Long-term outcome of cervical lymph node metastasis in superficial pharyngeal squamous cell carcinoma after endoscopic submucosal dissection.

BACKGROUND AND AIMS: Superficial pharyngeal squamous cell carcinoma (PSCC) has received increasing attention as a therapeutic target in the GI field with recent innovations in endoscopic submucosal dissection (ESD). However, there are currently no defined criteria for the application of ESD to superficial PSCC. One of the problems encountered during follow-up after ESD is cervical lymph node metastasis (LNM). Identifying the clinicopathologic predictors of cervical LNM can help to provide a basis for the refinement of therapeutic strategies for superficial PSCC. METHODS: The risk of cervical LNM was evaluated in 331 patients with superficial PSCC who underwent initial ESD between 2008 and 2021. Since tumor size, rather than depth, is the dominant factor in the current TNM classification for PSCC, the correlation between tumor size and thickness was investigated. RESULTS: The median follow-up period was 4.8 years. The cumulative 5-year cervical LNM rate was 6.1%. Multivariate Cox proportional hazards regression analysis identified tumor thickness ≥1000 µm and lymphatic invasion as significant independent predictors. Among 204 cases with subepithelial invasion, both factors were also revealed to be significant independent predictors, suggesting that tumor thickness was superior to tumor size in predicting cervical LNM. Despite the positive correlation between tumor thickness and size, there was noticeable variability in the values (R = .20), and the current staging was inadequate to identify groups at high risk for cervical LNM. CONCLUSIONS: Tumor thickness and lymphatic invasion are validated as significant independent predictors for cervical LNM and can be useful indicators to optimize the therapeutic strategies for superficial PSCC.

Comprehensive risk evaluation for metachronous carcinogenesis after endoscopic submucosal dissection of superficial pharyngeal squamous cell carcinoma.

BACKGROUND: Pharyngeal squamous cell carcinoma (PSCC) is associated with a high likelihood of metachronous carcinogenesis, which is known to have a poor prognosis. This study aimed to identify comprehensive risk evaluation indicators for metachronous carcinogenesis after endoscopic submucosal dissection (ESD) of superficial PSCC. METHODS: The risk of metachronous carcinogenesis was evaluated in 144 patients with superficial PSCC (with no history of PSCC or esophageal squamous cell carcinoma) who underwent initial ESD from 2008 to 2020. Multiple lugol-voiding lesions (LVLs) in the background pharyngeal and esophageal epithelium were evaluated as endoscopic indicators. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score was analyzed as a serum marker. RESULTS: The median follow-up period was 4.3 years. The coincidence rate for pharyngeal and esophageal LVL grade was 55%. The cumulative 3-year metachronous PSCC rate was 18.9%. The cumulative 3-year second metachronous PSCC rate was 43.9%. Forward stepwise multivariate Cox proportional hazards regression analysis identified pharyngeal LVL grade and a lower HALP score as significant independent predictors. Pharyngeal LVL grade was superior to esophageal LVL grade as a predictor of metachronous PSCC. A lower HALP score was significantly associated with younger age in forward stepwise multivariate logistic regression analysis. CONCLUSIONS: Patients with a history of superficial PSCC remain at risk for metachronous carcinogenesis over time, and long-term follow-up is imperative. Comprehensive evaluation of endoscopic features with a novel serum marker, namely, the HALP score, can help predict metachronous carcinogenesis.

Metachronous carcinogenesis of superficial esophagus squamous cell carcinoma after endoscopic submucosal dissection: incidence and risk stratification during long-term observation.

