haemodynamics and signal intensity of MRI, pathological findings, and frequency of malignant transformation. RESULTS: One hundred and one HBP-doughnut nodules without APHE were identified in 18 patients (6%), including seven of 59 (12%) patients with hepatitis-B-virus-related, nine of 230 (3.9%) with hepatitis-C-virus-related, and two of 33 (6.1%) with alcoholic cirrhosis. All nodules showed enhancement peaks in the portal phase, the same or increased intranodular portal supply on CT during arterial portography, and the same or decreased intranodular arterial supply on CT during hepatic arteriography. On T2-weighted and diffusion-weighted images, 37 (36%) and 24 (24%) nodules, respectively, showed hyperintensity predominantly in the central area. Three nodules were diagnosed by fine needle biopsy as non-neoplastic hepatic nodules. Ninety-three of 101 (92%) nodules in 16 patients were followed up during an observation period of 1163 ± 902 days (range 57-2920 days), and none showed malignant transformation. CONCLUSION: HBP-doughnut nodules without APHE in cirrhotic liver were not infrequent. None became malignant. We propose calling them 'multiacinar cirrhotic nodules' based on the classification by an International Working Party. KEY POINTS: • HBP-doughnut nodules without APHE were seen in 6% of patients with liver cirrhosis. • The enhancement peak of HBP-doughnut nodules without APHE was in the portal phase, which reflected the fact that they were supplied predominantly by the portal vein, based on angiography-assisted CT findings. • None of the HBP-doughnut nodules without APHE in cirrhotic liver became malignant, and in conjunction with limited pathological features, they may be corresponding to multiacinar cirrhotic nodules in the International Working Party classification.

Familial multifocal micronodular pneumocyte hyperplasia with a novel splicing mutation in TSC1: Three cases in one family.

Multifocal micronodular pneumocyte hyperplasia (MMPH) is a rare pulmonary disease, generally manifesting as a tuberous sclerosis complex (TSC), characterised by multiple, small ground-glass nodular shadows on chest computed tomography (CT). Histological examination typically reveals multicentric, well-demarcated, nodular type II pneumocystic growth. Herein, we describe three cases of this rare pulmonary disease occurring within one family. Using reverse transcription polymerase chain reaction (RT-PCR) and direct DNA sequencing, we identified a novel germline mutation, a point mutation in TSC1 intron 5, which yielded a splice variant and loss of function of TSC1. Furthermore, immunohistochemical staining indicated the expression of phospho-p70S6K and phospho-4E-BP1, suggesting that TSC1 function was impaired by the novel gene mutation in MMPH cells.

Evaluation of renal oxygen saturation using photoacoustic imaging for the early prediction of chronic renal function in a model of ischemia-induced acute kidney injury.

PURPOSE: To evaluate the utility of photoacoustic imaging in measuring changes in renal oxygen saturation after ischemia-induced acute kidney injury, and to compare these measurements with histological findings and serum levels of kidney function. MATERIAL AND METHODS: Acute kidney injury was induced by clamping the left renal pedicle in C57Bl/6 mice, with a 35-min ischemic period used to induce mild renal injury (14 mice) and a 50-min period for severe injury (13 mice). The oxygen saturation was measured before induction, and at 5 time-points over the first 48 h after induction, starting at 4 h after induction. Oxygen saturation, histological score, kidney volume, and the 24 h creatinine clearance rate and serum blood urea nitrogen were also measured on day 28. Between-group differences were evaluated using a Mann-Whitney U-test and Dunn's multiple comparisons. The association between oxygen saturation and measured variables was evaluated using Spearman's correlation. A receiver operator characteristic curve was constructed from oxygen saturation values at 24 h after heminephrectomy to predict chronic renal function. RESULTS: The oxygen saturation was higher in the mild than severe renal injury group at 24 h after induction (73.7% and 66.9%, respectively, P<0.05). Between-group comparison on day 28 revealed a higher kidney volume (P = 0.007), lower tubular injury (P<0.001), lower serum level of blood urea nitrogen level (P = 0.016), and lower 24 h creatinine clearance rate (P = 0.042) in the mild compared with the severe injury group. The oxygen saturation at 24 h correlated with the 24 h creatinine clearance rate (P = 0.036) and serum blood urea nitrogen (P<0.001) on day 28, with an area under the receiver operating curve of 0.825. CONCLUSION: Oxygen saturation, measured by photoacoustic imaging at 24 h after acute kidney injury can predict the extent of subsequent histological alterations in the kidney early after injury.