BACKGROUND: This study aimed to reveal long-term outcomes, such as incidence of metachronous esophageal and head and neck squamous cell carcinomas and overall survival rate, through long-term observation of patients with esophageal carcinoma post-endoscopic submucosal dissection. METHODS: Risk of metachronous carcinogenesis was evaluated in 88 patients with intramucosal esophageal carcinoma (without history of metachronous esophageal or head and neck squamous cell carcinomas) who underwent endoscopic submucosal dissection from 2007 to 2008 and were endoscopically observed for > 3 years. Histologically, the papillary vessel is defined as the clock gear-like structure composed of capillaries directly penetrating the epithelium (starting from the lamina propria) and covering at least two-thirds of it, around which the tumor cells are arranged in a spiral pattern. RESULTS: Median endoscopic follow-up period was 11.0 years. Cumulative 2-, 5-, and 10-year metachronous esophageal carcinoma rates were 11.4%, 20.6%, and 39.3%, respectively. Stepwise multivariate Cox proportional hazard regression analysis identified multiple Lugol-voiding lesions (LVLs) as the single significant independent predictor. Cumulative 2-, 5-, and 10-year metachronous head and neck squamous cell carcinoma rates were 6.9%, 10.4%, and 19.6%, respectively. Stepwise multivariate Cox proportional hazard regression analysis identified multiple LVLs, Brinkman index, papillary vessel, and younger age as significant predictive factors. Overall post-endoscopic submucosal dissection survival rates were 98.8% and 87.5% at 5 and 10 years, respectively. CONCLUSION: Patients with a history of esophageal carcinoma remain at risk for metachronous carcinogenesis even > 5 years after endoscopic submucosal dissection. Thus, long-term follow-up is important.

Advantage of liver stiffness measurement before and after direct-acting antiviral therapy to predict hepatocellular carcinoma and exacerbation of esophageal varices in chronic hepatitis C.

AIM: The risk of development of hepatocellular carcinoma (HCC) persisted in patients with advanced fibrosis, even after achieving sustained virologic response (SVR). This study aimed to show the advantage of liver stiffness measurement (LSM) at baseline and after SVR to predict HCC occurrence and esophageal varices (EV) exacerbation. METHODS: These risks were evaluated in 398 chronic hepatitis C patients without a history of HCC who achieved SVR after direct-acting antiviral agent and evaluated LSM at least twice during follow up. We defined liver cirrhosis and chronic hepatitis as LSM of ≥12 kPa and <12 kPa, respectively. RESULTS: LSM was significantly correlated with serum fibrosis markers, such as Fib-4 index and Wisteria floribunda agglutinin-positive Mac-2 binding protein, at baseline and SVR at 24 weeks after treatment (SVR24). Five patients received preventive treatment of EV, but no EV bleeding occurred after SVR, and their LSM at baseline and SVR24 was significantly higher than that of other cirrhosis patients. The annual rate of HCC during the first 4 years was 1.5%. LSM in HCC patients tended to decrease after direct-acting antiviral agent therapies, but significantly higher than that of cirrhosis patients without HCC before and after treatment. Multivariate analysis identified LSM and alpha-fetoprotein at baseline and LSM at SVR24 as significant independent predictors of HCC. CONCLUSIONS: Evaluating LSM not only at baseline, but also SVR24, was found to be useful for the detection of advanced fibrosis patients at high risk of HCC occurrence and EV exacerbation. We recommend focused surveillance of HCC and EV for these patients.

Long-term outcome of hepatocellular carcinoma occurrence, esophageal varices exacerbation, and mortality in hepatitis C virus-related liver cirrhosis after interferon-based therapy.

AIM: The long-term effects of sustained virologic response (SVR) to antiviral therapy on the risk of liver complications, such as exacerbation of esophageal varices (EV), hepatocellular carcinoma (HCC), malignant lymphoma, and liver-related and overall death in hepatitis C virus (HCV)-infected patients with liver cirrhosis are not fully known. METHODS: These risks were evaluated during long-term follow up of 457 patients with HCV-related Child-Pugh Class A liver cirrhosis without history of HCC. RESULTS: The respective cumulative 5- and 10-year rates of EV exacerbation were 2.0% and 3.1%. Multivariate analysis identified the presence of EVs, thrombocytopenia at baseline. and alcohol intake as significant independent predictors of EV exacerbation before and after SVR. The cumulative 5- and 10-year rates of HCC were 6.8% and 10.2%, respectively. Male sex and the presence of EV were significant independent determinants of HCC before and after SVR. Although the cumulative 5-year HCC recurrence rate was 49.4%, the overall survival rate since HCC was 73.6% at 5 years. The overall survival rates since SVR were 98.7% and 93.6% at 5 and 10 years, respectively. Progression of HCC was the most frequent all-cause mortality, but none of the patients died of liver decompensation. Male sex and Fibrosis-4 index of ≥3.0 after SVR were significant and independent predictors of mortality. CONCLUSION: Patients with HCV remain at risk of HCC for >10 years after achieving SVR, and HCC is the most common cause of mortality. We recommend long-term surveillance of cirrhotic patients with HCV, even after achieving SVR.

Serial changes in liver stiffness and controlled attenuation parameter following direct-acting antiviral therapy against hepatitis C virus genotype 1b.

Little information is available on the impact of direct-acting antiviral (DAA) therapy on changes in liver fibrosis and steatosis. Liver stiffness (LS) and controlled attenuation parameter (CAP) values were evaluated using transient elastography. The study subjects were 214 elderly patients infected with HCV genotype 1b who received 24-week daclatasvir and asunaprevir dual therapy. All patients of this retrospective study had no hepatocellular carcinoma before and during DAA therapy. LS and CAP were assessed before treatment (baseline), at end of treatment (EOT), and at 24, 48, 72 weeks (W) after EOT. The rate of sustained viral response (SVR) by daclatasvir and asunaprevir therapy was 91%. LS values for the entire group correlated with Fib-4 index at baseline (r = 0.565, P < 0.001). LS in both chronic hepatitis group (Fib-4 index <3.25) and cirrhosis group (Fib-4 index ≥3.25) decreased significantly at each time point compared with baseline (P < 0.001). Especially, a larger decrease in LS from baseline to EOT was seen in the cirrhosis group than chronic hepatitis group (P < 0.001). LS was also significantly lower in the SVR group at EOT, 24W, 48W, 72W compared with baseline (P < 0.001). Even in the non-SVR group, LS tended to be lower at EOT (P = 0.039), 24W (P = 0.009), 48W (P = 0.475), 72W (P = 0.033) compared with baseline. CAP increased significantly following the treatment from baseline to 48W post-EOT (P = 0.018). Our results showed significant improvement in LS in response to daclatasvir and asunaprevir dual therapy. In the other hand, there was a tendency that CAP increased from baseline.

Discovery of non-genomic drivers of YAP signaling modulating the cell plasticity in CRC tumor lines.

In normal intestines, a fetal/regenerative/revival cell state can be induced upon inflammation. This plasticity in cell fate is also one of the current topics in human colorectal cancer (CRC). To dissect the underlying mechanisms, we generated human CRC organoids with naturally selected genetic mutation profiles and exposed them to two different conditions by modulating the extracellular matrix (ECM). Among tested mutation profiles, a fetal/regenerative/revival state was induced following YAP activation via a collagen type I-enriched microenvironment. Mechanistically, YAP transcription was promoted by activating AP-1 and TEAD-dependent transcription and suppressing intestinal lineage-determining transcription via mechanotransduction. The phenotypic conversion was also involved in chemoresistance, which could be potentially resolved by targeting the underlying YAP regulatory elements, a potential target of CRC treatment.

Organoids transplantation as a new modality to design epithelial signature to create a membrane-protective sulfomucin-enriched segment.

BACKGROUND: The organoids therapy for ulcerative colitis (UC) is under development. It is important to dissect how the engrafted epithelium can provide benefits for overcoming the vulnerability to inflammation. We mainly focused on the deliverability of sulfomucin, which is reported to play an important role in epithelial function. METHODS: We analyzed each segment of colon epithelium to determine differences in sulfomucin production in both mice and human. Subsequently, we transplanted organoids established from sulfomucin-enriched region into the injured recipient epithelium following dextran sulfate sodium-induced colitis and analyzed the engrafted epithelium in mouse model. RESULTS: In human normal colon, sulfomucin production was increased in proximal colon, whereas it was decreased in the inflammatory region of UC. In murine colon epithelium, increased sulfomucin production was found in cecum compared to distal small intestine and proximal colon. RNA sequencing analysis revealed that several key genes associated with sulfomucin production such as Papss2 and Slc26a1 were enriched in isolated murine cecum crypts. Then we established murine cecum organoids and transplanted them into the injured epithelium of distal colon. Although the expression of sulfomucin was temporally decreased in cecum organoids, its secretion was restored again in the engrafted patches after transplantation. Finally, we verified a part of mechanisms controlling sulfomucin production in human samples. CONCLUSION: This study illustrated the deliverability of sulfomucin in the disease-relevant grafting model to design sulfomucin-producing epithelial units in severely injured distal colon. The current study is the basis for the better promotion of organoids transplantation therapy for refractory UC.