A phase II study of carboplatin, pemetrexed, and bevacizumab followed by erlotinib and bevacizumab maintenance for non-squamous non-small cell lung cancer with wild-type EGFR (HOT1101).

BACKGROUND: This study evaluated the efficacy and safety of switch maintenance erlotinib and bevacizumab after induction therapy with carboplatin/pemetrexed/bevacizumab for non-squamous non-small cell lung cancer (NSCLC) with wild-type EGFR. METHODS: Enrolled patients had treatment-naïve, advanced non-squamous NSCLC with wild-type EGFR. Carboplatin [area under the curve (AUC) 5.0], pemetrexed (500 mg/m2) and bevacizumab (15 mg/kg) were administered on day 1 every 3 weeks for 4-6 cycles. Maintenance therapy with erlotinib (150 mg/body) on day 1 through 21 plus bevacizumab on day 1 every 3 weeks was continued until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival (PFS); secondary endpoints included overall survival (OS), overall response rate (ORR), toxicity, and quality of life (QOL). RESULTS: Fifty-one patients were enrolled between September 2011 and June 2014. The median number of cycles for induction and maintenance therapy was 4 (range 1-6) and 4 (range 1-20). Twenty-nine patients (58%) received maintenance therapy. The 6-month PFS rate was 59.5% [95% confidence interval (CI) 45.0-72.6%]. The ORR was 48.0% (95% CI 34.8-61.5%), and disease control rate was 86.0% (95% CI 73.8-93.0%). The median PFS and OS were 6.5 months (95% CI 5.8-7.2 months) and 21.4 months (95% CI 15.9-26.9 months), respectively. Although grades ≥ 3 adverse events were observed in 33 patients (66.0%), most were hematologic; there was no febrile neutropenia. QOL was maintained throughout treatment. CONCLUSIONS: Carboplatin/pemetrexed/bevacizumab followed by erlotinib and bevacizumab maintenance showed modest efficacy and was well tolerated in non-squamous NSCLC patients with wild-type EGFR. TRIAL REGISTRATION: UMIN000005872.

Photoacoustic imaging of tumour vascular permeability with indocyanine green in a mouse model.

BACKGROUND: We analysed the haemodynamics of indocyanine green (ICG) in mouse organs and tumours and evaluated responses to anti-angiogenic agents in an allograft tumour mouse model by photoacoustic imaging. METHODS: Thirty-six male mice (aged 10-14 weeks; body weight 20-25 g) were used. Real-time photoacoustic imaging of organs and tumours after intravenous injection of ICG was conducted in mice until 10 min after ICG injection. ICG distribution in tumour tissues was assessed by immunohistochemical staining and observation of ICG-derived fluorescence. Vascular permeability changes induced by the vascular endothelial growth factor (VEGF)-blocking agent VEGF-trap on tumour photoacoustic signals were studied. RESULTS: The photoacoustic signals in salivary glands and tumours after intravenous injection of iCG (0.604 ± 0.011 and 0.994 ± 0.175 [mean ± standard deviation], respectively) were significantly increased compared with those in the liver, kidney, and great vessel (0.234 ± 0.043, 0.204 ± 0.058 and 0.127 ± 0.040, respectively; p < 0.010). In tumours, the photoacoustic signal increased within 30 s after ICG injection in a dose-dependent manner (r2 = 0.899) and then decreased gradually. ICG was found to extravasate in tumour tissues. In VEGF-trap-treated mice, the photoacoustic signal in the tumour decreased at the early phase before inhibition of tumour growth was detected (0.297 ± 0.052 vs 1.011 ± 0.170 in the control; p < 0.001). CONCLUSIONS: Photoacoustic imaging with ICG administration demonstrated extravasation of ICG in mouse organs and tumours, indicating the potential for early detection of changes in vascular permeability during cancer therapy.