Transplantation of intestinal organoids into a mouse model of colitis.

Intestinal organoids are fundamental in vitro tools that have enabled new research opportunities in intestinal stem cell research. Organoids can also be transplanted in vivo, which enables them to probe stem cell potential and be used for disease modeling and as a preclinical tool in regenerative medicine. Here we describe in detail how to orthotopically transplant epithelial organoids into the colon of recipient mice. In this assay, epithelial injury is initiated at the distal part of colon by the administration of dextran sulfate sodium, and organoids are infused into the luminal space via the anus. The infused organoids subsequently attach to the injured region and rebuild a donor-derived epithelium. The steps for cell infusion can be completed in 10 min. The assay has been applied successfully to organoids derived from both wild-type and genetically altered epithelial cells from adult colonic and small intestinal epithelium, as well as fetal small intestine. This is a versatile protocol, providing the technical basis for transplantation following alternative colonic injury models. It has been used previously for functional assays to probe cellular potential, and formed the basis for the first in-human clinical trial using colonic organoid transplantation therapy for intractable cases of ulcerative colitis.

Collagen type I-mediated mechanotransduction controls epithelial cell fate conversion during intestinal inflammation.

BACKGROUND: The emerging concepts of fetal-like reprogramming following tissue injury have been well recognized as an important cue for resolving regenerative mechanisms of intestinal epithelium during inflammation. We previously revealed that the remodeling of mesenchyme with collagen fibril induces YAP/TAZ-dependent fate conversion of intestinal/colonic epithelial cells covering the wound bed towards fetal-like progenitors. To fully elucidate the mechanisms underlying the link between extracellular matrix (ECM) remodeling of mesenchyme and fetal-like reprogramming of epithelial cells, it is critical to understand how collagen type I influence the phenotype of epithelial cells. In this study, we utilize collagen sphere, which is the epithelial organoids cultured in purified collagen type I, to understand the mechanisms of the inflammatory associated reprogramming. Resolving the entire landscape of regulatory networks of the collagen sphere is useful to dissect the reprogrammed signature of the intestinal epithelium. METHODS: We performed microarray, RNA-seq, and ATAC-seq analyses of the murine collagen sphere in comparison with Matrigel organoid and fetal enterosphere (FEnS). We subsequently cultured human colon epithelium in collagen type I and performed RNA-seq analysis. The enriched genes were validated by gene expression comparison between published gene sets and immunofluorescence in pathological specimens of ulcerative colitis (UC). RESULTS: The murine collagen sphere was confirmed to have inflammatory and regenerative signatures from RNA-seq analysis. ATAC-seq analysis confirmed that the YAP/TAZ-TEAD axis plays a central role in the induction of the distinctive signature. Among them, TAZ has implied its relevant role in the process of reprogramming and the ATAC-based motif analysis demonstrated not only Tead proteins, but also Fra1 and Runx2, which are highly enriched in the collagen sphere. Additionally, the human collagen sphere also showed a highly significant enrichment of both inflammatory and fetal-like signatures. Immunofluorescence staining confirmed that the representative genes in the human collagen sphere were highly expressed in the inflammatory region of ulcerative colitis. CONCLUSIONS: Collagen type I showed a significant influence in the acquisition of the reprogrammed inflammatory signature in both mice and humans. Dissection of the cell fate conversion and its mechanisms shown in this study can enhance our understanding of how the epithelial signature of inflammation is influenced by the ECM niche.

[A case of intraosseous lipoma in the frontal bone].

A case of intraosseous lipoma in the frontal bone was reported. A 62-year-old woman had a hard tumor affecting the right frontal bone. The slowly growing tumor was first noticed when she was in her late teens. The completely excised right frontal lesion was composed of mature adipose tissue with abundant fibrous stroma. Intraosseous lipoma affecting the skull is extremely rare, with only 17 cases having been reported previously. Presurgical diagnosis of intraosseous lipoma of the skull is difficult because of its non-specific radiological features. Pathological study is indispensable for a correct diagnosis.

Hemostasis achieved endoscopically for duodenal diverticular bleeding by removing a large blood clot using a snare.

An 80-year-old man was admitted to our hospital for repeated tarry stools and hemorrhage. He was taking aspirin and warfarin for atrial fibrillation and obstruction of the central retinal artery. Upper gastrointestinal endoscope revealed a large blood clot at the distal duodenum; however, further insertion was difficult. Insertion of a colonoscope attached with a transparent hood from the mouth enabled the visualization of the third portion of the duodenum. It revealed a large clot, which completely blocked the diverticulum and prevented visualization of the bleeding point. It was extremely difficult to remove the clot through the use of grasping forceps due to poor vision and maneuverability. Finally, the large clot was broken off and removed completely using a snare. The diverticulum was over 20 mm, and a large volume of fresh blood was continuously gushing out from an erosion of the diverticulum. Replacing the tip of the endoscope with a short ST hood and keeping an insulating distance from the bleeding point enabled maneuvering around the steep angles, achieving hemostasis using clips. We report a case of duodenal diverticular bleeding treated endoscopically with great effort in maneuvering to remove a blood clot using snare in a difficult position.

Pancreatic ductal adenocarcinoma with mismatch repair deficiency resected after long-term observation.

Pancreatic ductal adenocarcinoma (PDAC) with mismatch repair (MMR) deficiency is a rare subtype, clinicopathological features of which have not been fully understood. A 70-year-old woman was admitted for the investigation of a 20-mm pancreatic tumor in the pancreatic head, detected during the cause scrutiny of exacerbation of diabetes mellitus and panhypopituitarism. The tumor decreased in size after administration of hydrocortisone for panhypopituitarism. Autoimmune pancreatitis, complicated with hypophysitis, was suspected, and prednisolone treatment was administered. The tumor did not show enlargement for 3 years during which a dose of prednisolone was maintained. However, 1.5 years after the cessation of prednisolone administration, the tumor size increased again. On endoscopic ultrasonography, the tumor was found to be a 25.2-mm mass lesion with almost uniformly low echogenicity and blood flow signal, and anisonucleosis on cytodiagnosis was revealed. Pancreatoduodenectomy was performed, and on histological analysis, moderately differentiated tubular adenocarcinoma with massive lymphocytic infiltration was observed. Immunohistochemistry revealed a concomitant loss of MSH2 and MSH6 in the tumor cells, which implicated mutant MSH2 gene. She has remained well with no recurrence for 2.9 years since her surgery. We herein report a case of PDAC with MMR deficiency, resected after long-term observation.

Late recurrence of gastric carcinoma 15 years after surgery.

A 70-year-old man who had undergone total gastrectomy 15 years ago for mucinous gastric carcinoma on the lesser curvature of the cardia, visited our hospital complaining of cough. Chest X-ray showed a right hilar shadow and an infiltrative shadow in the left middle lung field, which was not seen in the previous year. Whole-body positron emission tomography-computed tomography (CT) revealed abnormal uptake in the irregular consolidation of the left lung, enlarged right hilar lymph nodes, and a mass lesion on the right adrenal gland. Advanced primary lung adenocarcinoma with multi-organ metastasis was suspected and a CT-guided percutaneous lung biopsy was performed. Histopathological examination showed immunostaining patterns in complete accordance with those of the resected specimen of stomach, and the diagnosis of late recurrence of gastric carcinoma was confirmed. Pulmonary metastasis might have occurred as a direct hematogenous metastasis rather than through the liver. He achieved 31 months survival after the diagnosis receiving some sequences of chemotherapy. Late recurrence over 10 years after gastrectomy is extremely rare and significant predictive factors of late recurrence are not known. We hope that this case will help in detecting significant factors predictive of late recurrence after gastrectomy for gastric carcinoma.