Pathology and images of radiation-induced hepatitis: a review article.

Recent advances in highly conformal radiotherapies greatly extend the indications for radiotherapy of liver tumors. However, because of poor tolerance to hepatic radiation, estimation of the intensity of irradiation of the liver is important, particularly for a cirrhotic liver. Knowledge of radiation-induced hepatitis is important for understanding how to optimize hepatic radiation therapy. Pathological changes of the irradiated liver, which include perivenular fibrosis, sinusoidal obstruction, and damage to Kupffer cells and hepatocytes, can be visualized using clinical imaging techniques. This review article discusses and illustrates the pathological and radiological changes of hepatic tumors and the surrounding parenchyma of the irradiated liver.

Extraskeletal osteosarcoma of the lung following treatment of primary small-cell lung carcinoma with chemoradiotherapy: A case report.

Primary pulmonary osteosarcoma is a rare entity, with only a few cases reported in the literature to date. Moreover, secondary extraskeletal osteosarcoma of the lung following chemoradiotherapy is extremely rare and, to the best of our knowledge, this is the first reported case. We herein present the case of an 80-year-old male patient with small-cell lung cancer (SCLC), who developed what it was initially considered as recurrence of the tumor after chemoradiotherapy. The patient eventually succumbed to the disease, and on autopsy it was discovered that the lung tumor was not in fact SCLC, but rather a secondary osteosarcoma. Osteosarcoma metastasis to the lung is very rare, but must be considered in the differential diagnosis when there is relapse following treatment for primary SCLC.

Clinical Course of Histologically Proven Multifocal Micronodular Pneumocyte Hyperplasia in Tuberous Sclerosis Complex: A Case Series and Comparison with Lymphangiomyomatosis.

BACKGROUND: Multifocal micronodular pneumocyte hyperplasia (MMPH) is a rare pulmonary manifestation of tuberous sclerosis complex (TSC). Because of its rarity, no previous study has described the detailed clinical course of this disease. OBJECTIVES: This study aimed to clarify the longitudinal clinical characteristics of subjects with MMPH. METHODS: Nine patients with MMPH diagnosed at Hokkaido University Hospital were retrospectively analyzed. Changes in computed tomography findings and pulmonary function were compared during the follow-up period. Serum levels of KL-6, surfactant protein (SP)-A, and SP-D were measured to clarify their potentials as blood biomarkers of the disease. Fourteen cases of lymphangiomyomatosis (LAM) were also included to compare their clinical characteristics with those of subjects with MMPH. RESULTS: Of the 9 patients, 7 were female and 2 were male. The median age at diagnosis was 43 years (range, 19-56), and all cases were diagnosed following incidental abnormal radiographic findings. During the follow-up, 1 patient died of lung cancer, but others were radiographically stable and had stable pulmonary function. Serum levels of SP-A in 5 patients (mean, 146.4 ng/mL) and SP-D in 6 patients (mean, 337.3 ng/mL) were elevated in subjects with MMPH, whereas KL-6 levels were within the reference range (mean, 230 U/mL) in all patients. Levels of SP-A and SP-D were significantly higher in subjects with MMPH than those with LAM (p < 0.05). CONCLUSIONS: Radiographic findings and pulmonary function were stable in all cases of MMPH. Serum SP-A and SP-D, but not KL-6, may be useful markers for suspicion of the presence of MMPH in patients with TSC.