Simultaneous macroamylasemia and macrolipasemia in a patient with mucosa-associated lymphoid tissue lymphoma.

We report a case of simultaneous macroamylasemia and macrolipasemia complicated with mucosa-associated lymphoid tissue (MALT) lymphoma. A 78-year-old man presented with hyperamylasemia and hyperlipasemia for 2 years and was misdiagnosed with chronic pancreatitis at another hospital. However, his other pancreatic enzymes were normal, his amylase-creatinine clearance ratio was low, and no definite findings of pancreatic disease were evident. Immunological analyses revealed that both amylase and lipase were bound to immunoglobulin (Ig) A-κ, and that serum IgA was high (827.1 mg/dL). He was diagnosed with simultaneous macroamylasemia and macrolipasemia. Since these diseases are associated with malignancy, an additional investigation was performed which revealed the complication of MALT lymphoma, and polymerase chain reaction analysis showed monoclonal immunoglobulin light chain gene rearrangement (κ >> λ). In this case, macroamylasemia and macrolipasemia may have developed due to the formation of macroenzymes resulting from excess IgA-κ secreted by the MALT lymphoma. Simultaneous macroamylasemia and macrolipasemia are very rare and difficult to diagnose and can lead to diagnostic and therapeutic errors. When encountering atypical clinical features associated with hyperamylasemia and hyperlipasemia, the possibility of macroenzymes and underlying diseases such as lymphoproliferative disorders should be considered.

Undifferentiated carcinoma of the liver demonstrated by contrast-enhanced ultrasonography.

A 78-year-old man had received interferon therapy and achieved sustained virologic response for chronic hepatitis C 10 years before. He came to our hospital due to liver damage. Abdominal ultrasonography showed a 90-mm mass lesion in the liver. The echoic level was high in the central part and low in the edge of the tumor. Moreover, there was an accumulation of low echoic irregular mass lesions around the hepatic portal region. Cervical ultrasonography also revealed several 15-mm mass lesions on the left clavicle, the imaging character of which was similar to the liver tumor. The liver tumor seemed to be hypovascular on dynamic computed tomography, but contrast-enhanced ultrasonography showed hyperenhancement at the early vascular phase and at maximum intensity projection showed a treelike branch vascular structure that derived from the central part to the margin of the mass. A needle biopsy of the liver tumor and a cervical lymph node resection were performed, which led to the definitive diagnosis of undifferentiated carcinoma of the liver with multiple lymph node metastasis, upon histological analysis. Undifferentiated carcinoma of the liver is extremely rare and contrast-enhanced ultrasonography was the most useful device for evaluating vascular characteristics in this case.

Poorly Differentiated Hepatocellular Carcinoma in a Low-risk Patient with an Otherwise Normal Liver.

We herein report a 48-year-old healthy woman who visited our hospital to investigate a 25-mm space-occupying lesion in the liver. The tumor was irregularly shaped and exhibited heterogeneous enhancement on dynamic computed tomography (CT). Whole-body positron emission tomography-CT showed an abnormal fluorodeoxyglucose uptake in the liver tumor, with a maximum standardized uptake value of 12.82. During the ensuing three months, the tumor grew rapidly and the serum alpha-fetoprotein levels also rose; partial hepatectomy was therefore performed. Microscopic findings revealed a moderately-to-poorly differentiated hepatocellular carcinoma in the normal liver.

Steakhouse Syndrome in Myotonic Dystrophy.

A 70-year-old man with myotonic dystrophy (MD) showed repetitive vomiting and decreased food ingestion. These symptoms were caused by acute mass of steak impaction occluding the esophagus, known as "steakhouse syndrome," which may have occurred in response to esophageal functional changes following gastrointestinal involvement due to MD pathology. The occluding food was successfully removed endoscopically, and his symptoms resolved without relapse. Our case suggests that MD patients can present with "steakhouse syndrome" due to bolus food impaction occluding the esophagus as one of their gastrointestinal manifestations, which underscores the need for its consideration in MD patients presenting with similar symptoms.

Perfusion characteristics of radiation-injured lung on Gd-DTPA-enhanced dynamic magnetic resonance imaging.

RATIONALE AND OBJECTIVES: A contrast-enhanced dynamic magnetic resonance (MR) study was performed experimentally and clinically to describe perfusion characteristics of radiation-injured lung according to pathologic phases. METHODS: The MR study was performed before and at 0.5, 1, 2, 3, 4, and 7 months after 40 Gy-dose irradiation to the right hemithorax in 8 dogs, and clinically in 12 lung lesions of 9 patients with acute or fibrotic radiation pneumonitis. Altered Gd-DTPA kinetics in the affected lungs was assessed by time-signal intensity curves. MR findings were correlated with lung histology and CT images. RESULTS: Within 1 month after irradiation, the irradiated animal lungs showed focal and persistent contrast enhancement relative to nonirradiated lungs. This abnormality was pronounced during the next 2 months. After 4 months, irradiated lungs conversely showed lower enhancement during the Gd-DTPA first-pass but were followed by persistently greater enhancement during Gd-DTPA redistribution phase. Similar differences in enhancement abnormalities between acute and fibrotic radiation pneumonitis were clinically observed. CONCLUSION: These findings indicate that Gd-DTPA kinetics can be altered according to the histopathologic change in early/acute radiation pneumonitis and radiation fibrosis and that the contrast-enhanced perfusion MRI may help differentiate the phases of radiation pneumonitis.

Regional lung functional impairment in acute airway obstruction and pulmonary embolic dog models assessed with gadolinium-based aerosol ventilation and perfusion magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA)-based aerosol ventilation and perfusion magnetic resonance (MR) images were used to define regional functional impairment in acute airway obstruction (AO) and pulmonary embolic (PE) dog models. METHODS: The aerosol study was performed in 10 anesthetized normal dogs in a supine position during 20-minute spontaneous inhalation of an aerosol of 100- or 200-mmol-Gd/L Gd-DTPA solute produced by an ultrasonic nebulizer in an open-circuit delivery system, combined with a dynamic perfusion study after a 3-second intravenous bolus injection of a 0.1 mmol/kg dose of Gd-DTPA. These MR studies were also performed in the same 10 dogs approximately 30 minutes after obstructing the segmental (n = 6) or lobar (n = 4) bronchus with a balloon catheter, and in another six dogs after segmental (n = 6) and lobar (n = 4) pulmonary arterial embolization with enbucrilate. Regional lung enhancement was assessed on time-signal intensity (SI)-curves and ventilation- and perfusion-weighted images produced by a subtraction technique. RESULTS: The normal lungs were gradually and gravity-dependently enhanced with time after Gd-DTPA aerosol inhalation regardless of the respiratory SI changes, except for three animals with the fastest breathing rate. The averaged maximal relative lung SI increase against the baseline in the successful animals was significantly greater in the slowly and deeply breathing animals than in the fast and shallow breathing animals, regardless of the difference in Gd-concentration (100 mmol Gd/L: 153.3% +/- 69.7% vs. 54.2% +/- 23%; P < 0.001; and 200 mmol Gd/L: 189.7% +/- 68.0% vs. 75.6% +/- 42.2%; P < 0.0001, respectively). There was an additional enhancement of 382% +/- 101 in the ventral lung and 722% +/- 160 in the dorsal lung on the pulmonary arterial phase perfusion image even in the slowly and deeply breathing animals who inhaled 200-mmol-Gd/L aerosol, and the enhancement effect was significantly greater compared with that with the aerosol (P < 0.0001). The ventilation- and perfusion-weighted images clearly defined the regionally matched perfusion-ventilation deficits in all the AO models, and the regionally mismatched perfusion-ventilation in all the PE models. CONCLUSION: Gd-based aerosol can provide efficient lung enhancement in spontaneously and adequately breathing animals, using a relatively noninvasive aerosol delivery system. The combined use of Gd-based perfusion MR imaging may be acceptable for defining regionally impaired function associated with acute AO and PE.